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Choline featured article

Choline is an essential nutrient critical for various bodily functions, including brain development, liver health, and muscle function. It acts as a precursor to acetylcholine, a neurotransmitter involved in memory, attention, and muscle control. Choline also contributes to the synthesis of phospholipid membranes and serves as a source of methyl groups necessary for metabolic processes. While the body can produce small amounts of choline, most of it must come from the diet to meet physiological needs.

The benefits of choline are wide-ranging. During pregnancy, adequate choline intake supports fetal brain development and may enhance memory, attention, and visual-spatial learning in children. It also plays a role in cardiovascular health by reducing the risk of heart disease and stroke. Additionally, sufficient choline levels have been linked to improved cognitive function and may lower the risk of cognitive decline and dementia. For athletes, choline is vital for muscle...

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Episodes

coffee

How To Use Coffee To Live Longer (Full Guide & Research)

Posted on June 9th 2025 (8 days)

Dr. Rhonda Patrick discusses coffee's remarkable ability to slow biological aging, reduce DNA damage, and lower cancer risk.

brain

Is Nicotine a Safe Cognitive Enhancer?

Posted on April 1st 2025 (3 months)

In this clip, Dr. Rhonda Patrick discusses nicotine's cognitive effects, risks to health, and safer alternatives for enhancing mental performance.

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Q&A #62 with Dr. Rhonda Patrick (9/7/24)

Posted on September 23rd 2024 (9 months)

Dr. Rhonda Patrick discusses if smoked salmon is carcinogenic, high-dose melatonin, creatine on workout vs. non-workout days, and the Neurocode brain scan.

Topic Pages

  • Aerobic exercise

    Aerobic exercise elevates cerebral perfusion and upregulates brain-derived neurotrophic factor, enhancing synaptic plasticity and neurogenesis.

  • Alcohol

    Alcohol penetrates the blood–brain barrier, allosterically potentiating GABA_A and inhibiting NMDA receptors, thereby depressing neuronal excitability.

  • Berberine

    Berberine penetrates the brain, activates neuronal AMPK, and suppresses microglial-driven neuroinflammation and oxidative stress.

  • Blood-brain barrier

    Brain microvascular endothelial tight junctions form the blood-brain barrier, selectively transporting nutrients while excluding neurotoxic blood-borne molecules.

  • Brain-derived neurotrophic factor (BDNF)

    Brain neurons and astrocytes synthesize BDNF that binds TrkB receptors, triggering signaling cascades for neuronal survival, differentiation and synaptic plasticity.

  • Breast milk and breastfeeding

    Nipple afferent stimulation activates maternal brain hypothalamic neuroendocrine release of prolactin and oxytocin, coordinating milk synthesis and let-down.

  • Choline

    In the brain, choline crosses the blood–brain barrier via high-affinity transporters and is acetylated to produce neurotransmitter acetylcholine.

  • Cold exposure

    Cold exposure triggers cutaneous thermoreceptors and hypothalamic pathways, increasing catecholamine release, thus enhancing cortical arousal and mood regulation.

  • Creatine

    Neurons uptake creatine via SLC6A8, convert it to phosphocreatine, which buffers ATP through creatine-kinase-mediated phosphate transfer.

  • Depression

    Depression involves brain network dysregulation: diminished prefrontal-limbic connectivity, impaired monoaminergic signaling, neuroplasticity deficits, and HPA axis hyperactivation.

  • Exercise Intensity

    Rising exercise intensity proportionally augments cerebral perfusion, catecholamine release and BDNF synthesis through neurovascular and neurochemical mechanisms.

  • Microplastics

    Experimental studies show ingested microplastics translocate across the blood–brain barrier, inducing oxidative stress, neuroinflammation and neuronal apoptosis.

  • Multivitamins

    Multivitamin micronutrients act as enzymatic cofactors supporting brain energy metabolism, neurotransmitter synthesis, and antioxidative neuroprotection.

  • Omega-3 fatty acids

    Docosahexaenoic acid, an Omega-3, integrates into brain neuronal phospholipid bilayers, modulating membrane fluidity, synaptic signaling, neuroinflammation.

  • Polyphenol-rich diets and neurodegeneration (glycemic control)
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    Polyphenol-rich diets supply brain-penetrant flavonoids that activate neuronal AMPK, enhance insulin signaling, suppress AGE accumulation, and thus curb glycemia-driven neurodegeneration.

  • Polyphenols

    Polyphenols cross the blood–brain barrier, mitigating oxidative stress and neuroinflammation by activating Nrf2 and inhibiting NF-κB signaling.

  • Red light therapy (photobiomodulation)

    Near-infrared photobiomodulation penetrates scalp, photons excite neuronal cytochrome-c oxidase, enhancing mitochondrial ATP, nitric oxide release, cerebral perfusion.

  • Salmon roe

    In the brain, DHA from salmon roe integrates into neuronal phospholipids, modulating membrane fluidity and synaptic signal propagation.

  • Sirtuins

    Brain-expressed NAD⁺-dependent sirtuins deacetylate histones and transcription factors, thereby augmenting neuronal mitochondrial biogenesis, synaptic plasticity, neuroprotection.

  • Small vessel disease

    Cerebral small-vessel disease disrupts brain microvascular endothelial integrity, driving chronic hypoperfusion, blood–brain barrier failure, and progressive neurodegeneration.

  • Sulforaphane

    Sulforaphane crosses the blood–brain barrier, activates Nrf2 transcription, elevates glutathione synthesis, and reduces microglial pro-inflammatory signaling.

  • Ultra-processed Foods (UPFs)

    Ultra-processed foods hyperactivate dopaminergic reward circuits, attenuate satiety signaling, and reinforce compulsive eating behaviors.

News & Publications

  • Seafood consumption during pregnancy may enhance a child's behavioral, social, and cognitive development, with benefits reported from infancy through adolescence. www.sciencedirect.com
    Brain Diet

    Seafood provides essential nutrients, but it also raises concerns during pregnancy. Although seafood is high in compounds that promote fetal brain development, worries about mercury levels have frequently shaped recommendations. A recent systematic review found that seafood consumption during pregnancy may enhance a child’s behavioral, social, and cognitive development.

    Researchers reviewed 40 studies (primarily long-term observational research) that tracked seafood consumption during pregnancy and children’s developmental outcomes, including behavior, social-emotional skills, and cognitive abilities. They screened each study for quality and assessed the strength of the evidence based on consistency, effect size, and study design.

    They found that children whose mothers consumed more seafood during pregnancy tended to demonstrate better behavioral and social-emotional development from infancy through adolescence and stronger overall developmental scores before age 4. Some studies linked higher seafood intake to improved attention, reasoning, and verbal intelligence, although findings in those areas were less consistent. The researchers found little to no evidence regarding seafood intake during lactation, and results were mixed for outcomes such as movement, language, attention-deficit/hyperactivity disorder, and autism spectrum disorder.

    These findings suggest that eating seafood during pregnancy—within current recommendations of 8 to 12 ounces per week—supports a child’s development, especially in social and behavioral areas. Learn more about optimizing one’s diet and lifestyle for pregnancy in Aliquot #100: Optimizing for a Healthy Pregnancy & Early Childhood

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  • Creatine supplements improve brain energy use and potentially slow cognitive decline among Alzheimer's disease patients, suggests preliminary research. pmc.ncbi.nlm.nih.gov
    Alzheimer's Brain

    The brain needs a steady supply of energy to function correctly, and this energy supply often breaks down in the early stages of Alzheimer’s disease. Some evidence suggests that problems with the brain’s creatine system may play a role in this decline. A recent study found that creatine supplements improved brain energy use, reduced the buildup of Alzheimer’s disease-related proteins, and boosted memory in mice.

    Researchers conducted an eight-week pilot study involving 20 people with cognitive impairment due to Alzheimer’s disease. All participants took 20 grams of creatine monohydrate daily and attended five in-person visits throughout the study. Researchers tracked their ability to complete the program, adherence to the supplement regimen, changes in brain creatine levels, cognitive function, mitochondrial activity in blood cells, and muscle strength and size.

    Because this was a feasibility trial, the primary focus was whether participants could tolerate and stick to the supplementation protocol, not efficacy. Preliminary results indicated that most participants completed the study, took the supplement as directed, and tolerated it well. Early data also pointed to potential changes in brain chemistry and mitochondrial function. However, the investigators cautioned that the study was not designed to determine whether creatine definitively improved cognition or muscle health.

    These findings suggest that creatine supplementation is safe and feasible for people with Alzheimer’s disease and may support brain energy metabolism. Larger and longer-term studies may demonstrate whether creatine can help slow cognitive decline or improve quality of life. Learn more about the health effects of creatine in this episode featuring Dr. Darren Candow.

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  • Chronic stress inhibits autophagy—the brain's recycling system—but restoring its functionality yields rapid antidepressant effects. pubmed.ncbi.nlm.nih.gov
    Brain Depression Stress Autophagy

    In small doses, stress can sharpen focus and improve resilience, but chronic stress gradually erodes emotional stability, increasing the risk of major depressive disorder. A recent study found that autophagy—the brain’s recycling and housekeeping system—helps maintain emotional stability by removing old or damaged proteins.

    Researchers explored how short-term and long-term stress influenced autophagy in mice and investigated whether antidepressant drugs could restore this process. Employing genetic techniques, the researchers selectively inhibited or enhanced autophagy in a region of the brain called the lateral habenula and then monitored how the animals reacted to stress.

    They found that acute stress activated autophagy, while chronic stress inhibited it. When autophagy ceased functioning properly, stress-related behaviors increased. However, restoring autophagy—even briefly—produced rapid antidepressant-like effects. Drugs commonly used to treat depression also reactivated autophagy in this brain region. Additional experiments indicated that autophagy helps regulate brain cell activity by breaking down excess glutamate receptors, which are often overactive in depression.

    These findings suggest that disrupted autophagy in the lateral habenula plays a central role in how chronic stress contributes to depression. Learn more about autophagy in this episode featuring Dr. Guido Kroemer.

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  • Artificial sweetener sucralose may disrupt the brain's appetite regulation by mimicking sweetness without increasing blood sugar, leading to increased hunger and altered brain activity. www.nature.com
    Brain Diet Obesity Sugar Weight Loss

    Artificial sweeteners like sucralose are marketed as healthier alternatives to sugar, but they may send mixed signals to the brain. A recent study found that sucralose increased hunger and altered activity in the part of the brain that regulates appetite, with effects differing by body weight.

    Researchers asked 75 young adults—some with a healthy weight and some with overweight or obesity—to drink a beverage sweetened with either sucralose (often marketed as Splenda), sucrose (table sugar), or plain water on three separate occasions. Afterward, the researchers measured the participants' blood glucose levels, collected their self-reported hunger ratings, and conducted brain scans to examine activity and connectivity in key regions involved in appetite control.

    Compared to sugar, sucralose increased blood flow to the hypothalamus and promoted stronger feelings of hunger. Sucralose also heightened hypothalamic activity more than water but didn’t influence hunger. Only sugar elevated blood glucose levels, an increase linked to reduced activity in the hunger-regulating regions of the brain.

    Interestingly, the brain’s response to sucralose differed based on body weight: In people with a healthy weight, sucralose enhanced connections between the hypothalamus and areas involved in attention and decision-making. In those with overweight, sucralose diminished connections to brain regions that process bodily sensations. And those with obesity exhibited little to no change in these neural connections. Compared to water, both sweeteners elicited distinct patterns of brain activity depending on weight status.

    These findings suggest that sucralose interferes with the brain’s normal appetite-regulating signals by mimicking sweetness without delivering the expected rise in blood sugar. This mismatch appears to increase hunger and alter brain connectivity in ways that vary depending on body weight. Artificial sweeteners also affect the gut microbiome. Learn more in this clip featuring Dr. Eran Elinav.

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  • Ketogenic diet raises brain blood flow by 22% and increases brain-derived neurotrophic factor by 47%, highlighting its potential to support cognitive function even in people without cognitive impairment. pubmed.ncbi.nlm.nih.gov
    Brain Diet Ketosis Memory BDNF Ketogenic Diet

    Glucose has long been considered the brain’s primary fuel, but ketone bodies may offer critical support, especially during periods of low carbohydrate availability. A recent study found that a ketogenic diet boosted levels of brain-derived neurotrophic factor (BDNF)—a key protein that supports brain health—by 47%, highlighting the diet’s potential to support brain health even in people without cognitive impairment.

    Researchers recruited 11 healthy but overweight adults to participate in a randomized, crossover study. Each participant followed two different diets: a ketogenic diet high in fat and low in carbohydrates, and a standard balanced diet. Each diet lasted three weeks and ended with brain imaging scans (using MRI and PET) and blood tests to measure brain blood flow and BDNF levels.

    They found that the ketogenic diet markedly increased ketone levels in the blood compared to the standard diet. Brain blood flow rose by 22% after eating the ketogenic diet, and BDNF levels increased by 47%. Researchers also found a strong link between ketone levels in the blood and higher brain blood flow.

    This was a small study, but the findings suggest that a ketogenic diet enhances brain blood flow and boosts vital brain-supporting proteins, even in people without memory loss. This opens up new possibilities for using ketogenic nutrition as a strategy to preserve cognitive function and support long-term brain health. Learn how to plan the optimal ketogenic diet in this clip featuring Dr. Dominic D'Agostino.

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  • Uphill walking, even at a slow pace, provides cognitive benefits by increasing brain lactate and stimulating BDNF production—a protein critical for memory and learning. www.sciencedirect.com
    Exercise Brain Memory BDNF Lactate

    If you’re struggling to remember things, a robust workout might help. Scientists have discovered that exercise can increase levels of brain-derived neurotrophic factor (BDNF), a protein that supports learning and memory. A recent study in rats found that low-speed uphill exercise raises blood lactate levels, increasing lactate and BDNF in key brain regions involved in cognition.

    Researchers divided rats into three groups: One remained inactive, another walked on a flat treadmill, and a third walked uphill at a 40% incline. The exercise sessions lasted either 30 or 90 minutes. To see if lactate from the blood contributed to brain changes, some rats also received a direct lactate injection.

    Uphill exercise increased lactate levels in the animals' blood and brains, while flat treadmill walking did not. After 90 minutes, uphill exercise also raised BDNF levels in brain regions linked to memory and learning. The lactate injection showed that blood lactate passed into the brain, reinforcing that exercise-induced increases in blood lactate can influence brain chemistry.

    These findings suggest that walking uphill—even slowly—provides cognitive benefits by raising brain lactate and stimulating BDNF production. This type of exercise could be a practical and safe way to support brain health, especially for older adults or those looking to enhance memory and learning. To learn more strategies to boost brain health, check out the Cognitive Enhancement Blueprint, a member-only perk.

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  • The combined effects of hypertension, diabetes, and smoking may accelerate brain aging, with hypertension being the most significant predictor of structural decline. spj.science.org
    Brain Aging Diabetes Blood Pressure

    Your brain may be aging faster than the rest of your body. While some people maintain brain health well into old age, others experience structural decline much earlier. A recent study found that multiple health factors—including hypertension, diabetes, smoking, and low educational attainment—may speed up brain aging, increasing the risk of cognitive decline and neurodegenerative diseases.

    Researchers analyzed brain scans and long-term health data from 964 adults in northern China, monitoring them for 16 years. They used machine learning to estimate brain age based on imaging techniques and compared brain aging among groups with various high-risk health factors. They also focused on people with high blood pressure to see how it affects brain structure.

    They found that people with four or five high-risk factors had considerably older-looking brains than those with fewer risks, suggesting that multiple health problems may accelerate brain aging. Hypertension, high blood sugar, elevated creatinine (a feature of metabolic disease), smoking, and lower education were the strongest predictors of brain structure decline. However, hypertension had the strongest link, with hypertensive participants exhibiting more substantial structural deterioration.

    These findings suggest maintaining good cardiovascular and metabolic health may help slow brain aging. Hypertension damages the brain’s microvasculature. Learn how exercise preserves these tiny blood vessels, helping to maintain cognitive health.

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  • Menopausal hormone therapy accelerates tau protein buildup in brain regions linked to Alzheimer's in women over 70, potentially contributing to their higher vulnerability to the disease. www.science.org
    Brain Alzheimer's Hormones Dementia

    According to some estimates, Alzheimer’s disease will affect nearly 14 million Americans by 2060, with women comprising two-thirds of those cases. Research indicates that this disparity arises from the buildup of tau, a protein linked to cognitive decline, which occurs earlier and progresses more rapidly in women. A recent study found that menopausal hormone therapy accelerates tau accumulation in older women, potentially contributing to this heightened risk.

    The study involved 146 cognitively healthy women between the ages of 51 and 89. Researchers used brain scans to measure the accumulation of amyloid-beta and tau proteins in the women’s brains and gathered information about their menopausal hormone usage.

    They found that women over 70 who had used hormone therapy showed faster tau buildup in key brain regions linked to Alzheimer’s disease. This increase in tau was also associated with greater cognitive decline. However, in younger women—those under 70—hormone therapy had little to no effect on tau accumulation.

    These findings suggest that the timing of hormone therapy plays a critical role in brain health, supporting the idea that initiating treatment earlier in menopause may be safer. Understanding how hormone therapy influences tau buildup could help refine guidelines for menopausal treatment and Alzheimer’s risk reduction. Learn more about factors that influence the risk of Alzheimer’s disease in this clip featuring Dr. Dale Bredesen.

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  • Even a brief five-day junk food binge can disrupt the brain's insulin function, potentially impairing memory and influencing eating decisions over the long term. www.nature.com
    Brain Diet Insulin

    Study link:

    Indulging in a junk food binge can have lasting effects on your brain, even after you return to your usual eating habits. A recent study found that five days of overeating high-calorie, nutrient-poor foods temporarily boosted brain insulin sensitivity but caused a drop in responsiveness once participants switched back to a healthier diet.

    Researchers assigned 29 healthy-weight men, ages 19 to 27, to one of two groups: One followed a junk food diet for five days, while the other stuck to their regular eating habits. They measured participants' brain insulin activity through imaging techniques and insulin administration before and after the binge.

    At the peak of the junk food binge, researchers observed heightened insulin activity in key brain regions. However, just one week after returning to their usual diet, participants who had overindulged experienced lower brain insulin sensitivity, particularly in areas associated with memory and food-related reward, such as the hippocampus and fusiform gyrus. Interestingly, while the junk food group showed increased liver fat, there were no noticeable changes in weight or peripheral insulin sensitivity.

    These findings suggest that the effects of overeating go beyond immediate metabolic changes, potentially contributing to cognitive decline and influencing eating behaviors over time. They also underscore how even a brief junk food binge can disrupt insulin function in the brain, impairing areas critical to memory and decision-making. Behavioral strategies like mindfulness can help curb overeating. Learn more in this clip featuring Dr. Ashley Mason.

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  • Sleep enhances the brain's waste removal through synchronized fluctuations in norepinephrine and blood volume, a process disrupted by the common sleep aid, zolpidem. https://www.cell.com/cell/abstract/S0092-8674\(24\)01343-6
    Brain Sleep Norepinephrine Neurodegeneration

    The brain doesn’t just rest during sleep—it actively clears out waste that can damage brain cells. This crucial process, known as glymphatic clearance, relies on the movement of cerebrospinal fluid to wash away harmful proteins linked to neurodegenerative diseases. A recent study found that synchronized fluctuations in norepinephrine, blood volume, and cerebrospinal fluid are key drivers of glymphatic clearance during deep sleep, but some popular sleeping pills disrupt this process.

    The researchers tracked blood and cerebrospinal fluid dynamics while mice slept naturally. Then, they examined how zolpidem, commonly known as Ambien, affected these dynamics during sleep.

    They found that norepinephrine fluctuations triggered by the brain’s locus coeruleus drove rhythmic changes in blood vessel size. This facilitated the movement of cerebrospinal fluid into the brain and the removal of waste products. However, zolpidem disrupted norepinephrine activity, reducing cerebrospinal fluid flow and hindering this waste removal process.

    These findings suggest that the brain’s waste removal system relies on a delicate balance of norepinephrine and blood vessel activity. Sleep aids like zolpidem disrupt this process, potentially contributing to neurodegenerative diseases like Alzheimer’s. Learn more about the effects of sleep aids like Ambien in this episode featuring Dr. Matthew Walker.

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  • Lower levels of active B12 linked to slower visual processing and cognitive decline, suggesting current guidelines may not adequately ensure brain health. onlinelibrary.wiley.com
    Brain Micronutrients Vitamin B12 Neurodegeneration

    Scientists have long known that severe B12 deficiency can cause neurological problems, but the exact threshold for deficiency-related damage remains unclear. A recent study found that older adults with B12 levels in the lower end of the normal range showed signs of neurological dysfunction.

    Researchers measured B12 levels and conducted brain scans on 231 healthy older adults. Participants underwent tests to evaluate brain function, including visual processing speed and cognitive performance. The researchers also assessed blood biomarkers associated with nerve damage and brain health.

    They found that lower B12 levels, particularly the active form of the vitamin, were associated with slower visual processing, cognitive decline, and increased signs of white matter damage in the brain. Surprisingly, high levels of the inactive form of B12 correlated with increased tau protein, a marker of neurodegeneration.

    These findings suggest that current B12 guidelines don’t fully capture what the brain needs to function correctly and that even “normal” B12 levels could contribute to neurological changes. They also highlight the role of adequate nutrition throughout the lifespan and support the “micronutrient triage theory"—the idea that the body prioritizes micronutrient utilization for survival over those used for long-term health. Learn more about micronutrient triage theory in this episode featuring Dr. Bruce Ames.

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  • Anthocyanins, potent antioxidants in berries, boost cognitive function in people at higher risk of dementia, particularly those with high inflammation. www.sciencedirect.com
    Brain Diet Inflammation Polyphenol

    Anthocyanins, the compounds that give berries their deep red and purple hues, may do more than add color to a meal. Evidence suggests these potent antioxidants protect brain health, particularly in people at higher risk of dementia. A recent study found that anthocyanins improved cognitive function in people with high inflammation levels, but not those with lower inflammation.

    Researchers conducted a 24-week randomized, placebo-controlled trial to examine anthocyanins' effects on cognition. They categorized participants into two groups based on inflammation levels, using blood biomarkers to make the distinction. Each participant received either anthocyanins or a placebo, and the researchers measured cognitive function before and after the intervention.

    The cognitive test results indicated that participants with high inflammation experienced marked cognitive improvements after anthocyanin treatment, while those with lower inflammation saw no benefit. Interestingly, participants in the high-inflammation group had higher body mass indexes, greater diabetes prevalence, and lower HDL (“good”) cholesterol levels.

    These findings suggest that anthocyanins improve cognitive function among people with high inflammation. Anthocyanins are polyphenolic compounds. Learn more about polyphenols in our overview article.

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  • Microplastics in the bloodstream may obstruct tiny blood vessels in the brain, impairing blood flow and causing neurological disorders, according to a recent study in mice. www.science.org
    Brain Pollution Neurodegeneration

    Microplastics are everywhere in the environment—from the water we drink to the air we breathe. Scientists have found these tiny plastic particles in human blood, organs, and even the brain, raising concerns about their potential health effects. A recent study in mice found that microplastics in the bloodstream can obstruct tiny blood vessels in the brain, impairing blood flow and driving neurological disorders.

    Researchers injected fluorescently labeled microplastics into mice and observed how the particles traveled through brain capillaries. In particular, they focused on how immune cells interacted with microplastics and whether they contributed to vascular blockages.

    They found that immune cells engulfed microplastics, driving unintended consequences. These microplastic-laden cells clogged capillaries in the brain, reducing blood flow and triggering neurological impairments in the mice. The blockages resembled tiny blood clots, highlighting a previously unknown way microplastics could harm brain function.

    These findings suggest that microplastics contribute to brain dysfunction by indirectly disrupting blood flow rather than directly penetrating brain tissue. Learn more about microplastics and brain health in this episode featuring Dr. Rhonda Patrick.

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  • Regular aerobic exercise in older rats reduces brain inflammation, nerve fiber demyelination, and iron-triggered cell death—potential contributors to Alzheimer's pathology. pubmed.ncbi.nlm.nih.gov
    Exercise Brain Alzheimer's Inflammation Dementia Iron

    The pathological brain changes that drive Alzheimer’s disease may begin as much as 20 years before cognitive signs become evident. However, evidence indicates that exercise can slow or prevent these changes. A recent study involving older rats found that regular aerobic exercise reduces age-related inflammation in the brain and improves the balance between nerve fibers and their protective myelin coating.

    Researchers had older rats exercise on a treadmill for eight weeks. Then, they examined the rats' brain tissue and analyzed changes in tau protein, amyloid plaques, and iron levels.

    They discovered that older rats engaging in regular physical exercise experienced reduced age-related inflammation and improved balance between nerve fibers and their protective myelin coating. They also learned that excessive iron in oligodendrocytes—cells that support and insulate nerve fibers—triggers a type of cell death known as ferroptosis, possibly contributing to the formation of amyloid-beta plaques linked to Alzheimer’s. They identified statistical connections between tau and amyloid proteins (hallmarks of Alzheimer’s), iron levels, and cells in the hippocampus, a brain region crucial for memory.

    These findings indicate that iron plays a critical role in Alzheimer’s pathology, but exercise can mitigate some of these effects. Learn more about preventing and reversing Alzheimer’s disease in this episode featuring Dr. Dale Bredesen.

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  • Exercise boosts language comprehension in monolingual older adults by enhancing cardiorespiratory fitness. www.tandfonline.com
    Exercise Brain Cardiovascular

    Regular exercise has long been known to protect cognitive functions such as attention, memory, and processing speed as we age. A recent study found that exercise may also improve older adults' language comprehension by enhancing cardiorespiratory fitness—the body’s capacity to deliver and use oxygen-rich blood.

    The study included 160 monolingual or bilingual older adults. Half of the participants followed a 26-week home-based high-intensity interval training (HIIT) program with three weekly sessions, starting with a four-week familiarization period. Afterward, they aimed for over 80% of their peak heart rate. Researchers measured their cardiorespiratory fitness and language comprehension before and after the intervention, using reaction times to spoken-word monitoring tasks.

    They found that monolinguals who participated in the HIIT program responded faster on comprehension tasks than non-exercisers. This improvement was linked to increased VO2peak (a measure of cardiorespiratory fitness), supporting the idea that exercise boosts language processing abilities in older adults. However, bilinguals did not experience these improvements, suggesting that the effects of exercise on language processing may be influenced by language proficiency.

    These findings support the growing evidence demonstrating that cardiorespiratory fitness protects cognitive function. HIIT robustly improves cardiorespiratory fitness. Learn more in this clip featuring Dr. Martin Gibala.

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  • A modified Mediterranean ketogenic diet boosts healthy brain fats and reduces Alzheimer's-associated markers, suggesting potential neuroprotective effects. pmc.ncbi.nlm.nih.gov
    Nutrition Brain Alzheimer's Diet Ketogenic Diet

    Roughly 60% of the human brain is made up of fat, which plays a crucial role in the structure and function of brain cells. In Alzheimer’s, fat metabolism in the brain becomes altered, influencing disease progression. A recent study found that a modified Mediterranean ketogenic diet boosted healthy fats in the brain and lowered Alzheimer’s-associated markers.

    The study included 20 adults with prediabetes who were at risk for developing Alzheimer’s. Participants followed the modified Mediterranean ketogenic diet or the American Heart Association diet for six weeks. After a six-week break, they switched to the opposite diet for another six weeks. Before and after each diet intervention, participants underwent cognitive testing, and the researchers evaluated their blood lipids and Alzheimer’s markers, including amyloid-beta and tau.

    They found that the modified Mediterranean ketogenic diet caused notable changes in blood lipids, increasing molecules linked to fat breakdown and energy use (such as free fatty acids and acylcarnitines) while lowering triglycerides. It also boosted healthy lipid types (plasmalogens) and reduced harmful ones (deoxyceramides). These alterations in blood lipids correlated with improved Alzheimer’s biomarkers and cognitive measures. The American Heart Association diet had little or no effect on blood lipids or cognitive function.

    The traditional ketogenic diet is high in fat and low in carbohydrates. The modified Mediterranean-ketogenic diet is rich in fish, lean meats, and fiber-rich green leafy vegetables, nuts, and berries. About 5% to 10% of its calories come from carbohydrates, 60% to 65% from fat, and 30% from protein. In the American Heart Association diet, about 55% to 65% of calories come from carbohydrates, 15% to 20% from fat, and 20% to 30% from protein.

    The findings from this small intervention study suggest that a modified Mediterranean ketogenic diet protects against Alzheimer’s disease. Learn more about the ketogenic diet and Alzheimer’s disease in this clip featuring Dr. Dale Bredesen.

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  • Traumatic brain injuries reactivate dormant herpes simplex virus, causing inflammation and accumulation of harmful proteins in the brain, a process potentially linked to Alzheimer's disease. www.science.org
    Brain Alzheimer's Inflammation Virus TBI

    Each year, millions of people sustain a traumatic brain injury (TBI), often resulting in serious, long-term consequences. Research indicates that even one head injury is linked to a higher risk of developing dementia, with the risk increasing further after two or more. A recent study found that TBIs can reactivate dormant herpes simplex virus type 1 (HSV-1), driving neuroinflammation and contributing to the development of Alzheimer’s.

    Researchers created a three-dimensional model of the human brain. Then, they subjected HSV-1-infected and non-infected brain tissue to multiple blows, emulating TBIs and their ensuing pro-inflammatory effects.

    They found that repeated mild blows to HSV-1-infected tissues reactivated the virus, triggering inflammatory processes in the brain and driving the buildup of amyloid-beta and phosphorylated tau—proteins linked to brain damage and memory loss. These harmful effects worsened with additional injuries but didn’t occur in uninfected tissue.

    These findings demonstrate that viral reactivation in the brain may contribute to the development of Alzheimer’s. HSV-1 is the virus responsible for causing cold sores and genital herpes. It infects approximately 80% of people by age 60 and is commonly found in the brains of older adults. In people with the APOE4 gene, HSV-1 markedly increases the risk of Alzheimer’s.

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  • Regular green tea consumption correlates with fewer cerebral white matter lesions, potentially reducing the risk of stroke, dementia, and disability. www.nature.com
    Brain Aging Green Tea Dementia Polyphenol

    About half of your brain is white matter—a network of nerve fibers that allow for the exchange of information and communication within the brain. Aging and lifestyle factors can damage the white matter, increasing the risk of stroke, dementia, and disability. However, a recent study found that the brains of regular green tea drinkers have fewer white matter lesions than non-drinkers.

    The study included nearly 8,800 older adults living in Japan. Participants provided information about their green tea and coffee consumption and underwent magnetic resonance imaging to assess their brain health and volume.

    They found that higher green tea consumption correlated with fewer cerebral white matter lesions but had little effect on brain volumes, even after accounting for demographic, lifestyle, and health factors. People who drank about three cups (~20 ounces) of green tea daily had 3% less white matter damage in their brains than those who drank just one cup (~7 ounces). Those who drank around seven to eight glasses (~50 ounces) daily had 6% less damage. Coffee consumption did not affect white matter or brain volume, suggesting that green tea protects against white matter damage.

    Green tea contains epigallocatechin gallate (EGCG), a polyphenolic compound that exerts robust antioxidant, anti-inflammatory, and neuroprotective effects. Evidence suggests that EGCG reduces the buildup of amyloid beta and tau—two proteins involved in the pathophysiology of Alzheimer’s disease. Learn more about EGCG and other polyphenols in our overview article.

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  • The brain's vagus nerve controls fat absorption in the intestine—a possible pathway for managing obesity. pubmed.ncbi.nlm.nih.gov
    Brain Diet Obesity Fat Isothiocyanates

    Fat is a vital energy source, but when consumed in excess, it can promote obesity. However, the amount of fat the body absorbs may be more related to the brain than the gut. A recent study in mice found that signals from the brain’s vagus nerve regulate fat uptake in the intestine, offering a potential means to moderate obesity.

    Researchers manipulated the dorsal motor nucleus of the vagus (DMV), which plays a crucial role in digestion. They inactivated DMV neurons that connect to the jejunum (the middle portion of the intestine), shortening the length of the microvilli in the gut and reducing fat absorption. However, stimulating DMV neurons increased fat absorption and promoted weight gain. Finally, they injected mice with puerarin, a bioactive compound derived from the kudzu plant, and found that the compound mimicked the effect of DMV suppression, further reducing fat absorption.

    These findings suggest that controlling the DMV-vagus-jejunum pathway could provide a novel approach to managing fat absorption and weight. They also highlight yet another way the brain-gut axis influences human health.

    Puerarin is an isothiocyanate, a class of sulfur-containing compounds known for their potent anti-inflammatory, anti-cancer, and anti-obesity effects. Sulforaphane, another well-known isothiocyanate, shares many of these beneficial properties. To learn more about the health effects of sulforaphane, check out our overview article.

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  • A diet abundant in antioxidants, iron-chelating nutrients, and polyunsaturated fatty acids mitigates harmful iron accumulation in the brain, preserving cognitive function. www.sciencedirect.com
    Brain Diet Iron Polyphenol

    Although iron is essential for many physiological processes in the body, it can also be harmful, inducing oxidative stress and hindering neurogenesis. The body typically stores iron in protein complexes until needed, but these storage processes decline with age, leading to iron accumulation in body tissues. A recent study revealed that iron can build up in the brain, impairing cognitive function. Nevertheless, dietary components can help reduce iron accumulation in the brain and maintain cognitive health.

    Researchers examined the brain health of 72 cognitively healthy older adults by conducting brain scans at baseline and two to three years later. Participants provided details about their dietary habits, physical activity, and overall health. They also underwent cognitive tests that evaluated their episodic memory and executive function.

    The brain scans revealed that iron levels increased markedly over time, and higher iron accumulation correlated with poorer cognitive function. However, a higher intake of antioxidants, vitamins, iron-chelating nutrients, and polyunsaturated fatty acids mitigated iron accumulation. Iron-chelating nutrients include polyphenolic compounds, such as gallic acid and catechins (in tea), caffeic acid (in coffee), quercetin (in apples and onions), ellagic acid (in walnuts and pomegranates), curcumin (in turmeric) and others.

    These findings suggest that diet mitigates iron accumulation in the brain, ultimately influencing cognitive health. Interestingly, alcohol can promote iron accumulation in the brain. Learn more in this episode featuring Dr. Rhonda Patrick.

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  • Omega-3-rich flaxseed oil boosts verbal fluency in older adults, improving cognitive function and potentially preventing Alzheimer's. www.mdpi.com
    Brain Diet Aging Omega-3 Memory

    Flaxseed oil is rich in alpha-linolenic acid (ALA), an omega-3 fatty acid. In the liver, ALA converts to docosahexaenoic acid (DHA), a crucial component of brain health. Evidence suggests that low DHA levels can impair cognitive function. However, a recent study in older adults found that supplemental flaxseed oil enhances cognitive function, particularly verbal fluency—the ability to retrieve and use words quickly.

    The study involved 60 cognitively healthy older adults between the ages of 65 and 80. Half of the participants received 3.7 grams of flaxseed oil containing 2.2 grams of ALA daily for 12 weeks, and the other half received corn oil. Before and after the intervention, researchers assessed aspects of their cognitive function, including verbal fluency.

    Verbal fluency relies on several cognitive skills, including recalling word meanings, finding the right words quickly, processing information efficiently, controlling impulses, holding and using information in the moment, switching between tasks or ideas, and adapting to new situations. It also involves multiple areas of the brain working together. Unfortunately, verbal fluency declines with age, impairing conversation and social interactions and serving as a predictor of Alzheimer’s disease.

    The researchers found that participants who received the ALA-rich flaxseed oil supplement had higher verbal fluency than their peers who received the corn oil, suggesting that flaxseed oil is suitable for delivering crucial omega-3s to the brain. Learn more about the effects of omega-3s on brain health in this clip featuring Dr. Axel Montagne.

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  • Cardiovascular risk and obesity accelerate brain atrophy in men a decade before similar effects occur in women, potentially increasing dementia risk. jnnp.bmj.com
    Brain Obesity Cardiovascular

    Cardiovascular health affects more than the heart—it shapes the brain. A recent study found that cardiovascular risk and obesity contribute to brain atrophy in men and women, with effects manifesting earlier in men.

    Researchers analyzed data from more than 34,000 adults aged 45 to 82 enrolled in the UK Biobank study. They measured the participants' grey matter volume, assessed their cardiovascular risk, and calculated the fat volume under their skin and around their internal organs.

    They found that men experienced considerable grey matter volume losses linked to cardiovascular risk and obesity between ages 55 and 64. However, volume losses in women manifested a decade later, between ages 65 and 74. These patterns were evident regardless of whether participants carried the APOE4 gene, a key genetic risk factor for Alzheimer’s disease.

    These findings suggest that cardiovascular disease-related dementia risks manifest earlier in men, underscoring the importance of tailoring interventions based on sex. One of the mechanisms linking cardiovascular disease, obesity, and dementia is vascular dysfunction, which contributes to blood-brain barrier failure. Learn more about vascular dysfunction in this clip featuring Dr. Axel Montagne.

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  • Glyphosate exposure in mice accelerates Alzheimer's disease processes, with the herbicide's metabolites persisting in brain tissue six months after initial exposure. jneuroinflammation.biomedcentral.com
    Brain Alzheimer's Dementia Pollution

    Glyphosate, a widely used herbicide, has been linked to widespread inflammation and neuronal damage in the brain. A recent study in mice found that glyphosate and its primary metabolite, aminomethylphosphonic acid, persist in brain tissue for months after exposure, potentially contributing to neurodegenerative changes.

    Researchers exposed ordinary mice and mice prone to developing Alzheimer’s to varying doses of glyphosate daily for 13 weeks. Six months later, they examined the animals' brain tissues for lingering glyphosate, metabolites, and key markers of Alzheimer’s pathology, including amyloid-beta plaques, tau tangles, and inflammation.

    They discovered that glyphosate’s primary metabolite remained in brain tissue even after six months of non-exposure. Glyphosate-exposed Alzheimer’s-prone mice had lower survival rates, more difficulty in spatial memory tasks, and increased markers of Alzheimer’s pathology, including larger and more numerous amyloid-beta plaques and higher levels of phosphorylated tau protein. Both groups of mice exhibited persistent inflammation in their brains and blood.

    These findings suggest that glyphosate exposure may contribute to long-lasting brain changes, accelerating processes involved in Alzheimer’s disease. Learn how to mitigate exposures to environmental toxins like glyphosate in this Aliquot featuring Drs. Dale Bredesen, Michael Snyder, and Rhonda Patrick.

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  • Athletes exhibit 63% better working memory performance than sedentary people, underscoring the cognitive benefit of regular physical activity. www.tandfonline.com
    Exercise Brain Aging Memory

    Working memory, the brain’s system for temporarily storing and managing information, is crucial for recalling strategies and adapting to rapidly changing situations. A recent meta-analysis found that athletes outperform non-athletes by as much as 63% on working memory tasks.

    Researchers analyzed 21 studies involving more than 1,400 participants across various sports, including basketball, football, and fencing. They assessed working memory through tasks like recalling sequences or matching stimuli after delays. The various studies compared athletes to non-athletes, including sedentary people, and examined factors like sports type and activity level.

    The analysis revealed that athletes had a slight but consistent advantage in working memory compared to non-athletes, with a 30% improvement overall. When athletes were compared to sedentary people, their working memory performance was 63% better. However, the advantage dropped to just 15% when sedentary participants were excluded, suggesting a notable disadvantage for people with inactive lifestyles.

    These findings suggest that sports expertise may enhance working memory, likely due to the cognitive demands of high-level performance. Moreover, sedentary lifestyles hinder working memory, underscoring the importance of regular physical activity for maintaining cognitive health. Physical activity also promotes longevity. Learn more about the longevity and brain-boosting effects of exercise in this episode featuring Dr. Rhonda Patrick.

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  • Beta-hydroxybutyrate, a ketone used by the brain during fasting or exercise, may help counteract toxic protein buildup in aging and Alzheimer's disease. pmc.ncbi.nlm.nih.gov
    Brain Alzheimer's Diet Ketosis Dementia Protein Ketogenic Diet

    Protein misfolding in the brain is a central player in both aging and Alzheimer’s disease, driving toxic protein buildup and brain cell dysfunction. However, evidence indicates that ketones—a critical brain fuel produced during fasting or exercise—may help reduce or prevent this damage. A recent cell study found that beta-hydroxybutyrate, a type of ketone, helps protect the brain by targeting toxic proteins for disposal.

    Researchers delivered beta-hydroxybutyrate to brain cells collected from mice and monkeys via an exogenous ketone ester. They examined the cells for changes in protein solubility and pathways involved in protein breakdown. They also studied beta-hydroxybutyrate’s effects on pathological proteins, such as amyloid-beta, in a nematode model of Alzheimer’s disease.

    They found that beta-hydroxybutyrate made pathological proteins insoluble, preventing their toxic spread while promoting their clearance through autophagy, the cell’s natural recycling process. This effect was specific to pathological proteins and wasn’t the result of changes in acidity or random chemical interactions. Beta-hydroxybutyrate also reduced amyloid-beta toxicity in nematodes.

    These findings suggest that a ketone ester of beta-hydroxybutyrate counteracts the toxic buildup of proteins in aging and Alzheimer’s disease. Further research is needed to translate these results to humans. Learn more about how ketone ester supplementation may improve brain health in this episode featuring Dr. Mark Mattson.

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  • Adolescent attention deficits are linked to higher cannabis use in young adulthood due to weaker connectivity in attention-related brain networks. elifesciences.org
    Brain Drug Development

    Cannabis use during adolescence has profound effects on critical cognitive functions, particularly sustained attention—the ability to focus on a task over time. A recent study found that problems with sustained attention in early adolescence may predict increased cannabis use later in life.

    The study involved more than 1,000 participants, starting at age 14 and continuing until age 23. Researchers measured the participants' attention performance and brain connectivity throughout the study. They also monitored their substance use over time to uncover long-term patterns.

    They found that poor sustained attention at age 14, in conjunction with weaker connectivity in attention-related brain networks, predicted higher cannabis use in young adulthood. Differences in these brain networks were stable over time, and the findings were consistent when tested in an external group of participants.

    These findings suggest that sustained attention and its underlying brain networks serve as reliable early markers of susceptibility to cannabis use. Cannabis use may disrupt the delicate balance of brain chemicals like dopamine, a neurotransmitter critical for attention and motivation. Learn how to improve attention by leveraging the effects of dopamine in this episode featuring Dr. Andrew Huberman.

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  • Women consuming five eggs weekly experience less decline in verbal fluency, a measure of semantic memory, highlighting the potential role of eggs in preserving cognitive function. www.mdpi.com
    Brain Diet Aging Cholesterol Memory Micronutrients

    Eggs are a dietary paradox: high in cholesterol but rich in brain-boosting nutrients, including choline, lutein, and zeaxanthin. While some studies indicate that eggs maintain cognitive health, others report the converse. A recent study found that eating eggs may help women preserve semantic memory—crucial for language comprehension and factual recall—as they age.

    Researchers analyzed data from 890 adults aged 55 and older. Participants reported their egg consumption using a food frequency questionnaire, and researchers measured their memory and thinking skills at two clinic visits about four years apart.

    They found that women who ate five eggs weekly experienced less decline in verbal fluency, a measure of semantic memory, than those who ate fewer eggs. In men, researchers found no clear relationship between egg intake and changes in cognitive performance. Eating eggs did not appear to harm cognitive function in either sex.

    These findings suggest that eggs play a small but beneficial role in preserving memory in women. They also align with other research demonstrating that people with moderate choline intake—roughly the amount in two eggs—are about half as likely to have low cognitive function than those with the lowest intake.

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  • A nasal spray delivering stem cell-derived extracellular vesicles reduces inflammation and improves brain function in a mouse model of Alzheimer's disease. isevjournals.onlinelibrary.wiley.com
    Brain Alzheimer's Inflammation Stem Cells Memory

    Stem cell-based therapies show promise as treatments for neurodegenerative diseases, including Alzheimer’s. However, transplanting stem cells into the brain carries considerable risks. A recent study found that a nasal spray that delivered neural stem cell extracellular vesicles—tiny particles that carry proteins and genetic material—reduced inflammation and improved brain function in a mouse model of Alzheimer’s disease, offering a safer, less risky approach.

    Researchers used neural stem cell-derived extracellular vesicles created from induced pluripotent stem cells. They administered the vesicles via nasal spray to three-month-old Alzheimer’s model mice. Then, they tracked the vesicles' interaction with brain cells, focusing on microglia and astrocytes, and analyzed gene activity, brain pathology, and behavioral changes.

    They found that the vesicles reduced inflammatory activity in brain cells, decreased levels of amyloid-beta plaques and phosphorylated tau (hallmarks of Alzheimer’s), and improved memory and mood in the mice. These effects persisted for at least two months after treatment without impairing the brain’s immune processes and protein clearance.

    These findings suggest that a nasal spray containing stem cell-derived extracellular vesicles offers a promising new therapy for Alzheimer’s disease, targeting inflammation and preserving brain function while avoiding the risks of direct stem cell transplantation. Other research demonstrates the effectiveness of stem cell therapies for eye diseases. Learn more in this clip featuring Dr. David Sinclair.

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  • Mediterranean diet variations, rich in polyphenols and targeted at metabolic health, halve brain atrophy markers, slowing age-related brain shrinkage by up to 50% over 18 months. www.sciencedirect.com
    Brain Diet Aging Polyphenol

    Brain atrophy occurs naturally with aging, but certain factors such as type 2 diabetes, high blood pressure, and inflammation can accelerate this process, increasing the risk of cognitive decline. However, eating a healthy diet may help slow brain aging. A recent study found that two versions of the Mediterranean diet reduced markers of brain atrophy by 50% over 18 months compared to general healthy eating guidelines.

    Researchers assigned participants aged 50 or older with abdominal obesity or abnormal blood lipids to one of three diets: one that followed standard healthy dietary guidelines, a calorie-restricted Mediterranean diet (which included walnuts and olive oil and substituted chicken and fish for lamb and beef), or a “green” calorie-restricted Mediterranean diet enriched with polyphenols from green tea and mankai, an aquatic plant. The participants underwent brain imaging to assess hippocampal atrophy, a key marker of brain aging, and the researchers tracked changes in body weight, blood sugar, and inflammation over the study period.

    Participants following the green Mediterranean diet showed the greatest preservation of brain volume, particularly in the hippocampus. They also experienced improvements in HbA1c (a marker of long-term blood glucose control), insulin resistance, fasting glucose, and C-reactive protein. Improvements in blood sugar levels and inflammation were closely linked to better brain health outcomes, and greater intake of polyphenol-rich foods like mankai and green tea further enhanced these benefits.

    Mankai, also called duckweed, is rich in polyphenols, omega-3 fatty acids, dietary fiber, and many micronutrients, including iron and vitamin B12. The polyphenols in mankai exert robust antioxidant activity and support healthy blood glucose levels—critical elements in maintaining brain health.

    These findings suggest that diets rich in polyphenols and designed to improve metabolic health may help protect against age-related brain atrophy and keep the brain biologically younger. Learn more about the health benefits of polyphenols in our overview article.

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  • Physical activity at any intensity boosts mental speed almost immediately, equating cognitive function to that of people four years younger. pubmed.ncbi.nlm.nih.gov
    Exercise Brain Alzheimer's Aging Memory Dementia

    Exercise boosts brain health, but some evidence suggests that even ordinary activities like dog walking or gardening can sharpen the mind. A recent study found that physical activity—no matter the intensity—can improve mental speed.

    The study involved 90 healthy participants between the ages of 40 and 65. Using smartphones, participants reported their physical activity five times daily and completed brief cognitive tasks to measure mental speed and memory. The smartphones captured activity levels ranging from light chores to vigorous exercise and assessed how these influenced brain function in real-time.

    The results indicated that being active within the previous 3.5 hours improved mental speed, equating to the cognitive function of someone four years younger. Both light and moderate-to-vigorous activities offered similar benefits. While memory accuracy did not improve, reaction times in memory tasks mirrored the gains in mental speed, especially in people who were more active overall.

    These findings suggest that everyday physical activity can deliver immediate cognitive benefits, potentially offering a simple way to boost brain health at any intensity level. Learn more about the brain benefits of exercise in the Cognitive Enhancement Blueprint, a members-only perk.

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  • Repetitive transcranial magnetic stimulation, a non-invasive brain stimulation technique, shows promise in improving brain connectivity and aiding people with treatment-resistant depression. pubmed.ncbi.nlm.nih.gov
    Brain Depression

    Depression is a major public health concern, affecting more than 322 million people worldwide. A hallmark of depression involves reduced activity in specific brain areas and heightened activity in others, impairing brain connectivity. A recent study found that repetitive transcranial magnetic stimulation (TMS)—a non-invasive procedure that uses magnetic fields to stimulate nerve cells in the brain—improved brain connectivity in people with treatment-resistant depression.

    The study involved 75 participants with treatment-resistant depression who underwent 20 treatment sessions over five consecutive days. Researchers randomly assigned them to three groups: a dual-target group receiving TMS to both sides of the brain, a single-target group, and a control group that received a sham treatment. Each session lasted 22 minutes, with functional magnetic resonance imaging conducted before and after treatment to assess changes in brain activity.

    They found that 47.8% of patients in the dual-target group responded favorably to treatment, compared to 18.2% in the single-target group and just 4.3% in the sham group. The active treatment demonstrated greater effectiveness at the four-week follow-up than the sham. Notably, many participants exhibited low baseline brain connectivity, and higher connectivity predicted better outcomes.

    These findings suggest that dual-target TMS promotes rapid and clinically significant improvements for people with treatment-resistant depression. Lifestyle behaviors, including sauna use and exercise, can help people with treatment-resistant depression, too. Learn more about the role of lifestyle in managing depression in our overview article.

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  • Early cannabis exposure disrupts brain development, reducing dendritic branching and neural spine complexity in areas critical for learning and emotional regulation. www.jneurosci.org
    Brain Memory Drug Cannabinoid Development

    Cannabis use is prevalent among teens, whose brains are undergoing massive developmental changes. Evidence suggests that THC (tetrahydrocannabinol), the primary psychoactive ingredient in cannabis, has profound effects on the brain, impairing neurodevelopment. A recent study in mice found that adolescent cannabis use influences gene expression and neural connections, potentially altering the brain’s structure.

    Researchers exposed adolescent male mice to THC and then analyzed changes in gene expression and brain cell structure within the cerebral cortex—a brain region responsible for memory, thinking, learning, reasoning, problem-solving, emotions, consciousness, and sensory functions. They also scanned the brains of more than 450 adolescent human males to compare the cerebral cortex thickness of those who tried cannabis before age 16 to those who did not.

    They found that adolescent mice exposed to THC exhibited less dendritic branching and fewer neural spines, indicating a loss of complexity in brain cells. Similarly, human teens who used cannabis had thinner cortex regions. Further analysis linked these structural changes to genes involved in brain development, including processes like learning and memory.

    These findings suggest that early cannabis exposure interferes with the normal development of brain structure, especially in areas critical for learning and emotional regulation. This interference likely occurs through effects on specific genes and brain cells responsible for building neural connections during adolescence.

    Teens aren’t the only ones at risk for the harmful developmental effects of THC exposure—the compound can pass into breast milk, influencing an infant’s neurodevelopment. Learn more in this clip featuring Dr. Rhonda Patrick.

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  • Frequent use of common household chemicals—including fluoride-based anti-caries agents, air fresheners, and disinfectants—increases the risk of cognitive decline in older adults. pubmed.ncbi.nlm.nih.gov
    Brain Aging Dementia Pollution Dental

    Cognitive decline—especially among older adults with dementia—can profoundly affect a person’s quality of life and increase their dependency on others. Evidence suggests that environmental exposures influence the risk of dementia. A recent study found that certain household chemicals, widely used for personal hygiene, cleaning, and disinfecting, may pose an unexpected risk for cognitive decline** in older adults.

    Researchers analyzed data from a large cohort study of adults over 65. They evaluated how frequently the participants used eight common household chemicals, including insecticides, air fresheners, and disinfectants, and then examined whether these products were linked to declines in cognitive function.

    They found that frequent use of anti-caries agents raised the likelihood of developing cognitive decline by 68%, while frequent use of air fresheners increased it by 148%, and disinfectants raised it by 40%. In general, more frequent chemical use was linked with worsening cognitive function.

    Anti-caries agents prevent or reduce the development of dental caries, also known as cavities or tooth decay. Common anti-caries agents include fluoride mouth rinses, toothpaste formulations, and dental varnishes or sealants. Air fresheners contain various indoor pollutants, including phthalates and benzene. When these substances react with ozone, they create harmful byproducts that can harm the central nervous system. Sulforaphane, a bioactive compound derived from broccoli, boosts the excretion of pollutants like benzene. Learn more in this clip featuring Dr. Jed Fahey.

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  • Higher folate levels during pregnancy may protect against lead's neurotoxic effects, potentially reducing risk of autism-like behaviors in children. ehp.niehs.nih.gov
    Brain Pregnancy Micronutrients Genetics Development Folate

    Lead exposure during pregnancy can harm a child’s developing brain, increasing the risk of autism-related behaviors. Some evidence suggests that folate, a B vitamin, might help protect against lead’s neurotoxic effects. A recent study found that higher folate levels during pregnancy may help reduce the risk of autism-like behaviors in children exposed to lead before birth.

    Researchers analyzed data from a large mother-infant cohort study that tracked participants from pregnancy through early childhood. They measured blood lead levels and plasma folate concentrations during the women’s first and third trimesters. They assessed the children for autism-related behaviors when they were three to four years old. They also examined whether folic acid supplementation and MTHFR, a maternal genetic variant influencing folate metabolism, affected these associations.

    They found that third-trimester blood lead levels were associated with more autism-like behaviors in children whose mothers had low third-trimester folate levels. They did not observe this association among mothers with higher folate levels. Additionally, folic acid supplementation appeared to reduce the harmful effects of lead exposure. The MTHFR genetic variant influenced the findings, but the effects were not statistically significant.

    These findings suggest adequate folate levels during pregnancy may help protect against the neurodevelopmental harm linked to prenatal lead exposure.

    Folate is the natural form of vitamin B9 found in foods, while folic acid is the synthetic form used in supplements and fortified foods. Folic acid has higher bioavailability, meaning the body more readily absorbs it than naturally occurring folate. Learn more about folate in this clip featuring Dr. Bruce Ames.

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  • 'Endurance training' for the brain improves cognitive function in older adults, offsetting the effects of fatigue. www.sciencedirect.com
    Exercise Brain Aging Memory

    Mental fatigue can severely impair cognitive and physical performance, especially in older adults, increasing their risk of falls, accidents, and other health concerns. A recent study found that combining cognitive and physical exercise training may help improve mental and physical function in older adults, particularly when tired.

    Researchers randomly assigned 24 women aged 65 to 78 to one of three groups: brain+exercise training, exercise-only training, or no training (control). The brain+exercise and exercise-only groups completed three weekly sessions for eight weeks consisting of 20 minutes of resistance training (squats and bicep curls) and 25 minutes of endurance exercise (walking outside). The brain training consisted of various assessments that measure reaction time and cognitive inhibition—the brain’s ability to block distractions or irrelevant information—completed four times throughout the study.

    The researchers found that the brain+exercise and exercise-only groups performed better than the control group on cognitive and physical tasks regardless of how tired they were. However, the brain+exercise group showed greater improvements, particularly when tired. On average, cognitive performance increased by 7.8% in the brain+exercise group compared to 4.5% in the exercise-only group. Similarly, physical performance improved by nearly 30% in the brain+exercise group compared to 22.4% in the exercise-only group.

    The findings from this small study suggest that combining cognitive and physical training boosts mental and physical abilities in older adults, particularly when tired. This approach may help mitigate age-related declines and reduce the risk of falls and other health complications. Learn about the brain-protective effects of physical exercise in this episode featuring Dr. Rhonda Patrick.

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  • Bilingualism staves off Alzheimer's-associated hippocampal volume loss, promoting brain resilience, according to new research. www.cambridge.org
    Brain Alzheimer's

    Speaking another language may help the brain resist aging and disease, staving off Alzheimer’s disease by as much as five years. A new study shows that bilingualism offers protection by enhancing the brain’s resilience against the cognitive decline linked to the disease.

    The study included 364 older adults, ranging from healthy people to those with subjective cognitive decline, mild cognitive impairment, or Alzheimer’s disease. Researchers assessed the thickness and volume of participants' brain regions associated with language and Alzheimer’s progression.

    They found that while bilingualism did not appear to boost the thickness or volume of language-related brain regions, bilingual participants with Alzheimer’s disease did not show the same hippocampal volume loss seen among monolingual participants. The hippocampus is a crucial brain area affected early in Alzheimer’s.

    These findings suggest that bilingualism helps maintain brain structure, particularly in regions vulnerable to Alzheimer’s. The researchers posited that early language learning might play a role in this protective effect, potentially contributing to brain resilience across the lifespan. Exercise and fasting help preserve hippocampal volume, too. Learn more in this clip featuring Dr. Mark Mattson.

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  • Omega-3 supplementation linked to lower levels of brain injury markers in athletes exposed to repeated subconcussive impacts. www.sciencedirect.com
    Exercise Brain Performance Omega-3

    Contact sports can take a toll on the brain, even without obvious concussions, and new evidence indicates that repetitive, subconcussive head impacts may cause subtle but considerable brain injury over time. A recent review and analysis found that some evidence points to lower brain injury markers among athletes who took omega-3 fatty acid supplements—especially among those with higher play time—but overall, results are mixed.

    Researchers conducted a systematic review and meta-analysis using data from three studies on American football players—who often receive multiple subconcussive head impacts during a typical season. They examined whether supplementation with omega-3s reduced levels of neurofilament-light, a protein that rises in the blood following brain injury.

    They found that across the three studies, omega-3 supplementation reduced neurofilament-light levels by 60% to 100% compared to a placebo in one study, prevented marked increases in another, and showed no effect in the third, with reductions primarily observed in starter players.

    A subconcussive head impact is a minor blow to the head that does not cause immediate symptoms of a concussion but can still lead to cumulative brain damage over time. Athletes frequently sustain hundreds of these minor impacts each season, allowing them to accumulate unnoticed. Because these injuries are usually asymptomatic, players may not receive the treatment or restrictions they need for recovery, exacerbating neurological damage.

    These findings indicate that omega-3 supplementation may protect the brain from the cumulative effects of subconcussive head impacts in contact sports. However, the investigators cautioned that their review only included three studies—with mixed results—and further research is needed to establish the optimal dose and timing for this potential protective effect. Learn about the many health benefits of omega-3s in this episode featuring Dr. Bill Harris.

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  • Increased iron levels in the brain worsen cognitive test performance by as much as 10% in older adults, a phenomenon linked to brain atrophy and decline in memory and attention. pubmed.ncbi.nlm.nih.gov
    Brain Alzheimer's Aging Memory Dementia Iron

    Iron is an essential nutrient that participates in oxygen transport, energy production, and other critical processes. However, iron can accumulate in the brain, impairing memory and thinking abilities, especially in conditions like Alzheimer’s. A recent study found that older adults with higher brain iron levels perform poorly on cognitive tests.

    Researchers used specialized MRI techniques to measure iron levels and atrophy in the brains of 770 older adults. Of these participants, 219 underwent cognitive testing roughly every year for about three years. The researchers focused on crucial brain regions associated with normal aging and Alzheimer’s disease to explore the relationship between iron buildup, brain atrophy, and cognitive performance.

    They found that higher iron levels were linked to worse cognitive performance, particularly in memory and attention. Participants with the highest iron levels in aging-related brain regions were more likely to experience cognitive decline over time, performing up to 10% worse on cognitive tests than those with lower iron levels. Additionally, increased iron levels corresponded with more severe brain atrophy in these regions.

    These findings suggest that brain iron accumulation impairs cognitive function and may be an early warning sign for the condition. Other lifestyle factors contribute to cognitive losses and brain atrophy, too, including alcohol consumption. Learn more in this episode featuring Dr. Rhonda Patrick.

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  • Distinct gut microbes found in cognitively impaired older adults—a potential link to beneficial species via dietary intervention and regular exercise. read.qxmd.com
    Brain Gut Aging Dementia Microbes

    The gut-brain axis may hold more clues about cognitive decline than previously realized, with some evidence suggesting that gut microbial populations might influence brain health and cognitive function. A recent study found that older adults with cognitive impairment had distinct differences in their gut microbes compared to those without impairment.

    Researchers assigned 229 adults aged 60 and older to one of two groups based on their cognitive function. They analyzed the diversity and composition of the participants' gut microbes and used machine learning to identify key bacterial species associated with cognitive impairment. They also investigated how lifestyle factors such as diet and exercise influenced these bacterial populations.

    They found that participants with cognitive impairment had less diverse gut microbial populations than those without, indicating a potential link between less microbial diversity and cognitive decline. They noted that higher numbers of specific bacteria, including Megamonas, Blautia, and Veillonella, were associated with better cognitive function. They also found that higher fruit intake and regular exercise were linked to increased abundance of these beneficial species.

    These findings suggest that maintaining a healthy gut microbiota through diet and exercise is essential in preserving cognitive function as we age. Time-restricted eating helps promote gut microbial diversity. Learn more in this clip featuring Dr. Satchin Panda.

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  • High-intensity interval training improves hippocampal function and reduces age-related brain shrinkage in older adults, supporting cognitive abilities better than other exercise regimens. athletechnews.com
    Exercise Brain Aging Memory

    The brain’s hippocampus is vital for memory and learning but tends to shrink with age, contributing to cognitive decline. A recent study found that high-intensity interval training (HIIT) improves hippocampal-dependent cognitive abilities in older adults better than other forms of exercise.

    Researchers randomly assigned 151 healthy adults aged 65 to 85 to one of three exercise regimens: low-intensity training, medium-intensity training, or HIIT. Over six months, participants attended 72 supervised sessions, underwent monthly cognitive testing, and provided blood samples. The researchers assessed the participants' brain volumes using magnetic resonance imaging (MRI) brain scans at various time points, with follow-ups continuing for five years.

    They found that the HIIT group experienced marked improvements in hippocampal function. HIIT also reduced age-related brain volume loss, particularly in the hippocampus, and strengthened the connections between critical brain networks. The HIIT group’s cognitive improvements were associated with higher levels of brain-derived neurotrophic factor—a growth factor that supports brain function—and cortisol.

    These findings suggest that HIIT protects against age-related cognitive decline and highlights its potential to preserve brain health in older adults. Learn more about the brain benefits of HIIT in this episode featuring Dr. Rhonda Patrick.

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  • Middle-aged adults with higher leptin availability, a hormone that regulates appetite and weight, show stronger brain structures and cognitive functions, potentially shielding against Alzheimer's. alz-journals.onlinelibrary.wiley.com
    Brain Alzheimer's Obesity Hormones

    Obesity has long been associated with a higher risk of developing Alzheimer’s disease, but scientists don’t fully understand what drives this link. However, some research indicates that leptin, a hormone that regulates appetite and body weight, may be vital in protecting brain health. A recent study found that middle-aged adults with higher leptin bioavailability had better brain structure and cognitive function than those with lower levels.

    Researchers analyzed data from more than 2,200 cognitively healthy participants enrolled in the Framingham Heart Study. They measured leptin and related markers in the participants' blood and tested their cognitive function. Then, they assessed their brain structure using magnetic resonance imaging scans to measure white matter integrity and signs of brain atrophy.

    They found that participants with greater leptin bioavailability had better white matter integrity, indicated by reduced brain degeneration markers and better brain connectivity. However, participants with higher levels of a leptin-related marker called soluble leptin receptor were more likely to have poorer brain structure.

    These findings suggest that leptin protects brain health, potentially reducing the risk of dementia later in life. They also highlight how metabolic health in midlife can influence cognitive aging, especially for those with obesity. Poor sleep can suppress the effects of leptin, ultimately impairing metabolic function. Learn more in this clip featuring Dr. Matt Walker.

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  • Pregnancy rewires the brain, enhancing memory and emotional processing. www.nature.com
    Brain Memory Pregnancy

    Pregnancy transforms nearly every aspect of a woman’s body, but research indicates it also affects the brain. A recent study found that massive brain alterations occur during pregnancy, making it a critical neural adaptation period.

    Researchers conducted an in-depth brain imaging analysis of a healthy 38-year-old woman who became pregnant for the first time. She underwent 26 brain scans, starting three weeks before conception and continuing for two years postpartum. They measured the woman’s hormone levels throughout the pregnancy and postpartum period.

    They found widespread reductions in gray matter volume and cortical thickness, which became more pronounced as the pregnancy progressed. These changes were particularly evident in brain areas related to memory and emotional processing, including the hippocampus and parts of the cortex. In contrast, white matter integrity improved, suggesting enhanced communication between different brain regions as gestational weeks advanced.

    These findings suggest that pregnancy is a dynamic period of brain remodeling, driven by rising hormone levels and possibly preparing the brain for motherhood. Learn how to optimize your health before, during, and after pregnancy in this Aliquot featuring Dr. Rhonda Patrick.

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  • A grandparent's fitness is linked to better memory in their grandchildren, an animal study suggests. www.jneurosci.org
    Exercise Brain Memory

    Exercise can profoundly affect your brain, boosting memory and enhancing cognitive performance. But imagine if your daily exercise routine could boost your grandchildren’s brainpower. A recent study in mice found that cognitive benefits from physical activity can be passed down to future generations, even if they don’t exercise.

    Researchers compared the cognitive performance of male mice whose grandfathers exercised regularly with those whose grandfathers were sedentary. They also analyzed genetic markers related to brain function in both groups.

    Mice with active grandfathers had better memory recall, particularly in tasks requiring spatial (recalling locations) and non-spatial (recalling facts and events) memory. Although their cognitive abilities improved, these mice didn’t experience the new brain cell growth observed in the exercising grandfathers. Additionally, the researchers identified 35 microRNA molecules related to brain function, with two associated with poorer cognitive performance.

    microRNAs are small molecules that regulate gene activity by determining which proteins are produced in cells. They play a key role in many biological functions, including development, disease progression, and how cells respond to changes in their environment.

    These findings suggest that the cognitive benefits of exercise can be passed down to future generations. Check out the Cognitive Enhancement Blueprint—a members' only perk—to learn more about the effects of exercise on brain health and function.

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  • A moderate intake of choline—two to three eggs worth—may cut your risk of cognitive decline in half. www.ncbi.nlm.nih.gov
    Brain Diet Dementia Acetylcholine

    Cognitive decline is a growing concern as populations age, and diet may play a key role in preserving cognitive function. A 2021 study found that people with moderate choline intake—about the amount in two to three eggs or a serving of salmon—were half as likely to experience cognitive decline than those with low intake.

    Researchers categorized roughly 2,400 older adults enrolled in NHANES based on their daily choline intake: low (less than 188 milligrams), moderate (188 to 400 milligrams), or high (more than 400 milligrams). Then, they ranked them according to their performance on various cognitive tests.

    They found that people with moderate choline intake were 33% to 50% less likely to have low cognitive function than those with the lowest intake. Interestingly, those with higher intake didn’t perform better on the cognitive tests, suggesting a “sweet spot” for choline intake.

    These findings indicate that incorporating moderate amounts of choline-rich foods into one’s diet may protect brain health during aging. This protective effect may be due to choline’s role in producing acetylcholine, a neurotransmitter involved in neurogenesis, synapse formation, learning, and memory. In addition, research in animal models shows that choline deficiency increases the risk of Alzheimer’s disease and damages vital organs in mice.

    Choline is found in many foods. Good sources of this essential nutrient include: - Eggs (1 large): ~147 milligrams - Fish (salmon, 3 ounces, cooked): ~187 milligrams - Cauliflower (1 cup, cooked): ~72 milligrams - Beef (3 ounces, cooked): ~78 milligrams Learn more about choline’s role in brain health in this Q&A featuring Dr. Rhonda Patrick.

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  • Just 1.5 teaspoons of olive oil daily reduces the risk of death from dementia by 28%, regardless of genetic factors. jamanetwork.com
    Brain Diet Genetics Dementia Polyphenol

    What we eat and drink can profoundly affect our disease risk as we age. A recent study found that consuming just 1.5 teaspoons of olive oil daily can reduce the risk of death from dementia by 28%, even among APOE4 carriers, a potent genetic risk factor for dementia.

    Researchers asked more than 92,000 healthy, middle-aged adults about their olive oil consumption over a 28-year period. They conducted genetic analyses to determine whether the participants carried the APOE4 gene. Then, using national death records, they ascertained which of the participants died of dementia.

    They found that more than 4,700 of the participants died of dementia during the study period. People who carried one APOE4 allele were roughly twice as likely to die from dementia; those with two APOE4 alleles were five to nine times more likely. However, people who consumed 7 grams or more of olive oil daily—roughly 1.5 teaspoons—were 28% less likely to die of dementia than those who didn’t consume olive oil, regardless of their APOE4 status. Replacing 5 grams (about a teaspoon) of margarine or mayonnaise with an equivalent amount of olive oil reduced the risk of death from dementia by as much as 14%.

    These findings suggest that eating olive oil markedly reduces the risk of death from dementia. Olive oil contains healthy fats and polyphenols—bioactive compounds with potent antioxidant and anti-inflammatory properties. Learn more about polyphenols in our overview article.

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  • Tiny brain hemorrhages found in 17% of people who've had a concussion—increasing their risk for dementia. jamanetwork.com
    Brain Dementia Concussion Blood-Brain Barrier

    “Seeing stars,” “getting your bell rung,” and “knocked for a loop” are everyday phrases often used to describe experiencing a concussion. However, these expressions can downplay that even a “mild” concussion is a traumatic brain injury with the potential for lasting, harmful effects, including dementia. A recent study found that 17% of people who have had a concussion have microbleeds—tiny hemorrhages—in their brains.

    The study involved more than 600 middle-aged adults with normal cognitive function. Researchers asked the participants if they had ever experienced a concussion—defined as a blow to the head where they lost consciousness—then assessed their brain health using magnetic resonance imaging (MRI). Then, they gave the participants various cognitive tests and asked about their sleep, mood, and overall health.

    They found that more than one-third of the participants had experienced a concussion. Of these, 17% had evidence of brain microbleeds, and the more concussions they experienced, the more microbleeds they had. Those who had experienced a concussion tended to have poorer sleep and more gait disturbances, depression symptoms, and memory deficits than those without a concussion.

    Microbleeds are markers of cerebral small vessel disease—age-related blood vessel impairments in the brain. These impairments compromise the blood-brain barrier, contributing to the development of cardiovascular disease, dementia, and stroke.

    These findings suggest that even mild concussions damage the brain, increasing a person’s risk of dementia. Other studies have demonstrated that mild concussions cause acute and chronic brain damage, and people who experience three or more concussions tend to exhibit cognitive deficits that worsen with each subsequent concussion.

    We’ve covered small vessel disease in great detail: - Listen to researcher Dr. Axel Montagne describe the prevalence of this condition as a cause of dementia. - Read more about the condition in our overview article.

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  • Vitamin D shapes neurodevelopment, influencing the development of dopamine-producing neurons and, ultimately, the risk of schizophrenia. onlinelibrary.wiley.com
    Vitamin D Brain Pregnancy Micronutrients Mental Health Development Schizophrenia Dopamine

    Vitamin D plays a crucial role in the early development of dopamine-producing neurons, shedding light on the potential neurodevelopmental origins of schizophrenia. Abnormalities in dopamine signaling are at the heart of this complex mental health disorder, and a recent study suggests that vitamin D deficiency during pregnancy influences these pathways, increasing the risk of schizophrenia in offspring.

    Researchers examined nerve growth, synapse formation, and dopamine release in various dopamine-producing cells exposed to vitamin D over time. They focused on SH-SY5Y cells—which can mature into dopaminergic (dopamine-releasing) neurons—and other brain cells.

    They found that vitamin D increased neuron outgrowth and branching in dopaminergic cells, enhancing the production and release of dopamine. It also altered the expression and distribution of critical presynaptic proteins involved in dopamine release, further supporting its role in dopaminergic development.

    These findings suggest vitamin D is crucial for developing and maturing dopamine-producing neurons. They provide new insights into how maternal vitamin D levels might influence the risk of schizophrenia in offspring by affecting early dopamine signaling pathways. Evidence suggests that vitamin D synergizes with omega-3 fatty acids to support neurodevelopment. Learn more about this relationship in this peer-reviewed article coauthored by Dr. Rhonda Patrick.

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  • Excess body fat in the arms and belly increases the risk of neurodegenerative disease. www.neurology.org
    Brain Alzheimer's Aging Fat Dementia Neurodegeneration

    Although many factors influence whether a person develops neurodegenerative diseases like Alzheimer’s and other forms of dementia, excess body fat stands out as a notable risk factor. Some research suggests that where that body fat is located modulates that risk, with a new study finding that higher body fat in the arms and belly increases the likelihood of neurodegenerative disease.

    The study involved more than 412,000 people enrolled in the UK Biobank study. Researchers measured the participants' body composition and tracked their health for about nine years.

    They found that participants with greater muscle strength, bone density, and body fat in their legs were 6% to 25% less likely to develop neurodegenerative diseases. However, those with more body fat in their arms and bellies were 13% to 18% more likely to develop neurodegenerative diseases. Between 10% and 35% of the link between these body composition patterns and neurodegenerative diseases was attributable to the influence of cardiovascular diseases—particularly cerebrovascular diseases.

    Cerebrovascular disease is an umbrella term for conditions that affect the blood vessels that supply the brain, such as strokes and aneurysms. Exercise helps maintain the health of these blood vessels, reducing the risk of neurodegenerative diseases. Learn more in this episode featuring Dr. Axel Montagne.

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  • Ketones may protect against cognitive decline by mitigating insulin resistance-induced neuronal damage. www.futurity.org
    Brain Aging Insulin Resistance Memory Insulin Ketogenic Diet

    Insulin regulates many processes involved in memory and cognitive function. However, age-related insulin resistance in the brain disrupts neuronal synaptic activity and contributes to cognitive decline. A recent study found that ketones may protect the brain from age-related insulin resistance in the brain.

    Researchers induced acute insulin resistance in mouse hippocampal tissue and determined its effects on neuronal function. Then, they administered beta-hydroxybutyrate, a type of ketone, to the tissues and evaluated the outcomes.

    They found that insulin resistance adversely affected aspects of neuronal communication, including synaptic activity, axonal conduction, network synchronization, synaptic plasticity, and action potential properties. However, ketones restored these functions.

    These findings suggest that ketones rescue the brain from the deleterious effects of acute insulin resistance. The high blood glucose levels associated with insulin resistance induce glucotoxicity, which causes structural damage and functional impairments of neuronal cells. Learn more about the effects of insulin resistance in the brain in this clip featuring Dr. Dale Bredesen.

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  • Caffeine impairs the brain's adaptive response to sleep restriction, reducing gray matter volume. www.nature.com
    Brain Sleep Caffeine

    Nearly three-fourths of adults in the United States don’t get enough sleep, and they often compensate for their sleep losses by consuming caffeine. A recent study found that caffeine and sleep deprivation reduce brain gray matter volume.

    The study involved 36 healthy adults who regularly consumed less than 450 milligrams of caffeine daily—about the amount in four or five cups of coffee. During five days of sleep restriction, 19 participants received 300 milligrams of caffeine in coffee, and 17 received decaffeinated coffee. Researchers analyzed changes in the participants' brains and performed PET scans to measure the availability of the A1 adenosine receptor—a protein involved in sleep regulation—and its relationship to brain plasticity.

    They found that caffeine and sleep restriction synergistically affected brain regions involved in visual processing, decision-making, executive functions, and regulating sensory information, sleep, and consciousness. Participants who had decaffeinated coffee during sleep restriction had more gray matter than those who had caffeinated coffee. Participants with lower baseline adenosine receptor availability generally demonstrated greater gray matter losses.

    These findings suggest an adaptive increase in gray matter volume occurs with sleep restriction, but caffeine impairs this adaptation. Caffeine may have beneficial effects on the body, however, such as boosting autophagy. Learn more in this Aliquot featuring Drs. Guido Kroemer, Satchin Panda, Elissa Epel, Matthew Walker, and Rhonda Patrick.

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  • Men with low testosterone are five to six times more likely to develop dementia. alz-journals.onlinelibrary.wiley.com
    Brain Hormones Testosterone Dementia Neurodegeneration

    Testosterone is the primary male sex hormone, crucial for maintaining fertility and maintaining male sexual characteristics. Some evidence suggests testosterone is neuroprotective. A recent study found that lower testosterone levels are linked with a higher risk for dementia.

    The study involved 581 cognitively healthy older men living in China. Researchers assessed the men’s cognitive function and measured their levels of testosterone and neurofilament light chain, a structural protein that maintains neuronal health and connectivity. Neurofilament light chain is a biomarker for neuronal damage and degenerative diseases, including Alzheimer’s.

    They found that men with lower testosterone levels were roughly five times more likely to experience cognitive decline than those with high levels. Those with low testosterone and high neurofilament light chain levels were approximately six times more likely to experience cognitive decline.

    These findings suggest that lower testosterone and neurodegeneration synergistically contribute to cognitive decline in men. Learn more about low testosterone in this clip featuring Dr. Peter Attia.

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  • High-intensity exercise improves cognitive function and prevents brain shrinkage in older adults. www.aginganddisease.org
    Exercise Brain

    Exercise boosts brain health, but what kind of exercise provides the greatest benefit? A recent study found that high-intensity exercise improved cognitive function and maintained brain volume in older adults—with effects lasting five years or more.

    The study involved 151 older adults (65-85 years old) who engaged in low, moderate, or high-intensity exercise three times a week for six months. They underwent regular cognitive testing (to assess hippocampal function), blood sampling, and MRI scans (to measure brain volume and connectivity) before, during, and after the intervention.

    Only the participants who engaged in high-intensity exercise showed improvement in their hippocampal function. They also maintained higher brain volumes and connectivity and higher levels of brain-derived neurotrophic factor (BDNF) than those who engaged in low to moderate-intensity exercise. Higher BDNF levels correlated with better hippocampal-dependent cognitive performance, which endured for five years or longer.

    These findings suggest that high-intensity exercise markedly improves brain function in older adults. Learn more about the brain-boosting effects of high-intensity exercise in this episode featuring Dr. Rhonda Patrick.

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  • Chronic inflammation in early adulthood can impair cognitive performance by midlife, with 39% of young adults showing high inflammation levels. pubmed.ncbi.nlm.nih.gov
    Brain Alzheimer's Aging Inflammation Memory Dementia

    Research demonstrates that inflammation in later life harms the brain, increasing the risk of dementia and cognitive decline. However, scientists don’t fully understand the effects of inflammation that begins in early adulthood. A recent study found that inflammation during early adulthood markedly impairs cognitive performance in midlife.

    The research involved more than 2,300 young adults (aged 24 to 58) enrolled in the Coronary Artery Risk Development in Young Adults study. Researchers tracked the participants' inflammation levels, measured by C-reactive protein (CRP), for about 18 years. Five years after their last CRP measurement, the participants completed tests that measured their verbal memory, processing speed, executive function, verbal fluency, category fluency, and overall cognition.

    The researchers identified three inflammation patterns among the participants: lower stable (45%), moderate/increasing (16%), and consistently higher (39%). Participants with consistently higher CRP levels were 67 percent more likely to experience poor processing speed and 36 percent more likely to have poor executive function than those with stable, low CRP levels. Those with moderate/increasing CRP levels were twice as likely to have poor processing speed. There were no significant associations between CRP levels and memory, verbal fluency, category fluency, or overall cognition.

    One of the many ways inflammation harms the brain is through its effects on pericytes, tiny cells that surround the brain’s blood vessels and help maintain the blood-brain barrier. Inflammation causes pericytes to release pro-inflammatory cytokines, compromising the barrier and facilitating neurodegeneration. Learn more about links between inflammation, pericytes, and cognitive decline in this clip featuring Dr. Axel Montagne.

    These findings indicate that more than one-third of young adults have high inflammation levels, adversely affecting executive function and processing speed by midlife. They also underscore the importance of managing inflammation throughout life. Omega-3 fatty acids have potent anti-inflammatory effects. Learn more in this episode featuring Dr. Bill Harris.

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  • Older adults with structural integrity in the anterior midcingulate cortex show greater cognitive resilience, reducing the risk of postoperative delirium. academic.oup.com
    Brain Aging Mental Health

    Delirium is a sudden and severe state of confusion that can affect attention and cognitive function. It is particularly common in older adults after surgery or hospitalization, increasing their risk of death, institutionalization, and dementia. A 2022 study found that structural integrity of the anterior midcingulate cortex may predict and mitigate the risk of postoperative delirium.

    The study involved 93 cognitively normal older adults undergoing elective surgery. Researchers divided the participants into two groups based on their performance on neuropsychological tests: “SuperAgers” (those whose cognitive function was comparable to that of young adults) and those whose cognitive function was typical for their ages. Participants underwent magnetic resonance imaging (MRI) to assess the structural integrity of various brain regions.

    The researchers found that none of the SuperAgers experienced postoperative delirium, whereas 20 percent of the typical older adults did. Those who did not experience postoperative delirium exhibited enhanced structural integrity of the anterior midcingulate cortex.

    The anterior midcingulate cortex is a brain region involved in a wide range of cognitive and motor functions. This critical area grows in response to activities that require considerable effort, such as exercise. Here’s what Dr. Andrew Huberman, our recent interview guest, had to say about it.

    These findings suggest that greater structural integrity of the anterior midcingulate cortex protects against delirium and predicts cognitive resilience in older adults. They also align with other evidence demonstrating that SuperAgers exhibit greater cortical thickness in the anterior midcingulate cortex and lower incidence of Alzheimer’s disease. Learn more about the anterior midcingulate cortex in this episode featuring Dr. Andrew Huberman.

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  • Probiotic improves cognition and normalizes circadian rhythms in sleep-deprived mice. www.sciencedirect.com
    Brain Gut Microbiome Sleep Probiotics

    The gut microbiome is crucial for maintaining normal brain processes, and disruptions in gut health can impair cognitive function. Sleep deprivation also impairs cognitive function, but some evidence suggests that probiotics mitigate these effects. A recent study in mice found that probiotics alleviated sleep-deprivation-induced cognitive impairments.

    Researchers fed sleep-deprived mice a probiotic containing Bifidobacterium breve and subjected them to memory and behavioral tests. They also analyzed changes in the animals' gut microbial composition and the presence of crucial microbial metabolites in the gut and serum.

    They found that Bifidobacterium breve improved the sleep-deprived animals' performance in the novel object recognition test – an assessment of recognition memory. The probiotic also altered their gut microbial composition toward a more favorable profile and increased levels of isovaleric acid and gamma-aminobutyric acid (also known as GABA), metabolites involved in melatonin production and circadian rhythm regulation, respectively.

    Bifidobacterium breve is a probiotic bacterium commonly found in the human gut, with particularly large numbers found in young, breastfed infants. It is known for its beneficial effects on digestive health and immune function, and it has been studied for its potential to alleviate various conditions, including gut disorders and Alzheimer’s disease

    These findings suggest that Bifidobacterium breve mitigates sleep-deprivation-induced cognitive impairments and circadian rhythm disturbances in mice. They also highlight a potential role for gut microbial manipulation in treating insomnia and other sleep disorders. Learn more about the relationship between the gut microbiome and sleep in this clip featuring Dr. Matt Walker.

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  • Urolithin A, a compound derived from pomegranates and walnuts, boosts mitophagy and enhances cognitive function in aged mice. neurosciencenews.com
    Brain Alzheimer's Diet Aging Memory Mitochondria Polyphenol

    Mitochondrial function declines with aging, driving many age-related conditions, including Alzheimer’s disease. A recent study in mice found that urolithin A, a compound derived from pomegranates and walnuts, promotes mitophagy – the targeted destruction of damaged mitochondria – in the brain.

    Researchers fed older mice urolithin A (200 milligrams per kilogram of body weight) daily for five months. They subjected the animals to various learning and memory tests, assessed their sense of smell, and examined their brains.

    They found that urolithin A markedly improved the animals' learning, memory, and sense of smell, enhanced memory-related brain functions, and reduced the accumulation of amyloid-beta and tau protein (hallmarks of Alzheimer’s disease). Urolithin A also improved the function of lysosomes, cellular structures that play a crucial role in mitophagy, by breaking down and recycling damaged mitochondria.

    These findings suggest that urolithin A boosts mitophagy in mice, improving brain health and cognitive function. Urolithin A is a byproduct of gut microbial metabolism of ellagic acid, a bioactive compound found in pomegranates and walnuts. The capacity to form urolithin A from ellagic acid varies considerably from person to person (depending on gut microbial composition) and decreases with age.

    Due to the low quantities of ellagic acid in foods and the poor conversion rate, achieving a human dose comparable to that used in this study likely would require supplemental intake. Nevertheless, the findings align with other evidence suggesting that long-term dietary intake of foods containing ellagic acid benefits cognitive health.

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  • Chronic migraines increase the risk of developing vascular dementia by 33 percent – even for younger, otherwise healthy individuals. journals.plos.org
    Brain Magnesium Dementia Migraine

    Migraine is a neurological disorder commonly manifested as severe headache pain accompanied by nausea, vomiting, and light sensitivity. Approximately 15 percent of people worldwide experience migraine, with women reporting migraine more often than men. A new study shows that migraine increases a person’s risk of vascular dementia.

    Researchers used data from a large, population-based cohort study involving nearly 6 million adults with or without regular migraines. They tracked the participants' health for about ten years and assessed their risk for developing vascular dementia.

    They found that people with chronic migraines were 33 percent more likely to develop vascular dementia than those without. Those with episodic migraines were 16 percent more likely. The risk of developing vascular dementia was greater among younger people, women, non-smokers, and those without hypertension or diabetes.

    These findings suggest that migraine increases the risk of developing vascular dementia, possibly manifesting in younger, otherwise healthy adults. Migraines and vascular dementia share many pathophysiological traits that may explain their interconnected risk. For example, both conditions elicit alterations in cerebral blood flow, with migraines characterized by impaired blood vessel tone and responsiveness and vascular dementia characterized by chronic cerebrovascular insufficiency. In addition, inflammatory processes contributing to brain endothelial dysfunction play a critical role in both disorders.

    However, some evidence suggests magnesium prevents migraines. Learn more in this clip featuring Dr. Rhonda Patrick.

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  • High-intensity training outperforms moderate exercise in boosting cognitive function. bmcsportsscimedrehabil.biomedcentral.com
    Exercise Brain Dementia BDNF

    The connection between physical exercise and enhanced cognitive function is well-established. However, the extent of benefit varies markedly depending on the intensity of the physical activity. A recent study found that high-intensity interval training (HIIT) boosted reaction time and cognitive flexibility better than moderate-intensity continuous exercise (MICE).

    The study involved 28 elite male boxers in their mid-twenties. The participants underwent cognitive performance tests and provided blood samples in five scenarios: after an hour of rest, immediately after HIIT, one hour after HIIT, immediately after MICE, and one hour after MICE.

    The blood tests revealed that participants' serum brain-derived neurotrophic factor (BDNF) levels immediately after exercise were considerably higher after HIIT than after rest or MICE. Interestingly, serum levels of S100B and neuron-specific enolase (proteins associated with brain injury) were also higher after HIIT than after rest but were comparable to those after MICE. HIIT and MICE improved cognitive performance, but HIIT was better at improving reaction time and incongruent task assessments (which measure cognitive flexibility).

    These findings suggest that HIIT and MICE elicit beneficial effects on the brain, with HIIT outperforming MICE in certain arenas. These effects may be attributable to increased BDNF, a growth factor known to influence neuronal health and mediate the beneficial cognitive effects associated with exercise. Learn more about BDNF in the Cognitive Enhancement Blueprint, located in the Members' Library.

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  • Higher-dose omega-3 supplementation elevates blood levels, even in Alzheimer’s high-risk APOE4 carriers, but obesity may hinder its brain availability. content.iospress.com
    Brain Alzheimer's Obesity Omega-3 Genetics Dementia

    Omega-3 fatty acids play critical roles in maintaining brain health and function, potentially reducing the risk of developing Alzheimer’s disease. People who carry the APOE4 gene variant and those with obesity have a higher risk of developing the disease, suggesting that differences in metabolism could be a factor. A 2022 study found that obesity influenced the amount of omega-3 in plasma phospholipid form that is important for brain transport.

    Fifty people (half of whom carried the APOE4 gene) took 2.5 grams of combined docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) daily for six months. Because omega-3 fatty acids must be in the free fatty acid form or phospholipid form to cross the blood-brain barrier, researchers measured these forms of the fatty acids in the participants' plasma before and after the intervention. They also investigated whether APOE genotype or body mass index (BMI, a proxy for overweight and obesity) influenced these measures.

    They found that supplemental omega-3s increased by up to fourfold in all participants, regardless of APOE status. However, participants with a high BMI experienced lower plasma phospholipid omega-3 increases than those with a low BMI. Having a high BMI is a well-established risk factor for Alzheimer’s disease. Interestingly, APOE4 did not influence the amount of plasma phospholipid omega-3.

    They also lend support to evidence suggesting that APOE4 carriers do not respond to lower dose omega-3 supplementation as well as non carriers possibly because they do not transport DHA in free fatty acid form across the blood-brain barrier as well. However, the transport of the phospholipid form of DHA across the blood-brain barrier bypasses the default in tight junctions, potentially providing a better means of DHA transport for people with the APOE4 gene and lowering their risk of developing the disease. Learn more about APOE4 and DHA transport in this peer-reviewed article by Dr. Rhonda Patrick.

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  • Exercise preserves cognitive function in mice by inhibiting neuroinflammation. www.sciencedirect.com
    Exercise Brain Inflammation Memory Dementia NRF2

    Cognitive function typically declines with aging, but evidence suggests physical activity can help mitigate some of these declines. A recent study in mice found that exercise improves memory and spatial learning by inhibiting neuroinflammation, primarily via the actions of irisin, a myokine, and brain-derived neurotrophic factor (BDNF), a growth factor and signaling protein.

    Researchers conducted a two-part study to investigate the effects of regular, low-intensity exercise on cognitive function in mouse models of inflammation-driven memory impairment and microglia (brain immune cell) degeneration.

    First, they assessed the animals' neuroprotective and antioxidant marker levels and subjected them to various memory and behavioral tests. They found that exercise reduced memory problems and cognitive losses by increasing the expression of irisin. In turn, irisin activated BDNF and nuclear factor erythroid 2-related factor 2 (Nrf2), reducing inflammation and blocking the activity of BACE-1, an enzyme critical for amyloid-beta production.

    Then, they studied the effects of irisin on microglia. They found irisin blocked the NF-κB/MAPK/IRF3 pro-inflammatory signaling pathway. It also lowered pro-inflammatory markers while increasing the expression of Nrf2.

    Nrf2 is a cellular protein that activates the transcription of more than 200 cytoprotective proteins that protect against oxidative stress due to injury, inflammation, and normal aging processes. It is an element of the Keap1-Nrf2-ARE biological pathway, a mediator of protective responses to oxidative and electrophilic stressors. Hormetic stressors like exercise, heat exposure, and dietary components trigger Nrf2 activity. Sulforaphane, a compound derived from broccoli, is the most potent naturally occurring hormetic inducer of Nrf2 activity. Learn more about Nrf2 in this clip featuring Dr. Jed Fahey.

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  • Omega-3 fatty acids preserve blood-brain barrier integrity, maintaining cognitive function. onlinelibrary.wiley.com
    Brain Omega-3 Dementia Blood-Brain Barrier

    The blood-brain barrier is a collection of membranes that separate the central nervous system from the peripheral circulation, facilitating the passage of nutrients and signaling compounds while excluding harmful substances. Loss of blood-brain barrier integrity increases the risk of many neurodegenerative diseases, including dementia and Alzheimer’s. A 2021 study found that having a higher omega-3 index preserves the blood-brain barrier and maintains cognitive function in older adults.

    Researchers assessed the cognitive performance of 45 healthy older adults. They measured the participants' red blood cell omega-3 concentrations (“omega-3 index”) and evaluated their blood-brain barrier integrity using magnetic resonance imaging.

    They found that participants with a higher omega-3 index had greater blood-brain barrier integrity than those with a lower index. They also performed better on tests of memory and language (functions most affected by Alzheimer’s disease) but not on executive function, speed, or motor control assessments.

    These findings suggest that higher blood concentrations of omega-3 fatty acids (measured via the omega-3 index) preserve blood-brain barrier integrity, potentially protecting against cognitive losses. The omega-3 index measures the amount of the omega-3 fatty acids EPA and DHA as a percentage of total fatty acids in red blood cell membranes. Evidence suggests it is a reliable biomarker of sudden cardiac death risk and may provide a means of standardizing methodologies used in clinical trials, facilitating more accurate interpretation of clinical trial outcomes. Learn more about the omega-3 index in our overview article.

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  • A single session of high-intensity resistance training boosts memory and brain connectivity – particularly in the hippocampus – an indicator of enhanced cognitive health. onlinelibrary.wiley.com
    Exercise Brain Aging Memory

    High-intensity resistance training, also known as functional training, requires the body to exert considerable effort against weights or resistance. Evidence suggests this type of training confers myriad physical and mental health benefits, including improved metabolic function and mood, particularly in older adults. A recent study found that engaging in a single session of high-intensity resistance training enhanced memory capabilities.

    The study involved 60 young, healthy adults who took memory tests and underwent resting-state functional magnetic resonance imaging of their brains. Then, half of the participants engaged in a single high-intensity resistance training session, while the other half did not. The training involved three resistant exercise sets at 75 to 80 percent of the participants' one-rep max, with one minute of rest between sets and a total duration of under seven minutes. Two days later, both groups repeated the memory tests and brain imaging scans.

    Those who participated in the resistance exercise session exhibited marked improvements in memory recall compared to the non-exercising group. These memory improvements correlated with greater connectivity in the left posterior region of the hippocampus, an area involved in memory.

    The findings from this small study suggest that just one session of high-intensity resistance training has considerable influence on memory, highlighting its potential to promote cognitive health and neural plasticity. Learn more about high-intensity resistance training in this clip featuring Dr. Martin Gibala.

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  • Yoga improves memory and boosts cognition in older women at risk for Alzheimer's, demonstrating increased hippocampal connectivity and expression of anti-aging markers. www.sciencedaily.com
    Exercise Brain Alzheimer's Aging Memory Dementia

    Yoga is an ancient Indian practice that engages the mind and body through physical poses, breathing techniques, and meditation. Robust scientific evidence suggests that yoga benefits both mental and physical health. A new study found that Kundalini yoga – a type of yoga that involves specific postures, breathing techniques, and meditation – boosted cognition and memory in older women at risk of developing Alzheimer’s disease.

    The study involved 63 older women who had self-reported memory problems and cerebrovascular conditions – risk factors for Alzheimer’s. About half the women participated in a weekly yoga session, while the other half participated in weekly memory training. Researchers assessed the women’s cognitive function and moods before and after the two interventions. They also measured markers of aging and inflammation in the women’s blood and assessed changes in their brains using magnetic resonance imaging (MRI).

    They found that the women who participated in yoga experienced marked improvements in memory, increased connectivity in the hippocampus, and increased expression of anti-inflammatory and anti-aging markers** compared to those who did memory work only. The MRIs revealed that the brains of the women in the yoga group showed less age-related volume loss.

    Women are at greater risk of developing Alzheimer’s disease than men, partly due to having higher rates of cardiovascular conditions, many of which share risk factors with Alzheimer’s. In addition, the decrease in protective estrogen during menopause may also amplify cognitive declines.

    These findings suggest that Kundalini yoga benefits women at risk for Alzheimer’s disease. Evidence indicates that vigorous exercise can boost cognitive function, too. Learn more in this episode featuring Dr. Martin Gibala.

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  • A prebiotic supplement containing inulin and fructo-oligosaccharides boosts cognitive performance in older adults, indicating beneficial effects via the gut-brain axis. www.kcl.ac.uk
    Brain Gut Diet Microbiome Fiber

    The gut-brain axis, a bidirectional signaling pathway between the gastrointestinal tract and the nervous system, plays a critical role in human health, including aspects of cognition. Key elements of this pathway are the tens of trillions of microbes that comprise the intestinal microbiota. A recent study found that taking a prebiotic supplement altered the gut microbiota, improving cognitive performance in older adults.

    The randomized controlled study involved 36 older adult twin pairs. One twin within each pair consumed a prebiotic supplement containing inulin and fructo-oligosaccharides for 12 weeks, while the other twin took a placebo. Participants provided information about their daily dietary intake and underwent cognitive tests before and after the supplement intervention. Researchers analyzed the participants' gut microbial populations.

    They found that the prebiotic supplement increased the number of Bifidobacterium – a type of bacteria commonly associated with gut health – in the participants' guts. Those who took the prebiotic performed better on cognitive tests than those who took the placebo. In particular, they performed better on a paired associate learning test, a memory assessment commonly used for the early detection of Alzheimer’s disease.

    These findings suggest that prebiotics influence cognitive health via gut-brain axis interactions. Prebiotics are food components that support the maintenance of a healthy microbiota and create an environment conducive to its survival. Inulin and fructo-oligosaccharides are among the most abundant prebiotics in the human diet, present in apples, bananas, legumes, and dietary supplement forms. Their fermentation by gut microbiota produces short-chain fatty acids, including acetate, propionate, and butyrate.

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  • Alcohol consumption is linked to increased iron accumulation in the brain, potentially impairing memory, learning, and reward-processing functions. journals.plos.org
    Brain Alcohol Dementia Iron

    Iron is an essential mineral, best known for its critical role in cellular oxygen transport. However, having too much iron in the brain drives cognitive deficits. A 2022 study found that alcohol consumption promotes iron deposition in the brain, compromising cognitive function, even among moderate drinkers.

    The investigation involved nearly 21,000 adults enrolled in the UK Biobank study. Participants provided information about their alcohol intake and completed a battery of cognitive tests. Researchers performed magnetic resonance imaging scans to assess iron levels in the participants' brains and livers.

    They found that, on average, participants consumed about 18 units of alcohol per week, roughly equivalent to ten 12-ounce beers or ten 5-ounce glasses of wine. Participants who consumed as few as 7 units of alcohol per week had higher levels of iron in the brain’s putamen and caudate (in the basal ganglia) and in the substantia nigra (in the midbrain), areas involved in learning, memory, reward processing, and movement. Higher iron levels in the basal ganglia were associated with slower executive function, lower fluid intelligence, and slower reaction times. Those who consumed more than 11 units of alcohol per week had higher iron levels in their livers.

    These findings suggest that moderate alcohol consumption has marked effects on the brain and cognition, likely due to excess iron deposition. Alcohol consumption is associated with a wide range of health problems, including heart disease, stroke, liver dysfunction, and cancer. However, vigorous exercise can help reduce alcohol cravings. Learn more in this video featuring Dr. Rhonda Patrick.

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  • A single dose of creatine monohydrate, approximately 20 to 30 grams, depending on body weight, mitigates sleep deprivation's harmful effects on brain function and cognition. www.nature.com
    Brain Diet Sleep Supplements

    Sleep deprivation profoundly affects the human body, negatively influencing cognitive performance, cardiovascular health, and metabolism. Evidence suggests creatine counters some of the harmful effects of sleep deprivation. A recent study found that a single dose of creatine monohydrate improved cognitive performance and prevented harmful metabolic effects in sleep-deprived people.

    The study involved 15 healthy participants who received a single large dose of creatine monohydrate (0.35 grams per kilogram of body weight) or a placebo to assess creatine’s effects on cognitive function during prolonged wakefulness. Participants underwent evaluations before and several hours after taking their respective treatments in the context of 21 hours of sleep deprivation. They underwent brain imaging scans and cognitive tests to measure the effects of creatine on brain chemistry and cognitive performance.

    The scans and tests revealed that creatine induced several critical changes in the brain, including:

    Increasing the ratio of phosphocreatine to inorganic phosphate, providing more energy for brain cells.

    Boosting the levels of ATP, supporting better brain activity and energy management.

    Altering the ratio of creatine to N-acetylaspartate, enhancing brain cell health and boosting energy reserves.

    Maintaining optimal brain pH levels, supporting brain function and neurotransmitter signaling.

    Enhancing cognitive performance and processing speed, making thinking and processing information faster and more efficient.

    These findings suggest that a large dose of creatine could mitigate some of the harmful effects of sleep deprivation on the brain and cognitive function. Creatine is a nitrogen-containing compound produced in the liver and kidneys and stored in the brain and muscles. It plays an essential role in the recycling of ATP and is widely used as a dietary supplement to build and maintain muscle mass. Although creatine is available in many forms, the bulk of the research on the compound has centered on creatine monohydrate. Learn more about creatine in this clip featuring Dr. Stuart Phillips.

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  • Altered serotonin levels in early life impair the development of the brain's prefrontal cortex – essential for higher cognitive functions. news.cuanschutz.edu
    Brain Depression Serotonin Mental Health Development

    Serotonin is crucial for early brain development, influencing how brain cells communicate and form networks. The prefrontal cortex, a brain region vital for complex cognitive tasks, such as decision-making and social interactions, is heavily influenced by serotonin levels during development. A recent study demonstrates that alterations in serotonin levels during early life impair prefrontal cortex development, driving changes in the density and function of dendritic spines, the tiny structures on neurons essential for brain communication.

    Researchers employed advanced imaging techniques to observe how dendritic spines develop and change in young mice. They also manipulated serotonin levels using genetic tools and monitored the resulting changes in spine density and synaptic function, providing insights into how serotonin shapes neural connectivity during critical developmental periods.

    They found that modifying serotonin levels during development induced notable alterations in the structure and functionality of dendritic spines in the prefrontal cortex. These changes were closely associated with the activity of specific serotonin receptors, which are vital for the growth and adaptability of neuronal connections. Furthermore, exposure to fluoxetine (commonly known as Prozac) during early life had similar effects on dendritic spine development, implicating common antidepressants in the complex interplay of serotonin signaling and brain maturation.

    These findings highlight the pivotal role of serotonin receptors in modulating the growth and plasticity of dendritic spines, underscoring their importance in the serotonin-driven development of the prefrontal cortex. Learn how vitamin D and omega-3 fatty acids influence serotonin levels and brain development in this open-access article coauthored by Dr. Rhonda Patrick.

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  • Aging undermines the brain's capacity for maintaining working memory, with subtle declines in neuron activity and connectivity in the prefrontal cortex. www.sciencedaily.com
    Brain Aging Memory Blood-Brain Barrier

    As the brain ages, cognitive functions decline, with working memory – a form of short-term memory necessary for reasoning, decision-making, and behavior – among the earliest affected. The brain’s prefrontal cortex is crucial in working memory, showing sustained activity during memory-guided behavior. A recent study in mice found that aging reduces the prefrontal cortex’s ability to maintain working memory, with older mice showing less effective communication between memory-coding neurons.

    Using imaging techniques to see how neurons behave during memory tasks involving touch and sound, researchers tracked brain activity in mice of varying ages. They also used light-based interventions to temporarily disrupt brain activity, observing how this affected the animals' ability to perform the tasks.

    They discovered that with aging, the prefrontal cortex had fewer neurons responsible for managing actions, and the signals from these neurons weakened. Furthermore, whereas young mice used both broad and specific memory strategies, older mice mainly relied on specific strategies, indicating a subtle decline in the brain’s memory circuits over time.

    The researchers also observed a drop in the resting brain connections among neurons managing actions, beginning around middle age. This drop in connections became even more pronounced when the mice were doing tasks, suggesting that the brain’s ability to retain thoughts might weaken with age. Additionally, the brains of middle-aged mice were more easily disrupted by light-based interventions, hinting at a greater risk to their thought-retention processes as they age.

    The findings in this mouse study suggest that aging leads to a marked decrease in brain connectivity and neuron activity in the prefrontal cortex, affecting memory retention and making it more susceptible to disruptions. The blood-brain barrier is a critical player in brain connectivity, and its impairment during aging contributes to cognitive dysfunction. Learn more in this episode featuring Dr. Axel Montagne.

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  • A ketogenic diet decreases alcohol cravings in people with alcohol use disorder, offering an alternative to the brain's energy needs. www.frontiersin.org
    Brain Alcohol Addiction Ketogenic Diet

    Alcohol use disorder accounts for approximately 2.8 million deaths worldwide. It’s a chronic condition marked by a strong desire to drink and persistent alcohol use despite its harmful effects. A recent study found that a ketogenic diet reduces alcohol cravings in people with alcohol use disorder.

    The study involved 33 adults with an alcohol use disorder enrolled in a three-week inpatient alcohol detoxification program. Slightly more than half of the patients received a ketogenic diet, while the remainder received a standard American diet. Once a week, using functional magnetic resonance imaging, researchers assessed the participants' brain function and craving responses during exposure to alcohol-related triggers. In addition, the participants reported their perceived alcohol cravings when exposed to the triggers.

    The imaging revealed that participants who ate a ketogenic diet showed reduced neural activity related to alcohol cravings than those who ate the standard American diet across the entire three weeks of treatment. Those who ate a ketogenic diet also reported fewer perceived cravings.

    Following alcohol consumption, the brain uses acetate, a metabolic byproduct of alcohol, for energy instead of glucose. As a result, glucose levels in the brain drop, and acetate levels increase – even after the effects of alcohol wear off. These alterations in fuel can contribute to withdrawal symptoms, cravings for alcohol, and a higher risk of relapse, especially when acetate levels drop. Ketones are structurally similar to acetate and can serve as an alternative energy source for the brain, providing energy in place of glucose.

    This was a small study, but its findings suggest that a ketogenic diet reduces alcohol cravings among people with alcohol use disorders. Other evidence suggests vigorous exercise reduces alcohol cravings, likely due to exercise’s effects on FGF21 – a hormone produced during vigorous activity. Learn more in this short video featuring Dr. Rhonda Patrick.

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  • Multivitamin/mineral supplements enhance memory and cognitive function in older adults, a finding from the COSMOS trial. www.sciencedirect.com
    Brain Alzheimer's Aging Micronutrients Dementia

    As the global population ages, the number of people at risk for Alzheimer’s disease and other forms of dementia increases. A robust and growing body of evidence indicates that lifestyle influences the risk of developing dementia. A recent study found that multivitamin/mineral supplements improve memory and slow cognitive aging in older adults – roughly equivalent to reducing cognitive aging by two years.

    Researchers investigated the effects of multivitamin/mineral supplementation on cognitive function in a subset of participants enrolled in the COSMOS study, a randomized, double-blind, placebo-controlled trial involving more than 21,000 older adults (60 years or older) in the U.S. Participants in COSMOS were randomly assigned to receive one of three interventions: cocoa extract (providing 500 milligrams of flavanols daily, including 80 milligrams of epicatechin), a multivitamin/mineral supplement, or both, daily for two years. A fourth group received a placebo. In the subset, called COSMOS-Clinic, 573 participants underwent extensive brain function tests before and after the study and again two years later.

    They found that multivitamin/mineral supplementation conferred modest improvements in overall cognitive function over two years in participants enrolled in the subset, particularly in episodic memory – the ability to recall specific events, experiences, and contextual details from one’s past. They did not observe improvements in the participants' executive function or attention. However, a meta-analysis involving more than 5,000 participants from the COSMOS-Clinic, COSMOS-Mind, and COSMOS-Web studies demonstrated that multivitamin/mineral supplementation markedly improved overall cognition and episodic memory.

    These findings from the COSMOS trials suggest that multivitamin/mineral supplementation – a low-cost, low-effort intervention – improves cognitive function in older adults. They also highlight the role of adequate nutrition throughout the lifespan and support the “micronutrient triage theory” – the idea that the body prioritizes the utilization of micronutrients for metabolic pathways needed for survival and reproduction over those used for long-term health. Learn more about micronutrient triage theory in this clip featuring Dr. Bruce Ames.

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  • Cold exposure boosts mood and enhances brain connectivity. www.mdpi.com
    Brain Inflammation Depression Cold Stress Norepinephrine

    Cold exposure has long been used to reduce muscle soreness and promote muscle recovery after physical activity. However, evidence indicates that regular cold exposure also improves glucose and lipid metabolism, decreases inflammation, enhances immune function, and improves cognitive performance. Now, findings from a recent study suggest that cold exposure improves mood and increases connectivity between brain networks.

    The study involved 33 men and women who were unaccustomed to regular cold exposure. The participants underwent functional magnetic resonance imaging (fMRI) to assess their brain network connectivity before and after soaking in a cold water (20°C, 68°F) bath. They also reported on their mood before and after the intervention.

    The participants reported feeling more active, alert, attentive, proud, and inspired after the cold exposure. The fMRIs revealed that the participants' positive moods correlated with increased connectivity in the default mode, frontoparietal, salience, and visual lateral networks, regions of the brain that contribute to self-reflection, attention, emotion regulation, and visual processing.

    The findings from this small study suggest that short-term cold exposure improves mood by enhancing brain connectivity in regions associated with mood. These benefits may arise from the effects of norepinephrine, a neurotransmitter involved in vigilance, focus, attention, and mood. Norepinephrine release is one of the most consistent and profound physiological responses to cold exposure. Learn more about cold exposure and the mechanisms that drive its effects in our comprehensive overview article.

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  • Sulforaphane from broccoli sprouts shows promise in preventing Alzheimer's disease – boosting memory and enhancing mitochondrial function in mice. www.mdpi.com
    Brain Alzheimer's Mitochondria Dementia Sulforaphane Oxidative Stress

    Alzheimer’s disease affects more than 24 million people worldwide, with numbers expected to grow as the population ages. A growing body of evidence links mitochondrial dysfunction and oxidative stress to the development of Alzheimer’s disease. A recent study in mice found that sulforaphane, a bioactive compound derived from broccoli and broccoli sprouts, boosts memory, improves mitochondrial function, and reduces oxidative stress.

    Researchers studied normal mice and mice prone to developing a condition similar to Alzheimer’s. They fed half of each type of mice standard mouse chow. They fed the other half normal chow supplemented with a broccoli sprout powder rich in glucoraphanin and myrosinase – the precursors to sulforaphane. They subjected the mice to various memory tests and assessed their mitochondrial function.

    They found that Alzheimer’s disease-prone mice that ate the broccoli sprout powder-supplemented chow performed better on memory tests than those that didn’t. These mice demonstrated higher levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α) and mitochondrial transcription factor A – proteins that regulate mitochondrial biogenesis (the production of new mitochondria). They also showed upregulated expression of cellular antioxidant defense system components that protect against oxidative stress.

    These findings suggest that sulforaphane from broccoli sprouts prevents age-related cognitive decline by maintaining mitochondrial function, thereby reducing oxidative stress in mice.

    Sulforaphane is an isothiocyanate compound with robust antioxidant, anti-inflammatory, and anti-cancer effects. It reduces oxidative stress by switching on the activity of Nrf2, a cellular protein that activates the transcription of cytoprotective proteins that protect against oxidative stress due to injury and inflammation. Sulforaphane is the most potent naturally occurring inducer of Nrf2. Learn how to grow your own broccoli sprouts – a terrific source of sulforaphane – in this short video.

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  • Strawberry consumption enhances memory and mood in middle-aged adults, potentially reducing dementia risk. www.uc.edu
    Brain Diet Aging Metabolism Dementia Polyphenol

    With age, cognitive and metabolic dysfunction increases, often coinciding. However, evidence suggests that consuming berries improves cognitive and metabolic health. A recent study found that strawberry consumption improved memory and mood in overweight people with mild cognitive decline.

    Researchers recruited 34 overweight middle-aged adults with insulin resistance who reported mild cognitive decline. Half of the participants consumed a strawberry powder supplement daily for 12 weeks, while the other half consumed a placebo. Both groups abstained from all berry consumption throughout the study. The researchers assessed the participants' cognitive and metabolic functions and moods before and after the intervention.

    They found that those who consumed the strawberry powder exhibited better memory function and fewer symptoms of depression than those who consumed the placebo. However, they did not show any improvements in metabolic function.

    These findings suggest that strawberry supplementation improves cognitive function in middle-aged adults, potentially reducing the risk of dementia, but has little effect on metabolic function. The study’s authors attributed the lack of metabolic response to the relatively low dose and the study’s short duration.

    Strawberries are rich in anthocyanins, a class of polyphenolic compounds that exert potent antidiabetic, anticancer, anti-inflammatory, and anti-obesity effects in humans. Anthocyanins lend their characteristic blue, red, or purple hues to strawberries, blueberries, and other fruits and vegetables. Learn about other polyphenols in our overview article.

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  • Cigarette smoking reduces brain volume, accelerating the brain's aging process. medicalxpress.com
    Brain Alzheimer's Aging Dementia

    Smoking cigarettes damages multiple organs, including the brain, possibly explaining why as many as 14 percent of Alzheimer’s cases worldwide are linked to smoking. A new study shows that cigarette smoking reduces brain volume, accelerating normal brain aging.

    Researchers investigated the relationship between smoking and brain volume in more than 32,000 adults enrolled in the UK Biobank study. They used a set of guidelines (called Bradford Hill’s criteria) to determine whether a potential cause-and-effect relationship exists between a specific factor (such as smoking) and a health outcome (such as a disease). They also investigated whether genetic factors predispose some people to initiate smoking.

    They found that regular smoking, especially heavier smoking, was linked to notable brain shrinkage, especially in terms of total gray matter volume. The more years a person smoked, the greater the shrinkage. They also found that daily smoking played a role in the relationship between the genetic risk score for smoking initiation and the total gray matter volume.

    These findings suggest that smoking cigarettes reduces drives brain volume losses, effectively aging the brain prematurely. They also align with other research demonstrating that regular (daily or nearly daily) cigarette smoking increases relative brain aging, driving poor cognitive function and declines in fluid intelligence. Many habits like smoking (and overeating) can be broken using mindfulness techniques. Learn more in this clip featuring Dr. Ashley Mason.

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  • Even minimal exercise linked to 47 percent lower anxiety risk in older adults. www.sciencedirect.com
    Exercise Brain Aging Mental Health Anxiety

    Many older adults have generalized anxiety disorder, a persistent feeling of anxiety or dread that interferes with everyday life. Evidence suggests that physical activity alleviates symptoms of anxiety, but scientists don’t know how much activity is optimal. A recent study found that older adults who engaged in regular physical activity were 47 percent less likely to experience symptoms of anxiety than those who engaged in no activity.

    Researchers drew on data from more than 7,600 older adults enrolled in The Irish Longitudinal Study on Ageing (TILDA). They gathered information about the participants' physical activity levels, worry symptoms, and anxiety levels over ten years. They assessed the participants' activity levels and categorized them as having no, low, medium, or high activity levels.

    They found that participants with high activity levels were 31 percent less likely to develop anxiety than those with no activity. However, participants who engaged in even minimal moderate-intensity physical activity – equivalent to just 10 minutes a day, five times a week – were 47 percent less likely to develop anxiety than those with no activity.

    These findings suggest that even a small amount of physical activity has robust effects on mood in older adults, markedly reducing the risk of developing anxiety. They also align with previous research, which found that older adults enrolled in TILDA who met WHO physical activity guidelines were 63 percent less likely to develop generalized anxiety disorder than those who did not.

    Exercise supports the health of pericytes, tiny contractile cells surrounding the brain’s capillaries that regulate vascular blood flow and maintain blood-brain barrier integrity. Pericytes detach from the blood vessels in aging, driving the pathophysiology of neurological dysfunction, vascular dementia, and mood disorders like anxiety. Learn more in this episode featuring Dr. Axel Montagne.

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  • BDNF emerges as a critical marker of omega-3 fatty acid levels in the brain. www.nature.com
    Brain Omega-3 BDNF

    The Omega-3 Index measures omega-3 fatty acid concentrations in red blood cells. It provides a reliable assessment of long-term intake and is highly reflective of fatty acid composition in most tissues, with one notable exception – the brain. A recent study suggests that brain-derived neurotrophic factor (BDNF), a protein involved in learning and memory, is a more reliable measure of brain omega-3 concentrations than the Omega-3 Index.

    Researchers gave rats and mice different types and amounts of supplemental omega-3 fatty acids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and dietary fish and krill oils. Then, they measured the fatty acids in the animals' red blood cells (Omega-3 Index) and the BDNF concentrations in their plasma and brain tissues.

    They found that increased brain omega-3 levels were positively associated with elevated plasma BDNF but inversely associated with red blood cell concentrations, suggesting that plasma BDNF is a more dependable biomarker than the Omega-3 Index for evaluating the effectiveness of omega-3 supplementation and dietary intake in enhancing brain function.

    BDNF is critical for brain function, neurogenesis, neuronal survival, memory, and body weight regulation. Low BDNF concentrations are typical in psychiatric disorders but typically rise after antidepressant treatment and high omega-3 fatty acid doses. Exercise and DHA-rich diets also elevate BDNF, and some evidence suggests that BDNF mediates DHA’s beneficial brain effects.

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  • The gut microbiome alters the brain's response to tempting foods, affecting dietary choices. www.sciencedaily.com
    Brain Obesity Microbiome Prebiotics

    The brain’s reward centers react more strongly to the sight of tempting food than to less tempting options, driving food choices. Evidence suggests the gut microbiome influences these neural activity patterns, ultimately modulating body weight and metabolic health. A recent study found that inulin, a prebiotic derived from chicory root, alters the gut microbiome, reducing the intensity of the brain’s reward system activation.

    Researchers gave 59 overweight young to middle-aged adults 30 grams of inulin or a placebo every day for two weeks. Then, the participants underwent functional MRI scans while viewing images of various foods and rating the foods' desirability. Finally, they ate the most desired food and underwent more MRIs. After a two-week break, they switched to the alternate treatment. The researchers collected blood and fecal samples from the participants before and after the two interventions.

    They found that the participants' reward-related brain activation in response to high-calorie food stimuli decreased after consuming the prebiotic inulin. A shift in the gut microbial composition accompanied these changes.

    These findings suggest that prebiotics influence dietary choices via alterations in the gut microbiome. They also highlight the complex interplay between the gut, brain, and the body’s microbial partners. Learn more about the gut microbiome in this episode featuring Dr. Eran Elinav.

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  • Female sex hormone influences Alzheimer's pathology in mice, with implications for prevention and treatment. www.sciencedaily.com
    Brain Alzheimer's Hormones Heat Stress Estrogen Acetylcholine

    Alzheimer’s disease disproportionally affects women, who account for nearly two-thirds of all cases worldwide. Some evidence suggests female sex hormones influence the pathology and progression of Alzheimer’s disease. A recent study in mice shows that the brains of male and female mice with Alzheimer’s regulate amyloid-beta protein differently, with the hormone estradiol playing a critical role.

    Researchers measured amyloid-beta accumulation in male and female mice when exposed to differing levels of cholinergic tone (acetylcholine release). Then, they examined the effects of removing the ovaries (the primary source of estradiol) and estradiol replacement on this relationship. Finally, using magnetic resonance imaging techniques, they assessed the amyloid-beta burden in the brains of 130 older adults.

    They found that acetylcholine activity and the development of amyloid-related issues in male and ovariectomized female mice were directly linked. This link, however, was not observed in female mice with intact ovaries or females without ovaries that received estradiol. They also found that the age-related decline in acetylcholine worsens the amyloid-beta burden in older adults.

    Amyloid-beta is a toxic protein that clumps together, forming plaques in the brain – a hallmark of Alzheimer’s disease. Cholinergic neurons are vital for cognition and perception. They release acetylcholine, a neurotransmitter that facilitates impulse firing between neurons. Cholinergic neurons are particularly vulnerable to amyloid-beta’s toxic effects, which impair acetylcholine release. The relationship between acetylcholine and amyloid-beta is bidirectional: amyloid-beta aggregation impairs acetylcholine production, in turn increasing amyloid-beta aggregation, creating a vicious cycle.

    These findings suggest that estradiol, a female sex hormone, influences amyloid-beta burden in mice. They also highlight the need for Alzheimer’s research to consider sex differences, the relationship between acetylcholine signaling and amyloid-beta buildup, and the effects of sex hormones to better develop treatment strategies.

    Heat shock proteins inhibit amyloid-beta clumping and reduce amyloid-beta plaque toxicity. Sauna use increases heat shock protein production and activity, potentially reducing the risk of Alzheimer’s disease. Learn more in our sauna overview article.

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  • Psychedelic drugs show potential in easing PTSD and TBI symptoms in military veterans. www.sciencedaily.com
    Brain Depression Anxiety Psychedelic TBI

    Military veterans, especially those engaging in special operations, are at greater risk for developing post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI). A recent study found that psychedelic drugs reduce the symptoms associated with PTSD and TBI and improve cognition in special operations veterans.

    The study involved 86 male special operations veterans who had reported experiencing various mental and physical health disorders, including memory/concentration problems, TBI, depression, anxiety, PTSD, sleep problems, anger/rage, and fatigue. Each participant received a single oral dose of ibogaine hydrochloride. On a separate occasion, they received at least three incrementally increasing amounts (totaling 50 milligrams) of 5-MeO-DMT. Before and after each treatment session, they documented their emotional well-being and any other symptoms they experienced.

    The participants reported marked improvements in their PTSD, depression, anxiety, insomnia, and anger symptoms, along with increased life satisfaction, even at six months post-treatment. In addition, their psychological flexibility and cognitive functioning increased, while post-concussion symptoms notably decreased, remaining improved at all follow-ups.

    Participants reported positive changes in attitudes, behaviors, and relationships, and many considered the experience highly meaningful, spiritually significant, and psychologically insightful.

    Ibogaine hydrochloride is a psychedelic drug found in the bark of the Tabernanthe iboga, a shrub native to Central and West Africa. It elicits prolonged effects (beginning 30 minutes to three hours after intake and peaking between 18 and 36 hours), often described as a “waking dream.”

    5-MeO-DMT (5-methoxy-N,N-dimethyltryptamine) is a psychedelic drug obtained from various plants and the glands of the _ Incilius alvarius_ toad. It is a fast-acting, short-duration psychoactive, inducing feelings of awe, visual and auditory hallucinations, and other sensations common with classic psychedelics.

    These findings suggest that psychedelic drugs improve symptoms associated with PTSD and TBI in military special operations veterans. These improvements were still evident at the six-month follow-up when the study ended. It is possible the effects endured even longer. Learn more about the effects of psilocybin and other psychedelic drugs in this episode featuring Dr. Roland Griffiths.

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  • Pericytes are pivotal in the formation and storage of long-term memories. www.sciencedaily.com
    Brain Hormones Memory Dementia Stroke Blood-Brain Barrier

    Tiny contractile cells surrounding the brain’s capillaries called pericytes regulate vascular blood flow and maintain blood-brain barrier integrity. Pericytes detach from the blood vessels in aging, driving the pathophysiology of neurological dysfunction, vascular dementia, and stroke. A recent study in rodents shows that pericytes also play roles in long-term memory formation.

    Researchers measured the amount of insulin-like growth factor 2 (IGF2) produced by various cells in the hippocampus of rodents. IGF2, a peptide hormone produced in multiple tissues, regulates growth during fetal development and participates in the cell cycle throughout the lifespan. After determining that pericytes contributed the greatest amount of hippocampal IGF2, they assessed learning’s influence on IGF2.

    They found that learning increased pericyte IGF2 production in the hippocampus, especially in the dentate gyrus, a highly vascularized area responsible for episodic memory – long-term memory that involves conscious recollection of previous experiences and their associated contexts, such as sounds and smells. Animals lacking the ability to produce IGF2 in their pericytes exhibited poor learning and memory.

    The detachment and loss of pericytes play a crucial role in the progression of cerebral small vessel disease and neurodegenerative disorders that involve blood-brain barrier dysfunction. These specialized endothelial cells envelop a significant portion, up to 80 percent, of the brain capillary surface area in the cortex and hippocampus of the human brain. They also enwrap the tiniest vessels constituting the blood-brain barrier.

    Exercise mitigates the proinflammatory state that drives pericyte loss in aging, possibly providing a mechanism for exercise’s memory-enhancing effects. Learn more about links between exercise, pericytes, and brain health in this episode featuring Dr. Axel Montagne.

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  • Deep sleep supports cardiovascular health by boosting left ventricular function. www.sciencedaily.com
    Brain Sleep Heart Disease

    Deep sleep, characterized by slow brain waves, heart rate, and respiration, is essential for memory formation and immune function. Evidence suggests deep sleep influences cardiovascular health, too. A recent study found that deep sleep enhances left ventricular function – how well the heart’s left ventricle pumps blood throughout the body with each heartbeat.

    Researchers recruited 18 healthy adult males to participate in a sleep study. They measured their brain and heart activity, blood pressure, and carotid pulse-wave velocity (a measure of arterial stiffness). When the participants reached deep sleep, the researchers exposed them to short bursts of pink noise (white noise with the high frequencies filtered out).

    They found that the pink noise enhanced the participants' slow-wave brain activity. Interestingly, it also improved their left ventricular function, as indicated by enhanced pumping and filling capacities. Exposure to pink noise increased systolic blood pressure slightly but did not influence arterial stiffness.

    Sleep occurs in distinct stages, the most prominent of which is non-rapid eye movement (NREM) sleep – typically referred to as “deep sleep” or “slow-wave sleep.” It comprises approximately 75 to 80 percent of a person’s total sleep time. During NREM sleep, the body produces growth hormone, which plays a role in metabolism.

    The findings from this small study suggest that pink noise promotes deep sleep, driving improvements in cardiovascular function. Other evidence suggests that deep sleep provides a homeostatic recalibration of blood pressure, further supporting cardiovascular health. Learn more in this clip featuring Dr. Matthew Walker.

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  • Gut microbes from Alzheimer's patients impair memory and neurogenesis in rats, suggesting a link between gut health and Alzheimer's disease. www.kcl.ac.uk
    Brain Alzheimer's Gut Microbiome Memory Neurogenesis

    The hippocampus, a small organ within the brain’s medial temporal lobe, is critical for memory, learning, and spatial navigation. The loss of hippocampal neurogenesis (the formation of new neurons) is an early indicator of Alzheimer’s disease. A recent study in rats shows that gut microbial transplants from people with Alzheimer’s inhibit hippocampal neurogenesis and impair memory.

    Researchers transplanted gut microbes from healthy older adults or those with Alzheimer’s disease into the guts of young adult rats. Then, using behavioral tests, they assessed the rats' cognitive function.

    They found that the rats that received transplants from people with Alzheimer’s exhibited impaired memory and altered mood – functions that rely on hippocampal neurogenesis. The extent of these impairments correlated with the donors' cognitive abilities and the presence of inflammation-promoting microbes. They also noticed differences in microbial metabolites in the rats' guts, including taurine, an amino acid that supports hippocampal neurogenesis.

    These findings suggest that symptoms of Alzheimer’s disease can be passed on to a healthy, young individual via the gut microbiota, confirming the role of the gut microbiota in causing Alzheimer’s. They also highlight the importance of developing and maintaining a healthy gut microbial population, a process that begins early in life. Learn more in this clip featuring Dr. Eran Elinav.

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  • Greater blood pressure variability is linked with cognitive decline in older adults. www.sciencedaily.com
    Brain Aging Dementia Blood Pressure

    Scientists have long understood that high blood pressure increases a person’s risk for cognitive decline and dementia. Now, evidence suggests that blood pressure variability carries similar risks. A recent study found that older adults with higher blood pressure variability performed worse on cognitive tests than those with lower variability.

    Blood pressure variability occurs in response to various physiological and environmental factors that influence arterial blood pressure. Scientists classify blood pressure variability according to five types: short-term (beat to beat), short-term (24 hours), mid-term (day to day), long-term (less than five years), or very long-term (more than five years). People with high blood pressure tend to have higher variability than those with normal pressure.

    Researchers measured the blood pressure of 70 older adults (aged 60 to 80) without dementia over several days. The participants took cognitive tests and underwent tests to determine their arterial stiffness – a well-established cardiovascular risk factor for cognitive impairment and closely linked with high blood pressure.

    The researchers found that regardless of the participants' average blood pressure, those with high systolic short-term exhibited poor attention and psychomotor speed, and those with mid-term blood pressure variability showed poor executive function. Those with higher systolic short-term blood pressure variability tended to have higher arterial stiffness.

    These findings suggest that higher blood pressure variability influences cognitive function, potentially reflecting early-stage decline better than average blood pressure. They also underscore the importance of maintaining healthy blood pressure throughout the lifespan. Learn how lifetime high blood pressure increases dementia risk in this clip featuring Dr. Axel Montagne.

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  • Common fungi may override the brain's defense system, impairing blood-brain permeability and driving amyloid plaque formation. www.bcm.edu
    Brain Alzheimer's Blood-Brain Barrier

    Fungi drive many chronic health conditions, including asthma, skin problems, gut disorders, and others. Recent research has highlighted potential links between the fungus Candida albicans and Alzheimer’s disease. A recent study in mice found that C. albicans triggers a dual-pronged defense system involving both the brain and the immune system; however, when elements of this system fail, the fungi can impair the blood-brain barrier and drive amyloid plaque formation.

    Researchers injected mice with different strains of C. albicans and measured fungal levels in the animals' brains. They assessed their immune responses and examined their transendothelial electrical resistance – a crucial measure of the integrity and functionality of the endothelial layer, which forms the blood-brain barrier.

    They found that Candida albicans employed enzymes called aspartic proteinases (Saps) to compromise blood-brain barrier integrity, facilitating fungal entry into the brain. Interestingly, the presence of Saps promoted the breakdown of amyloid precursor protein (APP) into smaller, potentially protective components to combat the fungal invasion.

    The fungi also released candidalysin, a toxin that contributes to Candida albicans virulence. When microglia (brain immune cells) recognized the altered APP components and candidalysin, they synergized their efforts, driving the eradication of the fungus from the brain. However, if the microglia failed to recognize the APP or candidalysin, the fungus persisted in the brain, eliciting damage to neuronal tissues.

    Amyloid precursor protein occurs naturally in the body, particularly in brain tissues. It participates in various cellular functions, including forming and maintaining synapses, which are essential for communication between nerve cells. Abnormal APP processing can promote amyloid-beta accumulation, a hallmark of Alzheimer’s disease.

    These findings suggest the brain employs a complex defense system to protect itself against Candida albicans, a common fungus. However, the system’s failure may drive amyloid-beta accumulation and possibly Alzheimer’s disease. Learn more about amyloid-beta in this clip featuring Dr. Dale Bredesen.

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  • Playing American football linked to a 61 percent higher risk of parkinsonism and Parkinson's disease. neurosciencenews.com
    Brain Parkinson's Aging TBI

    The relationship between repetitive blows to the head (as in boxing) and parkinsonism and Parkinson’s disease is well established. However, scientists don’t fully understand the relationship between American football and these conditions. A recent study found that playing American football increases a person’s risk of parkinsonism and Parkinson’s disease by 61 percent.

    Researchers conducted a cross-sectional study using data from 1,875 men enrolled in the Fox Insight study, in which participants completed online questionnaires regarding their health status. They collected data on aspects of football participation, including duration of play, highest level played, and age at first exposure. The analysis accounted for various factors, including age, education, medical history, body mass index, concussions, and family history of Parkinson’s disease.

    They found that those who had played football were 61 percent more likely to report having parkinsonism or Parkinson’s disease than those who did not. Those who experienced higher levels of play (such as college or professional level) were nearly three times more likely to report being diagnosed with these conditions.

    Parkinsonism is an umbrella term that describes a group of neurological disorders that share similar symptoms with Parkinson’s disease, including tremors, muscle stiffness, slow movement, and difficulties with balance and coordination. Parkinson’s disease is the primary cause of parkinsonism, driving approximately 80 percent of all cases.

    These findings suggest that playing American football markedly increases the risk of parkinsonism and Parkinson’s disease. However, this study does not prove causation but highlights a potential link between sports-related head injuries and long-term neurological consequences. Learn more about Parkinson’s disease in this episode featuring Dr. Giselle Petzinger.

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  • Breast milk lipid molecule stimulates brain stem cells to produce oligodendrocytes, effectively reversing white matter damage in neonatal mice. corporate.dukehealth.org
    Brain Development Breast Milk

    Premature infants are at greater risk for developing cerebral palsy, a motor disability caused by brain injury-related white matter losses, impairing movement, balance, and posture. However, a new study in mice indicates that a cholesterol-like molecule present in breast milk may protect against cerebral palsy. Mice administered breast milk were protected from the harmful effects of white matter losses.

    Researchers tested the ability of several oxysterols (naturally occurring cholesterol-like molecules) in human breast milk to promote the production of oligodendrocytes, a type of cell that stimulates white matter development. They found that the oxysterol 20-alpha hydroxycholesterol induced oligodendrocyte production through the sonic hedgehog pathway – a well-known pathway involved in neurodevelopment.

    Then, they gave neonatal mice that had experienced inflammation-driven brain injury and subsequent white matter losses 20-alpha hydroxycholesterol. They found that the compound promoted white matter formation, reversing the animals' brain injuries.

    These findings suggest that 20-alpha hydroxycholesterol, a compound present in breast milk, influences neonatal white matter development and may benefit infants at risk for cerebral palsy or other brain injury-related disorders. Learn more about the benefits of breast milk in our overview article.

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  • Time-restricted feeding corrects Alzheimer’s circadian disruptions in mice, reducing amyloid protein accumulation and improving memory. www.sciencedaily.com
    Brain Alzheimer's Dementia Time-Restricted Eating

    Alzheimer’s disease is the most common form of dementia, affecting more than 55 million people worldwide. People with Alzheimer’s disease often experience altered circadian rhythms, manifesting as altered sleep/wake cycles and difficulty in falling and staying asleep. A new study in mice suggests that time-restricted eating restores normal circadian rhythmicity and reduces amyloid-beta plaque formation in the brain.

    Using a mouse model of Alzheimer’s disease, researchers gave one group of mice free access to food throughout the day but fed another group on a time-restricted schedule (limited to a six-hour window each day), translating to about 14 hours of fasting for humans. Then, they evaluated the animals' gene expression, amyloid-beta accumulation, and cognitive performance.

    They found that the mice fed on the time-restricted schedule had better memory function, were less hyperactive at night, followed a more regular sleep schedule, and experienced fewer disruptions during sleep than the mice allowed free access to food. The restricted mice also performed better on cognitive assessments and exhibited less amyloid-beta accumulation in the brain. Time-restricted feeding also normalized gene expression in the hippocampus, an area of the brain involved in memory and often affected by Alzheimer’s disease.

    These findings suggest that time-restricted eating mitigates the behavioral symptoms and pathological features associated with Alzheimer’s disease. Robust evidence indicates that time-restricted eating influences multiple aspects of human health. Learn more about time-restricted eating in this clip featuring Dr. Satchin Panda.

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  • Extreme microdose of THC from cannabis (three to fou orders of magnitude lower than standard dose) produces long-term neuroprotection in mice subjected to acute neurological insults. www.frontiersin.org
    Brain Aging Cannabinoid Neurogenesis

    Delta-9-tetrahydrocannabinol – better known as THC – is the primary psychoactive compound found in cannabis. THC binds to endocannabinoid system receptors, eliciting a wide range of physical effects and producing the “high” associated with its use. A new study suggests that THC reverses brain aging in old mice.

    Researchers injected old mice with a microdose of THC that was roughly three to four orders of magnitude lower than a typical dose. Then, they assessed gene expression in the animals' hippocampal tissue at five days and five weeks post-treatment.

    After just five days, they found that the microdose THC treatment altered the expression of 18 genes related to neurogenesis (the production of new nerve cells). THC altered the expression of 88 genes related to nerve cell survival and development five weeks post-treatment. Interestingly, THC did not affect brain-derived neurotrophic factor, a protein noted for its effects on neurogenesis.

    These findings suggest that a single microdose of THC exerts potent, enduring effects on the rodent brain and may have potential applications in humans. It also aligns with results from a compelling case study in which THC microdosing ameliorated symptoms of Alzheimer’s disease. Lactate, a molecule produced during vigorous exercise, also has robust effects on the brain, influencing neurogenesis and promoting cognitive function. Learn more in this episode featuring Dr. George Brooks.

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  • Infant gut microbes including Actinobacteria and Bifidobacterium linked to improved social attention tests, suggesting a role for the microbiome in early cognitive development. neurosciencenews.com
    Brain Gut Microbiome Development

    The gut-brain axis is a complex communication system that links the gut microbial community, digestive system, and nervous system. A new study shows that the gut-brain axis plays a critical role in brain development. Infants demonstrating specific patterns of enhanced brain activity, such as rhythmic processing, exhibited unique gut microbial populations and metabolic processes.

    Researchers collected fecal samples from 56 infants between the ages of four and six months and analyzed their microbial composition through metagenomic sequencing. They evaluated the infants' brain activities while listening to a rhythmic beat via electroencephalogram (EEG). Then, using behavioral tests, they assessed aspects of the infants' cognitive abilities, including neural rhythm tracking, language discrimination, and joint attention.

    They found that infants who performed well in the joint attention test exhibited specific gut microbial patterns that included higher numbers of Actinobacteria, Bifidobacterium, and Eggerthella, and lower numbers of Firmicutes, Hungatella, and Streptococcus. The EEGs revealed unique neural activity patterns associated with enhanced rhythmic processing, which varied according to the presence of specific microbes. In addition, these neural activity patterns were associated with upregulated metabolic processes involving microbes linked with neurodevelopment.

    Neural rhythm tracking facilitates information organization across time, influencing perception, social communication, language, and cognition. Language discrimination differentiates between language and non-language. Joint attention is a social skill that influences infants' capacity to learn from others, affecting early language acquisition and overall cognition.

    This study was small; however, its findings suggest a potential connection between the gut microbiome and early cognitive development. It also highlights the intricacies of the gut-brain axis, with potential implications for understanding early brain development and cognitive function. Learn more about the role of the gut microbiota in this episode featuring Drs. Erica and Justin Sonnenburg.

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  • Neuroprotection across generations: Worm study highlights ursolic acid's effects. neurosciencenews.com
    Nutrition Brain Diet Development

    Maternal exposures during pregnancy can influence the physiology and development of a woman’s child. But scientists aren’t sure whether this influence extends across generations. A new study in worms suggests that consuming ursolic acid – a bioactive compound found in apples and herbs, such as rosemary and sage – during pregnancy promotes the production of key fats in the brain, boosting neuronal health and function in progeny.

    Researchers studied the effects of ursolic acid supplementation in roundworms – a well-established model of human genetics. They fed the worms ursolic acid and assessed its effects on subsequent generations.

    They found that the worms' neural transport processes (similar to synaptic connectivity in vertebrates) were more efficient after consuming ursolic acid. The worms also demonstrated reduced susceptibility to axonal fragility in adulthood. Interestingly, these benefits transcended a singular generation, manifesting within subsequent progeny.

    The mechanism driving these effects centered around the modulation of sphingosine-1-phosphate, a bioactive metabolite of sphingolipid – a type of fat implicated in neural protection. The offspring of worms that consumed ursolic acid demonstrated elevated sphingosine-1-phosphate levels, thereby conveying neural protection across multiple generations.

    These findings suggest that dietary-acquired lipid metabolites can provide neuroprotection across generations. They also underscore the importance of maternal nutrition during pregnancy. Learn about other aspects of maternal (and paternal) health that influence offspring in this clip featuring Dr. Elissa Epel.

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  • Enhancing brain health in older adults: Olfactory stimulation via aromatherapy shows promise in cognitive function preservation. neurosciencenews.com
    Brain Alzheimer's Memory Dementia Nose

    The limbic system – a complex system of nerves and networks in the brain – supports many brain functions, including memory, emotion, and learning. The olfactory system is the only sensory system directly linked to this critical brain region. A new study shows that olfactory stimulation via aromatherapy may enhance limbic system function, potentially preserving or improving cognitive function in older adults.

    Researchers assigned 23 older adults (aged 60 to 85) to an olfactory-enriched or control group. Using an aromatherapy diffuser, they exposed the enriched group to seven essential oil scents (rose, orange, eucalyptus, lemon, peppermint, rosemary, and lavender – one per night) for two hours per night for six months. They exposed the control group to a similar routine but with minimal amounts of scent. The participants underwent neuropsychological assessments and functional magnetic resonance imaging (fMRI) scans at the study’s outset and again after six months.

    The assessments revealed that the participants who received olfactory enrichment demonstrated a 226 percent improvement on learning and memory tests. Notably, only six of the 12 participants improved, five stayed the same, and one did worse, calling the data into question. The fMRIs showed that the enriched group also exhibited enhanced function in the left uncinate fasciculus – an area of the brain that plays a crucial role in memory, language, emotion, and memory retrieval.

    These findings suggest that olfactory enrichment administered at night improves cognitive and neural functioning and may provide an effective and low-effort means to improve brain health. This study was very small, so larger trials are needed to confirm the benefits of aromatherapy on cognitive health.

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  • Microglia's Alzheimer's defense impaired by oral bacteria, study reveals. www.sciencedaily.com
    Brain Alzheimer's Dental Blood-Brain Barrier

    Microglia, the brain’s resident immune cells, play a vital role in managing brain inflammation and neurodegenerative diseases by eliminating amyloid-beta, a harmful protein linked to Alzheimer’s disease, and forming barriers around insoluble amyloid-beta deposits. A new study in mice shows that oral bacteria over-stimulate microglia, impairing their anti-amyloid properties.

    Researchers induced periodontal disease in mice by placing ligatures around their teeth, creating an environment conducive to bacterial growth. Then they examined the effects of the disease on the animals' gums, bones, and microglial cells. They found that the gum infections caused progressive periodontal disease and bone loss in the mice. In addition, the severity of periodontal disease correlated with increased microglial cell activation in the brain. Then, the researchers exposed microglial cells to bacteria from the animals' infected gums. They found that this exposure increased inflammation and changes in the cells' ability to interact with amyloid-beta.

    These findings suggest that periodontal disease influences the brain’s immune response via changes in microglial activation and their interactions with amyloid-beta. This link between gum and brain health underscores the potential importance of oral hygiene in preventing or managing neuroinflammatory conditions like Alzheimer’s disease.

    Related studies have found that oral bacteria colonize the brain and release toxins that disrupt the blood-brain barrier, impairing its function and increasing the risk of Alzheimer’s disease. Learn more about the role of blood-brain barrier dysfunction in Alzheimer’s disease in this episode featuring Dr. Axel Montagne.

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  • Vitamin D supplementation associated with a 40 percent reduction dementia risk, particularly for females and cognitively normal people.
    Vitamin D Brain Aging Dementia

    Vitamin D is a steroid hormone that plays critical roles in many physiological processes, including blood pressure regulation, immune function, and cell growth. Findings from a new study suggest that vitamin D prevents dementia. People who took vitamin D were 40 percent less likely to develop dementia than those who didn’t.

    The study involved more than 12,000 older adults who did not have dementia at enrollment. Researchers categorized the participants based on their vitamin D exposure: those exposed to vitamin D before dementia onset and those not exposed before dementia onset. They also examined different forms of vitamin D (calcium + vitamin D, cholecalciferol [D3], and ergocalciferol [D2]) to see if their effects on dementia rates varied and explored potential interactions with other risk factors for dementia, such as age, sex, education, race, cognitive function, depression, and apolipoprotein E4 (APOE4) status.

    They found that participants exposed to vitamin D had a 40 percent lower risk of developing dementia. They were also dementia-free longer than those without vitamin D exposure. These effects were evident across various forms of vitamin D. Further analysis revealed that sex, cognitive status, and APOE4 status influenced the extent of vitamin D’s effects on dementia risk. For example, females, people with normal cognitive function, and those who did not carry the APOE4 gene variant seemed to gain greater protection against dementia.

    These findings suggest that vitamin D supplementation holds promise as a preventive measure for dementia, especially for people at higher risk of developing the condition. However, more research is required to fully understand the mechanisms behind this association and establish specific vitamin D supplementation guidelines to reduce dementia risk. Learn more about vitamin D in our comprehensive overview article.

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  • Every 1 percent drop in body weight slows brain aging by nearly nine months, highlighting the substantial, and often overlooked, neuroprotective benef elifesciences.org
    Brain Obesity Aging Dementia Sulforaphane Weight Loss Neurodegeneration

    Excess body fat harms multiple organ systems, including the central nervous system, potentially accelerating brain aging. A new study shows that a 1 percent weight loss delays brain aging by nearly nine months.

    Researchers conducted a study involving 102 participants enrolled in the DIRECT-PLUS study who underwent an 18-month lifestyle intervention to promote weight loss. Using magnetic resonance imaging, the researchers assessed the resting-state functional connectivity in the participants' brains and predicted their brain ages. They also evaluated how various health factors, such as body measurements, blood markers, and fat deposits, affect brain aging.

    They found that the brain age prediction model accurately predicted the participants' chronological ages. They also found that brain aging slowed by 8.9 months for every 1 percent of body weight loss, an effect linked with improved liver health and reduced liver, visceral, and subcutaneous fat. Their analysis revealed that lower consumption of processed foods, sweets, and beverages delayed brain aging.

    These findings suggest that weight loss may benefit the brain’s aging process, potentially slowing its aging trajectory. They also underscore the importance of maintaining a healthy weight throughout the lifespan to support overall brain health. Sulforaphane, a bioactive compound derived from broccoli, benefits brain health and may influence its aging, too. Learn more in this episode featuring Dr. Rhonda Patrick.

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  • Oral contraceptives influence how women process stress, disrupting the typical hormonal adjustment seen during social interactions. www.sciencedaily.com
    Brain Stress Pregnancy Behavior Sex

    Oral contraceptives are widely known for their role in preventing pregnancy, but evidence suggests they also influence the body’s stress response. A recent study shows that women who took oral contraceptives had lower levels of adrenocorticotropic hormone (ACTH), a component of the hypothalamic-pituitary-adrenal axis typically produced in response to stress.

    Researchers measured blood ACTH levels in 131 young women before and after the women participated in group activities designed to promote social bonding and reduce stress. The participants completed questionnaires about their moods before and after the activities.

    They found that ACTH levels decreased among women not using contraceptives during the stress-buffering group activities, but this effect varied depending on their menstrual cycle phase. However, women using oral contraceptives did not experience the same decrease in ACTH levels during the group activities, regardless of their menstrual cycle phase.

    These findings suggest that oral contraceptives not only affect the reproductive system but also influence the body’s response to stress. Learn about other effects of oral contraceptives in this clip from a live Q&A with Dr. Rhonda Patrick.

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  • Presence hallucinations, such as sensing an unseen person, in early Parkinson's may signal faster cognitive decline. www.medicalnewstoday.com
    Brain Parkinson's Dementia

    Cognitive decline and hallucinations are common features of late-stage Parkinson’s disease. However, during the early stages of the disease, many people experience minor hallucinations – such as sensing an unseen person nearby or seeing a shadow pass in one’s peripheral vision – potentially indicating future cognitive deline. A recent study found that people with Parkinson’s disease who experienced minor hallucinations exhibited altered brain wave activity.

    Researchers interviewed 75 people with Parkinson’s disease to determine whether they experienced minor hallucinations. Then, using electroencephalography (EEG), they analyzed their brain wave activity. They repeated the EEG five years later.

    They found that those who experienced minor hallucinations – roughly half of the participants – had altered theta oscillations in the frontal part of their brains. These alterations were associated with poorer cognitive abilities in the frontal and subcortical regions of the brain. At the five-year follow-up, they found that participants with more frontal theta alterations during the initial assessment had a greater decline in their frontal and subcortical cognitive functions.

    Theta oscillations are rhythmic, electrical brain waves occurring at approximately four to eight cycles per second, typically observed during deep relaxation, daydreaming, and certain stages of sleep. Theta waves play a crucial role in various cognitive processes, such as memory formation, learning, and spatial navigation. They enable communication and synchronization between brain regions, facilitating efficient information processing and integration.

    These findings suggest that changes in frontal theta oscillations could be an early marker for cognitive decline in people with Parkinson’s disease. Exercise may slow the progression of Parkinson’s disease. Learn more in this episode featuring Parkinson’s expert Dr. Giselle Petzinger.

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  • Obesity disrupts the brain's sensing of glucose and lipid signals; MRIs reveal dysregulation and altered dopamine release, which persists even after w www.genengnews.com
    Nutrition Brain Obesity

    Signals from the foods we consume help regulate eating behaviors, such as whether we should stop or continue eating. A new study has found that obesity diminishes the brain’s responses to these signals, and weight loss doesn’t correct the problem.

    The study involved 60 participants: 30 with a healthy body weight and 30 with obesity. To avoid the influence of taste or preference cues on brain activity, they infused glucose, lipids (fats), and water (as a control) directly into the participants' stomachs. Then they measured the participants' brain activities and dopamine release in the striatum, an area involved in reward and motivation. To determine whether weight loss influenced this brain activity, they repeated the experiment 12 weeks later, after the participants achieved a 10 percent weight loss through dieting.

    They found that the brain responded to glucose and lipids in participants with healthy body weight. However, obesity impaired the brain’s response to these nutrients. Interestingly, the impaired brain responses did not improve, even after successful weight loss.

    These findings suggest that impaired brain responses to the signals sent after eating may contribute to overeating and obesity. They also provide insights into why many people struggle to maintain weight loss, as their brains continue to resist these signals even after significant weight reduction.

    Notably, this was a relatively small study, and the amount of weight loss – just 10 percent – might have been insufficient to induce global changes in the brain regarding nutrient sensing. Future studies that include more participants and induce greater weight loss may provide different results.

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  • DHA-rich diet protects against memory deficits and loss of smell in Alzheimer's-prone APOE4 mice, reveals new study. link.springer.com
    Brain Alzheimer's Aging Omega-3 Memory Genetics

    A diminished or lost sense of smell is a common feature of the early stages of Alzheimer’s disease and other forms of dementia. But a new study in mice that carry the APOE4 gene variant, the primary genetic risk factor for Alzheimer’s disease, shows that DHA – a type of omega-3 fatty acid found in fish – protects against these losses. APOE4-carrying mice that ate a DHA-rich diet retained their sense of smell and the ability to distinguish between objects based on their scent.

    Researchers fed normal mice and APOE4 carriers a regular diet or one supplemented with DHA. Then, using MRI scans, they assessed the animals' brain structures and studied their behavior related to smell and the recognition of new objects. They also measured biomarkers related to cell death and inflammation.

    They found that the APOE4-carrying mice given a regular diet exhibited memory deficits and difficulty adjusting to new smells and distinguishing between different objects. In addition, their brains showed increased signs of inflammation in the olfactory bulb – the area responsible for the sense of smell. However, APOE4-carrying mice that ate the DHA-rich diet did not exhibit these characteristics.

    These findings suggest that a DHA-rich diet benefits APOE4 carriers. Learn more about the beneficial effects of DHA in our comprehensive omega-3 overview article.

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  • Microglial dormancy in depression challenges conventional understanding centered on inflammation, but highlights the immune cell's crucial role in neu medicalxpress.com
    Brain Inflammation Depression Immune System

    Chronic inflammation is a dominant feature in people who have depression, suggesting that an overactive immune response drives the disease’s symptoms. But a new study demonstrates something counterintuitive in spite of that: Immune cells in the brain called microglia are less active in people with depression, impairing their ability to clear damaged neuronal connections, undermining neurotrophic support, and driving the disease.

    Researchers studied gene expression in the microglia of brain tissues collected during autopsies of 13 people with depression and 10 healthy people. They also examined gene expression of neuronal factors that regulate microglial function.

    They found that the expression of genes in the microglia of people with depression was markedly lower than that of healthy people, especially genes involved in immune responses and phagocytosis (which facilitates the clearance of damaged cells). In addition, the expression of factors involved in immune suppression (CD200 and CD47) was higher.

    These findings suggest that people with depression have a distinct disease-associated microglia gene expression profile that impairs microglia activity. Microglia play critical roles in the development, homeostasis, and diseases of the central nervous system and contribute to neuronal plasticity in the healthy brain. Microglial changes are common features of many neuropsychiatric disorders, including schizophrenia, autism spectrum disorder, and bipolar disorder. Learn more about microglia suppression in depression in this clip featuring Dr. Charles Raison.

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  • Maternal vitamin D deficiency linked to potential developmental disorders, emphasizing a role in dopamine signaling. neurosciencenews.com
    Vitamin D Brain Omega-3 Neurotransmitter Schizophrenia Dopamine

    Dopamine is a neurotransmitter best known for its role in motor, motivation, and pleasure control. A new study highlights vitamin D’s influence on dopamine signaling and emphasizes its essential role in the normal development of dopamine-producing cells.

    Researchers developed three cell lines to mimic the natural process of embryonic development, during which cells differentiate (specialize) into dopamine-producing neurons. Then they cultured the cells in the presence or absence of vitamin D.

    They found that vitamin D participated in neuronal growth and branching, the rearrangement of presynaptic proteins, and the production and release of dopamine. The researchers posited that glial-derived growth factor, a vitamin D-dependent factor that promotes dopamine neuron differentiation, was the mechanism driving these effects.

    These findings suggest that vitamin D plays multiple roles in dopamine signaling, with potential implications for neurodevelopmental disorders like schizophrenia, ADHD, and autism. They also underscore the importance of adequate maternal vitamin D status during pregnancy.

    Interestingly, vitamin D and omega-3 fatty acids may synergistically work to support neurodevelopment further. Read this open-access peer-reviewed article by Dr. Rhonda Patrick to learn more.

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  • Right versus left nostril breathing differentially influences brain activity, with distinct effects on language and introspection. www.nature.com
    Brain Breathing Technique

    Breathwork has profound effects on the human brain. A new study shows that breathing through the right nostril versus the left differentially influences brain activity. Whereas right-nostril breathing promoted brain activity in areas related to language and sense of direction, left-nostril breathing promoted activity in areas related to introspection.

    Scientists monitored the brain activity of 30 healthy adults practicing unilateral nostril breathing (UNB). Participants breathed through a CPAP-like device (like those used by people with sleep apnea) that delivered pressurized air through one nostril with greater force than the other. This capitalized on the phenomenon of nostril dominance – the tendency for one nostril to have greater airflow than the other. Nostril dominance changes roughly every two to three hours. The experimental session consisted of a resting phase, a 10-minute UNB session using the dominant nostril, and a 10-minute UNB session using the non-dominant nostril.

    They found that breathing through the dominant nostril increased brain activity in the left inferior frontal and left parietal lobes – brain areas involved in language and spatial orientation. Conversely, breathing through the non-dominant nostril had a more widespread effect on the posterior areas of the brain, particularly those involved in the brain’s default mode network.

    The belief that UNB can influence brain function is an ancient one, practiced by Indian yogis for many centuries. For example, the yogis believed that blocking one nostril and forcefully breathing through the other would activate the opposing cerebral hemisphere. Modern research supports these claims, which observed increased activity in the contralateral hemisphere during UNB. In addition, breathing through the right nostril may promote alertness, while breathing through the left nostril may promote calm.

    These findings indicate that the cognitive effects of breathing through the right nostril versus the left differ and may have applications in treating various brain disorders.

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  • Improved memory and emotional recognition linked to nasal breathing. www.jneurosci.org
    Brain Memory Mental Health Breathing Technique

    Breathing is an essential and regular process that provides the body with oxygen and removes carbon dioxide. But new research indicates that breathing influences brain function. People who breathed through their noses performed better on memory and emotional expression interpretation tests than when they breathed through their mouths.

    Researchers investigated the relationship between breathing, the brain, and thinking. First, they conducted intracranial electroencephalograms (EEGs) to assess the effects of nasal versus oral breathing in eight people. Then they administered various tests to 107 healthy young people to determine the effects of nasal versus oral breathing on memory and the ability to interpret emotional expressions.

    The intracranial EEGs revealed that when the participants breathed through their noses, their brainwaves in areas related to smell and emotions synchronized with their breathing patterns. However, breathing through their mouths diminished these effects. Similarly, when participants breathed through their noses, they performed better on memory tests. Interestingly, breathwork also influenced their ability to interpret emotional expressions. For example, their ability to interpret fear was faster during inhalation versus exhalation.

    These findings suggest that breathing, especially nasal breathing, has more complex effects on the body than previously understood. They also highlight a novel means to improve cognitive function. Learn about other effects of breathing techniques in this clip featuring Wim Hof.

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  • Consuming 500 milligrams of cocoa flavanols daily improves hippocampal memory function in older adults, study finds. www.pnas.org
    Brain Memory Polyphenol Cocoa

    Dietary components play critical roles in cognitive function as we age. A new study shows that flavanols – bioactive compounds found in tea, apples, berries, grapes, cocoa, and other fruits and vegetables – improve memory. People who took a flavanol-rich cocoa supplement performed better on memory tests than those who didn’t.

    Researchers conducted a three-year study involving more than 3,500 older adults. Half of the participants received a cocoa extract containing 500 milligrams of flavanols daily, while the other half received a placebo. The researchers gave the participants memory tests before and after the intervention, and they assessed the participants' overall diet quality using the Healthy Eating Index.

    They found that people with higher flavanol intake and better overall diet quality at the beginning of the study had better memory performance, particularly in tasks involving the hippocampus – the area of the brain responsible for memory consolidation. However, after one year of intervention, the researchers found that memory improved among those with lower diet quality or low flavanol intake.

    These findings suggest that low dietary flavanol intake contributes to age-related cognitive decline, specifically hippocampal-dependent memory, but flavanol supplementation counteracts these effects. They also underscore the importance of including flavanol-rich foods in the diet throughout the lifespan for optimal cognitive performance.

    Evidence suggests flavanols promote angiogenesis (the formation of new blood vessels), which is crucial for adequate blood flow to the brain. Learn how blood flow to the brain influences cognitive function in this episode featuring Dr. Axel Montagne.

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  • Links identified between open-mindedness, brain volume, and cognitive function. europepmc.org
    Brain Aging Norepinephrine Intelligence

    Openness – a sense of curiosity, open-mindedness, and interest in new experiences – is critical to preserving cognitive function as we age. A new study has found that a tiny region in the brain called the locus coeruleus may provide the link between openness and better cognitive health. People with greater locus coeruleus integrity demonstrated more openness and – interestingly – had higher intelligence.

    Researchers gave 135 young adults a battery of tests to gauge their openness and intelligence. Then, using an imaging technique called voxel-based morphometry, they measured the participants' locus coeruleus volumes.

    They found that the participants with greater locus coeruleus volumes tended to have more openness and higher intelligence, regardless of age, gender, or total brain volume. Because locus coeruleus volume is associated with cognitive function, these findings suggest that activities that maintain locus coeruleus volume may be beneficial for preserving cognitive function.

    The locus coeruleus is the primary region of the brain responsible for norepinephrine production. It is located in the pons and participates in the body’s response to stress, attention, emotion, motivation, decision-making, learning, and memory. Poor sleep has profound effects on locus coeruleus integrity and cognitive function. Learn more about the brain effects of poor sleep in this episode featuring Dr. Matt Walker.

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  • Exercise may enhance focus and attention. www.nature.com
    Exercise Brain Norepinephrine

    Selective attention – the ability to focus on what’s important and manage distraction – can be elusive. But findings from a new study suggest that exercise enhances selective attention. People who engaged in just a single exercise session before completing a task exhibited better focus and less distraction.

    The study involved 24 healthy adults who participated in two protocols (20 minutes of exercise or 30 minutes of seated rest) on separate occasions. Participants completed a task before and after each protocol that tested their attention to attended versus unattended stimuli. Attended stimuli are things a person needs to focus on; unattended stimuli are those a person should ignore, such as background noise. Researchers measured the participants' brain activity during the task completion.

    They found that participants focused better on the task after a single exercise session than after sitting. However, neither of the protocols influenced the participants' performance on the task. Processing of attended stimuli increased after exercise, while processing of unattended stimuli decreased, suggesting that exercise allocated neural resources to support attention.

    One mechanism that drives the increased focus after exercise may be related to norepinephrine, a neurotransmitter produced in the locus coeruleus. Exercise increases norepinephrine release, which in turn promotes attention and vigilance.

    This was a small study; nevertheless, it supports other evidence suggesting that exercise has potent effects on the brain. Learn more about the effects of exercise in our overview article.

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  • Exercise boosts memory and brain connectivity in older adults. sph.umd.edu
    Exercise Brain Aging Memory

    A new study finds that exercise maintains critical connections in the brains of older adults while boosting fitness. Older adults who walked regularly performed better on tests of cognitive function and memory and had better cardiorespiratory fitness.

    The study involved 33 older adults (average age, 78 years). Participants walked on a treadmill for 30 minutes a day, four times a week, for 12 weeks and underwent tests before and after the intervention to assess their physical and cognitive performance. In addition, researchers performed functional MRIs to examine the neural connections in their brains.

    They found that participants' cardiorespiratory fitness improved by more than 10 percent. They also demonstrated improvements in cognitive performance, particularly in verbal fluency, verbal learning, and memory. The MRIs revealed that participants experienced increased connectivity between the default mode network and regions of the brain involved in memory.

    The default mode network is a collection of interconnected neural structures involved in attention and focus. Disturbances in default mode network connectivity are associated with poor working memory, reduced performance, and work-related productivity losses.

    Although this was a small study, it supports a growing body of evidence suggesting exercise is a potent strategy for staving off cognitive decline in aging. One contributor to cognitive decline is the loss of blood-brain barrier integrity. Learn how vigorous exercise helps maintain blood-brain barrier integrity as we age in this episode featuring Dr. Axel Montagne.

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  • Vitamin D may boost neurodevelopment, reducing childhood behavioral problems. jamanetwork.com
    Vitamin D Brain Behavior Mental Health Development

    Although vitamin D is best known for its role in bone health, this fat-soluble vitamin participates in many physiological processes, such as blood pressure regulation, immune function, and cell growth. Now, new research shows that vitamin D also supports neurodevelopment. Young children who received supplemental vitamin D were less likely to have neurobehavioral problems later in childhood than those who didn’t.

    Researchers gave 346 infants either low-dose (400 IU) or high-dose (1,200 IU) vitamin D daily from two weeks to two years of age. Then, when the children were between six and eight years old, their parents completed questionnaires regarding their children’s behavior, particularly internalizing behaviors, such as depression, anxiety, and withdrawal. They also collected information about the mothers' prenatal vitamin D status.

    They found that nearly 12 percent of the children on low-dose vitamin D exhibited internalizing behaviors between the ages of six and eight. However, fewer than 6 percent of those on the high-dose vitamin D exhibited internalizing behaviors, even after considering other factors that influence behavior, such as sex, maternal depression, and living in a single-parent household. Notably, 48 children in the low-dose group whose mothers had low prenatal vitamin D levels exhibited more internalizing behaviors than those in the high-dose group, suggesting that vitamin D supplementation in early childhood compensated for low prenatal exposure.

    These findings highlight yet another role of vitamin D in human health. Learn more about vitamin D in our overview article.

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  • Exercise, vitamin D, and cognitive training boost cognitive function. link.springer.com
    Vitamin D Exercise Brain Aging Dementia

    Changes in brain function and connectivity often occur many years before the clinical manifestation of cognitive impairment and dementia. A new study shows that lifestyle modifications, including exercise, vitamin D intake, and cognitive training, improve functional brain connectivity in older adults with mild cognitive impairment.

    The study involved 120 older adults (ages 60 to 80 years) with mild cognitive impairment. The participants engaged in 30 minutes of cognitive training and 60 minutes of exercise three times a week for 20 weeks. Thirty-eight of the participants received vitamin D supplements, while the remainder received a placebo. Researchers measured the participants' functional brain connectivity using MRI before and after the interventions.

    They found that physical exercise alone, exercise combined with cognitive training, or exercise combined with both cognitive training and vitamin D supplementation increased functional brain connectivity in regions of the brain’s default mode network, including the hippocampus and angular gyrus.

    The default mode network is a collection of interconnected neural structures involved in attention and focus. Disturbances in default mode network connectivity are associated with poor working memory, reduced performance, and work-related productivity losses.

    This study’s findings suggest that lifestyle behaviors, particularly exercise, enhance functional brain connectivity, potentially staving off age-associated cognitive decline. Learn more about the effects of exercise on the brain in this episode featuring Dr. Axel Montagne.

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  • Is omega-6 a villain? New study highlights omega-6, -7, and -9 may promote better memory and a larger brain volume. medicalxpress.com
    Nutrition Brain Dementia

    A recent study showed that people with higher blood concentrations of key fatty acids had larger brain volumes and better cognitive function than those with lower concentrations.

    Researchers collected nutrition-related blood biomarkers, brain images, and memory and intelligence scores of 111 older adults. Then, using a data-fusion approach, they investigated how these factors work together to promote brain and cognitive health in aging.

    They found that participants with higher blood concentrations of omega-6, -7, and -9 fatty acids tended to score higher on memory tests than those with lower concentrations. They also had larger gray matter volumes.

    These findings suggest that nutrition plays a critical role in brain health and cognitive function in aging. They also underscore the importance of consuming healthy fats for optimal brain health.

    Studies like this one emphasize that omega-6 fatty acids are not inherently villainous; rather, they become problematic when they serve as a marker for processed food consumption. In certain contexts, specific omega-6 fatty acids, particularly linoleic acid, exhibit beneficial effects. Instead of eliminating omega-6 fatty acids found in healthy foods, it may be more effective to focus on reducing processed food intake while increasing consumption of omega-3 fatty acids and whole foods containing beneficial forms of omega-6, -7, and -9. By consuming more whole foods, we benefit from not only the presence of healthy omega-6, -7, and -9 fatty acids, but also from fiber, the food matrix, improved glycemic impact, and an abundance of micronutrients that are often stripped away in processed foods. This holistic approach to nutrition ensures that we receive the full spectrum of nutrients required for optimal health.

    In addition, although older research showed that the ratio of omega-6s to omega-3s in blood was cause for concern, those concerns are likely unfounded. Rather than focusing on decreasing omega-6 intake to improve the ratio, most people would probably benefit from increasing omega-3 intake instead to improve overall blood concentrations. Learn more about the omega-6/omega-3 ratio in this clip featuring Dr. Bill Harris.

    Omega-6s are found in sunflower seeds; walnuts; and pumpkin seeds. They are also found in safflower, sunflower, corn, and soybean oils. Omega-7s are found in salmon, anchovies, macadamia nuts, olive oil, and avocados. Omega-9s are found in various nut oils.

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  • Harmful effects of concussion are still present six months post-injury. medicalxpress.com
    Brain Memory Concussion Sulforaphane

    Press release:

    The harmful effects of concussion on the brain can linger long after the initial injury, a new study shows. Nearly half of all people who experienced even a mild concussion exhibited altered brain connectivity and impaired emotional and cognitive function six months post-injury.

    Researchers compared brain scans of 108 people who had experienced a mild concussion to those of 76 healthy people. They also assessed those who had had a concussion for persistent symptoms.

    They found that 47 percent of the people with mild concussion were not fully recovered six months post-injury, demonstrated by hyperconnectivity in the thalamus – a region of the brain that relays sensory impulses from receptors in various parts of the body to the cerebral cortex. This hyperconnectivity was associated with impaired emotional and cognitive function.

    A concussion is a disruption in normal brain function caused by an external mechanical force. Even mild concussions have been shown to elicit acute and chronic damage to the brain. Symptoms of concussion include depression, cognitive impairment, headaches, and fatigue, many of which are still present as late as six months post-injury. People who experience three or more concussions tend to exhibit cognitive deficits that worsen with each subsequent concussion.

    These findings indicate that even mild concussions can have long-term deleterious effects on the brain. Evidence suggests that sulforaphane, a bioactive compound derived from broccoli, promotes recovery from concussion. Learn more in this clip featuring Dr. Rhonda Patrick.

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  • Deep breathing exercises moderate heart rate variability – and may reduce Alzheimer's disease risk. gero.usc.edu
    Brain Alzheimer's Meditation Dementia Breathing Technique

    Deep breathing exercises may reduce the risk of Alzheimer’s disease, a new study shows. People who practiced deep breathing exercises had blood lower levels of amyloid-beta protein – a risk factor for Alzheimer’s disease.

    The study involved 108 healthy adults. Half of the participants practiced slow-breathing techniques in a 10-second rhythm (five seconds in, five seconds out) to maximize their heart rate variability. The other half tried to keep their heart rate steady by practicing relaxation techniques, such as picturing calm settings or listening to calming music. Each group practiced their respective techniques for about 20 minutes, twice daily for four weeks.

    They found that participants who practiced the slow-breathing techniques (inducing greater heart rate variability) had lower blood levels of amyloid-beta 40 and 42 – two toxic proteins that are typically increased in people with Alzheimer’s disease – than those who kept their heart rates steady. The reductions in the two amyloid-beta proteins corresponded to decreased production of proteins involved in noradrenergic signaling, part of the body’s “fight-or-flight” response.

    Heart rate variability refers to the physiological phenomenon of variation in the time interval between heartbeats, measured by the variation in the beat-to-beat interval. Decreased parasympathetic nervous system activity or increased sympathetic activity will lead to lower heart rate variability, a robust predictor of poor health outcomes, including a greater risk of death after a heart attack.

    These findings suggest that breathing techniques that moderate heart rate variability reduce amyloid-beta burden in healthy people, potentially reducing the risk of Alzheimer’s disease. Learn about other strategies to reduce the risk of Alzheimer’s disease in this episode featuring Dr. Dale Bredesen.

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  • Exercise and supplemental lactate may improve cognitive function. www.nature.com
    Exercise Brain Dementia BDNF Lactate

    Lactate boosts cognitive function in mice, according to a new study. Mice had better spatial working and long-term memory after exercising and receiving supplemental lactate.

    Researchers studied the effects of exercise – with or without supplemental lactate – on cognitive function in mice. The mice engaged in moderate-intensity exercise (about 55 to 60 percent of their VO2 max) five days a week for five weeks. This level of intensity is just below the “lactate threshold” – the point at which lactate builds up in the bloodstream and compromises performance. At the end of the five-week period, they tested the animals' memory skills.

    They found that exercise plus supplemental lactate improved the animals' spatial working and long-term memory. In addition, the expression of various proteins produced in the hippocampus, including FNDC5 (also called irisin) and brain-derived neurotrophic factor (BDNF), increased, suggesting that supplemental lactate augments the beneficial effects of exercise on the hippocampus and subsequent cognitive function.

    Lactate is a compound produced in muscles during exercise via the breakdown of glucose. It is thought to participate in a sort of “lactate shuttle” in which it is transported from the muscles into tissues like the heart and brain, where it is used for energy. Evidence suggests that lactate mediates some of the benefits of exercise on learning and memory via inducing neuronal BDNF expression. Learn more about the lactate shuttle and its effects on the brain in this episode featuring Dr. George Brooks.

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  • Low bone density may increase dementia risk. www.medscape.com
    Nutrition Brain Aging Dementia Bone Small Vessel Disease

    A new study shows that having low bone density may increase a person’s risk for cerebral small vessel disease – a driver of dementia. People with the lowest bone density in their upper femur were twice as likely to develop dementia over a ten-year period than those with the highest bone density.

    Researchers categorized nearly 1,200 people over the age of 50 years according to their small vessel health status and bone density. They also measured serum bone turnover markers and microRNAs related to cerebral small vessel disease and bone metabolism.

    They found that cerebral small vessel disease scores increased as bone mineral density decreased. They also found that levels of microRNA-378f, a non-coding RNA molecule that inhibits bone formation, were higher among participants with low bone density.

    In older adults, dementia and low bone mineral density often coincide. In addition, physical inactivity and poor nutrition, common among people with dementia, can accelerate bone loss. Scientists don’t fully understand the extent to which bone loss is present before the onset of dementia, however. (Read more about bone health in the two reviews presented below.)

    The findings from this study suggest that bone and brain health are closely linked, possibly via a bone-brain axis that regulates brain health. However, whether bone loss causes cerebral small vessel disease and subsequent dementia remains unclear. The findings also highlight the importance of maintaining bone health throughout the lifespan. Learn how resistance exercise helps increase bone density in this clip featuring Dr. Brad Schoenfeld.

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  • Untreated sleep apnea may impair men's social cognition – the ability to understand and recognize social cues and emotions. www.sciencealert.com
    Brain Aging Sleep

    Untreated sleep apnea may harm the brain, a new study shows. Middle-aged men with sleep apnea performed worse on tests of cognitive and social function than healthy men.

    Researchers compared 27 middle-aged men who had either mild or severe untreated sleep apnea with seven healthy men. Each of the men underwent a sleep study and apnea assessment and took a battery of neuropsychological tests.

    The researchers found that the men with sleep apnea had worse cognitive function, including poorer attention, memory, and decision-making capabilities, compared to the healthy men. They also found that sleep apnea impaired the men’s social cognition – the ability to understand and recognize social cues and emotions. Social cognition can be impaired in certain mental health conditions, such as depression, and may be connected to sleep patterns.

    Sleep apnea is a common, but serious, sleep disorder characterized by brief moments of paused or shallow breathing. People with sleep apnea are at greater risk of high blood pressure, stroke, abnormal heart rhythms, heart failure, diabetes, weight gain, and heart attacks.

    The findings from this small study suggest that sleep apnea impairs cognitive function as early as middle age in men. Larger studies that also include women are needed to confirm the role that sleep apnea plays in cognitive decline. Learn about the role that sleep plays in preventing dementia in this short video featuring Dr. Rhonda Patrick.

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  • High blood pressure in early adulthood is linked to late-life neurodegeneration and loss of white matter integrity. www.news-medical.net
    Brain Aging Dementia Blood Pressure Neurodegeneration

    A new study shows that having high blood pressure in early adulthood harms brain health later in life, especially in men. Men who had high blood pressure as young adults had poorer brain health than those with normal blood pressure.

    Researchers performed brain scans on 427 older adults to assess their brain volume and white matter integrity. Then they compared the scans of those who had high blood pressure in early adulthood (between the ages of 30 and 40 years) with those who had normal blood pressure.

    They found that those who had high blood pressure had lower brain volumes and poorer white matter integrity – an indication of impaired cognitive plasticity. The link between high blood pressure and lower brain volume was stronger in men, especially in the frontal cortex and cerebral gray matter.

    These findings suggest that prolonged exposure to high blood pressure has marked effects on brain health later in life, increasing one’s risk of dementia. Exercise can have profound blood pressure-reducing effects, however. Learn more about the brain-protective effects of exercise in this clip featuring Dr. Axel Montagne.

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  • Higher cardiovascular fitness may delay the onset of dementia by 9.5 years. www.medscape.com
    Exercise Brain Aging Dementia Cardiovascular

    Higher cardiovascular fitness delays brain aging and the onset of dementia in women, a 2018 study showed. Women with high cardiovascular fitness levels experienced nearly a decade’s delay in dementia onset than those with moderate fitness levels.

    The study involved 191 middle-aged women. Participants completed a cycling test to gauge their cardiovascular fitness and underwent regular neuropsychiatric testing to determine if they developed dementia during their lifetime.

    Compared to women with moderate cardiovascular fitness levels, women with high cardiovascular fitness levels were 88 percent less likely to develop dementia. However, those with low fitness levels were 41 percent more likely to develop dementia. Higher fitness delayed the onset of dementia by 9.5 years compared to those with moderate fitness.

    Cardiovascular fitness is a measure of how well the heart, lungs, and blood vessels transport oxygen to the muscles during exercise. Exercise contributes to cardiovascular fitness because it exerts robust effects on the cardiovascular system, boosting heart rate, blood pressure, and cardiac output. Interestingly, sauna use exerts similar effects on the cardiovascular system. Learn more in our overview article.

    These findings suggest that cardiovascular fitness protects against dementia in women. Learn more about the effects of cardiovascular fitness on brain health in this short video featuring Dr. Rhonda Patrick.

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  • Magnesium may delay age-related brain shrinkage. www.medscape.com
    Brain Diet Aging Magnesium Dementia

    Magnesium may protect the brain from age-related volume losses, a new study showed. People with the highest magnesium intake had larger brain volumes than those with lower intake – a protective effect that corresponded to roughly one year less aging.

    The study involved more than 6,000 adults between the ages of 40 and 73 years enrolled in the UK Biobank study. The participants completed questionnaires about their typical daily magnesium intake. They also underwent brain scans that measured their brain volumes and identified the presence of white matter lesions – areas in the brain that often indicate cerebral small blood vessel disease, a risk factor for dementia.

    The scans revealed that participants with the highest magnesium intake – 550 milligrams or more daily – had larger gray matter and hippocampal volumes than those with normal intake (about 350 milligrams daily). In middle-aged adults, this effect on brain health corresponded to about one year of aging. The protective effects of magnesium were more pronounced in women than in men.

    Magnesium is an essential mineral. It is found in green leafy vegetables, legumes, nuts, seeds, and whole grains, and is widely available as a dietary supplement. Evidence suggests that low magnesium levels are involved in the pathogenesis of various age-related brain disorders. In addition, people with Alzheimer’s disease often have lower magnesium levels than healthy people. More than half of people living in the United States likely have magnesium deficiency

    These findings suggest that magnesium protects the brain against age-related volume losses, which are associated with dementia. It also aligns with other research showing that people who follow the MIND diet, which emphasizes the consumption of magnesium-rich green leafy vegetables, were 40 percent less likely to develop Alzheimer’s disease.

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  • Air pollution exposure impairs strategic decision-making. www.sciencedaily.com
    Brain Pollution

    Exposure to air pollution increases a person’s tendency to make mistakes, a new study shows. Chess players who were exposed to fine particulate matter in air pollution made more frequent – and more serious – mistakes during play than when not exposed.

    The study involved 121 elite chess players. Researchers measured the players' exposure to air pollutants during tournament play over a period of about three years. Then, using artificial intelligence, they assessed the players' performance during each of the tournaments.

    They found that a modest increase in particulate matter of just 10 micrograms per cubic meter increased a player’s probability of making a mistake by more than 26 percent. In general, this modest increase raised mistake severity by nearly 11 percent. However, later in the matches, when decision-making time became limited, the increase in the particulate matter raised mistake severity by more than 20 percent.

    Particulate matter in air pollution is a mixture of solid particles and liquid droplets. It is present in fine inhalable particles, with diameters that are generally 2.5 micrograms or less. Evidence suggests that exposure to particulate matter in air pollution promotes oxidative stress, increases the risk of developing many chronic diseases, and accelerates aging.

    These findings suggest that exposure to particulate matter in air pollution impairs decision-making and increases mistakes. Such findings may have relevance for people who work in professions that require strategic decision-making while experiencing exposure to particulate matter, such as firefighters or air traffic controllers, or for those who live or work downwind from pollution sources.

    People who live in highly urban environments near busy roads may wish to consider using a high-quality air purifier such as a HEPA filter to help reduce their exposure to particulate matter.

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  • Botox injections may impair a person's interpretation of facial expressions. www.newscientist.com
    Brain

    Botox injections in the forehead may impair a person’s interpretation of facial expressions, according to a new study. Brain scans showed that when people who had Botox injections viewed emotional facial expressions, they exhibited altered activity in their amygdala – an area of the brain involved in processing fearful and threatening stimuli.

    Researchers injected Botox into the glabellar muscles (responsible for frowning) of 10 women. Using functional magnetic resonance imaging, they measured the women’s brain activity while viewing emotional faces, both before and after the injections.

    They found that activity in the amygdala was altered when viewing both happy and angry faces. Similarly, activity in the fusiform gyrus (an area of the brain involved in the processing of faces) was altered when viewing happy faces.

    Botox is the tradename for botulinum toxin A, a prescription medication derived from a neurotoxin produced by the bacterium Clostridium botulinum. It is commonly used to temporarily reduce the appearance of skin wrinkles and works by inhibiting the release of acetylcholine (a neurotransmitter) at motor nerve endings.

    The findings from this small study suggest that Botox injections in the forehead impair the interpretation of emotional expressions. They also support what is referred to as the facial feedback hypothesis, which asserts that when we see an emotional expression on a face, we respond by trying to recreate the expression. Doing so helps us identify and experience the emotions we see. Larger studies are needed to confirm these findings.

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  • Fewer amyloid plaques and tau tangles found in the brains of people who follow the MIND or Mediterranean Diets. www.sciencedaily.com
    Brain Alzheimer's Diet

    People who followed the MIND or Mediterranean Diets had fewer amyloid plaques and tau tangles – hallmarks of Alzheimer’s disease – in their brains than those who didn’t, according to a new study. They were also 40 percent less likely to develop Alzheimer’s disease.

    The study involved nearly 600 adults who agreed to postmortem examination of their brains. Researchers scored the participants' adherence to the two dietary patterns over a period of approximately seven years and analyzed the effects of specific dietary components on brain health.

    They found that the brains of people who closely adhered to either of the two diets had fewer signs of Alzheimer’s disease – specifically, amyloid-beta load, phosphorylated tau tangles, and global Alzheimer’s disease pathology – than those who didn’t, even after considering the participants' physical activity levels, smoking status, and vascular disease burden. Those who closely followed the diets were also 40 percent less likely to develop the disease over a period of, on average, about seven years. Green leafy vegetables stood out as having the greatest beneficial influence on brain health and Alzheimer’s disease pathology.

    The Mediterranean Diet emphasizes the consumption of vegetables, fruits, legumes, healthy fats, and at least three servings of fish weekly. The MIND diet, which is short for Mediterranean-DASH Intervention for Neurodegenerative Delay, recapitulates aspects of the Mediterranean Diet and the DASH diet, with an emphasis on the consumption of green leafy vegetables, berries, and at least one serving of fish weekly. Both the MIND and Mediterranean diets permit small amounts of wine daily.

    These findings suggest that the MIND and Mediterranean Diets confer protection against Alzheimer’s disease. Learn about other strategies to prevent Alzheimer’s disease in this episode featuring Dr. Dale Bredesen.

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  • Vitamin D may reduce the risk of developing Alzheimer's disease. www.sciencedaily.com
    Vitamin D Brain Alzheimer's Aging

    Taking vitamin D may prevent Alzheimer’s disease, a new study shows. People who took vitamin D were 40 percent less likely to develop Alzheimer’s disease than those who did not.

    The study involved more than 12,000 adults who were dementia-free at the time of enrollment. Participants provided information about their vitamin D intake and underwent regular cognitive evaluations over a period of 10 years.

    Even after taking other risk factors into account, such as age, sex, education, race, cognitive diagnosis, depression, and whether they carried the APOE4 gene, people who took vitamin D were 40 percent less likely to develop Alzheimer’s disease during the study period than those who did not. APOE4 carriers who took vitamin D were 33 percent less likely to develop the disease than carriers who did not. Interestingly, women were more likely than men to develop Alzheimer’s disease, but taking vitamin D countered this effect.

    Vitamin D is a fat-soluble vitamin that is stored in the liver and fatty tissues of the body. Perhaps best known for its role in maintaining calcium balance and bone health, vitamin D plays critical roles in many physiological processes, such as blood pressure regulation, immune function, and cell growth. Poor vitamin D status is implicated in the pathogenesis of many acute and chronic diseases, including rickets, osteoporosis, multiple sclerosis, and cancer. Evidence suggests that low vitamin D concentrations are linked with severe outcomes in COVID-19.

    The findings from this large study suggest that vitamin D protects the brain against Alzheimer’s disease. The researchers did not measure the participants' blood vitamin D concentrations, so they could not identify cutoffs that define risk. However, the Endocrine Society has determined that vitamin D concentrations less than 20 ng/mL (50 nmol/L) define “deficiency,” and concentrations ranging from 52.5 to 72.5 nmol/L (21 to 29 ng/mL) define “insufficiency.” They also recommend widespread testing for at-risk populations. Learn more about vitamin D in our overview article.

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  • As little as nine minutes of moderate or vigorous activity daily may improve cognitive function. www.news-medical.net
    Exercise Brain Aging

    A new study shows that engaging in even a few minutes of daily exercise improves memory and cognitive function. Middle-aged adults who engaged in just nine minutes of moderate to vigorous activity daily performed better on tests of memory, planning, and organization than those who engaged in sedentary or light activities.

    Researchers tracked the activity patterns of nearly 4,500 adults over a period of a week. The participants took cognitive tests that assessed their verbal memory and executive function – the ability to plan, monitor, and execute one’s goals.

    People who engaged in moderate to vigorous activity scored higher on the cognitive tests than those who were sedentary or engaged in only light activity. Surprisingly, just nine minutes of moderate to vigorous activity markedly improved cognitive performance versus sedentary activity.

    Physical activity is a broad term that includes exercise, work-related exertion, and even some hobbies. Moderate-intensity physical activities, which include activities like brisk walking, doubles tennis, or raking leaves, increase a person’s heart rate to about 50 to 60 percent of their maximum. Vigorous-intensity physical activities, which include activities like running, swimming, or cycling, increase the heart rate to 70 to 80 percent of one’s maximum.

    Robust evidence demonstrates that vigorous activity maintains the blood-brain barrier, a critical component of brain health and cognitive function. Learn more in this episode featuring Dr. Axel Montagne.

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  • Running may be as effective as traditional antidepressant therapies for reducing symptoms of depression. www.sciencedirect.com
    Exercise Brain Depression

    Running may be as effective as traditional antidepressant therapies for reducing symptoms of depression.

    A new study found that running was as effective as traditional antidepressant drugs at reducing symptoms of depression. In addition, people who ran had better physical health than those who did not.

    The study involved 141 people with depression. Participants chose which 16-week therapy intervention they preferred: running at least twice a week with a group (96 participants) or taking traditional antidepressant medication (45 participants). They underwent mental and physical health assessments before and after the interventions.

    The two therapies were comparable in terms of reducing depressive symptoms. However, running therapy improved many aspects of the participants' health, including body weight, waist size, blood pressure, heart rate, and heart rate variability.

    Nearly 25 million adults living in the United States take some form of antidepressant medication. Most antidepressants work by altering the brain’s chemistry to affect mood. Side effects of the drugs include nausea, weight gain, decreased libido, and anxiety, among others. Evidence suggests that antidepressants are only about 20 to 30 percent more effective at reducing symptoms of depression than placebo treatments.

    Exercise boosts the production of molecules that enhance mood and promote mental health. Learn more about the mental health effects of exercise in this video featuring Dr. Rhonda Patrick.

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  • Blocking activity of aryl hydrocarbon receptor in T Cells shuts off multiple sclerosis autoimmunity newsroom.uvahealth.com
    Brain Gut Microbiome Multiple Sclerosis Autoimmunity

    Blocking a key regulator of autoimmunity reduces the inflammation associated with multiple sclerosis.

    A protein found on the surface of some immune cells regulates autoimmunity in multiple sclerosis, a new study has found. Blocking the protein’s activity reduced the inflammation associated with the disease.

    Researchers studied the role that the aryl hydrocarbon receptor – a protein found on specific immune cells called T cells – plays in autoimmunity in a mouse model of multiple sclerosis. They bred mice that lacked the aryl hydrocarbon receptor and examined the effects its absence had on T cell activity.

    They found that the absence of the aryl hydrocarbon receptor altered the types and numbers of microbial metabolites produced in the animals' guts. Specifically, the microbes produced more bile acids and short-chain fatty acids – both of which exhibit robust anti-inflammatory properties.

    Multiple sclerosis (MS) is a progressive autoimmune disorder that targets the central nervous system. A dominant feature of MS is inflammation of the nerves. T cells play an instrumental role in the inflammation and pathophysiology of MS.

    These findings suggest that blocking the key regulator of inflammation in MS prevents the inflammation associated with the disease. Some evidence suggests that the fasting-mimicking diet reduces the number of autoimmune cells in people with multiple sclerosis. Learn more in this episode featuring Dr. Valter Longo.

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  • Lactate produced from high-intensity exercise may play crucial memory role and correlates closely with plasma BDNF. www.mdpi.com
    Exercise Brain Aerobic BDNF Neurodegeneration Lactate

    From the article:

    Current research has shown that (i) increased peripheral lactate levels (following high intensity exercise) are associated with increased peripheral BDNF levels, (ii) lactate infusion at rest can increase peripheral and central BDNF levels and (iii) lactate plays a very complex role in the brain’s metabolism. In this review, we summarize the role and relationship of lactate and BDNF in exercise induced neuroplasticity.

    […]

    Several trials have used blood lactate for the monitoring of exercise intensity. These studies indicate that higher lactate concentrations are associated with increased BDNF plasma and/or serum levels. Furthermore, current evidence indicates that high intensity interval training evokes larger BDNF levels compared to moderate and/or intensive continuous exercise […] Current research indicates that lactate transport from astrocytes to neurons plays a crucial role for memory formation and could be a link between exercise and neuroplasticity. Pharmacological inhibition of MCT 2 irreversibly impairs long-term memory. Van de Hall et al. have shown that lactate uptake in the brain increases from 8% at rest up to 20% during exercise.

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  • Higher fetal exposure to air pollution during the second and third trimester of pregnancy score lower in cognition, motor coordination, and language www.colorado.edu
    Brain Pregnancy Development Pollution

    Exposure to air pollution during mid-to-late pregnancy interferes with fetal neurodevelopment.

    Exposure to air pollution during mid-to-late pregnancy interferes with fetal neurodevelopment, a new study shows. Children whose mothers were exposed to high levels of air pollution scored roughly three points lower on cognitive tests than children exposed to lower levels.

    The study involved 161 mother-child pairs living in Southern California, an area known for its high air pollution levels. The researchers gauged the mothers' exposure to particulate matter (a mixture of solid particles and liquid droplets that may have neurotoxic properties) during their pregnancies. When the children reached the age of two years, they underwent tests to assess their neurodevelopment.

    The researchers found that children who were exposed to particulate matter in air pollution during pregnancy – especially during the second and third trimesters – had lower composite cognitive scores than children exposed to lower levels. They also performed worse on measures of fine and gross motor skills, language, and expressive communication.

    These findings suggest that fetal exposure to particulate matter in air pollution during the second and third trimesters of pregnancy impairs cognitive performance later in life. These trimesters correspond with periods during which critical neurodevelopmental processes occur, such as myelination, neuronal migration, synaptogenesis, and neurogenesis.

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  • High-dose omega-3 treatment expression of Mfd2a omega-3 DHA transporter in retina and blood vessels www.sciencedirect.com
    Brain Omega-3 Eyes Blood-Brain Barrier

    From the publication:

    Most importantly, our results revealed that high-dose fish oil supplementation was able to induce the expression of Mfsd2a, a major DHA transporter in the retina on both transcriptional and translational levels, simultaneously increasing the Mfsd2a expression on the blood vessels after only three weeks of treatment. It was suggested that the low expression of Mfsd2a in the retina might be one reason why DHA therapy fails to alleviate the symptoms of diabetic retinopathy (DR) and that the combined use of Mfsd2a overexpression and DHA therapy may have synergistic effects. It is thus conceivable that the high dose fish oil supplementation can serve as a potential adjuvant in the therapies or as a prophylactic in the early stages of disease for the impaired blood-retinal barrier through the up-regulation of Mfsd2a expression.

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  • Three or more concussions may worsen brain function later in life. www.sciencedaily.com
    Brain Alzheimer's Aging Dementia Concussion Lactate

    Experiencing multiple concussions increases a person’s risk of poor brain function later in life, a new study shows. People who experienced three or more concussions exhibited cognitive deficits that worsened with each subsequent concussion.

    Researchers collected self-reported concussion histories from more than 5,700 adults between 50 and 70 years old. They administered cognitive tests to gauge changes in the participants' brain function every year for up to four years.

    They found that participants who experienced three mild concussions in their lifetime had difficulty with attention and performing complex tasks later in life. Participants who experienced four mild concussions had difficulty with processing speed and working memory – an aspect of cognitive function that allows a person to remember information for relevant tasks. However, experiencing even one moderate-to-severe concussion impaired the participants' attention and the ability to perform complex tasks and process information.

    These findings underscore the risks associated with even mild brain injury. Some evidence suggests that lactate and ketones may be beneficial in treating brain injury. Learn more in this clip featuring Dr. Dominic D'Agostino.

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  • The effects of obesity on the brain mirror those of Alzheimer's disease. www.sciencedaily.com
    Brain Alzheimer's Obesity Aging

    Excess body weight drives gray matter losses similar to those seen in Alzheimer’s disease, a new study shows. The brains of people who were obese showed marked signs of gray matter atrophy in areas of the brain responsible for attention, problem-solving, and reasoning.

    Using neuroimaging data, researchers compared the grey matter patterns of more than 1,300 older adults. Participants included those with Alzheimer’s disease and those who were cognitively healthy, obese but otherwise healthy, or lean.

    The scientists found that obesity and Alzheimer’s disease had similar effects on the brain. Both conditions were associated with gray matter atrophy in the right temporoparietal cortex (an area involved in attention) and the left prefrontal cortex (an area involved in reason, problem-solving, and comprehension). They also found that obesity-related gray matter atrophy patterns didn’t overlap with amyloid-beta or tau protein distribution in the brains of people with Alzheimer’s disease. Amyloid-beta and tau accumulation are widely considered hallmarks of Alzheimer’s disease.

    Excess body weight drives many metabolic disorders, including type 2 diabetes, hypertension, and dyslipidemia. Recent evidence demonstrates that excess body weight impairs cognitive function. The findings from this study suggest that excess body weight drives gray matter losses similar to those seen in Alzheimer’s disease.

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  • Vitamin D deficiency may cause the brain to age faster. www.valleycentral.com
    Vitamin D Brain Aging

    According to findings from a recent study, the brains of people with vitamin D deficiency age faster than those with adequate vitamin D levels. This is particularly true for males.

    Researchers measured blood vitamin D concentrations in the blood of more than 1,800 healthy adults. Then they scanned the participant’s brains to assess their brain aging. They calculated the participants' brain age based on chronological age and brain volume.

    They found that participants with vitamin D deficiency (which the researchers defined as less than 16.08 nanograms (ng) per milliliter (ml) for the purposes of this study) were more likely to have accelerated brain aging, as evidenced by lower total brain and gray matter volumes. Interestingly, the association between low vitamin D concentrations and older brain age was only statistically significant for male participants.

    Vitamin D is a fat-soluble vitamin that is stored in the liver and fatty tissues of the body. Perhaps best known for its role in maintaining calcium balance and bone health, vitamin D plays critical roles in many physiological processes. Poor vitamin D status is implicated in the pathogenesis of many acute and chronic diseases, including osteoporosis, multiple sclerosis, and cancer.

    Although the researchers that conducted this study used 16.08 ng/ml as the cutoff for vitamin D deficiency, public health experts and physicians disagree regarding the appropriate cutoffs and terminology that define vitamin D status. Learn more about vitamin D in our overview article.

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  • Just six minutes of vigorous exercise a day may be sufficient to protect the brain against Alzheimer's disease and cognitive decline. medicalxpress.com
    Exercise Brain Alzheimer's BDNF

    Six minutes of vigorous exercise increased brain levels of BDNF – a protein that may protect against Alzheimer’s disease and other neurodegenerative conditions – as much as five times more than light exercise, a new study has found.

    Researchers measured BDNF levels after fasting, light exercise, or vigorous exercise in healthy, physically active adults. Participants fasted for 20 hours, engaged in light cycling (90 minutes at 25 percent VO2 max), or engaged in vigorous cycling (six 40-second bursts at 100 percent VO2 max interspersed with 20 seconds of light cycling).

    They found that on average, 90 minutes of light cycling increased serum BDNF levels by approximately 6 percent. However, six 40-second vigorous-intensity cycling bursts increased both plasma and serum BDNF levels four to five times more than light cycling.

    BDNF, or brain-derived neurotrophic factor, is a growth factor that controls and promotes the growth of new neurons and is necessary for the formation and storage of memories and overall cognitive performance. BDNF exerts robust protective effects on crucial neuronal circuitry involved in Alzheimer’s disease. Evidence suggests that endothelial cells that line the blood vessels of the brain release BDNF in response to shear stress – the increase in force that occurs during increased blood flow (as in exercise).

    Interestingly, fasting for 20 hours had no effect on BDNF levels, but it did promote a ninefold increase in ketone delivery to the brain. Evidence suggests that ketones increase blood flow to the brain and improve memory and brain function in certain contexts. Learn more about the brain benefits of ketones in this clip featuring Dr. Dominic D'Agostino.

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  • Rising blood pressure in young adulthood damages brain blood vessels, reducing blood flow to the brain. journals.lww.com
    Brain Aging Blood Pressure Stroke

    Gradual increases in blood pressure from young adulthood to middle age increased the risk of poor brain health in older age, a 2022 study found. Having higher blood pressure over time damaged the brain’s delicate blood vessels, reducing blood flow to the brain.

    The study involved 885 adults whose blood pressures were monitored regularly over a 30-year period. Using magnetic resonance imaging studies, researchers assessed the participants' brain health at the beginning and end of the study period.

    The researchers found that participants who had either high blood pressure in young adulthood or moderate blood pressure that gradually increased over time showed marked signs of microvascular disease in the white matter of their brains. The two groups also showed reduced blood flow in the gray matter of their brains.

    Microvascular disease, also called small vessel disease, is a condition characterized by blood vessel dysfunction. It commonly occurs with aging and contributes to the development of cardiovascular disease, dementia, and stroke. Small vessel disease in the brain contributes to approximately 50 percent of dementia cases worldwide.

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  • Olive oil protects the brain against changes associated with Alzheimer's disease. www.medicalnewstoday.com
    Brain Alzheimer's Diet

    Extra virgin olive oil boosts brain function and halts the effects of aging on the brain, a 2019 study in mice found. Mice that ate an olive oil-rich diet had fewer abnormal deposits of tau – a protein associated with Alzheimer’s disease – in their brains and performed better on memory tests than mice that didn’t eat olive oil.

    Researchers fed mice that are predisposed to developing abnormal tau deposits in their brains an olive oil-enriched diet or their regular chow from young adulthood to older adulthood. They subjected the mice to various cognitive tests and then they examined the animals' brains for the presence of abnormal tau deposits.

    They found that the mice that ate the olive oil-rich diet had approximately 60 percent fewer abnormal tau deposits than mice that ate regular chow. The olive oil-eating mice also demonstrated enhanced hippocampal synaptic activity, short-term plasticity, and memory.

    Olive oil is rich in bioactive compounds, including polyphenols, carotenoids, oleic acid, and others. Olive oil is a fundamental component of the Mediterranean diet, which is associated with a wide range of health benefits, including reduced incidence of Alzheimer’s disease.

    This study in mice suggests that olive oil reduces the risk of abnormal changes in the brain associated with Alzheimer’s disease. Diets rich in omega-3 fatty acids may have beneficial effects on brain health, too. Learn more in our omega-3 overview article.

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  • Calming children with electronic devices may harm kids' emotional and behavioral development, a new study finds. www.sciencedaily.com
    Brain Development

    Calming children with electronic devices may harm kids' emotional and behavioral development, a new study finds. This is particularly true for boys, especially those who are more emotionally reactive.

    Researchers asked 422 parents how often they relied on electronic devices to calm their preschool-age children over a period of six months. They also asked the parents to complete assessments of their children’s executive functioning and behavior.

    The researchers found that children who were frequently calmed with electronic devices were more likely to exhibit emotional dysregulation. This association was strongest in boys with high surgency – a quality characterized by high-intensity pleasure-seeking, high activity levels, low shyness, and impulsivity.

    Emotional regulation refers to the ability to understand and manage one’s behavior and feelings in appropriate ways. Most children develop emotional regulation during the preschool years of two to five years of age, coinciding with frontal lobe development. Emotional dysregulation is characterized by heightened impulsivity and sudden changes in mood or feelings.

    These findings indicate that calming preschool-age children with electronic devices may have negative effects on emotional and behavioral development. The study’s authors recommended that parents help children develop coping skills that are not reliant upon tech devices.

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  • APOE4 disrupts fat metabolism in brain cells, increasing Alzheimer's disease risk – but choline may restore normal metabolism. news.mit.edu
    Nutrition Brain Alzheimer's Micronutrients Dementia

    Disrupted fat metabolism drives the link between the APOE4 gene and Alzheimer’s disease risk, according to a new study. Choline supplementation helps restore normal fat metabolism, however.

    Researchers studied the effects of the APOE4 gene on fat metabolism in astrocytes – a type of brain cell. They found that astrocytes that carried the APOE4 gene accumulated unsaturated triglycerides, causing an imbalance in the types of fats in the cells. However, when they applied choline to the cells, the normal balance was restored.

    Choline is an essential nutrient that participates in the synthesis of fats necessary for cell membrane integrity and function. It is produced in the liver and is also found in foods such as eggs, meat, fish, beans, and nuts and as a dietary supplement. Most people living in the United States don’t consume enough choline – 550 milligrams per day for men and 425 milligrams per day for women – potentially increasing their risk for various diseases.

    The findings from this cell study suggest that APOE4-driven impairments in fatty acid metabolism increase the risk of developing Alzheimer’s disease, but supplemental choline may reduce this risk. Other evidence suggests that impaired brain transport of DHA, a type of omega-3 fatty acid, increases Alzheimer’s disease risk. Learn more in this open-access, peer-reviewed article by Dr. Rhonda Patrick.

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  • Estrogen fluctuations may trigger atypical hippocampal working memory function in women with a BDNF genotype present in one in four women. (2017) www.sciencedaily.com
    Brain Hormones Memory Mental Health Anxiety Genetics Estrogen Schizophrenia BDNF

    From the article:

    The findings may help to explain individual differences in menstrual cycle and reproductive-related mental disorders linked to fluctuations in the hormone. They may also shed light on mechanisms underlying sex-related differences in onset, severity, and course of mood and anxiety disorders and schizophrenia, which are often marked by working memory deficits. The gene-by-hormone interaction’s effect on circuit function was found only with one of two versions of the gene that codes for BDNF [Val66Met genotype] (brain-derived neurotrophic factor), a chemical messenger operating in the circuit. This version occurs in about a fourth of white women.

    The researchers experimentally manipulated estrogen levels over several months in healthy women with both versions of the gene while monitoring their brain activity as they performed a working memory task. When exposed to estrogen, an area in the brain’s memory hub that is typically suppressed during such tasks instead activated in those with the uniquely human gene variant. Both PET (positron emission tomography) and fMRI (functional magnetic resonance imaging) scans showed the same atypical activation. Such gene-hormone interactions may confer risk for mental illnesses, say the researchers.

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  • Pubertal activation of estrogen receptor α in the medial amygdala is essential for the full expression of male social behavior in mice. (2016) www.sciencedaily.com
    Brain Hormones Behavior Testosterone Estrogen

    From the article:

    Behavioral responses to sexually receptive females such as mounting, and toward intruder males such as biting and attacks, were recorded in adult mice. The reduction of both sexual and aggressive behavior by ERα [estrogen receptor alpha] silencing in the MeA [medial amygdala] before puberty but not in adults suggests the importance of the receptor in this location during puberty. “ERα knockdown in the MeA may even have affected the onset of puberty itself,” first author Dr. Kazuhiro Sano says. “This contrasts with the silencing of ERα in the MPOA [medial preoptic area], which reduced sexual but not aggressive behavior in mice, regardless of the time of knockdown treatment.” These findings suggest that ERα gene expression in the MPOA does not control male aggression through either the organizational role of testosterone at puberty, or its regulatory role in adulthood.

    To understand why ERα silencing in different areas of the brain had varying effects, the team examined MeA cells. They found that neuronal cells were greatly reduced in MeA in which ERα expression had been inhibited before puberty. “ERα in the MeA seems to be necessary for testosterone to masculinize the neural circuitry for social behavior during puberty,” corresponding author Dr. Sonoko Ogawa explains. “If this masculinization is incomplete, social signals that enable adults to express male social behavior may not function correctly.”

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  • Memory-enhancing effects of hippocampal estrogen receptor activation involve metabotropic glutamate receptor signaling, mouse study suggests. (2013) www.sciencedaily.com
    Brain Alzheimer's Hormones Memory Neurotransmitter Estrogen Dementia

    From the article:

    The research, published in the the Journal of Neuroscience today, focused on estrogen effects in a brain region called the hippocampus, which deteriorates with age or Alzheimer’s disease. The researchers found that each of the two known estrogen receptors rapidly activate a specific cellular pathway necessary for memory formation in the hippocampus of female mice, but only if they interact with a certain glutamate receptor, called mGluR1.

    The study revealed that when this glutamate receptor is blocked, the cell-signaling protein ERK cannot be activated by the potent estrogen, 17β-estradiol. Because ERK activation is necessary for memory formation, estradiol failed to enhance memory among mice in which mGluR1 was blocked.

    Frick’s team also found evidence that estrogen receptors and mGluR1 physically interact at the cell membrane, allowing estradiol to influence memory formation within seconds to minutes.

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  • Silencing of estrogen receptor α in a brain area of the hypothalamus led to metabolic syndrome in mice. (2007) www.sciencedaily.com
    Brain Metabolism Hormones Fat Estrogen Blood Sugar Metabolic Syndrome Weight Loss Visceral Fat

    From the article:

    Estrogen receptors are located on cells throughout a woman’s body. Previous studies have shown that one type of estrogen receptor, known as estrogen receptor alpha or ER-alpha, plays a role in regulating food intake and energy expenditure. But scientists have been unable to pinpoint exactly where these fat-regulating receptors reside or how they work to govern these behaviors.

    To determine the effect of dwindling estrogen levels in the brain, Clegg and her colleagues are focusing on two ER-alpha rich regions located in the hypothalamus, an area of the brain that controls body temperature, hunger and thirst. The first region, called the ventromedial nucleus or VMN, is a key center for energy regulation.

    Using a relatively new gene-silencing technique called RNA interference, the researchers in earlier research deactivated the alpha-receptors in the VMN. The estrogen receptors in other regions of the brain maintained their normal capacity.

    When estrogen levels in the VMN dipped, the animals' metabolic rate and energy levels also plummeted. The findings show the animals quickly developed an impaired tolerance to glucose and a sizable weight gain, even when their caloric intake remained the same. What’s more, the excess weight went straight to their middle sections, creating an increase in visceral fat.

    The findings suggested that the ER-alpha in this region plays an essential role in controlling energy balance, body fat distribution and normal body weight.

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  • Gut microbes may drive the motivation to exercise. medicalxpress.com
    Exercise Brain Microbiome Microbes Dopamine

    Microbes in your gut may trigger your motivation to exercise, a new study in mice has found. Compounds produced by the microbes signal the release of dopamine – a neurotransmitter produced in the brain that promotes the “runner’s high” and the desire to exercise.

    Researchers analyzed the gut microbial species and the byproducts of their metabolism from nearly 200 mice with diverse genetic backgrounds. They also tracked the animals' daily exercise activity and measured their endurance.

    They found that mice that had certain species of gut microbes – Eubacterium rectale and Coprococcus eutactus – exercised more and had greater endurance than mice lacking these microbes. These two species produce compounds called fatty acid amides, which interact with gut neurons and ultimately activate dopamine-producing neurons in the brain, turning on the brain’s reward circuits and triggering the desire to exercise00394-0.pdf).

    This study in mice reveals a novel way in which the gut microbiome influences human health and behavior. It may also provide evidence to support the use of therapeutic microbial transfer to promote exercise behavior and improve aspects of mood.

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  • Estradiol may heighten the sensitivity of sound-processing neurons and activate genes that instruct the brain to lay down memories of sounds. (2009) www.sciencedaily.com
    Brain Hormones Memory Estrogen Hearing Neurons

    From the article:

    Previous studies have hinted at a connection between estrogen and hearing in women who have low estrogen, such as often occurs after menopause, says Pinaud. No one understood, however, that estrogen was playing such a direct role in determining auditory functions in the brain, he says. “Now it is clear that estrogen is a key molecule carrying brain signals, and that the right balance of hormone levels in men and women is important for reasons beyond its role as a sex hormone,” says Pinaud.

    Pinaud, along with Liisa Tremere, a research assistant professor of brain and cognitive sciences, and Jin Jeong, a postdoctoral fellow in Pinaud’s laboratory, demonstrated that increasing estrogen levels in brain regions that process auditory information caused heightened sensitivity of sound-processing neurons, which encoded more complex and subtle features of the sound stimulus. Perhaps more surprising, says Pinaud, is that by blocking either the actions of estrogen directly, or preventing brain cells from producing estrogen within auditory centers, the signaling that is necessary for the brain to process sounds essentially shuts down. Pinaud’s team also shows that estrogen is required to activate genes that instruct the brain to lay down memories of those sounds.

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  • During 3rd trimester of pregnancy, multiple sclerosis relapse rate is reduced by 70%, possibly due to the neuroprotective effects of estrogen. (2017) www.sciencedaily.com
    Brain Hormones Multiple Sclerosis Estrogen

    From the article:

    The third trimester of pregnancy has been previously shown to reduce relapse rates by approximately 70 percent as compared to before pregnancy, and other studies have shown benefit over the long term due to multiple pregnancies. An estrogen unique to pregnancy that is made by the fetus and placenta has been proposed by Dr. Rhonda Voskuhl and colleagues to mediate this pregnancy protection in both the MS mouse model as well as in two successfully completed clinical trials of estriol treatment in MS patients.

    How that happens has remained a critical question. Voskuhl, who led the latest study, reported mouse studies showing that estrogen protected the brain from damage by activating a protein called estrogen receptor beta (ERb). Her new research identifies which cells within the brain are mediating this protective effect.

    The researchers first genetically eliminated ERb in either immune cells of the brain or in oligodendrocytes, the cells that make the myelin sheath, as a way of making cells unresponsive to estrogen during the MS like disease in mice. They then treated mice without or with ERb in these cells to ask if disease protection was lost or not. Loss of protection during treatment meant that the treatment was acting on the cell that had the receptor removed. Results showed that the estrogen-like treatment was acting on both immune cells of the brain as well as on oligodendrocytes, together resulting in repair of myelin and less disability.

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  • Vitamin D may protect against dementia and cognitive impairment. apple.news
    Vitamin D Brain Alzheimer's Dementia

    People with higher brain concentrations of vitamin D were 25 to 33 percent less likely to develop dementia or cognitive impairment, a recent study has found. Those with higher vitamin D concentrations also performed better on tests of cognitive function than those with lower concentrations.

    The study involved 290 participants enrolled in the Rush Memory and Aging Project who had undergone regular physical and cognitive assessments when they were alive and agreed to donate their brains for study upon their deaths. Researchers measured concentrations of vitamin D in four regions of the participants' brains and reviewed the participants' cognitive assessments.

    They found that higher brain concentrations of vitamin D were associated with 25 to 33 percent lower odds of having dementia or mild cognitive impairment at the last assessment before death. Participants with higher vitamin D concentrations had better word recall, working memory, episodic memory, and perceptual speed – the ability to compare similarities and differences quickly and accurately among sets of letters, numbers, objects, pictures, or patterns.

    The findings from this study suggest that vitamin D is neuroprotective. Vitamin D is a fat-soluble vitamin that is stored in the liver and fatty tissues of the body. Perhaps best known for its role in maintaining calcium balance and bone health, vitamin D plays critical roles in many physiological processes. Poor vitamin D status is implicated in the pathogenesis of many acute and chronic diseases, including rickets, osteoporosis, multiple sclerosis, and cancer. Learn more about vitamin D in our overview article.

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  • High estradiol levels may interfere with latent inhibition, resulting in impaired attention and learning, rat study suggests. (2010) www.sciencedaily.com
    Brain Hormones Memory Estrogen

    From the article:

    Human females have high estrogen levels while they are ovulating. These high levels have also been shown to interfere with women’s ability to pay attention.

    […]

    Latent inhibition is observed in many species and is believed to be the important part of learning, which enables individuals to interact successfully in their environment. It is a test of new memory formation.

    In the Brake protocol, rats received a pre-exposure phase during which they were repeatedly exposed to a tone, with no consequence. Once they became used to this tone and ignored it, the test dynamics changed and another stimulus was linked to the tone. Rats with low levels of estrogen quickly learned that the tone was associated with the new stimulus whereas those with higher levels of estrogen took longer to form this memory.

    “We only observed this effect in adult female rats,” says Brake. “This and our other findings indicate that estrogen directly effects the brain, perhaps by interfering with brain signaling molecules. Our study helps clear up the controversy about the effects of estrogen, the next step is to look at how this occurs.”

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  • Estradiol may induce BDNF/TrkB signaling in non-estrogen-dependent breast cancer to promote brain metastases, mouse study suggests. (2019) www.sciencedaily.com
    Brain Cancer Hormones Breast Cancer Estrogen BDNF

    From the article:

    After all, triple negative breast cancers lack estrogen receptors (along with progesterone receptors and HER2, thus the name triple negative), and so these cancers can’t possibly be influenced by estrogen. Right?

    […]

    Technically, Cittelly and colleagues including postdoctoral researcher, Maria Contreras-Zarate, PhD, found that estrogen induces astrocytes (brain cells) to produce growth factors called brain-derived neurotrophic factor (BDNF) and Epidermal Growth Factor (EGF), and that these factors turns on two genetic migration/invasion switches in cancer cells, namely TRKB and EGFR.

    “This may explain why breast cancers diagnosed in younger women are more likely to metastasize to the brain – pre-menopausal women have more estrogen, and it may be influencing the microenvironment of the brain in ways that aid cancer,” Cittelly says.

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  • Estradiol administered to the amygdala of a menopause rat model prevented weight and abdominal fat gain and improved glucose tolerance. (2017) www.sciencedaily.com
    Brain Hormones Fat Estrogen Blood Sugar Weight Loss Visceral Fat

    From the article:

    “We know as women age and enter into menopause, they tend to gain body weight and body fat, particularly in the abdominal or ‘belly’ area. Excess abdominal fat greatly increases risk for cardio-metabolic diseases,” says Solomon. “While there are likely many factors that are associated with these risks in menopausal women, estrogen loss is associated with body weight and fat gain during menopause. In fact, estrogen treatment can offset this weight gain in many women.”

    The medial amygdala (MeA) is a region of the brain that helps regulate body weight and contains an abundance of estrogen receptors (molecules that respond to estrogen). The researchers used an experimental model in rats, which involves removing the ovaries to mimic the hormonal changes of menopause. They targeted estrogen replacement directly in the MeA and found that it prevented weight and abdominal fat gain and improved glucose tolerance, compared to rats in a placebo group. This suggests that the MeA is important in the metabolic health of menopausal females and may be a useful target for treatment.

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  • Estrogen therapy initiated around the onset of menopause may protect the hippocampus from shrinking, thereby reducing the risk of Alzheimer's. (2016) www.sciencedaily.com
    Brain Alzheimer's Hormones Estrogen Dementia

    From the article:

    A sample of 80 women who had used estrogen supplements through menopause was compared with 80 women who had never used estrogen supplements. All had participated in the Nord-Trøndelag Health Study (HUNT), a general population-based study in mid-Norway.

    […]

    MRIs of the brains of the women in the study showed that those who had taken estrogen supplements throughout menopause had a larger hippocampus. The hippocampus is one of the most important structures for memory and sense of place, and is one of the structures that is affected early in the progression of Alzheimer’s disease.

    “We also examined the shape of the hippocampus and found that areas where hormone therapy had the greatest effect are the same areas that are affected by Alzheimer’s disease in its early stages,” says Pintzka.

    Other studies have shown that women who start estrogen supplements several years after menopause do not benefit from the same positive effect on the hippocampus.

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  • The brain's reward center may be much more sensitive to the addictive effects of alcohol during estrogen-rich periods of the menstrual cycle. (2017) www.sciencedaily.com
    Brain Hormones Alcohol Estrogen Addiction

    From the article:

    “When estrogen levels are higher, alcohol is much more rewarding,” said Lasek, who is the corresponding author on the paper and a researcher in the UIC Center for Alcohol Research in Epigenetics. “Women may be more vulnerable to the effects of alcohol or more likely to overindulge during certain stages of their cycle when estrogen levels are higher, or may be more likely to seek out alcohol during those stages.”

    Studies indicate that gender differences in psychiatric disorders, including addiction, are influenced by estrogen, one of the primary female sex hormones. Women are more likely to exhibit greater escalation of abuse of alcohol and other drugs, and are more prone to relapse in response to stress and anxiety.

    […]

    “In mice in diestrus, estrogen levels increase to about 10 times higher than they are in estrus, the phase in which ovulation occurs and estrogen levels drop,” Lasek said.

    VTAs [ventral tegmental area - “reward center”] were taken from mice in both estrus and diestrus and kept alive in special chambers. Electrodes recorded the activity of individual dopamine-sensitive neurons in the VTA. Next, the researchers added alcohol to the chamber. Activity increased twice as much in neurons from mice in diestrus compared to the response of neurons from mice in estrus.

    Lasek and her colleagues then blocked estrogen receptors on dopamine-sensitive neurons in VTA in mice in estrus and diestrus. With the blocker present, the response to alcohol in neurons from mice in diestrus was significantly lower compared with neurons where estrogen receptors remained functional. The estrogen receptor blocker reduced the alcohol response to levels seen in mice in estrus. The responses to alcohol in neurons from mice in estrus were unaffected by the estrogen receptor blocker.

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  • The omega-3 fatty acid DHA increased estradiol production in the brains of mice by more than twofold, thereby suppressing induced seizures. (2017) www.sciencedaily.com
    Brain Hormones Omega-3 Estrogen

    From the article:

    One group was fed a diet consisting of soybean oil, another on cottonseed oil, and a third on cottonseed oil in addition to DHA supplements.

    These two oils used were chosen due to the differing yields of DHA obtained from them, i.e. the body produces more DHA from soybean oil than cottonseed oil. The third group were also fed on cottonseed oil, but also crucially along with DHA supplements.

    After 28 days on these diets, the three groups were exposed to seizure inducing drugs. The group fed on soybean oil took longer to exhibit seizures, and when they did occur they were of a shorter duration than those fed on cottonseed oil. However, the mice fed on cottonseed oil with DHA supplementation, took far longer for seizures to take hold – proving that dietary sourced DHA was a key contributing factor.

    When the researchers examined the brains of these mice they found that the soybean oil fed ones had over twice the concentration of estrogen present as those fed solely on cottonseed oil. The mice fed on cottonseed with DHA supplementation had even higher levels of the hormone, suggesting that estrogen production affects seizures, and that this is directly connected to DHA’s presence.

    In order to prove this link between estrogen concentration in the brain and omega-3 fatty acid intake/DHA-synthesis, a second experiment was carried out.

    This time, one group of mice were again fed on cottonseed oil, and another group on cottonseed oil with DHA supplementation. In addition, a third group was fed on cottonseed oil with DHA supplements – and also Letrozole – a drug which prevents estrogen synthesis.

    When seizures were induced this time round, the group exposed to Letrozole were found to have seizures much earlier than those fed on cottonseed fortified with DHA, thus confirming estrogens importance in preventing seizures.

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  • Monkey study suggests that estrogen produced in the brain may play a role in ovulation and undiagnosed infertility problems. (2017) www.sciencedaily.com
    Brain Hormones Pregnancy Estrogen

    From the article:

    They implanted capsules under the monkeys' [who’d had their ovaries removed] skin that released estradiol, fooling their brains into thinking there were ovaries at work preparing for ovulation. At the same time, the scientists kept the animals from making any of their own estrogens by inhibiting the work of an enzyme, aromatase, necessary for estrogen production.

    Without the help of estradiol produced by the monkeys, the rising release of luteinizing hormone began, but fell short of the full surge required to spark ovulation by about 70 percent compared to animals whose estrogen production wasn’t suppressed.

    To zero in on where the estrogen was doing its work, the researchers repeated the process, but blocked estradiol production specifically in the hypothalamus in the monkeys. They watched for the emergence of hypothalamic hormones – called gonadotropin-releasing hormone and kisspeptin – that indicated the key neurons were ramping up to cue the luteinizing hormone surge.

    In this case, the releases of all three ovulation-signaling hormones were reduced, indicating that the brain was where the estradiol effects were happening.

    “The ovarian estrogen starts the surge, but the brain estrogen allows the surge to continue,” says Kenealy. “When we block the production of brain estrogen, we still start the surge, but basically we cut the top off the mountain and the surge is drastically reduced.”

    “This shows the brain’s estrogen is a huge helper, necessary for the release of an egg that makes pregnancy possible”

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  • Alzheimer’s risk gene APOE4 undermines insulation of brain’s “wiring” by accumulating excess cholesterol in endoplasmic reticulum of oligodendrocytes news.mit.edu
    Brain Alzheimer's Cholesterol Memory

    From the article:

    Using a variety of techniques to look directly at the tissue, the team saw that in APOE4 brains, aberrant amounts of cholesterol accumulated within cell bodies, especially of oligodendrocytes, but was relatively lacking around neural axons.

    To understand why, the team used patient-derived induced pluripotent stem cells to create lab cell cultures of oligodendrocytes engineered to differ only by whether they had APOE4 or APOE3. Again APOE4 cells showed major lipid disruptions. In particular, the afflicted oligodendrocytes hoarded extra cholesterol within their bodies, showed signs that the extra internal fats were stressing organelles called the endoplasmic reticulum that have a role in cholesterol transport, and indeed transported less cholesterol out to their membranes. Later, when they were co-cultured with neurons, the APOE4 oligodendrocytes failed to myelinate the neurons as well as APO3 cells did, regardless of whether the neurons carried APOE4 or APOE3.

    The team also observed that in postmortem brains there was less myelination in APOE4 carriers than APOE3 carriers.

    […]

    Eager to find a potential intervention, the team focused on drugs that affect cholesterol, including statins (which suppress synthesis) and cyclodextrin, which aids cholesterol transport. The statins didn’t help, but applying cyclodextrin to APOE4 oligodendrocyte cultured in a dish reduced accumulation of cholesterol within the cells and improved myelination in co-cultures with neurons. Moreover, it also had these effects in APOE4 mice.

    Finally, the team treated some APOE4 mice with cyclodextrin, left others untreated, and subjected them all to two different memory tests. The cyclodextrin-treated mice performed both tests significantly better, suggesting an association between improved myelination and improved cognition.

    Tsai said a clear picture is emerging in which intervening to correct specific lipid dysregulations by cell type could potentially help counteract APOE4’s contributions to Alzheimer’s pathology.

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  • Estrogen-sensitive brain circuit may help women control obesity by stimulating physical activity and thermogenesis, animal study suggests. (2022) www.sciencedaily.com
    Brain Obesity Metabolism Hormones Estrogen Thermogenesis

    From the article:

    The team reveals in the journal Science Advances an estrogen-activated neurocircuit that stimulates thermogenesis, or body heat production, and physical activity in animal models. The circuit begins in neurons located in a region of the hypothalamus called the ventrolateral subdivision of the ventromedial hypothalamic nucleus (vlVMH). These neurons interact with estrogen via estrogen receptor-alpha (ER-alpha) and respond to the hormone by connecting to and communicating with serotonin-producing neurons located in another brain region called dorsal raphe nucleus (DRN).

    The circuit not only responds to estrogen, but also to changes in ambient temperature and in the nutritional status of the animal. Interestingly, the circuit seems to be functional in males but, at this point, its physiological relevance is not clear.

    […]

    “For example, the circuit can be activated when it’s cold, stimulating thermogenesis and physical activity, which would help the animal stay warm,” Xu said. “The circuit can be inhibited when the animal is hungry, which would shut down thermogenesis and physical activity, saving energy to adapt to the lack of nutrients.”

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  • Low estrogen levels may make women more susceptible to the development of post-traumatic stress disorder (PTSD). (2017) www.sciencedaily.com
    Brain Epigenetics Hormones Mental Health Anxiety Genetics Estrogen

    From the article:

    The scientists examined blood samples from 278 women from the Grady Trauma Project, a study of low-income Atlanta residents with high levels of exposure to violence and abuse. They analyzed maps of DNA methylation, a modification of DNA that is usually a sign of genes that are turned off.

    […]

    “We knew that estrogen affects the activity of many genes throughout the genome,” […] “But if you look at the estrogen-modulated sites that are also associated with PTSD, just one pops out.”

    That site is located in a gene called HDAC4, known to be critical for learning and memory in mice. Genetic variation in HDAC4 among the women was linked to a lower level of HDAC4 gene activity and differences in their ability to respond to and recover from fear, and also differences in “resting state” brain imaging. Women with the same variation also showed stronger connections in activation between the amygdala and the cingulate cortex, two regions of the brain involved in fear learning.

    On top of that, experiments with female mice showed that the HDAC4 gene was activated in the amygdala while the mice were undergoing fear learning, but only when estrogen levels in the mice were low.

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  • Estrogens may act on distinct hypothalamic neurons to regulate energy homeostasis and reproduction, mouse study suggests. (2011) www.sciencedaily.com
    Brain Obesity Metabolism Hormones Estrogen Neuron Metabolic Syndrome

    From the article:

    “When women approach menopause, they gain weight in fat and their energy expenditure goes down,” says Deborah Clegg of the University of Texas Southwestern Medical Center. Estrogen levels decline and women grow increasingly susceptible to obesity and metabolic syndrome.

    Estrogen acts on receptors found throughout the body, in fat, on ovaries and in muscle. But when it comes to the hormone’s influence on metabolism, Clegg suspected receptors in the brain.

    […]

    The researchers showed female mice lacking ERα [estrogen receptor-α (ERα)] in one part of the brain (the hypothalamic steroidogenic factor-1 or SF1 neurons) gained weight without eating any more. Loss of ERα from another brain area (the hypothalamic pro-opiomelanocortin or POMC neurons) had the opposite effect: animals ate more without gaining weight. Loss of ERα receptors in those same neurons also led to various problems in ovulation and fertility.

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  • The brain may be capable of rapidly producing and releasing large amounts of estrogen, animal study suggests. (2013) www.sciencedaily.com
    Brain Hormones Neurotransmitter Estrogen

    From the article:

    “Discovering that the hypothalamus can rapidly produce large amounts of estradiol and participate in control of gonadotropin-releasing hormone neurons surprised us,” says Ei Terasawa, professor of pediatrics at the UW School of Medicine and Public Health and senior scientist at the Wisconsin National Primate Research Center. “These findings not only shift the concept of how reproductive function and behavior is regulated but have real implications for understanding and treating a number of diseases and disorders.”

    For diseases that may be linked to estrogen imbalances, such as Alzheimer’s disease, stroke, depression, experimental autoimmune encephalomyelitis and other autoimmune disorders, the hypothalamus may become a novel area for drug targeting, Terasawa says. “Results such as these can point us in new research directions and find new diagnostic tools and treatments for neuroendocrine diseases.”

    […]

    In the first experiment, a brief infusion of estradiol benzoate administered into the hypothalamus of rhesus monkeys that had surgery to remove their ovaries rapidly stimulated GnRH release. The brain took over and began rapidly releasing this estrogen in large pulsing surges.

    In the second experiment, mild electrical stimulation of the hypothalamus caused the release of both estrogen and GnRH (thus mimicking how estrogen could induce a neurotransmitter-like action). Third, the research team infused letrazole, an aromatase inhibitor that blocks the synthesis of estrogen, resulting in a lack of estrogen as well as GnRH release from the brain.

    […]

    Leading up to this discovery, Terasawa said, recent evidence had shown that estrogen acting as a neurotransmitter in the brain rapidly induced sexual behavior in quails and rats.

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  • For women, greater exposure to estrogen in life may protect brain regions that are vulnerable to Alzheimer’s. (2021) www.sciencedaily.com
    Brain Alzheimer's Hormones Estrogen

    From the article:

    The analysis covered 99 women aged 46-58 and a comparison group of 29 similarly aged men. It confirmed that the post-menopausal and peri-menopausal (starting menopause) women, compared with the pre-menopausal women and the men, had significantly lower GMV – adjusted for age and head size – in brain areas such as the hippocampus, entorhinal cortex and temporal lobe regions, which are heavily affected by Alzheimer’s.

    By contrast, among the women, having more estrogen exposure as implied by various factors was associated with greater GMV [gray matter volume] in certain brain areas. Longer reproductive span, for example, was significantly linked to more GMV in a cluster of regions near the top of the brain including the superior parietal lobule and precuneus of the left hemisphere. Having had more children was significantly associated with more GMV in inferior and middle frontal gyri, and middle and inferior temporal gyri. Having used hormone replacement therapy was associated with more GMV in superior frontal gyrus and several other brain regions. All these brain regions are known to be affected by aging and Alzheimer’s.

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  • The gut microbiome influences brain development and social skills – could it be an effect of reduced synaptic pruning? www.quantamagazine.org
    Nutrition Brain Gut Diet Microbiome Autism Development

    The gut microbiome influences the development of social skills later in life, a recent study in fish has found. Fish that have delayed microbiome development show distinct differences in their brain structure and behavior compared to those with appropriately timed development.

    Researchers studied zebrafish, which are naturally social, to see how the microbiome affected the animals' behavior. Using a special type of zebrafish that lacked a microbiome, they inoculated one group of fish with bacteria immediately after birth to promote microbiome development. They delayed the inoculation of another group of fish by one week.

    They found that the fish that had delayed microbiome development exhibited more neural circuits in their brains and fewer microglia – a type of immune cell that “prunes” the brain and is necessary for normal development. These fish were also less social than the fish that had appropriately timed microbiome development.

    This study suggests that the microbiome influences the social behavior of zebrafish by reducing microglial pruning. Although the study was conducted using fish, other research suggests that these findings could translate to mammals, including humans. Learn more about the role of the gut microbiome in this episode featuring Dr. Eran Elinav.

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  • Low vitamin D levels promote brain aging. www.sciencedirect.com
    Vitamin D Brain Aging

    Low vitamin D levels promote brain aging and loss of brain volume and gray matter.

    A recent study found that the brains of people with low vitamin D levels age faster. Having high vitamin D levels may protect the brain, however.

    Researchers measured vitamin D levels and reviewed MRI brain studies of more than 1,800 adults to identify associations between vitamin D levels and total brain, gray matter, and hippocampal volumes. They found that having low vitamin D levels was closely tied to brain aging. As vitamin D levels decreased, total brain and gray matter volumes decreased as well, particularly in males.

    Between the ages of 30 and 40 years, the connections between cells in a person’s brain begin to diminish, causing the brain to shrink in volume. The rate of shrinkage increases as a person reaches the age of 60, impairing thinking, memory, and executive function. The loss of brain volume is a hallmark of Alzheimer’s disease.

    These findings suggest that vitamin D plays a role in protecting the brain from the effects of aging. Vitamin D plays many other roles in human health. Learn more about vitamin D in our overview article.

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  • Testosterone deprivation therapy in men may be associated with a loss of memory consolidation. (2004) www.sciencedaily.com
    Brain Hormones Memory Testosterone

    From the article:

    “A colleague looked at (the study results) and said, ‘Wow, that looks exactly like what happens with a lesion in the hippocampus,’” Janowsky said. “When others have done studies like this on people who have hippocampal damage from early Alzheimer’s disease or lesions due to strokes, this is the pattern.”

    The study examined 30 individuals - 14 men undergoing androgen deprivation treatment for prostate cancer and 16 healthy, age-matched men - from the Portland area. Participants were shown lists of words and, to encode them, were asked to identify whether the words were in capital or lowercase letters, which requires shallow or “perceptual” processing, or whether they represented objects that occurred in nature or were artificially made, which requires deep or “semantic” processing.

    Participants were then shown another list containing words they’d just seen as well as new words and were asked whether they’d seen each word before. This test was performed at three time intervals: immediately, after two minutes and after 12 minutes.

    Testosterone-deprived men can “immediately get the information in, but then the hippocampus can’t consolidate it and send it off for storage,” Janowsky said. “When you look at their memory, they’re perfectly normal when they’re immediately asked to recall something, but they can’t hold or save the information as well in order to recall it over a retention interval, over a period of time. They’re faster at forgetting.”

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  • Elevated testosterone induces apoptosis in neuronal cells, cell study suggests. (2006) www.sciencedaily.com
    Brain Alzheimer's Hormones Testosterone Apoptosis Neurons Neurodegeneration

    From the article:

    The researchers showed that high levels of testosterone triggered programmed cell death in nerve cells in culture. Cell death, or apoptosis, is critical in many life processes, including development and disease. It is characterized by membrane instability, activation of caspases, which are the executioner proteins in apoptosis, change in membrane potential, and DNA fragmentation.

    “In the present study we have demonstrated for the first time that the treatment of neuroblastoma cells with elevated concentrations of testosterone for relatively short periods, six to 12 hours, induces a decrease in cell viability by activation of a cell death program,” Ehrlich said. “Low concentrations of testosterone had no effects on cell viability, whereas at high concentrations the cell viability decreased with incremental increases in hormone concentration.”

    The testosterone-induced apoptosis described in this study occurs through overactivation of intracellular Ca2+ signaling pathways. Overstimulation of the apoptotic program in neurons has been associated with several neurological illnesses, such as Alzheimer disease and Huntington disease.

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  • Higher levels of omega-3s in mid-life protect the brain from shrinkage and preserve cognitive function. www.nutritionaloutlook.com
    Brain Aging Omega-3

    Having higher blood levels of omega-3 fatty acids in midlife is linked with greater brain volume and better cognitive function, potentially reducing the risk of cognitive decline later in life, new research finds. The fatty acids may also protect the brain against white matter hyperintensities – areas in the brain that often indicate cerebral small blood vessel disease, a risk factor for dementia.

    Researchers measured the red blood cell concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of more than 2,100 middle-aged adults and calculated each participant’s Omega-3 Index, which gauges long-term exposure to EPA + DHA in red blood cells. They measured the participants' brain volumes, reviewed their scores on cognitive tests, and determined whether they were carriers of APOE-4, a gene that influences dementia risk.

    They found that the effects of omega-3s differed according to APOE-4 status. Whereas non-carriers of APOE-4 who had a higher Omega-3 Index or DHA concentrations had larger hippocampal volumes, APOE-4 carriers who had higher EPA concentrations tended to have better abstract reasoning. APOE-4 carriers also had fewer white matter hyperintensities if all their omega-3 measures were higher.

    Omega-3 fatty acids play critical roles in human health and may reduce the risk of many aging-related diseases. The findings from this study suggest that having higher blood concentrations of omega-3s in mid-life preserves brain health and promotes aspects of cognitive function. Learn more about the Omega-3 Index in this clip featuring Dr. Bill Harris.

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  • Higher testosterone levels may be associated with better cognitive function in older men. (2002) www.sciencedaily.com
    Brain Alzheimer's Aging Hormones Memory Testosterone

    From the article:

    “Our study only looked at natural testosterone levels and so it doesn’t prove that testosterone supplements can prevent cognitive decline. We will need results of large randomized clinical trials in older men before we can confidently say that testosterone supplements are beneficial and safe,” she said.

    Taking testosterone, or over-the-counter supplements that boost levels of the hormone, can have side effects including increased risk of prostate cancer, increased cholesterol levels, acne and male pattern baldness, Yaffe said.

    […]

    The cognitive tests measured concentration, memory, attention, language, and other cognitive skills. When scores on these tests decline significantly, or are well below average, this serves as a warning of a high risk of Alzheimer’s disease, Yaffe said.

    In addition to testosterone, the researchers measured estrogen and sex hormone binding globulin, a protein that binds these two hormones. Although testosterone was linked to better scores on the tests, estrogen had essentially no effect on performance, Yaffe said. Previous studies of women have shown that higher estrogen levels can reduce their risk of cognitive decline.

    Other research has shown that men have higher levels of both estrogen and testosterone than women, and that women have a 30 percent greater risk of developing Alzheimer’s Disease, Yaffe said. Some researchers hypothesize that women’s increased Alzheimer’s risk is related to lower hormone levels.

    This study doesn’t explain how testosterone acts on the brain, Yaffe said, but other studies of mice have shown that the parts of the brain that handle learning and memory tasks are replete with receptors for testosterone.

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  • Testosterone rapidly potentiates the response of neural circuits mediating threat processing and aggressive behavior in men. (2014) www.sciencedaily.com
    Brain Hormones Behavior Testosterone

    From the article:

    The researchers recruited 16 healthy young male volunteers, who completed two test days on which they received either testosterone or placebo. On both testing days, the men first received a drug that suppressed their testosterone. This step ensured that testosterone levels were similar among all study participants. The amount of testosterone administered in this study only returned testosterone levels to the normal range. Subjects then completed a face-matching task while undergoing a functional magnetic resonance imaging scan.

    Data analyses revealed that, compared with placebo, testosterone increased reactivity of the amygdala, hypothalamus and periaqueductal grey when viewing angry facial expressions.

    “We were able to show for the first time that increasing levels of testosterone within the normal physiological range can have a profound effect on brain circuits that are involved in threat-processing and human aggression,” said Carré, Assistant Professor at Nipissing University.

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  • Immune cells in the brain influence high-order cognitive function but increase the risk of neuropsychiatric disorders. www.science.org
    Brain Immune System

    The dorsolateral prefrontal cortex is a functional region of the brain that mediates complex cognitive functions. It is unique to primates. Findings from a recent study suggest that specialized immune cells called microglia are present in the dorsolateral prefrontal cortex of humans only, setting them apart in terms of cognitive abilities but making them more vulnerable to language and neuropsychiatric disorders.

    Microglia are the brain’s resident immune cells. Their acute activation modulates inflammation and neurotoxicity, but chronic activation promotes brain inflammation and damage. Evidence suggests that microglia activation influences mood.

    Researchers profiled the expression of genes in more than 600,000 cells found in the dorsolateral prefrontal cortices of four primate groups, including humans, macaques, chimpanzees, and marmosets. They identified 109 cell types that were conserved across the four species and five that were species-specific.

    Of the species-specific cell types, they noted that one type of microglia was only found in humans, while another was found in both humans and chimpanzees. They also found that microglia express a gene called FOXP2, which is involved in language disorders, schizophrenia, and autism.

    These findings suggest that microglia play critical roles in establishing higher-order cognitive function in humans, but they may also increase humans' risk for language and neuropsychiatric disorders.

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  • Electrical stimulation of the brain improves memory in older adults. www.nature.com
    Brain Memory

    Memory loss often occurs with aging and may be the result of health disorders, emotional problems, mild cognitive impairment, or another type of dementia. Findings from a new study suggest that transcranial alternating current stimulation improves memory in older adults.

    Transcranial alternating current stimulation is a non-invasive therapy that passes a mild electrical current to the brain via electrodes attached to the scalp, altering brain rhythms and improving functionality. It is currently under study as a treatment for depression, anxiety, and cognitive, speech, or motor symptoms related to various movement disorders, such as Parkinson’s disease.

    The study involved 150 healthy older adults (aged 65 years and older). The researchers applied transcranial alternating current stimulation to the participants' brains at varying frequencies once a day for four days. As a placebo treatment, participants received a much shorter duration treatment. Participants took memory tests before and after their respective treatments.

    Participants that received the transcranial alternating current stimulation showed improvements in both working and long-term memory as early as two days after initiating treatment. These improvements were still present at follow-up testing one month later. Participants with poorer cognitive function at the beginning of the treatment showed greater, longer-lasting memory improvements.

    These findings suggest that transcranial alternating current stimulation improves memory in older adults and may be suitable as a non-invasive therapy for memory loss.

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  • Testosterone may facilitate social approach by specifically activating the amygdalae if social approach is desired (2015) www.sciencedaily.com
    Brain Hormones Behavior Anxiety Testosterone

    From the article:

    In a double-blind, placebo-controlled study, 54 young healthy women were given 0.5 mg of testosterone (or a placebo) four hours before a brain scan. This dosage is much lower than, for example, that used for a sex change treatment, or as a supplement for sportspeople, but it is sufficient to have a measurable effect on brain activity.

    […]

    It seems that testosterone facilitates social approach by specifically activating the amygdalae only if social approach is desired. This is interesting for two reasons. It explains previous research that showed that testosterone makes approaching a social threat easier. Even more important, it shows that the amygdalae are not necessarily linked to dealing with emotions, but rather to motivation. Many studies forget to look at motivation. We are the first to demonstrate that the impact of testosterone on amygdala response depends on the motivational context."

    Also in cases of social anxiety?

    “We’re now going to repeat this study in people with social anxieties. We have already discovered that these people have lower testosterone levels. We are going consider how we can apply these results with testosterone to improving the treatment for anxiety disorders.”

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  • Interleukin-6 (IL-6) acutely and directly induces hyperexcitability associated with epilepsy and autism in rat brain. (2012) www.sciencedaily.com
    Brain Autism IL-6

    From the article:

    Garcia and Atzori hypothesized that the protein IL-6 acutely and directly induces hyper-excitability by altering the balance between excitation and inhibition within synaptic communication. In other words, IL-6 is not just present when hyper-excitability occurs in the nervous system. It may actually cause it in some circumstances, Garcia said.

    The UT Dallas research team administered IL-6 to rat brain tissue and monitored its synaptic excitability. The brain tissue exhibited higher than normal excitability in their synapses, a symptom that may lead to misfiring of signals in epilepsy and other conditions.

    The researchers then injected sgp130 -a novel drug that acts as an IL-6 blocker- into the laboratory animals' brains. The substance limited excitability and appeared to prevent the conditions that lead to related neurological and psychiatric disorders, Garcia said.

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  • Infection-induced interleukin-6 secretion in mice increases the risk for schizophrenia- and autism-like behaviors in offspring. (2007) www.sciencedaily.com
    Brain Virus Pregnancy Autism Schizophrenia IL-6

    From the article:

    It has been known for some time that schizophrenia is more common among people born in the winter and spring months, as well as in people born following influenza epidemics. Recent studies suggest that if a woman suffers even one respiratory infection during her second trimester, her offspring’s risk of schizophrenia rises by three to seven times.

    […]

    To prove this, they triggered an artificial immune response in pregnant mice–giving them a faux case of the flu. The trigger they used was a snippet of double-stranded RNA called poly(I:C), which fools the immune system into thinking there has been an infection by an RNA virus.

    A single, mid-gestation injection of poly(I:C) creates a strong immune response in a pregnant mouse. When her offspring reach adulthood, they display behavioral and tissue abnormalities similar to those seen in schizophrenia in humans.

    Though there might be some disagreement over what it means for a mouse to be schizophrenic, these abnormalities are generally marked by inappropriateness of response and difficulty in coping.

    […]

    The team tried injecting the pregnant mice with individual cytokines, rather than with poly(I:C). It turned out that after a single dose of a specific cytokine known as interleukin-6 (or IL-6), a mouse would give birth to offspring who, at maturity, exhibited the familiar schizophrenia- and autism-like behaviors.

    To confirm the role of IL-6, Steve Smith, the lead researcher, gave fake colds (poly(I:C)) to two groups of pregnant, IL-6-free mice. One group had received anti-IL-6 antibodies which blocked IL-6; the other consisted of so-called IL-6 knockout mice (mice whose genetic makeup prevents them from synthesizing IL-6). In both groups, offspring grew up normal, showing that IL-6 is necessary for the maternal poly(I:C) treatment to alter fetal brain development and subsequent behavior in the offspring.

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  • Interleukin-6, CRP and triglycerides are likely shared causal risk factors for depression and coronary heart disease. (2019) www.sciencedaily.com
    Brain Heart Disease Inflammation Depression Triglycerides IL-6 CRP

    From the article:

    Together, these results suggest that the link between heart disease and depression cannot be explained by a common genetic predisposition to the two diseases. Instead, it implies that something about an individual’s environment – such as the risk factors they are exposed to – not only increases their risk of heart disease, but at the same time increases their risk of depression.

    […]

    Of these common biomarkers, they found that triglycerides (a type of fat found in the blood) and the inflammation-related proteins IL-6 and CRP were also risk factors for depression.

    Both IL-6 and CRP are inflammatory markers that are produced in response to damaging stimuli, such as infection, stress or smoking. Studies by Dr Khandaker and others have previously shown that people with elevated levels of IL-6 and CRP in the blood are more prone to develop depression, and that levels of these biomarkers are high in some patients during acute depressive episode. Elevated markers of inflammation are also seen in people with treatment resistant depression. This has raised the prospect that anti-inflammatory drugs might be used to treat some patients with depression. Dr Khandaker is currently involved in a clinical trial to test tocilizumab, an anti-inflammatory drug used for the treatment of rheumatoid arthritis that inhibits IL-6, to see if reducing inflammation leads to improvement in mood and cognitive function in patients with depression.

    While the link between triglycerides and coronary heart disease is well documented, it is not clear why they, too, should contribute to depression. The link is unlikely to be related by obesity, for example, as this study has found no evidence for a causal link between body mass index (BMI) and depression.

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  • Maternal immune activation during pregnancy is associated with changes in the newborns' stimulus processing and long-term development. (2018) www.sciencedaily.com
    Brain Inflammation Pregnancy Autism Schizophrenia IL-6 CRP

    From the article:

    Blood drawn from mothers during their third trimester was tested for levels of IL-6 and CRP – two proteins that are found at higher levels when the immune system is activated. Peterson’s team also monitored fetal heart rate as an indicator for nervous system development. The team found that CRP did correlate with variability of the fetal heart rate, which is influenced heavily by the nervous system, indicating that maternal inflammation was already beginning to shape brain development.

    When the babies were born, they were given MRI scans in their first few weeks of life, providing researchers a unique view of early neural development and the influence of prenatal factors. Brain imaging revealed a striking finding – significant changes in the communication between specific brain regions correlated with elevated maternal IL-6 and CRP levels. These brain regions are known collectively as the salience network, whose job is to filter stimuli coming into the brain and determine which deserve attention.

    […]

    “The salience network sifts through that information and decides what is important and warrants action.” Disturbances in the functioning of this network, as well as various kind of infection and other triggers of a pregnant woman’s immune response, have been linked to development of psychiatric illnesses, such as schizophrenia and autism spectrum disorders.

    […]

    The correlations of elevated maternal inflammatory markers were not limited to the newborn period, but continued to persist into toddlerhood. When the babies turned 14 months of age, researchers assessed them for motor skills, language development, and behavior. Following the established Bayley Scales of Infant and Toddler Development-Third Edition, Peterson found significant changes in the scores of toddlers born to mothers with elevated levels of both IL-6 and CRP.

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  • Higher maternal interleukin-6 (IL-6) levels are associated with changes in the newborn amygdala leading to altered impulse control. (2017) www.sciencedaily.com
    Brain Pregnancy Mental Health Autism Schizophrenia IL-6

    From the article:

    “We discovered that higher levels of interleukin-6, an inflammatory marker, were associated with changes in the neonatal amygdala in terms of its anatomy and connectivity. Furthermore, our subsequent findings showed that these changes were also associated with lower impulse control at 2 years of age,” explains Prof. Buß. “We therefore conclude that a link exists between higher levels of maternal inflammatory markers and an increased risk of psychiatric disorders that are commonly associated with impaired impulse control.” Animal models have shown that infections and inflammation in the pregnant animal lead to both changes in offspring brain development and behavior. Epidemiological studies also support the findings of this study, suggesting that maternal infections and other clinical phenotypes associated with increased interleukin-6 concentrations (such as obesity) during pregnancy increase the risk of psychiatric disorders such as schizophrenia and autism.

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  • Stress-induced chronic inflammation is associated with depression and other diseases. (2015) www.sciencedaily.com
    Exercise Brain Inflammation Depression Stress Meditation Mental Health NSAID IL-6 CRP

    From the article:

    The authors found that in addition to being linked to numerous physical health issues, including cancer and diabetes, systemic inflammation is linked to mental health issues such as depression. Among patients suffering from clinical depression, concentrations of two inflammatory markers, CRP and IL-6, were elevated by up to 50 percent.

    Fagundes said chronic inflammation is most common in individuals who have experienced stress in their lives, including lower socio-economic status or those who experienced abuse or neglect as children. Other contributing factors are a high-fat diet and high body mass index.

    […]

    The study also found that depression caused by chronic inflammation is resistant to traditional therapy methods, but can be treated with activities such as yoga, meditation NSAIDS and exercise.

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  • Interleukin-6 (IL-6) may play a causal role in the increased ischemic damage after stroke associated with social isolation in mice. (2009) www.sciencedaily.com
    Brain Stroke IL-6

    From the article:

    Researchers at Ohio State University found that all the male mice that lived with a female partner survived seven days after a stroke, but only 40 percent of socially isolated animals lived that long.

    […]

    The amount of tissue damage in the brain was about four times larger in the mice housed alone compared to those housed with another mouse.

    “The number of neurons dying is significantly decreased in the pair-housed mice,” DeVries said.

    In addition, socially housed mice had significantly less edema, or excess water in the brain, when compared to the isolated animals.

    “In clinical stroke, edema is a major concern because it can lead to additional neuronal damage, so it is significant that pair housing reduced edema,” Karelina said.

    […]

    In addition, findings revealed that mice that lived with others had significantly higher levels of a cytokine in their brain called interleukin-6 (IL-6) that has an anti-inflammatory response in the brain, helping to limit damage caused by the stroke.

    The finding about IL-6 is especially interesting, Karelina said, because IL-6 appears to have opposite effects in the brain than it does in the rest of the body.

    “IL-6 reduces inflammation in the brain, so it is protective in a stroke, but it is a pro-inflammatory in the periphery of the body,” Karelina said.

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  • Blockade of IL-6 receptor improved cognition in patients with schizophrenia. (2016) www.sciencedaily.com
    Brain Memory Schizophrenia IL-6

    From the article:

    After just two intravenous doses in eight weeks of tocilizumab, an immune-suppressing drug regularly prescribed for rheumatoid and juvenile arthritis, study participants had significantly improved cognitive ability, said Dr. Brian J. Miller, a psychiatrist at the Medical College of Georgia at Augusta University.

    […]

    Anywhere from 25 to 50 percent of patients may have inflammation in the brain contributing to that dysfunction. Problems range from having trouble remembering important numbers to impairment of executive function that enables them to analyze, organize, and generally manage their lives.

    Tocilizumab targets the receptor for IL-6, a protein which helps regulate inflammation that is often elevated in patients with schizophrenia. Higher IL-6 levels also have been correlated with a smaller hippocampus, a center for learning and memory in the brain, as well as experiencing more psychiatric symptoms.

    The five study patients did not experience improvement in overall levels of psychiatric symptoms, such as hallucinations and delusions, more classic symptoms of schizophrenia, which were already well-controlled with antipsychotics, Miller said.

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  • Maternal IL-6 during pregnancy can be estimated from newborn brain connectivity and negatively correlates with offspring working memory. (2018) www.sciencedaily.com
    Brain Memory Pregnancy IL-6

    From the article:

    […] collected blood samples from 84 expectant mothers at each pregnancy trimester. The samples were measured for levels of the cytokine interleukin-6, or IL-6, an inflammatory marker known to play a role in fetal brain development.

    Four weeks following birth, brain connectivity patterns of the offspring were assessed using functional magnetic resonance imaging, or fMRI, scans. At age 2, the children were also tested for working memory performance, a key skill that supports academic achievement and is frequently compromised in mental health disorders.

    The data from mother and child show that differences in the levels of inflammatory markers are directly associated with differences in newborn brain communication, and later to working memory scores at age 2. Higher levels of the marker during pregnancy tended to result in less working memory capacity in the child.

    “Importantly, this doesn’t mean that every exposure to inflammation will result in a negative impact to the child; however, these findings provide new avenues for research, and can help health care providers think about how, and when, inflammation might impact a child’s long-term learning development and mental health,” said Alice Graham, Ph.D., postdoctoral fellow in behavioral neuroscience in the OHSU School of Medicine.

    A notable aspect of the study, according to Graham, is the development of a model that can accurately estimate information about maternal inflammation during pregnancy based only on newborn brain functioning.

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  • Interleukin-6 (IL-6) mediates delirium-like phenotypes in a mouse model of urinary tract infection. (2021) www.sciencedaily.com
    Brain Memory IL-6

    From the article:

    In a Y-shaped maze with three arms to explore, uninfected mice tended to explore all three arms, while mice with UTIs [urinary tract infection] kept returning to the same one, suggesting a lapse in short-term memory, another feature of delirium.

    The investigators also observed structural changes in the brains of mice with UTIs.

    In a previous study led by Lahiri, published in February in the American Journal of Respiratory Cell and Molecular Biology, investigators found a connection between ventilator-induced lung injury and delirium. Lahiri and colleagues theorized that in both cases this was because of the reaction of IL-6, which helps regulate immune response, to the lung injury or the UTI.

    “Occasionally, when the response of IL-6 is excessive, our research indicates that there can be brain injury,” Lahiri said. “IL-6 induces changes within the neurons that our studies connected with delirium-like behavior. This is the first time this type of structural and functional change has been demonstrated. We’ve now shown two distinct models of this connection, one non-infectious and one infectious.”

    In the current study, when investigators treated some of the infected mice with antibodies that blocked the effects of IL-6, the delirium-like behavior of those animals resolved. “Treatment with anti-IL-6 antibody in the UTI group normalized all the brain changes, both structural and functional,” Lahiri said. “A wealth of studies have shown a link between IL-6 and delirium, but only this study and our previous study have shown that IL-6 may play a direct pathological role in delirium.”

    If symptoms are treated early, he added, full recovery is possible, and the next step is to design clinical trials with anti-IL-6 antibodies as a treatment for patients with UTI-induced delirium.

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  • Intranasally administered interleukin-6 (IL-6) helps the brain retain emotional and procedural memories during REM sleep. (2009) www.sciencedaily.com
    Brain Memory IL-6

    From the article:

    “Here, we provide the first evidence that the immunoregulatory signal interleukin-6 plays a beneficial role in sleep-dependent formation of long-term memory in humans.”

    To make this discovery, Marshall and colleagues had 17 healthy young men spend two nights in the laboratory. On each night after reading either an emotional or neutral short story, they sprayed a fluid into their nostrils which contained either interleukin-6 or a placebo fluid. The subsequent sleep and brain electric activity was monitored throughout the night. The next morning subjects wrote down as many words as they could remember from each of the two stories. Those who received the dose of IL-6 could remember more words.

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  • Social rank and rank uncertainty predicted levels of the pro-inflammatory proteins CRP, IL-6 and TNF-alpha in monkeys. (2016) www.sciencedaily.com
    Brain Inflammation IL-6 TNF-Alpha CRP

    From the article

    The team found that social rank and rank uncertainty predicted key risk factors for poor health, specifically pro-inflammatory proteins (C-reactive protein, interleukin-6, and tumor necrosis factor-alpha) which are risk factors for chronic diseases such as cardiovascular disease and diabetes.

    […]

    The researchers discovered that high ranking monkeys with low certainty of their social status showed higher markers of inflammation, which can be a sign of a chronic disease state such as diabetes, than those with very certain status. So high-ranking monkeys may experience some health risks, but only when their position is questionable and they are consequently at risk of losing their status.

    The opposite pattern was found for low ranking monkeys – high dominance certainty was associated with higher markers of inflammation, whereas low certainty was associated with lower levels of inflammatory proteins. Monkeys that are uncertain in their low rank might have opportunities for upward mobility in the hierarchy, which may be associated with better health outcomes.

    Vandeleest said the results of the study show that status uncertainty alone may be a risk factor for acute diseases. The results also indicate that uncertainty in status over longer periods in relationship to rank are related to chronic disease states as well.

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  • TNF is associated with reversible depression-like phenotype in hamsters induced by chronic nocturnal dim light exposure. (2012) www.sciencedaily.com
    Brain Depression Circadian Rhythm TNF-Alpha

    From the article:

    While hamsters exposed to light at night for four weeks showed evidence of depressive symptoms, those symptoms essentially disappeared after about two weeks if they returned to normal lighting conditions.

    Even changes in the brain that occurred after hamsters lived with chronic light at night reversed themselves after returning to a more normal light cycle.

    These findings add to the growing evidence that suggest chronic exposure to artificial light at night may play some role in the rising rates of depression in humans during the past 50 years, said Tracy Bedrosian, lead author of the study and doctoral student in neuroscience at Ohio State University.

    “The results we found in hamsters are consistent with what we know about depression in humans,” Bedrosian said.

    […]

    Most importantly, hamsters that lived in dim light showed increased expression of the gene that produces tumor necrosis factor.

    […]

    They found that blocking effects of that protein, called tumor necrosis factor, prevented the development of depressive-like symptoms in hamsters even when they were exposed to light at night.

    […]

    However, hamsters that were returned to a standard light-dark cycle after four weeks of dim light at night saw their TNF levels and even their density of dendritic spines return essentially to normal.

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  • Mice that were socially isolated before a heart attack had increased TNF-alpha levels and 5 to 8 times more brain neuron damage. (2008) www.sciencedaily.com
    Brain Heart Disease TNF-Alpha

    From the article:

    Results showed that the mice that were socially isolated prior to the heart attack showed five to eight times more damage to their neurons compared to mice that were housed together, said Weil, who is now a post-doctoral researcher at Rockefeller University in New York.

    Socially isolated mice also showed evidence of greater inflammation in the hippocampus, when compared to socially housed and control mice.

    […]

    Socially isolated mice showed increased activation of microglia, a type of immune cell in the central nervous system that responds to damaged neurons, the study found.

    One of the ways microglia respond is by releasing tumor necrosis factor alpha (TNF-a), one of a large family of proteins called cytokines – chemical messengers that are mobilized when the body is injured or has an infection. These cytokines cause inflammation in their effort to repair an injured or infected area of the body.

    Levels of TNF-a were elevated in isolated mice, but not in socially housed mice, compared to the control mice.

    The higher levels of TNF-a in the socially isolated mice, and the inflammation it caused, was the main reason for the increased neuronal damage in these animals, Nelson said.

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  • TNF-alpha may upregulate enzyme expression that appears to be important in the conversion of mild cognitive impairment to Alzheimer's disease. (2013) www.sciencedaily.com
    Brain Alzheimer's TNF-Alpha

    From the article:

    In the current study, researchers examined autopsied brain tissue from 18 patients with clinically well-characterized AD, 18 patients with MCI, and 18 non-demented patients. They found that BACE1 enzymatic activity was significantly increased in both MCI and AD brains. In 11 of 18 MCI patients, who had undergone a mini-mental state examination (MMSE) before death, the brain cortex BACE1 levels increased during early dementia followed by a precipitous decrease as the decline in cognition progressed. Increased BACE1 activity correlated with plaque numbers and cognition status. Interestingly, they also observed that there was no significant difference in BACE1 activity between MCI and AD.

    The researchers also found an increase in tumor necrosis factor alpha (TNFα) in MCI brains. TNFα is an inflammatory cytokine or cell signaling protein required for amyloid protein induced neuronal death. Biochemical examination of the autopsy tissue showed that TNFα rather than other cytokines increases the response to BACE1 protein expression. The increased levels of TNFα in MCI and AD patients were not significantly different from each other.

    “There is more and more evidence that BACE1 is intricately involved in the development of AD,” says the study’s lead investigator Yong Shen, PhD, of the Center for Advanced Therapeutic Strategies for Brain Disorders at Roskamp Institute, Sarasota, Florida. “Our previous studies have demonstrated elevated BACE1 enzymatic activity in AD brains and in the cerebrospinal fluid from MCI and AD patients. Our findings here suggest that BACE1 increases early in the course of MCI and is possibly induced by inflammatory molecules like TNFα and that BACE1 enzymatic activity may be important for conversion of MCI to AD. Importantly, we found that the BACE1 activity in tissue from people with MCI was significantly increased by 27%, compared with that from people with no dementia.

    “We believe that BACE1 activity precedes the clinical diagnosis of AD and could be an early indicator of neuronal dysfunction or pathology in AD. Moreover, it may be a good therapeutic target for AD, as evidenced by recent promising clinical trials on BACE1 inhibitors,” he concludes.

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  • Microglial TNF-alpha suppresses cocaine-induced plasticity and behavioral sensitization in a mouse model. (2016) www.sciencedaily.com
    Brain Addiction TNF-Alpha

    From the article:

    “What we discovered is that cocaine activates these microglia, which causes the release of an inflammatory signal which then tries to reverse the changes that cocaine is inducing in the neurons,”

    […]

    The team found that TNF suppresses specific synaptic changes caused by cocaine-changes that are thought to underlie addiction. But Dr. Stellwagen explains that this beneficial mechanism doesn’t last. “The microglia response fades over time. One of the things that could transition somebody from just casual use into chronic dependency might be the fading of this adaptive signal which then allows the drugs to solidify their change to the neural circuitry.”

    So can microglia be enticed to keep going? To find out, the team used a pharmaceutical agent that stimulates microglial production of TNF. Researchers observed that a cocaine-induced behavioral change in mice, the progressive increase in movement induced by cocaine,-was reduced in the animals who received this agent.

    This exciting result holds promise for one day developing treatments that could cut down on drug relapse rates, which can run as high as 80 per cent.

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  • RCT suggests that TNF-alpha antagonism may improve depressive symptoms in patients with high inflammatory biomarkers. (2012) www.sciencedaily.com
    Brain Inflammation Depression TNF-Alpha CRP

    From the article:

    Prior studies have suggested that depressed people with evidence of high inflammation are less likely to respond to traditional treatments for the disorder, including anti-depressant medications and psychotherapy. This study was designed to see whether blocking inflammation would be a useful treatment for either a wide range of people with difficult-to-treat depression or only those with high levels of inflammation.

    […]

    Study participants all had major depression and were moderately resistant to conventional antidepressant treatment. Each participant was assigned either to infliximab or to a non-active placebo treatment.

    When investigators looked at the results for the group as a whole, no significant differences were found in the improvement of depression symptoms between the drug and placebo groups. However, when the subjects with high inflammation were examined separately, they exhibited a much better response to infliximab [TNF inhibitor] than to placebo.

    Inflammation in this study was measured using a simple blood test that is readily available in most clinics and hospitals and measures C-reactive protein or CRP. The higher the CRP, the higher the inflammation, and the higher the likelihood of responding to the drug.

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  • Selective inhibition of soluble TNF prevented neuron loss and reduced motor deficits in a rat model of Parkinson's disease. (2014) www.sciencedaily.com
    Brain Parkinson's TNF-Alpha

    From the article:

    Evidence has been piling up that inflammation is an important mechanism driving the progression of Parkinson’s disease. XPro1595 targets tumor necrosis factor (TNF), a critical inflammatory signaling molecule, and is specific to the soluble form of TNF. This specificity would avoid compromising immunity to infections, a known side effect of existing anti-TNF drugs used to treat disorders such as rheumatoid arthritis.

    […]

    Postdoctoral fellow Christopher Barnum, PhD and colleagues used a model of Parkinson’s disease in rats in which the neurotoxin 6-hydroxydopamine (6-OHDA) is injected into only one side of the brain. This reproduces some aspects of Parkinson’s disease: neurons that produce dopamine in the injected side of the brain die, leading to impaired movement on the opposite side of the body.

    When XPro1595 is given to the animals 3 days after 6-OHDA injection, just 15 percent of the dopamine-producing neurons were lost five weeks later. That compares to controls in which 55 percent of the same neurons were lost. By reducing dopamine neuron loss with XPro1595, the researchers were also able to reduce motor impairment. In fact, the degree of dopamine cell loss was highly correlated both with the degree of motor impairment and immune cell activation.

    When XPro1595 is given two weeks after injection, 44 percent of the vulnerable neurons are still lost, suggesting that there is a limited window of opportunity to intervene.

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  • TNF-alpha blocker administration clinically improved patients with chronic neurological dysfunction following stroke and traumatic brain injury (2012) www.sciencedaily.com
    Brain Stroke TBI TNF-Alpha

    From the article:

    The observational study¹ of 629 patients, conducted over the course of nearly two years, documents a diverse range of positive effects, including statistically significant rapid clinical improvement in motor impairment, spasticity, cognition, etc. in the stroke group, with a similar pattern of improvement seen in the traumatic brain injury (TBI) group. The study involved 617 patients treated an average of 42 months after stroke and 12 patients treated an average of 115 months after TBI, long after further spontaneous meaningful recovery would be expected.

    The study was conducted at the Institute of Neurological Recovery (INR) in the USA.

    The drug utilized was etanercept [a TNF blocker], a therapeutic that selectively binds and neutralizes an inflammatory immune molecule that may remain elevated for years following stroke. Etanercept was administered utilizing a novel delivery method, invented by Edward Tobinick M.D., lead author of the study.

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  • Systemic inflammation accompanied by an increase in serum TNF-alpha is associated with an increase in cognitive decline in Alzheimer's disease. (2009) www.sciencedaily.com
    Brain Alzheimer's TNF-Alpha

    From the article:

    The study found that people who had respiratory, gastrointestinal or other infections or even bumps and bruises from a fall were more likely to have high blood levels of tumor necrosis factor-α, a protein involved in the inflammatory process, and were also more likely to experience memory loss or other types of cognitive decline than people who did not have infections and who had low levels of the protein.

    The blood levels and cognitive abilities of 222 people with Alzheimer’s disease with an average age of 83 were measured at the beginning of the study and three more times over six months. Caregivers were interviewed to determine whether the participants had experienced any infections or accidental injury that could lead to inflammation.

    A total of 110 people experienced an infection or injury that led to inflammation during the study. Those people experienced memory loss that was at twice the rate of those who did not have infections or injuries.

    People who had high levels of the protein in their blood at the beginning of the study, which may indicate chronic inflammation, had memory loss at four times the rate of those with low levels of the protein at the start of the study. Those who had high levels of the protein at the start of the study who also experienced acute infections during the study had memory loss at 10 times the rate of those who started with low levels and had no infections over the six-month period.

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  • TNF-alpha can bring digestion to a halt by stimulating the corresponding control area of the brain, animal study suggests. (2000) www.sciencedaily.com
    Brain TNF-Alpha

    From the article:

    Cells in the NST [nucleus of the solitary tract] are a critical part of the neural circuitry that regulates digestive functions, including vomiting.

    […]

    The researchers conducted a study in rats to determine how these brainstem neurons responded to TNF. Rats were injected with levels of TNF comparable to concentrations present during a chronic infection. This TNF concentration activated NST neurons and caused digestion to stop - a condition called stasis. This leads to nausea, loss of appetite, and vomiting.

    […]

    In this research, many NST neurons exposed to TNF did not return to a normal level of function during the course of the study. Furthermore, these neurons became overly sensitive to normal gastrointestinal events for a prolonged time.

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  • Hypoxic brain injury in preemies may be treatable well after birth by administration of TNF-alpha blocker, animal study suggests. (2022) www.sciencedaily.com
    Brain Pregnancy TNF-Alpha

    From the article

    Over a third of cases of cerebral palsy are still linked to being born extremely prematurely. Clinical studies have shown that severe injury can appear many weeks after birth. “The current thinking is that this form of brain injury is so severe that there is no point trying to understand it, let alone treat it,” says senior research fellow Dr Christopher Lear, lead author on the new study. “Just the concept that it might be treatable is revolutionary.”

    Critically, giving the well-established anti-inflammatory drug, Etanercept (also known as ‘Enbrel’) [a TNF blocker] three days after a period of oxygen deprivation was able to almost completely prevent severe injury from developing after three weeks' recovery. The article has just been published in a leading journal, Brain. “Virtually all proposed treatments so far need to be started within the first six hours of life,” says Professor Laura Bennet. “This is often not realistic when families are overwhelmed by events around birth.”

    “A therapeutic window of at least three days is exceptionally long. Much more research is needed before this approach can be tested in humans, but this remarkably wide window for treatment gives us real hope that these findings will one day lead to a new treatment in humans to prevent cerebral palsy,” says Professor Bennet.

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  • Estrogen improves symptoms in a mouse model of Parkinson's disease. (2019) www.sciencedaily.com
    Brain Parkinson's Hormones Estrogen

    From the article

    Estrogen is thought to protect movement neurons from Parkinson’s disease, but how is unknown. Since the patients more susceptible to Parkinson’s disease – men and post-menopausal women – have low estrogen levels, estrogen treatment might be an effective way to delay and reduce symptoms.

    Silke Nuber and colleagues at Harvard Medical School treated mouse models of Parkinson’s disease with brain-selective estrogen and compared the motor performance of males and females before and after treatment. The female mice showed less severe symptoms at a later age, but estrogen still improved their symptoms. In male mice, the estrogen treatment reduced alpha-synuclein breakdown and buildup and helped with severe symptoms, suggesting that estrogen could be a viable treatment option for Parkinson’s patients with low estrogen levels.

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  • TNF-alpha may be a major contributor to impaired memory formation in Alzheimer's disease, rat study suggests. (2019) www.sciencedaily.com
    Brain Alzheimer's TNF-Alpha

    From the article:

    Professor Cliff Abraham and Dr Anurag Singh from the Department of Psychology have identified that a protein in the brain – tumor necrosis factor-alpha (TNFα) – normally associated with inflammation, becomes abnormally active in the Alzheimer’s brain, impairing the memory mechanism.

    The overproduction of this protein (TNFα) may be one of the reasons behind the disease-related impairments of memory formation in the brain.

    “While TNFα has been linked previously with Alzheimer’s and memory studies, it has not been understood that neural overactivity can drive the production of this protein to inhibit memory mechanisms in the brain,” Professor Abraham, a Principal Investigator with the University’s Brain Health Research Centre, explains.

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  • Blocking soluble TNF signaling attenuates loss of dopaminergic neurons in rat models of Parkinson's disease. (2006) TNF-alpha plays a central role in nerve and brain self-repair in a mouse model of demyelination. (2001)
    Brain Parkinson's TNF-Alpha

    From the article:

    In addition to its beneficial role, TNF has been a suspected player in Parkinson’s because elevated levels of it are found in post-mortem brains and cerebrospinal fluid of people with the disease. A previous study by other researchers found that non-steroidal anti-inflammatory drugs that block production of TNF and related molecules can reduce the risk of developing Parkinson’s by 46 percent.

    In the current study, UT Southwestern researchers injected two different substances into the rats' brains to cause cell death in the substantia nigra —low-dose infusion of LPS, a toxin from bacteria often used to mimic chronic inflammation of the central nervous system, and 6-hydroxydopamine, which kills cells by creating an overwhelming amount of reactive oxygen and nitrogen molecules. Cell death was measured by counting neurons in stained brain slices.

    When an experimental TNF inhibitor called XENP345, designed specifically to block soluble TNF, was also introduced into the brain, dopamine neuron death was reduced by about half.

    The same effect was found on cultured dopamine neurons exposed to either toxin.

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  • TNF-alpha plays a central role in nerve and brain self-repair in a mouse model of demyelination. (2001) www.sciencedaily.com
    Brain Multiple Sclerosis TNF-Alpha

    From the article:

    The UNC scientists treated those mice and others whose genes were functional with a toxin called cuprizone that slowly stripped away the myelin coating on nerves in their brains and then observed myelin regeneration indicative of nerve repair. Normal mice recovered completely, but those lacking the functioning tumor necrosis factor-alpha gene did not, which indicated how critical the protein was to the repair process.

    “We’ve found that these tumor necrosis factor molecules are very important for the white matter in the brain to repair itself,” Ting said. “White matter is part of the brain that allows motor skills, and if you don’t have it, you can’t move.”

    “We further found that the repair process acts through a particular pathway that appears to induce the production of nerve precursor cells,” Arnett added. “Those cells will eventually differentiate into oligodendrocytes – cells that make myelin and surround nerve axons.”

    […]

    Recent clinical trials of several drugs designed to block the alpha form of TNF, which was considered to be a problem, actually made patients’ conditions worse, Arnett said. In part, the UNC experiments were designed to find out why.

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  • Administration of an anti-TNF therapeutic to Alzheimer's patients led to cognitive improvement within minutes. (2008) www.sciencedaily.com
    Brain Alzheimer's TNF-Alpha

    From the article:

    This new study highlights the importance of certain soluble proteins, called cytokines, in Alzheimer’s disease. The study focuses on one of these cytokines, tumor necrosis factor-alpha(TNF), a critical component of the brain’s immune system. Normally, TNF finely regulates the transmission of neural impulses in the brain. The authors hypothesized that elevated levels of TNF in Alzheimer’s disease interfere with this regulation. To reduce elevated TNF, the authors gave patients an injection of an anti-TNF therapeutic called etanercept. Excess TNF-alpha has been documented in the cerebrospinal fluid of patients with Alzheimer’s.

    The new study documents a dramatic and unprecedented therapeutic effect in an Alzheimer’s patient: improvement within minutes following delivery of perispinal etanercept, which is etanercept given by injection in the spine. Etanercept (trade name Enbrel) binds and inactivates excess TNF. Etanercept is FDA approved to treat a number of immune-mediated disorders and is used off label in the study.

    […]

    While the article discusses one patient, many other patients with mild to severe Alzheimer’s received the treatment and all have shown sustained and marked improvement.

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  • Exercise protected mice from toxin-induced hippocampal damage by stimulating the production of interleukin-6 in the brain. (2011) www.sciencedaily.com
    Brain Memory Neurodegeneration IL-6

    From the article:

    Previous research has already demonstrated that exercise after brain injury can help the repair mechanisms. This new study shows that exercise before the onset of damage modifies the brain environment in such a way that the neurons are protected from severe insults. The study used an experimental model of brain damage, in which mice are exposed to a chemical that destroys the hippocampus, an area of the brain which controls learning and memory. Mice that were exercised regularly prior to exposure produced an immune messenger called interleukin-6 in the brain, which dampens the harmful inflammatory response to this damage, and prevents the loss of function that is usually observed.

    Pharmacological therapies to downregulate inflammation and address cognitive decline in older adults, and those with Alzheimer’s disease, have been less successful. This research helps understand how exercise could be used to affect the path of many human conditions, such as neurodevelopmental disorders and neurodegenerative diseases. In addition, as a chemical model of neuronal damage was used, it also raises the possibility that exercise could offer protection against the potentially harmful effects of environmental toxins.

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  • Association of serum interleukin-6 and C-reactive protein in childhood with depression and psychosis in young adult life. (2014) www.sciencedaily.com
    Brain Heart Disease Diabetes Depression Mental Health IL-6 CRP

    From the article:

    Now, researchers have carried out the first ever longitudinal study – a study that follows the same cohort of people over a long period of time – to examine the link between these markers [cytokines such as interleukin-6] in childhood and subsequent mental illness.

    A team of scientists led by the University of Cambridge studied a sample of 4,500 individuals from the Avon Longitudinal Study of Parents and Children – also known as Children of the 90s – taking blood samples at age 9 and following up at age 18 to see if they had experienced episodes of depression or psychosis. The team divided the individuals into three groups, depending on whether their everyday levels of IL-6 were low, medium or high. They found that those children in the ‘high’ group were nearly two times more likely to have experienced depression or psychosis than those in the ‘low’ group.

    […]

    The research indicates that chronic physical illness such as coronary heart disease and type 2 diabetes may share a common mechanism with mental illness. People with depression and schizophrenia are known to have a much higher risk of developing heart disease and diabetes, and elevated levels of IL-6 have previously been shown to increase the risk of heart disease and type 2 diabetes.

    Professor Peter Jones, Head of the Department of Psychiatry and senior author of the study, says: “Inflammation may be a common mechanism that influences both our physical and mental health. It is possible that early life adversity and stress lead to persistent increase in levels of IL-6 and other inflammatory markers in our body, which, in turn, increase the risk of a number of chronic physical and mental illness.”

    […]

    This potential common mechanism could help explain why physical exercise and diet, classic ways of reducing risk of heart disease, for example, are also thought to improve mood and help depression. The group is now planning additional studies to confirm whether inflammation is a common link between chronic physical and mental illness.

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  • Social stress-triggered increase of interleukin-6 in the brain exacerbates an animal model of multiple sclerosis. (2007) www.sciencedaily.com
    Brain Stress Multiple Sclerosis IL-6

    From the article:

    To create a stressful environment, researchers housed three young male mice together for several weeks. After the mice established a stable social hierarchy, researchers introduced an older aggressive male into the residence for a couple of hours. The intruder exhibits aggressive behavior – posturing, fighting, wounding, pursuit – that results in submissive behaviors and social defeat in the younger resident mice. This procedure was repeated for three consecutive nightly two-hour sessions with one night off, followed by an additional three nightly sessions. To keep the mice from getting used to the intruder, a new intruder was introduced for each session.

    What they found was this stress appears to elevate levels of IL-6, which subsequently increases the severity of the MS-like illness. Furthermore, using specific IL-6 neutralizing antibody treatments during the stress exposure can prevent the stress-related worsening of the disease, said the authors.

    […]

    Furthermore, interventions that prevented or reversed the stress-induced increases in IL-6 in the mouse model may have implications for humans, said Meagher. It is possible that the adverse effects of social conflict on people who are vulnerable to certain inflammatory diseases may be prevented or reversed by treatments aimed at blocking increases in this cytokine. Recent evidence suggests that some potential interventions include certain anti-inflammatory drugs, exercise, antidepressant medication, omega-3 fatty acids, and mindfulness relaxation training. However, human clinical trials are needed to fully evaluate this issue.

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  • Mouse study suggests that blocking the action of interleukin-6 may reduce symptoms of depression. (2010) www.sciencedaily.com
    Brain Depression IL-6

    From the article:

    Activation of the immune system caused mice to learn to run less on wheels in their cages – an activity they normally like. The mice resumed their normal activity when the action of interleukin-6, an immune hormone that carries “sickness” signals to the brain, was blocked.

    “Our findings suggest that blocking the action of interleukin-6 might reduce depression symptoms, like fatigue or loss of interest in pleasurable activities, in people who are depressed and who have elevated levels of interleukin-6,” said Simon Sydserff, PhD, a senior research scientist at BrainCells Inc., who conducted the research while with AstraZeneca Pharmaceuticals.

    Scientists previously observed that some people became depressed due to an immune response to illness or stress. Elevated levels of immune hormones like interleukin-6 have been found in some depressed patients who are otherwise healthy.

    Learn more about depression in our overview article.

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  • Evidence in mice suggests that TNF-alpha release in response to viral infection causes learning problems. (2017) www.sciencedaily.com
    Brain Inflammation Memory TNF-Alpha

    From the article:

    Evidence in mice suggests that the entry of a virus anywhere in the bloodstream turns on “first responder” immune cells called CX3CR1highLY6Clow monocytes, which then release the inflammatory signaling protein TNF-α. According to the authors of the study, TNF-α then travels to the brain where it blocks the formation of nerve cell connections needed to turn sensory information into memories.

    […]

    Researchers also measured the levels of pro-inflammatory signaling proteins (cytokines) in mice at several time points after the injection of poly(I:C), and found a larger, longer-lasting increase in levels of TNF-α than in other cytokines. Given their findings, the team guessed that the impact of systemic immune response on brain cell connections was executed through TNF-α signaling. Indeed, mice engineered to lack TNF-α signals in white blood cells saw neither a drop in dendritic spine formation nor in motor learning ability when exposed to the viral mimetic.

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  • Mouse study suggests that interleukin-6-releasing immune cells outside the brain influence the propensity to develop depression. (2013) www.sciencedaily.com
    Brain Inflammation Depression IL-6

    Psychosocial stress promotes the release of IL-6, potentially driving the development of depression.

    Psychosocial stress, such as that experienced with divorce, discrimination, trauma, or the death of a child, can have profound effects on the human body. For example, evidence indicates that stress alters the immune system, driving inflammatory processes and impairing antiviral responses. Findings from a 2013 study suggest that psychosocial stress promotes the release of interleukin 6 (IL-6), potentially driving the development of depression.

    IL-6 is a pro-inflammatory cytokine that plays an important role as a mediator of fever and the body’s immune response. It is produced by almost all immune cells and is induced in the context of infection, autoimmunity, or cancer. Many physiological processes are influenced by IL-6, including glucose metabolism, blood cell production, neuroendocrine regulation, and fatigue, among others. IL-6 levels are often elevated in people who have depression.

    The investigators conducted their study using mice that had undergone radiation to destroy their bone marrow, compromising their immune function. Then they transplanted bone marrow from mice that exhibited either high or low levels of IL-6 levels in response to stress into the immune-compromised animals. Then they exposed the animals to a social stressor.

    They found that mice that received transplants from those that exhibited high IL-6 levels in response to stress demonstrated more depression-like behaviors than the mice that received transplants from those that exhibited low IL-6 levels. These findings suggest that IL-6 promotes a pro-inflammatory state that promotes depression-like symptoms in response to psychosocial stress. Identifying therapeutic strategies that inhibit IL-6 may benefit people who are vulnerable to the effects of psychosocial stress.

    Interestingly, hyperthermia, such as that experienced with sauna use or hot baths, has been shown to reduce IL-6 levels. Learn more about the beneficial effects of sauna use in our overview article.

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  • Microglial interleukin-6 signaling and prostaglandin synthesis may regulate depressive symptoms in neurological disorders. (2021) www.sciencedaily.com
    Brain Inflammation Depression Mental Health IL-6

    Microglia and IL-6 drive the negative mood often associated with inflammation.

    People who have certain neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, or stroke, often exhibit low mood. Evidence suggests that inflammation plays a role in the pathogenesis of these neurological disorders and likely influences mood, as well. Findings from a 2021 study suggest that microglia activation drives the low mood often associated with neurological disorders.

    Microglia are the brain’s resident immune cells. They serve an essential role in maintaining brain microenvironment homeostasis. Acute activation of microglia modulates inflammation and neurotoxicity, but chronic activation promotes brain inflammation and damage. Evidence suggests that microglia activation influences mood.

    The investigators used chemogenetics, a research technique that uses drugs or other chemicals to modulate neural activity, to stimulate microglia activation in the brains of mice. They noted that levels of interleukin-6 (IL-6, a pro-inflammatory cytokine) and prostaglandins (hormone-like molecules that are involved in inflammation) increased in the animals' brains. In addition, the animals exhibited a low mood. Blocking microglia activity restored the animals' positive mood, however.

    These findings suggest that microglia drive the low mood often associated with inflammation and that IL-6 is a prominent player in this process. Learn more about the role of inflammation and mood in this episode featuring Dr. Charles Raison.

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  • Blocking soluble TNF signaling attenuates loss of dopaminergic neurons in models of Parkinson’s disease. (2006) www.sciencedaily.com
    Brain Parkinson's Neurons TNF-Alpha

    Blocking the action of TNF-alpha may slow the progression of Parkinson’s disease.

    Parkinson’s disease is a progressive neurodegenerative disorder that affects the central nervous system. It is caused by the destruction of nerve cells in the part of the brain called the substantia nigra. Approximately 1 percent of all adults over the age of 60 years lives with Parkinson’s disease. Findings from a 2006 study suggest that blocking the action of tumor necrosis factor-alpha slows the progression of Parkinson’s disease.

    Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine that is produced by a wide range of cells, including macrophages, lymphocytes, glial cells, and others. TNF-alpha signaling inhibits tumorigenesis, prevents viral replication, and induces fever and apoptosis. Dysregulation of the TNF-alpha signaling pathway has been implicated in a variety of disorders, including cancer, autoimmune diseases, Alzheimer’s disease, and depression.

    The investigators injected the brains of mice with either lipopolysaccharide (LPS, an endotoxin that promotes acute inflammation) or 6-hydroxydopamine (a neurotoxin) and assessed the animals' brains for evidence of substantia nigra cell death. They injected a compound called XENP345 (a TNF-alpha inhibitor) into the brains of some of the mice. They also applied LPS and 6-hydroxydopamine to cultured neuronal cells and assessed the effects of XENP345 on cell death.

    They found that both LPS and 6-hydroxydopamine caused marked cell death in the substantia nigra region of the animals' brains. They also found that inhibiting TNF-alpha via XENP345 in the brains and in cultured cells reduced cell death by roughly half.

    These findings suggest that inhibiting the activity of the pro-inflammatory cytokine TNF-alpha reduces cell death in an animal model of Parkinson’s disease. Robust evidence indicates that exercise, which also reduces inflammation, slows the progression of Parkinson’s disease. Learn more about the effects of exercise on Parkinson’s disease in this episode featuring Dr. Giselle Petzinger.

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  • Mouse study suggests that interleukin-6 (IL-6) may regulate body weight by increasing substances in the brain that trigger weight loss. (2012) www.sciencedaily.com
    Brain Metabolism Satiety Weight Loss IL-6

    From the article:

    The results show that the cells that are affected by interleukin-6 produce substances that not only affect our sense of hunger and fullness but also control the body’s ability to burn fat. “Interleukin-6 increases levels of substances in the brain that trigger weight loss, which could explain why high levels of this molecule lead to weight loss,” says doctoral student Erik Schéle, who is presenting the results in his thesis.

    It is known that our normally low levels of interleukin-6 in the brain increase dramatically during an infection, typically accompanied by reduced hunger and fatigue.

    “Our previous findings would indicate that interleukin-6 can play a key role in regulating the metabolism of healthy individuals too,” says Erik Schéle.

    “This is clearly substantiated by our finding that mice which lack interleukin-6 get fat, and that the metabolism of rats injected with interleukin-6 directly into the brain increases.”

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  • TNF-alpha production within the brain may partially explain the behavioral changes in mice with cholestatic liver damage. (2006) www.sciencedaily.com
    Brain Inflammation Behavior TNF-Alpha

    TNF-alpha in the brain drives sickness behaviors associated with liver disease.

    Many liver disorders cause behavioral symptoms, often referred to as sickness behaviors, such as fatigue, loss of appetite, and “brain fog.” Evidence suggests that these symptoms arise from alterations in the central nervous system, but scientists don’t fully understand what drives them. Findings from a 2006 study suggest that sickness behaviors in the setting of cholestasis, a common liver disorder, are caused by the presence of tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, in the brain.

    Cholestasis is characterized by impaired bile flow and subsequent retention of bile acids, bilirubin, and other substances, including lipopolysaccharide, an endotoxin, in the liver and blood. It is a common disorder of pregnancy but can affect all demographics, including children. Most people with cholestasis report experiencing sickness behaviors, especially fatigue, which occurs in roughly 86 percent of people with the disorder.

    TNF-alpha is produced by many types of immune cells. It exists in soluble and transmembrane forms, both of which mediate a variety of opposing physiological and pathological functions, depending on which of its receptors it binds to. For example, binding to TNF receptor 1 promotes apoptosis (programmed cell death) and inflammation; binding to TNF receptor 2 promotes cell survival, resolution of inflammation, immunity, and cellular repair. Elevated TNF-alpha is associated with chronic pain syndromes and anxious behaviors.

    The investigators tied off the bile ducts of healthy mice to induce cholestasis. Then they isolated endothelial cells from the blood vessels in the animals' brains to see if the cells were activated and if the cells interacted with immune cells. They also measured TNF-alpha production by monocytes (white blood cells).

    They found that endothelial cells were activated in the setting of cholestasis, and these activated cells readily interacted with immune cells that had been recruited to the brain. In turn, the immune cells increased their production of TNF-alpha. In light of the known effects of TNF-alpha on sickness behaviors, these findings suggest that TNF-alpha production in the brain mediates sickness behaviors in mice with liver disease.

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  • In a mendelian randomization study, genetically predicted levels of interleukin 6 (IL-6) were associated with neuropsychiatric disorders. www.sciencedaily.com
    Brain Inflammation Mental Health Genetics IL-6

    IL-6 may drive inflammation in neuropsychiatric disorders.

    Neuropsychiatric disorders are the leading cause of disability among people living in the United States, accounting for nearly 20 percent of all years of life lost to disability and premature death. Evidence suggests that brain inflammation is a key player in neuropsychiatric disorders, the effects of which may be bidirectional. A recent study identified potential links between inflammation and structural alterations in regions of the brain implicated in neuropsychiatric disorders.

    The brains of people with neuropsychiatric disorders exhibit a range of abnormal structural alterations, but researchers don’t fully understand what drives these abnormalities. One possible player is interleukin-6 (IL-6), a cytokine that can cross the blood-brain barrier, increasing the barrier’s permeability and promoting brain inflammation. In turn, this inflammation can impair synaptic pruning, a natural process that occurs in the brain between early childhood and adulthood and eliminates extra synapses. Inappropriate synaptic pruning is associated with some neuropsychiatric disorders, including schizophrenia and autism.

    The investigators searched for evidence of potential causality in the association between inflammatory cytokines and altered brain structure using Mendelian randomization, a research method that provides evidence of links between modifiable risk factors and disease based on genetic variants within a population. Using data from more than 20,000 adults enrolled in the UK Biobank study, the researchers looked for associations between genetic variants that influence levels of interleukin-6 (IL-6, a pro-inflammatory cytokine), as well as other inflammatory factors. and changes in gray matter volume in specific areas of the brain. They also examined postmortem brain tissue to assess gene expression in the brain areas of interest.

    They found that genes that influence the production of pro-inflammatory molecules, especially IL-6, are strongly linked with brain structure in the temporal and frontal regions of the brain, areas of the brain commonly implicated in neuropsychiatric disorders. The postmortem analyses revealed that the overproduction of these pro-inflammatory genes is associated with disorders such as epilepsy, cognitive disorder, schizophrenia, psychotic disorder, and autism spectrum disorder.

    These findings suggest that pro-inflammatory pathways, especially those associated with IL-6, are essential for normal brain structural development and IL-6 elevation may drive structural alterations implicated in neuropsychiatric disorders. Evidence suggests that heat stress reduces symptoms associated with depression, a type of neuropsychiatric disorder. Learn about a clinical trial that is investigating the benefits of heat stress in this episode featuring Dr. Ashley Mason.

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  • Chronic stress can inflame our brain, destroy the connections between our neurons and result in depression. (2019) www.sciencedaily.com
    Brain Immune System

    From the article:

    The complement system, named because it was first found to help the immune system fight invaders, is part of this innate immune response, and Pillai has found elevated levels of C3 – which he calls the hub of all complement activation pathways – in both the brains of people with depression and animal models.

    The complement system also has the important job during development of removing bad connections between neurons, and there is good evidence the same thing happens in a developed brain in problems like major depressive disorder and Alzheimer’s, when losing these important connections, called synapses, is problematic rather than helpful.

    “You have to have a functioning complement system during development,” says Pillai. But he and his research colleagues have put together some of the first evidence that in depression, the complement also is active, causing inflammation and synaptic loss in the prefrontal cortex, an area of the brain important to working memory, personality and executive function. “Under chronic stress you are losing your synapses,” he says.

    C3 is known to play a key role in inflammation in the brain, and microglia, the resident immune cells in the brain, are known to use C3 during brain development to eliminate synapses.

    “We expect that chronic stress increases C3,” Pillai says as he continues to put the complex puzzle together.

    […]

    Their early findings indicate that when NF-kappa B, a transcription factor that regulates both innate and adaptive immunity and is implicated as a key regulator of inflammation in depression, is inhibited, stress-induced increases of C3 in a mouse’s prefrontal cortex are reduced. Depleting microglia appears to do essentially the same thing.

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  • Interleukin-6 (IL-6) may have a neuroprotective function, mouse study suggests. (2003) www.sciencedaily.com
    Brain Neurons IL-6

    From the article:

    One of the biggest challenges we face as a society is the eventual loss and degeneration of neurons from many causes, including many diseases – from Alzheimer’s disease to multiple sclerosis to Parkinson’s disease – and other sorts of injury.

    […]

    To function in a cell, IL-6 has to bind in a specific place – called a “receptor site” – in a specific way. Dr. Rodriguez and colleagues were intrigued that IL-6 uses the same receptor site used by compounds whose job is to promote neuronal survival. “To me, that was pretty wild,” Dr. Rodriguez says. “So I hypothesized that maybe this IL-6 is also playing a role in protecting neurons.”

    Testing this idea required extensive genetic work to produce different mouse groups that varied in their ability to produce IL-6. All were infected with a virus that causes a degenerative nerve disease. Animals with the IL-6 gene got mildly sick, but did not die. Mice lacking the IL-6 gene got severely sick and started dying. Why?

    To find a cause of death, the Mayo Clinic team analyzed the animals' tissues. Their findings: neurons in the spinal cords of mice lacking IL-6 were degenerating dramatically. This evidence supported their hypothesis of a neuron-protection role for IL-6. It also led them to their next question: Where is IL-6 made?

    An analysis of the brains of healthy mice possessing the IL-6 gene surprised them. “You look for IL-6 in the brain of a normal, healthy animal, and there is no IL-6 in a normal healthy animal!” Dr. Rodriguez says. “So then we infected the animals with the virus. Now when we looked for IL-6, guess what? It was everywhere.”

    Specifically, IL-6 was found in astrocytes.

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  • Low levels of interleukin-6 (IL-6) in the prefrontal cortex enhanced reversal learning in rats. (2014) www.sciencedaily.com
    Brain IL-6

    Cytokine signaling in the brain promotes cognitive flexibility.

    Cytokines are small signaling proteins that play essential roles in the body’s inflammatory process. They are produced primarily by immune cells, but they are also produced at basal levels in the brain, where they participate in memory and learning. Findings from a 2014 study suggest that cytokine signaling in the brain is necessary for reversal learning.

    Reversal learning is a form of cognitive flexibility. It allows an organism to determine that a reward for a particular activity has changed and then adjust its behavior accordingly. Reversal learning enables an organism to disengage from ongoing behavior, a quality that is related to impulsive or compulsive actions. Evidence suggests that reversal learning is impaired in neuropsychiatric disorders such as depression, schizophrenia, and obsessive-compulsive disorder.

    The researchers conducted a three-part experiment. First, they blocked the production of interleukin-6 (IL-6), a type of cytokine, in the brains of rats. They subjected one-half of the rats to cold stress (which has been shown to impair reversal learning), and the other half was left in a non-stressful environment. Then they tested both the stressed and non-stressed animals' reversal learning capacities. Surprisingly, they found that blocking IL-6 impaired reversal learning in both groups of animals, suggesting that basal IL-6 activity in the brain (in the absence of stress or inflammation) may aid learning.

    In their second experiment, the researchers determined that IL-6 is produced in the orbitofrontal cortex, a region of the brain responsible for decision-making and learning. They also determined that the mechanism by which IL-6 facilitates reversal learning was a signaling pathway called JAK/STAT, which is involved in multiple physiological processes.

    Finally, they restored IL-6 levels in the orbitofrontal cortex region of the animals' brains. They subjected them to cold stress again and re-tested their reversal learning capacities. They found that restoring IL-6 to the animals' brains attenuated the stress-induced reversal learning losses.

    These findings suggest that a basal level of the cytokine IL-6 is essential for reversal learning in rats. The researchers posited that although IL-6 is typically a pro-inflammatory cytokine, it may exert differential effects under different conditions. For example, it may promote learning deficits under inflammatory conditions, but facilitate learning under basal (non-stressed, non-inflammatory) conditions.

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  • Children who lack sleep may experience detrimental impact on brain and cognitive development that persists over time www.eurekalert.org
    Brain Sleep

    Children who don’t get enough sleep have altered brain structure and impaired brain function.

    Sleep is essential for normal brain development in children. The American Academy of Pediatrics recommends that children between the ages of six and 12 years sleep nine to 12 hours every night for optimal health, but many children do not meet these recommendations. Findings from a recent study suggest that children who don’t get enough sleep have altered brain structure and impaired brain function.

    The investigators analyzed structural magnetic resonance imaging data and medical records for more than 8,300 children between the ages of nine and ten years who were enrolled in the Adolescent Brain Cognitive Development (ABCD) Study. They also assessed the children’s cognitive performance and mental health status. The parents of the children in the study provided information about their child’s nightly sleep duration. Assessments were repeated when the children reached the ages of 11 to 12 years.

    The study revealed that brain volumes in areas responsible for attention, memory, and inhibition were lower in sleep-deprived children than in those who received adequate sleep. In addition, children who had shorter sleep duration were more likely to experience depression and anxiety and exhibit impulsive behavior and poor cognitive performance. The association between poor sleep and depression persisted at the two-year follow-up.

    These findings underscore the importance of adequate sleep for proper brain function, especially in the developing brain. Learn more about the importance of sleep in this episode featuring Dr. Matthew Walker.

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  • New study explores infection effect on fetal brain development medicalxpress.com
    Brain Immune System Development

    Maternal infection during pregnancy influences fetal neurodevelopment.

    Maternal immune activation due to infection, allergies, or other exposures during pregnancy switches on the activity of a wide array of inflammatory pathways and proinflammatory molecules. These molecules can cross the blood-brain barrier and the placenta, potentially disrupting fetal neurodevelopment and impairing sensory processing abilities later in life. These impairments are often manifested in neuropsychiatric disorders such as autism or schizophrenia. Findings from a recent study suggest that interleukin-15 modulates the effects of a simulated viral infection during pregnancy.

    Interleukin 15, a cytokine that is found primarily in immune cells, plays important roles in regulation of the antiviral immune response. IL-15 also participates in the development of natural killer cells, a type of immune cell that is present in large numbers in the uterus during early pregnancy and participates in placental development.

    The study investigators injected pregnant normal mice and mice that lacked IL-15 with polyinosinic:polycytidylic (poly I:C), a chemical used in the laboratory setting to simulate a viral infection. Poly I:C interacts with toll-like receptors to elicit an immune response. Other normal and IL-15-deficient mice received saline injections. The investigators tested the animals' offspring in adolescence and adulthood to identify behavioral problems and auditory hypersensitivity. They collected brain tissue samples from a subset of the offspring for examination.

    They found that offspring of IL-15-deficient mice that experienced immune activation during pregnancy were more likely to exhibit behavioral problems and auditory hypersensitivity, suggesting that IL-15 plays roles in brain development. They also noted that exposure to poly I:C and IL-15 deficiency independently altered behavioral manifestations in the mice. However, IL-15 deficiency influenced some of the effects of poly I:C exposure.

    These findings suggest that IL-15 modulates the effects of maternal immune activation during pregnancy, with potential long-lasting effects on offspring behavior. They also underscore the importance of appropriate vaccination before and during pregnancy to minimized immune activation and its potential harms.

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  • With amino acid diet, mice improve after brain injury www.sciencedaily.com
    Brain Diet

    Branched chain amino acids ameliorate cognitive losses associated with brain injury.

    Approximately 1.5 million people living in the United States experience a traumatic brain injury (TBI) – a disruption in normal brain function caused by an external mechanical force – each year. TBI causes both acute and chronic effects, including cognitive dysfunction. Findings from a 2009 study suggest that a branched chain amino acid-rich supplement ameliorates TBI-associated cognitive dysfunction.

    The branched chain amino acids, which include leucine, isoleucine, and valine, play important roles in muscle protein synthesis. However, they also influence brain health because they contribute nitrogen molecules essential for neurotransmitter synthesis (particularly glutamate and gaba) and modulate brain neurochemistry.

    The investigators measured branched chain amino acid concentrations in the brains of mice that had experienced a brain injury. Then they provided branched chain amino acids in the drinking water of brain-injured and non-injured mice for five days, commencing on the second day post-injury. Finally, they subjected both groups of mice to cognitive performance tests.

    They found that brain concentrations of branched chain amino acids were markedly lower in the brain-injured mice, resulting in decreased function in the hippocampus, an area of the brain involved in learning. However, brain-injured mice that received the amino acids exhibited higher amino acid concentrations in their brains and better performance on cognitive tests.

    These findings suggest that branched chain amino acids restore aspects of brain neurochemistry and ameliorate cognitive losses after TBI. Some bioactive compounds in plants may be beneficial in managing the symptoms of TBI, including sulforaphane, a compound derived from broccoli, which increases brain glutathione concentrations. Learn more in this clip featuring Dr. Rhonda Patrick.

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  • Using a HEPA filter during pregnancy increased child full-scale IQ by 2.8 points. medicalxpress.com
    Brain Pregnancy Development Pollution

    Background: Developmental exposure to air pollution is associated with diminished cognitive abilities in observational studies, but no randomized controlled trial has examined the effect of reducing air pollution on cognition in children.

    Objectives: We sought to quantify the impact of reducing exposure to particulate matter (PM) during pregnancy on children’s cognitive performance at 4 y of age.

    Methods: In this single-blind, parallel-group, randomized controlled trial in Ulaanbaatar, Mongolia, we randomly assigned 540 nonsmoking pregnant women (268 intervention and 272 control) to receive 1–2 portable high-efficiency particulate air (HEPA) filter air cleaners or no air cleaners. The air cleaners were used from a median of 11 wk gestation until the end of pregnancy. The primary outcome was full-scale intelligence quotient (FSIQ) assessed using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) when children were a median of 48 months old. We imputed missing outcome data using multiple imputation with chained equations, and our primary analysis was by intention to treat.

    Results: After excluding known miscarriages, stillbirths, neonatal deaths, and medical conditions that impeded cognitive testing and imputation, 475 (233 control and 242 intervention) children were included in our analyses. In an unadjusted analysis, the mean FSIQ of children who were randomly assigned to the intervention group was 2.5 points [95% confidence interval (CI): −0.4, 5.4 points] higher than that of children in the control group. After adjustment to account for an imbalance in preterm birth between groups, the effect estimate increased to 2.8 points (95% CI: −0.1, 5.7).

    Conclusions: Reducing PM air pollution during pregnancy may improve cognitive performance in childhood.

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  • The microbiome of people with Alzheimer's disease may mediate disease risk. content.iospress.com
    Brain Alzheimer's Microbiome

    Alzheimer’s disease, the most common cause of dementia, has been the subject of a large body of research in recent decades. However, the number of effective therapies for the disease is small, demonstrating the need for additional research into the mechanisms of dementia. Findings from a group of scientists researching the gut microbiota suggest the microbiota-gut-brain axis may contribute to Alzheimer’s pathology.

    The microbiota-gut-brain axis is a recently developed way to understand the relationship between the behavior of microbes in the gut and behaviors generated by the brain. This bidirectional highway of information delivers commands from the brain to the gut using nervous and endocrine signals and sends information from bacteria in the gut to the brain using nervous, circulatory, and immune pathways. Previous research has identified alterations in the composition and function of the gut microbiota in people with neurodegenerative diseases such as Parkinson’s disease and amyotrophic lateral sclerosis; however, the relationship between the microbiota and brain in people with Alzheimer’s disease requires additional research.

    The authors recruited 43 participants who had Alzheimer’s disease and 43 healthy participants who were matched with age and sex. Participants completed questionnaires about their mental health and cognitive function and provided a stool sample, which the researchers used to sequence the bacterial DNA in each participants' gut microbiome. Finally, the researchers selected twelve participants to receive a positron emission tomography (PET) scan to measure amyloid-beta deposition in the brain, which is the clinically standard way to diagnose Alzheimer’s disease.

    The microbiome of participants with Alzheimer’s disease differed from those without Alzheimer’s disease at the phylum, order, and family levels (i.e., scientific categories used to organize microbes into groups using their genes), with higher levels of phyla Bacteroidetes and lower levels of the phyla Actinobacteria and Verrucomicrobia and family Ruminococcaceae. Altered levels of these bacteria may be related to diet, as previous research has shown that some members of the Ruminococcaceae produce harmful compounds from bile acids released by the liver in response to dietary fat. Also, Akkermansia muciniphila, a member of the Verrucomicrobia has been shown to produce beneficial products from dietary fibers, but may increase inflammation and attack the gut barrier in diseases such as ulcerative colitis.

    In this cross-sectional study, the authors found important differences between the microbiomes of participants with and without Alzheimer’s disease. The authors did not measure microbial metabolites in this study; however, the authors suggest these compounds are a key mechanisms of these associations.

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  • Low levels of vitamin D were associated with lower brain volumes and an increased risk of dementia and stroke, genetic analyses suggest causal effect unisa.edu.au
    Vitamin D Brain Aging Dementia

    Vitamin D deficiency is associated with the development of dementia.

    Vitamin D is a fat-soluble vitamin that plays critical roles in many physiological processes, such as blood pressure regulation, immune function, and cell growth. Poor vitamin D status is implicated in the pathogenesis of many acute and chronic diseases, including rickets, osteoporosis, multiple sclerosis, cancer, and COVID-19. Evidence from a recent study suggests that vitamin D deficiency is associated with the development of dementia.

    Health experts disagree on the terminology and cutoffs used to determine vitamin D status. The Institute of Medicine (IOM) has determined that serum vitamin D concentrations less than 30 nmol/L (less than 12 ng/mL) place people “at risk for vitamin D deficiency”; those ranging from 30 to 50 nmol/L (12 to 20 ng/mL) place some populations “at risk for inadequacy”; and those of 50 nmol/L (20 ng/mL) or greater are considered “sufficient.” However, the Endocrine Society has suggested that vitamin D concentrations ranging from 52.5 to 72.5 nmol/L (21 to 29 ng/mL) define “insufficiency,” and those less than 20 ng/mL (50 nmol/L) define “deficiency.”

    The study involved more than 425,000 healthy adults (ages 60 to 73 years) enrolled in the UK Biobank study who had undergone magnetic resonance imaging (MRI) studies to assess brain volumes and whose vitamin D status was known. The investigators categorized the participants according to their vitamin D status based on literature and Institute of Medicine and Endocrine Society Clinical Practice guidelines. They collected information about the participants' demographics, lifestyles, and various health factors and tracked the participants for approximately 10 years. Then they used Mendelian randomization, a research method that provides evidence of links between modifiable risk factors and disease based on genetic variants within a population, to identify causal links between vitamin D status and brain health, dementia, and stroke.

    They found that lower total brain volume tended to reflect a higher rate of dementia and stroke. The participants with low vitamin D concentrations were more likely to have lower brain volumes, an increased risk for dementia and stroke, and more white matter hyperintensities (brain lesions that indicate small vessel disease) than those with high concentrations. Vitamin D conferred the greatest protection against dementia at concentrations of 50 to 74.9 nmol/L. The Mendelian randomization revealed that participants whose concentrations were less than 25 nmol/L were 54 percent more likely to develop dementia.

    These findings suggest that low vitamin D increases a person’s risk for dementia. The authors suggested that as many as 17 percent of dementia cases might be prevented by achieving vitamin D sufficiency (50 nmol/L). Learn more about the beneficial health effects of vitamin D in our overview article.

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  • Air pollution may attenuate the beneficial association vigorous physical activity with low white-matter hyperintensity volume n.neurology.org
    Exercise Brain Aging Pollution Aerobic Neurodegeneration Small Vessel Disease

    Air pollution negates some of the beneficial effects of vigorous-intensity exercise.

    Components present in air pollution – a mixture of toxic chemicals, gases, and particulate matter – can cross biological barriers, including the blood-brain barrier. Exposure to air pollutants is associated with poor health outcomes and an increased risk for both acute and chronic diseases. A recent study suggests that air pollution negates some, but not all, of the beneficial effects of vigorous-intensity aerobic exercise.

    Robust evidence demonstrates that vigorous-intensity aerobic exercise (defined as activity that achieves a heart rate that is 70 to 80 percent of one’s maximum) benefits brain health. For example, vigorous-intensity aerobic exercise appears to activate the endocannabinoid system to promote motor sequence memory and learning. Other evidence suggests it improves mood.

    The study involved 8,600 adult participants enrolled in the UK Biobank study. Participants wore wrist accelerometers to track their physical activity. They also underwent magnetic resonance imaging (MRI) to assess their structural brain volumes and identify the presence of white matter hyperintensities – areas of the brain that show up as distinct white areas on MRIs and indicate cerebral small blood vessel disease. The investigators estimated the participants' exposure to air pollution based on where the participants lived.

    The investigators found that the more physically active participants were, the less their brains showed evidence of shrinkage, and the fewer white matter hyperintensities they exhibited – an effect roughly equivalent to being three years younger. Participants who were exposed to more air pollution exhibited greater brain shrinkage than those with less exposure – about the amount observed in one year of normal aging. However, participants who exercised the most and had the most exposure to air pollution demonstrated no evidence of more brain shrinkage, but they exhibited more white matter hyperintensities, especially if they engaged in vigorous-intensity aerobic exercise.

    These findings support earlier studies that demonstrate the beneficial health effects of vigorous-intensity exercise on the brain but suggest that exercising in areas where air pollution is high negates some of these benefits. The authors recommended that because most air pollution comes from vehicle exhaust, people should exercise in areas far from heavily trafficked roads.

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  • Periodontal Condition Is Correlated with Deep and Subcortical White Matter Hyperintensity Lesions in Japanese Adults www.mdpi.com
    Brain Aging Inflammation Small Vessel Disease

    Gum disease may increase the risk of white matter hyperintensities, a type of brain lesion.

    White matter hyperintensities are brain lesions that appear as intense white spots on magnetic resonance imaging (MRI) scans. They are often indicators of cerebral small blood vessel disease and are considered a risk factor for dementia. High blood pressure is the primary contributor to white matter hyperintensity formation, but other factors likely play roles, as well. Findings from a 2020 study suggest that periodontitis is associated with white matter hyperintensities.

    Periodontitis is a chronic inflammatory condition of the gums, characterized by red, tender, swollen, or bleeding gums. It is typically caused by poor oral hygiene and is more common with age, manifesting in more than two-thirds of adults over the age of 65 years. Periodontitis is diagnosed using a periodontal probe, which is used to assess the depth of pockets in the gum. In a healthy mouth, a pocket can be anywhere from 1 to 3 millimeters deep. Deeper pockets are indicators of gum inflammation and disease.

    The study involved more than 400 adults (average age, 54 years) who underwent a routine dental exam that included pocket depth probing. The investigators performed MRI scans on the participants to identify the presence of white matter hyperintensities, which were classified according to their size, number, and severity. They gathered information about the participants' general health and lifestyles and measured their C-reactive protein (CRP, a biomarker of inflammation). They found that nearly half of the participants had white matter hyperintensities. Those who did were nearly three times more likely to be at least 65 years old, more than twice as likely to have elevated systolic blood pressure, and nearly twice as likely to have deeper pocket depth (6 millimeters or more). Having white matter hyperintensities was not associated with the participants' CRP levels.

    These findings suggest that older age, elevated blood pressure, and periodontitis are associated with an increased risk of developing white matter hyperintensities, but inflammation is not a driver of this association. Evidence indicates that white matter hyperintensities are predictive of the amount and degree of leakage of the blood-brain barrier leakage. Learn more in our overview article.

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  • Systemic immune-inflammation index is associated with white matter hyperintensity volume: among cSVD pathologies, WMH may be more inflammation-related www.nature.com
    Brain Aging Inflammation Small Vessel Disease

    From the article:

    Systemic immune-inflammation index (SII) is a novel inflammatory marker based on the composition ratio of blood cell counts. In this study, we evaluated the association between the SII and cerebral small vessel disease (cSVD) in health check-up participants. We evaluated participants from our health check-up registry between 2006 and 2013. The SII was calculated using the following formula: SII = (platelet count × neutrophil count)/lymphocyte count. cSVD was assessed by considering white matter hyperintensity (WMH) volume, lacunes, and cerebral microbleeds (CMBs). A total of 3187 participants were assessed. In multivariable linear regression analysis, the SII was significantly related to WMH volume [β = 0.120, 95% confidence interval (CI) 0.050–0.189]. However, lacunes and CMBs showed no statistical significance with the SII. In the subgroup analysis by age, the SII was significantly associated with WMH volume only in participants aged ≥ 60 years (β = 0.225, 95% CI 0.068–0.381). In conclusion, a high SII was associated with cSVD. Since this association was more pronounced in WMH than in lacunes or CMBs, WMH might be closer to the inflammation-related pathological mechanisms.

    Age-related changes in systemic inflammation:

    Interestingly, the close association between the SII and WMH volume in our study was significant only in older participants aged ≥ 60 years. This might be related to the aging-related changes in the homeostatic maintenance of our body’s inflammation and immunity (e.g., inflammaging, immunosenescence, and homeostenosis)

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  • Antidepressant effects of omega-3 EPA may occur in the brain even though brain content is low (it is present in microglia and involved in signaling) www.sciencedirect.com
    Brain Omega-3 Inflammation Depression Immune System Behavior

    From the article:

    It was previously assumed that because EPA is extremely low in the brain it did not cross the blood-brain barrier and any therapeutic effects it exerted would be via the periphery. However, more recent studies have established that EPA does enter the brain, but is rapidly metabolised following entry. While EPA does not accumulate within the brain, it is present in microglia and homeostatic mechanisms may regulate its esterification to phospholipids that serve important roles in cell signaling. Furthermore, a variety of signaling molecules from EPA have been described in the periphery and they have the potential to exert effects within the brain. If EPA is confirmed to be therapeutic in major depression as a result of adequately powered randomized clinical trials, future research on brain EPA metabolism could lead to the discovery of novel targets for treating or preventing major depression.

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  • Lost memory in menopause explained: Estrogen provides a protective role in mitigating effects of visceral fat on brain structural networks and memory jamanetwork.com
    Brain Alzheimer's Obesity Memory Estrogen Visceral Fat

    Estrogen mitigates the association between visceral fat on cognitive decline.

    Estradiol, a form of estrogen, is the primary female sex hormone. It participates in menstrual cycle regulation and drives the development of female secondary sex characteristics, such as breasts, a wider pelvis, and gynoid fat – fat that forms around the hips, thighs, and breasts. Evidence suggests that estradiol exerts both cardioprotective and neuroprotective effects. Findings from a 2020 study demonstrate that estradiol mitigates the association between visceral fat on cognitive decline.

    Cognitive decline is characterized by altered brain structural networks and accelerated degeneration with aging. Scientists don’t fully understand the biological mechanisms that drive cognitive decline, but evidence indicates that visceral fat – a type of fat that accumulates in the abdominal cavity – may play a role. Visceral fat is metabolically active and is associated with increased markers of inflammation and oxidative stress, and decreased levels of anti-inflammatory proteins, such as adiponectin

    The cross-sectional study involved 974 cognitively healthy females and males (average age, ~50 years). Using magnetic resonance imaging, the investigators measured the participants' gray matter volume, cerebral cortex area, intracranial blood vessels, and visceral fat. They also measured estradiol concentrations in a subset (390) of the females. All the participants completed neuropsychological testing to assess memory performance.

    The investigators found that visceral fat exacerbated the harmful effects of aging on the brain’s structural networks in both females and males. However, estradiol mitigated some of these effects in the females, but not the males. Females between the ages of 35 and 55 years (the period surrounding menopause) who had lower estradiol concentrations were more likely to exhibit greater structural network impairments and worse memory performance.

    These findings suggest that estradiol mitigates some of the harmful effects of visceral fat on the brain’s structural networks and cognitive health. Interestingly, the fasting-mimicking diet preferentially depletes visceral fat. Learn more in this clip featuring Dr. Valter Longo.

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  • Nerve Stimulation Promotes Resolution of Inflammation. neurosciencenews.com
    Brain Inflammation

    Vagus nerve stimulation promotes the resolution of inflammation.

    Inflammation is a necessary component of the body’s immune response. But unresolved inflammation is harmful to the body and can promote a wide range of chronic diseases. Findings from a recent study suggest that stimulation of the vagus nerve promotes the resolution of inflammation.

    The vagus nerve is the tenth cranial nerve. Its name, “vagus,” comes from the Latin term for “wandering” – a characteristic of the nerve, which arises in the brain and extends to organs in the neck, chest, and abdomen. The vagus nerve is the primary component of the parasympathetic nervous system, which regulates many crucial biological processes, including mood control, digestion, heart rate, and immune response. Evidence from animal studies suggests that stimulating the vagal nerve reduces the release of proinflammatory cytokines that drive acute inflammation.

    Using a mild electrical current, the investigators stimulated the vagus nerve of mice. Then, after inducing an inflammatory response in the animals' abdomens, they measured neutrophils (immune cells) and anti-inflammatory markers in fluid taken from the abdominal region.

    They found that mice that received the vagus nerve stimulation had higher levels of specialized pro-resolving mediators, or SPMs, in their abdominal fluid. SPMs are byproducts of omega-3 fatty acid metabolism that play critical roles in resolving inflammation. The stimulated mice also had fewer neutrophils in their abdominal fluid, an indication that neutrophil infiltration had ceased, a key process in the resolution of inflammation.

    These findings suggest that vagus nerve stimulation promotes the resolution of inflammation via the promotion of SPM biosynthesis. Learn more about SPMs and omega-3 metabolism in this episode featuring Dr. Bill Harris.

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  • Researchers discover fundamental roles of glucosamine in brain www.sciencedaily.com
    Brain

    Glucosamine plays important roles in brain function.

    Glucosamine is a type of sugar found in the muscles, cartilage, and other soft tissues of the body. It is commonly marketed as a dietary supplement used for joint pain and stiffness. Evidence from a 2021 study suggests that glucosamine is prevalent in brain glycogen, where it plays important roles in glycosylation.

    Glycogen is a multi-branched polysaccharide that serves as the stored form of glucose in the human body. Most of the body’s glycogen stores are found in the muscles and liver, but some glycogen is found in the brain, primarily in the astrocytes, a type of cell involved in neurogenesis and blood-brain barrier maintenance. In diseases in which glycogen storage is impaired, glycogen-like cellular aggregates called polyglucosan bodies can form in the brain, altering brain function and driving dementia.

    Glycosylation is a biochemical process in which glucose is added to an amino acid. It plays important roles in determining the structure, function, and stability of proteins. Glycosylation influences neurological function, and disturbed glycosylation is implicated in the pathogenesis of many neurological disorders, including cognitive decline.

    The investigators conducted a multi-part study. First, they determined the overall composition of the sugars in the glycogen of liver, muscle, and brain tissue of mice using gas chromatography and mass spectrometry. They found that liver glycogen contained just 0.1 percent glucosamine, and muscle glycogen contained approximately 1 percent of the sugar. However, brain glycogen contained 25 percent glucosamine.

    Then, using a special form of mass spectrometry (called “MALDI TW IMS”), they quantified and tracked the movement of the glucosamine in the brains of healthy mice and mice that had glycogen storage diseases. They found that the mice with the glycogen storage diseases had impaired glucosamine movement, abundant polyglucosan bodies, and evidence of impaired cell metabolism and glycosylation.

    These findings suggest that glucosamine in brain glycogen is essential for brain health. They also may help identify strategies for treating glycosylation disorders, which cause severe neurological symptoms, including dementia.

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  • Keep exercising: New study finds it's good for your brain's gray matter www.sciencedaily.com
    Exercise Brain

    Cardiorespiratory fitness helps prevent age-related brain volume losses.

    The brain loses about 5 percent of its volume every decade after the age of 40 years, likely due to the death of neurons in the gray matter. These losses contribute to age-related cognitive decline and loss of neuroplasticity, the brain’s ability to change and adapt to new exposures. Findings from a 2020 study suggest that having greater cardiorespiratory fitness helps prevent age-related brain volume losses.

    Cardiorespiratory fitness is a measure of the body’s aerobic capacity – the ability to deliver oxygen to skeletal muscles – during sustained physical activity. Poor cardiorespiratory fitness, along with dyslipidemia, family history, hypertension, age, cigarette smoking, diabetes mellitus, obesity, and physical inactivity, increases a person’s risk for cardiovascular disease and death. The most accurate way to assess cardiorespiratory fitness involves measuring maximal oxygen uptake, often referred to as VO2 max, during a graded exercise test in a laboratory, clinical, or research setting.

    The study involved more than 2,000 healthy adults (average age, 52 years) who were enrolled in a larger, ongoing study. The investigators measured the participants' cardiorespiratory fitness, assessed via VO2 max while riding on an exercise bike. They collected the participants' demographic data, and they measured their brain volumes via magnetic resonance imaging scans.

    They found that participants with greater cardiorespiratory fitness tended to have greater gray matter and total brain volumes. They also had more clusters of gray and white matter tissue in brain areas responsible for cognitive function rather than movement. These findings held true even when taking the participants' ages, education levels, smoking status, blood pressure, and body weights into consideration.

    These findings suggest that having greater cardiorespiratory fitness ameliorates some of the brain volume losses associated with aging and underscore the importance of exercising throughout the lifespan. Learn more about the health benefits of exercise in our overview article.

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  • High and low exercise intensity found to influence brain function differently www.sciencedaily.com
    Exercise Brain

    Aerobic exercise influences many aspects of human health, including brain health. For example, exercise promotes the release of brain-derived neurotrophic factor, better known as BDNF, a cell-signaling protein that influences the formation, growth, survival, and development of neurons. Findings from a 2020 study suggest that exercise intensity determines which parts of the brain are affected during a workout.

    Exercise intensity is defined as how hard the body works during exercise. During low-intensity aerobic exercise, a person’s heart rate is typically maintained at a steady pace of about 50 percent of its maximum ability, and workouts last for at least 30 minutes. During high-intensity aerobic exercise, a person’s heart rate is typically 75 percent of its maximum ability or higher. For example, high-intensity interval training, often referred to as HIIT, is a popular form of high-intensity exercise involving short bursts of intense aerobic exercise interspersed with periods of rest or lower-intensity exercise. During a typical HIIT session, exercisers typically achieve 80 to 100 percent of their VO2max (a measure of respiratory function) or maximum heart rate. Most HIIT workouts are brief, lasting just 15 to 30 minutes.

    The study involved 25 healthy male athletes who engaged in both low-intensity and high-intensity aerobic exercise sessions on a treadmill. The sessions lasted for approximately 30 minutes and were separated by at least two days. The participants underwent a battery of tests to determine their mental state, cognitive performance, and attention. Before and after the exercise sessions, they underwent resting-state functional magnetic resonance imaging (rs-fMRI), a technique that characterizes the functional connectivity of neuronal networks when the brain is at rest.

    The investigators found that the participants' moods improved after both exercise intensities. However, the rs-fMRIs revealed that the different intensities affected different parts of their brains. The low-intensity exercise turned on the activity of brain networks involved in cognitive function and attention processing. On the other hand, the high-intensity exercise turned on networks involved in mood and emotions and turned off networks involved in motor function.

    These findings suggest that differing exercise intensities affect different parts of the brain during exercise and underscore the importance of varying workout programs. Learn more about the effects of aerobic exercise on health in our overview article.

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  • Heightened dream recall ability linked to increased creativity and functional brain connectivity www.psypost.org
    Brain Sleep

    People who frequently recall their dreams tend to be more creative.

    Dreams are a state of consciousness that occurs during sleep. Typically characterized by sensory, cognitive, and emotional experiences, dreams share many similarities with hallucinations. Scientists formerly believed that dreams only occurred during the rapid eye movement, or REM, stage of sleep, but recent research indicates that they can occur at any time during sleep. Findings from a recent study suggest that people who frequently recall their dreams tend to be more creative and exhibit increased functional connectivity in the brain’s default mode network.

    The default mode network is a collection of interconnected neural structures that demonstrate low activity when a person is engaged in a particular task but high activity when not. It also demonstrates activity when a person tries to remember past events or imagine future events. Although some evidence suggests that the default mode network is involved in self-focused, ruminative thought, other evidence suggests it is involved in creativity and spontaneous thought processes.

    The study involved 55 healthy adults (19 to 29 years old) who had normal sleep patterns. Roughly half of the participants reported that they frequently recalled their dreams, recalling about six dreams per week, and the other half reported that they rarely recalled their dreams, recalling fewer than one dream per week. All participants underwent functional magnetic resonance imaging (fMRI) scans while sleeping. Before their scans, they answered questions about their personality, anxiety levels, cognitive ability, and sleep quality. They also completed a battery of tests to gauge memory and creativity.

    They found that both groups of participants had similar personalities, anxiety levels, sleep quality, and cognitive abilities. But participants who frequently recalled their dreams performed better on creativity tests than those who rarely recalled their dreams, suggesting they had greater creative skills. The fMRIs revealed that frequent recallers also exhibited enhanced functional connectivity within the default mode network of their brains than infrequent recallers.

    These findings suggest that high recall of dreams is associated with greater creativity and functional connectivity in the default mode network of the brain, and this connectivity promotes creative thinking during both wakefulness and sleep. Learn more about the roles of dreams in creativity in this clip featuring Dr. Matthew Walker.

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  • Visceral fat and total brain volume inversely linked independent of BMI and insulin resistance: a relationship between dementia and obesity www.sciencedaily.com
    Brain Obesity Insulin Resistance Metabolic Syndrome Visceral Fat

    From the article:

    Preliminary findings suggest a relationship between obesity and dementia that could lead to promising prevention strategies in the future.

    […]

    “Our results confirm the inverse association of increasing BMI with lower brain volumes in older adults and with younger, middle-aged adults and extends the findings to a much larger study sample,” […] “More importantly our data suggests a stronger connection between central obesity, particularly the visceral fat component of abdominal obesity, and risk of dementia and Alzheimer’s disease,” Dr. Seshadri added. The research showed the association between visceral adipose tissue and total brain volume was most robust and was also independent of BMI and insulin resistance."

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  • Peripheral amyloid-beta produced in the liver in type 2 diabetes may be a crucial link to Alzheimer’s disease www.sciencedaily.com
    Brain Alzheimer's Diabetes Neurodegeneration

    Amyloid-beta produced in peripheral tissues provides a link between diabetes and Alzheimer’s disease risk.

    Type 2 diabetes, a metabolic disorder characterized by glucose intolerance and insulin resistance, poses a significant public health concern, affecting roughly 470 million people worldwide. Having type 2 diabetes greatly increases a person’s risk of developing Alzheimer’s disease, but scientists don’t fully understand the mechanisms that drive the increased risk. Findings from a recent study suggest that amyloid-beta produced in tissues outside the brain provides the link between type 2 diabetes and Alzheimer’s disease.

    Amyloid-beta, a toxic peptide produced in the brain, clumps together and forms plaques with age. Its accumulation is a pathological hallmark of Alzheimer’s disease. However, amyloid-beta is produced in peripheral tissues, as well, including those that are sensitive to glucose or insulin, such as the pancreas, adipose tissues, skeletal muscles, and liver. Scientists don’t fully understand the roles peripheral amyloid-beta plays in human health.

    The investigators conducted a three-part experiment in mice, live mouse tissues, and cell cultures. First, they injected mice with glucose after they had fasted for 16 hours to examine the effects of glucose and insulin on blood amyloid-beta levels. They found that the mice experienced a transient increase in blood levels of glucose, insulin, and amyloid-beta. Then they injected amyloid-beta and glucose into mice that can’t produce the protein and found that amyloid-beta suppressed the animals’ insulin response.

    Next, they applied glucose and insulin to live tissues from the pancreas, adipose tissue, skeletal muscle, liver, and kidneys of mice. They found that glucose stimulated the release of amyloid-beta from the pancreas, whereas insulin stimulated its release from adipose tissue, skeletal muscle, and liver tissue. However, when the scientists added glucose along with amyloid-beta to the pancreatic tissue, insulin release was suppressed.

    Finally, they used antibodies that target the amyloid-beta protein to determine where the protein was produced. They found that amyloid-beta was produced and stored in the beta cells of the pancreas and released into circulation when stimulated with glucose.

    These findings suggest that amyloid-beta protein produced in peripheral tissues modulates insulin secretion. They may further provide a mechanism linking type 2 diabetes to Alzheimer’s disease. The investigators posited that high blood glucose and insulin levels that occur in the setting of diabetes increase peripheral amyloid-beta production, altering the balance between brain and peripheral amyloid-beta levels and suppressing the protein’s efflux from the brain. Furthermore, high insulin levels in the brain may impair normal degradation of brain amyloid-beta, increasing the protein’s levels in the brain and driving its accumulation. Learn more about the role of amyloid-beta in Alzheimer’s disease in this clip featuring Dr. Dale Bredesen.

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  • Greater visceral and total body fat associated with vascular brain injury and impaired cognitive scores www.sciencedaily.com
    Brain Obesity Dementia Metabolic Syndrome Blood-Brain Barrier Small Vessel Disease Visceral Fat

    From the article:

    In the study, 9,166 participants were measured by bioelectrical impedance analysis to assess their total body fat.

    As well, 6,733 of the participants underwent magnetic resonance imaging (MRI) to measure abdominal fat packed around the organs known as visceral fat, and the MRI also assessed vascular brain injury – areas in the brain affected by reduced blood flow to the brain.

    […]

    Co-author Eric Smith, a neurologist, scientist and an associate professor of clinical neurosciences at the University of Calgary, said that “preserving cognitive function is one of the best ways to prevent dementia in old age. This study suggests that one of the ways that good nutrition and physical activity prevent dementia may be by maintaining healthy weight and body fat percentage.”

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  • Brain insulin sensitivity determines fat distribution: insulin sensitivity in the hypothalamus form little visceral, but no influence on subcutaneous www.sciencedaily.com
    Exercise Brain Obesity Metabolic Syndrome Visceral Fat

    From the article:

    If the person’s brain responds sensitively to the hormone, a significant amount of weight can be lost, unhealthy visceral fat reduced, and the weight loss can be maintained over the long term. However, If the person’s brain responds only slightly or not at all to insulin, the person only loses some weight at the beginning of the intervention and then experiences weight regain. Over the long term, the visceral fat also increases.

    […]

    Since the insulin action in the hypothalamus is crucial for the regulation of peripheral energy metabolism, the researchers also investigated how insulin sensitivity in this area of the brain is related to the distribution of body fat. For this purpose, they examined a cross-sectional cohort of 112 participants. The analysis of the data showed that people with high insulin sensitivity in the hypothalamus form little visceral fat. However, insulin sensitivity has no influence on the mass of subcutaneous fat.

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  • Long-Chain Omega-3 Fatty Acids Improve Brain Function and Structure in Older Adults academic.oup.com
    Brain Omega-3

    Omega-3 fatty acids improve brain function and structure in older adults.

    Alzheimer’s disease is the most common disease of aging, affecting as many as 70 million people worldwide. The pathological processes that contribute to Alzheimer’s disease often precede diagnosis of the condition by several decades, underscoring the importance of identifying strategies that might forestall or even prevent the disease. Findings from a 2017 study suggest that omega-3 fatty acids improve brain function and structure in older adults.

    Omega-3 fatty acids are essential nutrients. Found in both plants and fatty fish, they influence cell membrane integrity, affect the function of membrane-bound cellular receptors, and participate in pathways involved in the biosynthesis of hormones that regulate blood clotting, arterial function, and inflammation. The fish-sourced omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both play important roles in brain health, but DHA in particular regulates transport across the blood-brain barrier, a critical aspect in maintaining the barrier’s integrity.

    The study involved 65 healthy adults between the ages of 50 and 75 years. The investigators randomly assigned participants to receive a supplement providing 2.2 grams of fish oil (1320 milligrams EPA + 880 milligrams DHA) or a placebo daily for 26 weeks. Before and after the intervention, participants underwent neuropsychological testing, structural magnetic resonance imaging (MRI) of the brain, body measurement, and blood tests for assessment of metabolic biomarkers (i.e., blood lipids, insulin, glucose, hemoglobin A1c), inflammatory markers, brain-derived neurotrophic factor (BDNF, a protein involved in learning and memory) and the Omega-3 Index, a measure of omega-3 fatty acid concentration in red blood cells.

    At the end of the intervention, Omega-3 Index concentrations were approximately 2 percent higher among participants who took the supplemental fish oil, compared to those who took the placebo. The supplemented participants performed better on tests of executive function and exhibited improved white matter microstructural integrity and increased gray matter volume in their brains. In addition, their BDNF increased, and their peripheral insulin decreased.

    These findings suggest that supplemental omega-3 fatty acids EPA and DHA increase the Omega-3 Index and improve multiple markers of brain health and cognitive function in older adults. Learn more about the Omega-3 Index in this episode featuring one of its creators, Dr. Bill Harris.

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  • Four pathologies of SVD associate with dementia: white matter hyperintensities, cerebral microbleeds, lacunar infarcts, enlarged perivascular spaces www.sciencedaily.com
    Brain Dementia Cardiovascular Blood-Brain Barrier Small Vessel Disease

    The four pathologies that were detectable by MRI included:

    From the article:

    The subjects were given cognitive tests and brain MRIs. The MRIs were examined for four main components of small vessel disease (SVD). These four components, which include evidence of microbleeds and minor strokes, then were added to create a total SVD score. The score ranges from zero points (no SVD) to 4 points (severe SVD).

    The study found that that 61 percent of the subjects had zero points on the total SVD score, 20 percent had 1 point, 12 percent had 2 points, 5 percent had 3 points and 2 percent had 4 points. The higher the SVD score, the greater the cognitive decline. Researchers also found that each individual component of SVD predicted cognitive decline as well as the total SVD score did.

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  • Small-vessel disease could provoke amyloid pathology while Alzheimer's-associated cerebral amyloid pathology may lead to auxiliary vascular damage www.sciencedaily.com
    Brain Alzheimer's Cardiovascular Blood-Brain Barrier Small Vessel Disease

    Cerebral small vessel disease is associated with amyloid-beta deposition in the brain, especially among APOE4 carriers.

    Small vessel disease is a collection of conditions characterized by damage to arterioles and capillaries, resulting in reduced or interrupted blood flow to the affected organ. These conditions typically affect organs that receive substantial blood flow, such as the brain, kidney, and retina, and are principal drivers of chronic diseases such as strokes, renal failure, dementia, and blindness. Findings from a 2014 study suggest that people who have small vessel disease in the brain exhibit greater deposition of amyloid-beta plaques, especially if they are carriers of the APOE4 gene.

    Amyloid-beta is a toxic 42-amino acid peptide that aggregates and forms plaques in the brain with age. Amyloid-beta deposition is associated with Alzheimer’s disease, a progressive neurodegenerative disease that can occur in middle or old age and is the most common cause of dementia.

    APOE is a protein involved in lipid transport. A variant in the APOE gene, called apolipoprotein E4 (APOE4), is the major genetic risk factor for Alzheimer’s disease. Having one APOE4 allele increases a person’s Alzheimer’s disease risk as much as threefold; carrying two APOE4 alleles increases risk as much as 15-fold.

    The cross-sectional study included more than 900 patients enrolled in the Amsterdam Dementia Cohort study who had been diagnosed as having Alzheimer’s disease, vascular dementia, or self-reported memory complaints. The investigators analyzed the patients' cerebrospinal fluid for the presence of amyloid-beta and other markers of Alzheimer’s disease and genotyped the patients to assess APOE status.

    They also performed magnetic resonance imaging (MRI) of the patients' brains to identify the presence of white matter hyperintensities and microbleeds. White matter hyperintensities, areas in the brain that appear as intense white spots on MRIs, are often indicators of cerebral small vessel disease and are considered a risk factor for dementia. Microbleeds are small, chronic hemorrhages that are indicative of cerebral amyloid angiopathy, a condition in which amyloid-beta accumulates on the walls of brain arteries.

    They found that patients with Alzheimer’s disease had lower levels of amyloid-beta in their cerebrospinal fluid, an effect that was more pronounced among APOE4 carriers. Patients with low amyloid-beta levels in their cerebrospinal fluid were more likely to have white matter hyperintensities and microbleeds, indicating a direct relationship between a pathological hallmark of Alzheimer’s disease and small vessel disease.

    These findings suggest that Alzheimer’s disease and small vessel disease are intrinsically linked, especially among APOE4 carriers. [Learn more about small vessel disease in our overview article.](Coming soon)

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  • Living in Areas With More Greenery May Boost Cognitive Function neurosciencenews.com
    Brain Pollution

    Residential greenspace exposure improves cognitive function.

    Spending time in nature is associated with a variety of beneficial effects on mental and physical health. For example, recent research demonstrated that spending time in the natural environment reduces ruminative thinking. Other research indicates that walking in forested areas improves immune function, likely due to beneficial bioactive compounds produced by trees and inhaled by walkers. Findings from a new study suggest that residential greenspace exposure improves cognitive function in middle-aged women.

    The investigation included more than 13,000 women enrolled in the Nurses' Health Study II, an ongoing study of health outcomes of female nurses living in the United States. The participants completed an online battery of cognitive tests that gauged psychomotor speed, attention, learning, and working memory. The investigators calculated the participants' exposure to greenspace based on satellite imagery of their residential address and evaluated the effects of possible mediators of cognitive function, such as air pollution exposure, depression, and physical activity.

    They found that even after considering the participants' ages at assessment, race, and socioeconomic status, women who had greater greenspace exposure scored higher on aspects of psychomotor speed and attention than women with less exposure. The difference in scores was roughly equivalent to one year of chronological aging. Greenspace exposure did not appear to affect learning or working memory. They also found that exposure to pollution was not a mitigating factor, but depression was, aligning with previous research.

    These findings suggest that residential greenspace exposure benefits cognitive performance in middle-aged women. They also underscore the importance of public health efforts to promote the incorporation of natural areas into urban planning.

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  • Children whose mothers used acetaminophen during pregnancy were more likely to have ADHD symptoms or hyperkinetic disorder at age 7 www.sciencedaily.com
    Brain Pregnancy Behavior ADHD Development Acetaminophen

    Acetaminophen use during pregnancy may impair fetal neurodevelopment.

    Acetaminophen, a drug used to treat pain and reduce fever, has a generally favorable safety profile and is considered safe for use during pregnancy. However, evidence from studies in rodents and humans suggests that acetaminophen exerts endocrine-disrupting properties, which could alter neurological development. Findings from a 2014 study suggest that children of women who took acetaminophen during pregnancy are more likely to develop attention-deficit/hyperactivity disorder (ADHD)-like behavioral problems or hyperkinetic disorders.

    ADHD is a neurobehavioral condition characterized by inattention and/or hyperactive or impulsive behavior that interferes with functioning, learning, or development. The condition affects more than 9 percent of children living in the United States. Hyperkinetic disorders are conditions characterized by abnormal involuntary movements, such as tremors or tics. The disorders affect 1 to 2 percent of people worldwide and are more common among males.

    The investigators drew on data from nearly 65,000 children and mothers enrolled in the Danish National Birth Cohort study. They collected information about the mothers' acetaminophen use during pregnancy via phone interviews and identified children with ADHD or hyperkinetic disorders via parental reports, medical records, and prescription records.

    They found that more than half of the women reported taking acetaminophen during their pregnancies. Children of the women who took the drug during pregnancy were 13 percent more likely to have ADHD-like behaviors at the age of 7 years; 29 percent more likely to take ADHD medications; and 37 percent more likely to be diagnosed with a hyperkinetic disorder at birth. These findings held true even after considering possible confounders, such as maternal inflammation, infection during pregnancy, the mother’s mental health problems, or others. The investigators noted longer prenatal exposure strengthened the associations between acetaminophen use and neurodevelopmental disorders.

    These findings suggest that acetaminophen use during pregnancy influences fetal brain development, potentially increasing the risk of ADHD or hyperkinetic disorders. The investigators posited that if their findings are indicative of causal associations, acetaminophen should no longer be considered safe for use during pregnancy. However, the American College of Obstetrics and Gynecology continues to support the use of acetaminophen during pregnancy.

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  • Acetominohen use during pregnancy linked to language delay in girls www.sciencedaily.com
    Brain Pregnancy Development Acetaminophen

    From the article:

    In the first study of its kind, researchers have found an elevated rate of language delay in girls at 30 months old born to mothers who used acetaminophen during pregnancy, but not in boys.

    […]

    Language delay was seen in 10 percent of all the children in the study, with greater delays in boys than girls overall. However, girls born to mothers with higher exposure – those who took acetaminophen more than six times in early pregnancy – were nearly six times more likely to have language delay than girls born to mothers who did not take acetaminophen. These results are consistent with studies reporting decreased IQ and increased communication problems in children born to mothers who used more acetaminophen during pregnancy.

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  • Anesthesia and Surgery Impair Blood–Brain Barrier and Cognitive Function www.frontiersin.org
    Brain Dementia Blood-Brain Barrier IL-6

    Surgery and anesthesia may contribute to cognitive impairment.

    Anesthesia, a medical treatment that involves the use of anesthetic drugs, is a widely accepted strategy for managing pain during surgery. Evidence suggests that mice that have undergone surgery that involved anesthetic treatment exhibited signs of postoperative cognitive impairment. Findings from a 2017 study suggest that surgery in combination with the anesthetic drug isoflurane induces blood-brain barrier dysfunction, contributing to cognitive impairment.

    Anesthetic drugs can be administered orally, intravenously, or via inhalation. Isoflurane is one of the most common inhaled anesthetics used in humans. Scientists don’t fully understand the mechanisms by which inhaled anesthetics work, but they appear to affect the central nervous system by depressing neurotransmission pathways. Previous research has shown that isoflurane increases several markers of inflammation.

    The investigators wanted to determine whether the effects of surgery and anesthesia on blood-brain barrier permeability and cognitive function were related to age and/or the action of interleukin-6 (IL-6), a proinflammatory molecule. The experiment involved three types of mice: young female mice, old female mice, and young female mice that don’t carry the gene for IL-6. Previous research has shown that female mice are more vulnerable to the cognitive impairment associated with surgery and anesthesia. Half of the mice underwent a simple surgical procedure under anesthesia (isoflurane), while the remaining half did not. After the mice that had had surgery recovered, the investigators assessed all the animals' cognitive performance via a maze test, measured IL-6 in the animals' blood, and quantified proteins involved in maintaining blood-brain barrier integrity in the animals' brains.

    They found that the mice that underwent anesthesia and surgery had greater blood-brain permeability and higher IL-6 levels than those that did not undergo the procedures. Notably, permeability increased as IL-6 levels and age increased. Levels of proteins involved in maintaining blood-brain barrier integrity were lower in the mice that underwent the procedure, and older mice were more likely to experience cognitive deficits after the procedures than younger mice.

    These findings suggest that surgery with anesthesia induces cognitive decline in an age-dependent manner, and this decline may be due to inflammatory processes that drive blood-brain barrier dysfunction. Learn more about the blood-brain barrier in our new overview article.

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  • Repeated head injury damage the blood-brain barrier and produce an autoimmune response that promotes neurological disease www.sciencedaily.com
    Brain Aging Autoimmunity Blood-Brain Barrier

    From the article:

    A new study suggests that brain injury from repeat blows to the head – observed among football players and soldiers – might not be a traumatic phenomenon, but an autoimmune phenomenon. It indicates that brain injury may be the result of an out-of-control immune response, much like multiple sclerosis. This is an entirely new way of thinking about how trauma could cause long term degeneration and opens the door to investigating a vaccine/drug to prevent head trauma.

    […]

    Researchers found that S100B, a well-accepted protein biomarker for traumatic brain injury, was present in varying degrees in the blood samples of the 67 football players after every game – even though none of them suffered a concussion. This demonstrates that even the most routine hits have some impact on the blood-brain barrier and possibly the brain itself, Bazarian said.

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  • Blood-brain barrier may be impaired by even mild head trauma: 50% of rugby players and a similar amount in MMA fighters show damage after a season Blood-Brain Barrier Damage Occurs Even With Mild Head Trauma
    Brain Blood-Brain Barrier

    Mild head trauma not resulting in a concussion may cause damage to the blood-brain barrier.

    From the article:

    In the study, which was published online Sept. 5 in the Journal of Neurotrauma, scientists scanned the brains of adolescent and adult rugby players with a special type of magnetic resonance imaging. They found damage to the protective barrier that separates the brain from bloodborne pathogens and toxins in roughly half of adolescent rugby players after a full season — even those who did not report a concussion. Professional mixed martial arts fighters showed similar damage after a fight.

    Extremely frequent BBB disruption in rugby players:

    Ten of 19 adolescent rugby players showed signs of blood-brain barrier disruption by the end of the season. The barrier breakdown appeared on the scans as red blips concentrated throughout the inner regions of the brain. The researchers also scanned eight college rugby players after a match and saw disruptions of the barrier in two of them. Notably, the injuries most study participants experienced were below the current bar for mild head trauma since they did not suffer a concussion.

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  • Hsp70 shown to preserve locomotor function and reduce cell death through a stable binding to toxic amyloid-beta42, blocking ability to attack neurons www.sciencedaily.com
    Brain Alzheimer's Heat Stress Sauna Neurodegeneration

    Heat shock proteins suppress amyloid-beta toxicity in the brain.

    Amyloid-beta is a toxic peptide that aggregates and forms plaques in the brain with age. These plaques are widely considered a hallmark of Alzheimer’s disease, a progressive neurodegenerative disease that occurs with age and is the most common cause of dementia. Findings from a 2016 study suggest that heat shock proteins suppress amyloid-beta toxicity in the brain.

    Heat-shock proteins comprise a large, highly conserved family of proteins that are present in all cells, across many species. They play prominent roles in many cellular processes and facilitate several aspects of the protein synthesis machinery, including assembly and folding. Increased expression of heat shock proteins prevents protein disorder and aggregation by repairing proteins that have been damaged or misfolded and may offer protection against neurodegenerative diseases and inhibit the aggregation of amyloid-beta, reducing plaque formation.

    The study involved fruit flies, which serve as useful models for studying amyloid-beta anomalies. The investigators engineered a form of heat shock protein 70, called Hsp70, that could pass into the extracellular space and interact with amyloid-beta and studied its effects on the flies' neurological health.

    They found that Hsp70 suppressed the toxicity of amyloid-beta in cells of the flies' eyes, reduced cell death in brain neurons, and helped maintain the neurons' architecture and function. The investigators posited that these neuroprotective effects were directly related to Hsp70’s capacity to bind to amyloid-beta rather than via refolding mechanisms.

    These findings indicate that heat shock protein 70 may suppress amyloid-beta toxicity, thereby reducing amyloid-beta plaque formation in the brain and serving as a potential therapeutic strategy for Alzheimer’s disease. Heat stress, such as that experienced during sauna use, robustly induces expression of heat shock proteins. Learn more about heat shock proteins and sauna use in our overview article.

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  • Effective clinical treatment of depression may require addressing underlying loss of blood-brain barrier integrity www.sciencedaily.com
    Brain Depression Blood-Brain Barrier

    From the article:

    The researchers examined blood-brain barrier cells in depressed stressed mice, resilient stressed mice, and control mice. Their observations show that the epigenetic processes that allow the expression of the claudin-5 gene are more readily activated in resilient mice. They also observed that the resilient mice produce less of one of the proteins that inhibit expression of the claudin-5 gene.

    Conversely, depressed stressed mice express more of an enzyme called HDAC1 that triggers a loss of claudin-5. “When a chemical compound is used to block HDAC1, the depressive mice produce more claudin-5 and their social interactions spontaneously increase,” says Professor Ménard.

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  • Restoring integrity of blood-brain barrier critical for epilepsy: blood-brain barrier disruption was a key driver of seizure activity www.sciencedaily.com
    Brain Blood-Brain Barrier Ketogenic Diet

    Probably one of the better known and highly effective non-pharmacological approaches to changing seizure threshold is achieving nutritional ketosis via a ketogenic diet. Which begs the question… what effect does nutritional ketosis have on maintenance of the blood-brain barrier?

    From the article:

    Scientists have announced a significant advance in our understanding of epilepsy, as they have identified a potential method of preventing damaging seizure activity. Brain cells are nourished by an intricate network of capillaries that forms the so-called blood-brain barrier (BBB). Fundamentally, it is disruption to the integrity of these capillaries and the BBB that a group of scientists believe is a key driver of seizure activity in humans. Promisingly though, their new research shows that restoring that integrity can prevent seizures.

    Animal and human evidence:

    Importantly, the work was translational in nature and included both basic and clinical research arms involving patients diagnosed with epilepsy. Using similar techniques in humans and in pre-clinical models, the scientists were able to show that BBB disruption was a key driver of seizure activity.

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  • APOE4 carriers had a 4.92 higher odds of committing suicide in a high air pollution environment (mexico city) www.sciencedaily.com
    Brain Alzheimer's Depression Genetics Pollution

    Air pollution exposure promotes Alzheimer’s disease-related hallmarks in the brains of children.

    Components present in air pollution – a mixture of chemicals, gases, and particulate matter – can cross biological barriers, including the blood-brain barrier. Evidence suggests that children exposed to air pollution exhibit altered brain structure and metabolic function and demonstrate impaired cognitive performance. A 2018 study identified pathological hallmarks associated with Alzheimer’s disease in the brains of children and young adults living in Mexico City, an area known for its high levels of air pollution.

    The primary pathological hallmarks associated with Alzheimer’s disease are amyloid-beta plaques and tau neurofibrillary tangles. Amyloid-beta is a toxic 42-amino acid peptide that clumps together, forming plaques in the brain. Tau is a protein that, when modified via the chemical process of phosphorylation, can form aggregates called neurofibrillary tangles in the brain. Scientists classify the severity of neurofibrillary tangle formation according to the Braak staging system, which ranks severity on a scale of I to VI, with VI being the most severe.

    The investigators examined autopsy-derived brain tissues from 203 subjects living in Mexico City, ranging in age from 11 months to 40 years, to identify the presence of amyloid-beta plaques and tau neurofibrillary tangles. They calculated the subjects' cumulative burden of particulate matter exposure based on their place of residence and noted the subjects' cause of death. They also conducted genotyping to determine whether the subjects were carriers of APOE4, a genetic variant that increases a person’s risk of developing Alzheimer’s disease.

    They found that 99.5 percent of the subjects' brains exhibited abnormally high levels of amyloid-beta and hyperphosphorylated tau, even as early as 11 months of age. Approximately one-fourth of subjects between the ages of 30 and 40 years exhibited stage III or IV neurofibrillary tangles. Subjects who carried the APOE4 variant were at least 23 times more likely to exhibit stage IV tangles. Interestingly, APOE4 carriers were nearly five times more likely to commit suicide than non-carriers.

    These findings suggest that exposure to air pollution in early life increases a person’s risk for developing Alzheimer’s disease. People who carry the high-risk genetic variant APOE4 are at substantially greater risk and may, additionally, be vulnerable to greater suicide risk. Omega-3 fatty acids help maintain blood-brain barrier integrity and may reduce the risk of Alzheimer’s disease in APOE4 carriers. Learn more in this open-access peer-reviewed article by Dr. Rhonda Patrick.

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  • Air pollution may promote the production of autoantibodies against tight-junctions and neural proteins: neuroinflammation in children in Mexico City www.sciencedaily.com
    Brain Alzheimer's Inflammation Pollution Autoimmunity Blood-Brain Barrier

    Exposure to air pollution promotes the production of autoantibodies against tight-junctions of the blood-brain barrier.

    Separately, evidence has also shown that even very young children show evidence of amyloid-beta build up under these conditions.

    From the article:

    The study found when air particulate matter and their components such as metals are inhaled or swallowed, they pass through damaged barriers, including respiratory, gastrointestinal and the blood-brain barriers and can result in long-lasting harmful effects.

    The results found that the children living in Mexico City had significantly higher serum and cerebrospinal fluid levels of autoantibodies against key tight-junction and neural proteins, as well as combustion-related metals.

    “We asked why a clinically healthy kid is making autoantibodies against their own brain components,” Calderón-Garcidueñas said. “That is indicative of damage to barriers that keep antigens and neurotoxins away from the brain. Brain autoantibodies are one of the features in the brains of people who have neuroinflammatory diseases like multiple sclerosis.”

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  • Routine tests ignore breakdown of blood-brain barrier and altered cerebral blood flow that precede Alzheimer's diagnosis www.sciencedaily.com
    Brain Alzheimer's Neurodegeneration Blood-Brain Barrier

    From the article:

    “Cognitive impairment, and accumulation in the brain of the abnormal proteins amyloid and tau, are what we currently rely upon to diagnose Alzheimer’s disease, but blood-brain barrier breakdown and cerebral blood flow changes can be seen much earlier,” said Berislav Zlokovic, the Mary Hayley and Selim Zilkha Chair in Alzheimer’s Disease Research at the Keck School of Medicine of USC. “This shows why healthy blood vessels are so important for normal brain functioning.”

    […]

    BBB leaks can be detected with an intravenously administered contrast substance in concert with magnetic resonance imaging. Brain microbleeds, another sign of leakage, also can be picked up with MRI. A slowdown in the brain’s uptake of glucose, visible via PET scan, can be a another result of BBB breakdown. Zlokovic notes that these aren’t tests routinely offered at a doctor’s office.

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  • Model of blood-brain barrier malfunctions when stem cells are derived from cells of patients with Huntington's disease www.sciencedaily.com
    Brain Neurodegeneration Blood-Brain Barrier

    From the article:

    For their study, a team led by Cedars-Sinai investigators generated stem cells known as induced pluripotent stem cells, which can produce any type of cell, using an individual adult’s blood samples. They used these special cells to make neurons, blood-vessel linings and support cells that together make up the blood-brain barrier. The team then placed the various types of cells inside Organ-Chips, which recreated the body’s microenvironment with the natural physiology and mechanical forces that cells experience within the human body.

    The living cells soon formed a functioning unit of a blood-brain barrier that functions as it does in the body, including blocking entry of certain drugs. Significantly, when this blood-brain barrier was derived from cells of patients with Huntington’s disease or Allan-Herndon-Dudley syndrome, a rare congenital neurological disorder, the barrier malfunctioned in the same way that it does in patients with these diseases.

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  • Sulforaphane from broccoli sprouts increase glutathione in the brain by an average of 30% with a 100 micromole per day dose www.sciencedaily.com
    Brain Alzheimer's Parkinson's Schizophrenia Glutathione Antioxidant Neurodegeneration

    Increases of glutathione reverse pattern of brain cell activity associated with schizophrenia:

    They used the chemical sulforaphane found in broccoli sprouts, which is known to turn on a gene that makes more of the enzyme that sticks glutamate with another molecule to make glutathione. When they treated rat brain cells with glutathione, it slowed the speed at which the nerve cells fired, meaning they were sending fewer messages. The researchers say this pushed the brain cells to behave less like the pattern found in brains with schizophrenia.

    However, the impact of sulforaphane may be broader due to the broader effect of increasing glutathione, including in the hippocampus (region impacted by Alzheimer’s disease):

    For their study, published in April 2018 in Molecular Neuropsychiatry, the researchers recruited nine healthy volunteers (four women, five men) to take two capsules with 100 micromoles [17.729mg] daily of sulforaphane in the form of broccoli sprout extract for seven days.

    […]

    The researchers used MRS again to monitor three brain regions for glutathione levels in the healthy volunteers before and after taking sulforaphane. They found that after seven days, there was about a 30% increase in average glutathione levels in the subjects' brains. For example, in the hippocampus, glutathione levels rose an average of 0.27 millimolar from a baseline of 1.1 millimolar after seven days of taking sulforaphane.

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  • Inherited Parkinson's LRRK2 mutations promote excessive inflammatory cytokines that cross blood-brain barrier, trigger neuron damage via microglia www.sciencedaily.com
    Brain Parkinson's Aging Inflammation Immune System Blood-Brain Barrier Lipopolysaccharide

    From the article:

    Suspecting that the LRRK2 mutations might be acting outside of the brain, the researchers used an agent – the outer shell of bacteria, called lippopolysaccharide (LPS) – that causes an immune reaction. LPS itself does not pass into the brain, nor do the immune cells it activates, which made it ideal for testing whether this second hit was acting directly in the brain.

    When the researchers gave the bacterial fragments to the mice carrying the two most common LRRK2 gene mutations, the immune reaction became a “cytokine storm,” with inflammatory mediators rising to levels that 3-5 times higher than a normal reaction to LPS. These inflammatory mediators were produced by T and B immune cells expressing the LRRK2 mutation.

    Despite the fact that LPS did not cross the blood-brain barrier, the researchers showed that the elevated cytokines were able to enter the brain, creating an environment that caused the microglia to activate pathologically and destroy the brain region involved in movement.

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  • Repurposed chemo drug acting on the blood-brain barrier shows dose-dependent increase of dopamine in Parkinson's disease patients www.sciencedaily.com
    Brain Parkinson's Cancer Aging Neurodegeneration Blood-Brain Barrier

    Repurposed chemo drug inactivates protein that destroy’s the blood-brain barrier in Parkinson’s disease:

    The current part of the study just published, examined the cerebrospinal fluid of patients via epigenomics, which is a systematic analysis of the global state of gene expression, in correlation with continuing clinical outcomes. The new analysis helps explain the clinical findings.

    Nilotinib inactivated a protein (DDR1) that was destroying the ability of the blood brain barrier to function properly. When DDR1 was inhibited, normal transport of molecules in and out of the brain filter resumed, and inflammation declined to the point that dopamine, the neurotransmitter depleted by the disease process, was being produced again.

    After 27 months, nilotinib was found to be safe, and patients who received nilotinib showed a dose-dependent increase of dopamine, the chemical lost as a result of neuronal destruction.

    First study to show blood-brain barrier as therapeutic target for Parkinson’s disease:

    “Not only does nilotinib flip on the brain’s garbage disposal system to eliminate bad toxic proteins, but it appears to also repair the blood brain barrier to allow this toxic waste to leave the brain and to allow nutrients in,” Moussa explains. “Parkinson’s disease is generally believed to involve mitochondrial or energy deficits that can be caused by environmental toxins or by toxic protein accumulation; it has never been identified as a vascular disease.”

    “To our knowledge, this is the first study to show that the body’s blood brain barrier potentially offers a target for the treatment for Parkinson’s disease,” Moussa says.

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  • Environmental toxins inhaled through nose may induce inflammation which culminates in the deposit of Lewy bodies in the brain, promoting Parkinson's www.sciencedaily.com
    Brain Parkinson's Aging Dementia Neurodegeneration Lipopolysaccharide

    Lewy bodies found in olfactory areas suggest not only is lost smell a sign of neural damage, but rather a direct link to the mechanism creating the disorder:

    The loss of a sense of smell is known to be one of the earliest signs of Parkinson’s disease (PD) and can even appear years before the characteristic tremors and loss of motor function are seen. Some scientists believe that olfactory dysfunction may not just be a sign of broader neural damage, but rather may have a more direct linkage to the generation of the disorder itself. In support of this idea, deposits of a protein called alpha-synuclein that form Lewy bodies can be found in olfactory areas, as well as in dying dopamine neurons whose loss triggers PD, and mutations in the gene encoding alpha-synuclein produce PD.

    Inflammation triggered in the areas where the olfactory neurons project (recapitulated by lipopolysaccharide) culminate in alpha-synuclein that can cross the blood-brain barrier:

    Results of the study, published in the journal Brain Pathology, showed that application of an irritating component of a bacterium’s cell wall induces inflammation in the areas exactly where the olfactory neurons project, called the olfactory bulb. Moreover, these areas show the hallmark signs of PD, depositions of alpha-synuclein, the core components of Lewy bodies. PD is characterized by progressive motor and non-motor symptoms linked to alpha-synuclein pathology and the loss of dopaminergic neurons in the nigrostriatal system. Toxic aggregates of alpha-synuclein can arise from either overexpression of the protein, changes in protein modifications, and from hereditary mutations.

    […]

    “Data from our study show that the bacterial trigger does not move across the blood-brain barrier,” said Quan. “Rather, a sequential inflammatory activation of the olfactory mucosa triggers a subsequent expression of inflammatory molecules within the brain, propagating the inflammation.”

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  • Pomegranate juice as a neuroprotective for infants at risk of hypoxia in the womb: differences in white matter and functional connectivity in brain www.sciencedaily.com
    Brain Pregnancy Development Urolithin A

    From the article:

    “Our study provides preliminary evidence suggesting potential protective effects for newborns exposed to pomegranate juice while in utero,” said senior author Terrie Inder

    […]

    Polyphenols are known to cross the blood-brain barrier, and studies in animal models have demonstrated protective effects against neurodegenerative diseases. To date, no clinical studies had evaluated the potential effects of giving pregnant women pomegranate juice to protect the brains of at-risk newborns.

    […]

    Women were randomized to receive 8 ounces of pomegranate juice daily or a taste/calorie matched placebo that was polyphenol free. Women drank the juice daily from enrollment until delivery. The team measured several aspects of brain development and injury, including infant brain macrostructure, microstructural organization and functional connectivity.

    While the team did not observe differences in brain macrostructure, they did find regional differences in white matter microstructure and functional connectivity.

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  • Amyloid-beta can travel, cancer-like, to brain from other parts of body: insights from parabiosis experiments www.sciencedaily.com
    Brain Alzheimer's Aging Blood-Brain Barrier

    From the article:

    The scientists demonstrated this cancer-like mobility through a technique called parabiosis: surgically attaching two specimens together so they share the same blood supply for several months. […] Normal mice that had been joined to genetically modified partners for a year “contracted” Alzheimer’s disease. Song says the amyloid-beta traveled from the genetically-modified mice to the brains of their normal partners, where it accumulated and began to inflict damage.

    The problem is partly due to an increased permissiveness of the blood-brain barrier as we age that allows entry from other parts of the body:

    “The blood-brain barrier weakens as we age,” says Song, a Canada Research Chair in Alzheimer’s Disease and the Jack Brown and Family Professor. “That might allow more amyloid beta to infiltrate the brain, supplementing what is produced by the brain itself and accelerating the deterioration.”

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  • Microbiota play important role in preventing blood-brain barrier permeability: germ-free mice have greater leakiness, resolved with fecal transplant www.sciencedaily.com
    Brain Microbiome Blood-Brain Barrier

    From the article:

    The investigators reached this conclusion by comparing the integrity and development of the blood-brain barrier between two groups of mice: the first group was raised in an environment where they were exposed to normal bacteria, and the second (called germ-free mice) was kept in a sterile environment without any bacteria.

    “We showed that the presence of the maternal gut microbiota during late pregnancy blocked the passage of labeled antibodies from the circulation into the brain parenchyma of the growing fetus,” says first author Dr. Viorica Braniste at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet. “In contrast, in age-matched fetuses from germ-free mothers, these labeled antibodies easily crossed the blood-brain barrier and was detected within the brain parenchyma.”

    However, it can be resolved with fecal transplant:

    Interestingly, this ‘leakiness’ could be abrogated if the mice were exposed to fecal transplantation of normal gut microbes.

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  • Spike proteins that extrude from SARS-CoV-2 promote inflammatory responses on the endothelial cells that form the blood-brain barrier. www.sciencedaily.com
    Brain Inflammation Immune System COVID-19 Blood-Brain Barrier

    SARS-CoV-2, the virus that causes COVID-19, disrupts the blood-brain barrier.

    COVID-19 is widely regarded as a respiratory illness, but evidence suggests it affects multiple organ systems, including the central nervous system. For example, some people with COVID-19 experience headaches, nausea, vomiting, or “brain fog” – indicators of neurological involvement. Evidence from a 2020 study suggests that SARS-CoV-2, the virus that causes COVID-19, disrupts the blood-brain barrier.

    SARS-CoV-2 enters cells via the angiotensin-converting enzyme 2 (ACE2), a protein that is widespread among the body’s tissues and plays important roles in blood pressure control. Once inside the cell, SARS-CoV-2 replicates, triggering a robust immune response and eliciting widespread inflammation.

    The blood-brain barrier, a semi-permeable barrier that separates the blood from the brain’s extracellular fluid, prevents the entry of neurotoxic substances into the brain. Disruption of the blood-brain barrier has been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, among others.

    The investigators first examined postmortem brain tissue from healthy people as well as people who had been diagnosed with hypertension (high blood pressure) or dementia to identify the presence of ACE2 in the brain blood vessels. They found that not only was ACE2 present in the blood vessels, but it was particularly abundant in people with hypertension or dementia. Then, using an in vitro model of the blood-brain barrier, they assessed the effects of exposure to the SARS-CoV-2 spike protein, the primary infectious particle on the virus. They found that exposure to the spike protein impaired blood-brain barrier function and integrity. Finally, using a tissue model that mimics the movement of fluid in the barrier, they found that the spike protein increased barrier permeability.

    These findings suggest that SARS-CoV-2 binds to ACE2 receptors in the brain and impairs blood-brain barrier function and integrity. These effects may be exacerbated in people with co-existing illnesses such as hypertension or dementia.

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  • Leaky blood-brain barrier caused by cerebral small vessel disease increases the prevalence of white-matter hyperintensities and brain damage www.sciencedaily.com
    Brain Aging Dementia Blood-Brain Barrier Small Vessel Disease

    Poor blood-brain barrier integrity drives white matter losses.

    White matter hyperintensities are areas in the brain that appear as intense white spots on magnetic resonance imaging (MRI) scans. They are often indicators of cerebral small blood vessel disease and are considered a risk factor for dementia. A 2021 study found that breaches in blood-brain barrier integrity are associated with brain tissue losses and precede the appearance of white matter hyperintensities.

    The blood-brain barrier, a specialized system of endothelial cells that shields the brain from toxins present in the blood, supplies the brain’s tissues with vital nutrients and substances necessary for neuronal and metabolic function. The structural integrity of the blood-brain barrier is therefore critical for homeostatic maintenance of the brain microenvironment.

    The study involved 43 patients (average age 58 years) who had been diagnosed with cerebral small vessel disease, as evidenced by having experienced a stroke or demonstrating mild cognitive impairment. At the beginning of the study and two years later, participants underwent a variety of MRI techniques that quantified their overall blood-brain barrier permeability as well as the areas surrounding white matter hyperintensities.

    The MRIs revealed that participants who had the greatest amount of leaky brain tissue at the beginning of the study exhibited greater white matter tissue losses two years later. These tissue losses translated to greater permeability, a phenomenon particularly evident in the areas surrounding the brain lesions associated with white matter hyperintensities.

    These findings suggest that losses in blood-brain barrier integrity damage brain tissue, driving increased permeability and white matter losses. In turn, these changes potentiate the disease processes associated with cerebral small vessel disease. Learn more about the blood-brain barrier in our overview article.

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  • Alzheimer’s risk allele APOE4 triggers early breakdowns in blood-brain barrier, predicting cognitive decline www.sciencedaily.com
    Brain Alzheimer's Aging Memory Blood-Brain Barrier

    From the article:

    Severe damage to vascular cells called pericytes was linked to more severe cognitive problems in APOE4 carriers. APOE4 seems to speed up breakdown of the blood-brain barrier by activating an inflammatory pathway in blood vessels, which is associated with pericyte injury."

    […]

    Zlokovic’s previous research shows that people who develop early memory problems also experience the most leakage in their brain’s blood vessels – independent of amyloid plaque or tau, two common contributors to Alzheimer’s. The leakage starts when cells called pericytes, which line the walls of blood vessels in the brain and maintain blood-brain barrier integrity, are damaged.

    […]

    In participants who had the APOE4 gene, researchers found damaged capillaries in the brain’s memory center, the hippocampus and medial temporal lobe. The damage correlated with increased levels of a protein that causes inflammation, cyclophilin A – an early sign of the disease in people already at higher risk of developing Alzheimer’s.

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  • Hunger inhibition hormone leptin directly contributes to cardiovascular disease in those desensitized by obesity by increasing cardiovascular activity www.sciencedaily.com
    Brain Obesity Heart Disease Satiety Blood Pressure Metabolic Syndrome

    From the article:

    In both cell culture and animal models, the researchers have shown that fat-derived leptin directly activates aldosterone synthase expression in the adrenal glands, resulting in production of more of the steroid hormone aldosterone.

    High aldosterone levels are known to contribute to widespread inflammation, blood vessel stiffness and scarring, enlargement and stiffness of the heart, impaired insulin sensitivity and more.

    Aldosterone, which is produced by the adrenal gland, has a direct effect on blood pressure by regulating salt-water balance in the body. High levels of aldosterone are an obesity hallmark and a leading cause of metabolic and cardiovascular problems. But exactly how it gets high in obesity was a mystery.

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  • Intense cycling exercise at 80% maximum heart rate improves memory via endocannabinoid action on the hippocampus www.sciencedaily.com
    Exercise Brain Performance Memory Cannabinoid Aerobic

    Exercise activates the endocannabinoid system to promote learning and memory formation.

    Scientists have identified robust links between physical exercise and brain health. Some of the mechanisms that drive the beneficial effects of exercise on the brain include increases in brain volume and connectivity, improved blood flow, enhanced synaptic plasticity, and increased neurogenesis – the formation of new neurons. Findings from a 2020 study suggest that moderate- to vigorous-intensity exercise improves motor sequence memory via endocannabinoid action on the hippocampus.

    Motor sequence memory involves learning predefined sequences of interrelated motor actions, such as playing the piano or dancing. The hippocampus interacts with various neural networks to support the formation of motor sequency memory.

    Endocannabinoids are small lipid molecules produced in the body that bind to cannabinoid receptors in the central and peripheral nervous systems. Endocannabinoids regulate many physiological processes, including movement control, pain processing, brain development, and learning and memory. The two major endocannabinoids in the body are anandamide and 2-arachindonyl glycerol.

    The study involved 15 healthy adults (average age, 23 years) who had at least fair respiratory fitness, as measured via VO2 max. Participants completed a serial reaction time task (a widely used measure of learning and memory) before and after three conditions: moderate-intensity exercise, vigorous-intensity exercise, and rest. Prior to performing the task, participants consumed a standardized carbohydrate-rich breakfast. During the task, the investigators measured the participants' behavior, brain activity, and circulating anandamide (endocannabinoid) levels.

    They found that vigorous-intensity exercise markedly improved motor sequence memory compared to rest. Moderate-intensity exercise also improved motor sequence memory, but to a lesser degree. The improvements coincided with increased levels of the endocannabinoid anandamide and enhanced hippocampal activity.

    These findings suggest that vigorous-intensity exercise promotes motor sequence memory and learning and underscore the benefits of exercise on cognitive function. Learn about the beneficial effects of aerobic exercise in our overview article.

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  • Omega-3 prevents memory and learning impairment caused by high-fructose diets in mice www.sciencedaily.com
    Brain Diet Omega-3 Memory Sugar

    From the article:

    Gomez-Pinilla and study co-author Rahul Agrawal, a UCLA visiting postdoctoral fellow from India, studied two groups of rats that each consumed a fructose solution as drinking water for six weeks. The second group also received omega-3 fatty acids in the form of flaxseed oil and docosahexaenoic acid (DHA), which protects against damage to the synapses – the chemical connections between brain cells that enable memory and learning.

    […]

    The animals were fed standard rat chow and trained on a maze twice daily for five days before starting the experimental diet. The UCLA team tested how well the rats were able to navigate the maze, which contained numerous holes but only one exit. The scientists placed visual landmarks in the maze to help the rats learn and remember the way.

    Six weeks later, the researchers tested the rats' ability to recall the route and escape the maze. What they saw surprised them.

    “The second group of rats navigated the maze much faster than the rats that did not receive omega-3 fatty acids,” Gomez-Pinilla said. “The DHA-deprived animals were slower, and their brains showed a decline in synaptic activity. Their brain cells had trouble signaling each other, disrupting the rats' ability to think clearly and recall the route they’d learned six weeks earlier.”

    The DHA-deprived rats also developed signs of resistance to insulin, a hormone that controls blood sugar and regulates synaptic function in the brain.

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  • Inhibiting the Mfsd2a transporter that brings omega-3 DHA into the brain promotes leakage of brain barrier www.sciencedaily.com
    Brain Cancer Aging Omega-3 Blood-Brain Barrier

    Impaired transport of DHA disrupts the blood-brain barrier.

    Lipid rafts – cholesterol-filled “bubbles” found in the cell membrane – serve as staging areas for many cellular activities. One type of lipid raft, called caveolae, facilitates the transport of substances across the membrane of endothelial cells. Findings from a 2017 study demonstrate that suppression of caveolae-mediated transport in brain endothelial cells protects the integrity of the blood-brain barrier.

    The blood-brain barrier is a highly selective semi-permeable barrier made up of endothelial cells connected via tight junctions. This barrier separates the circulating blood from the brain’s extracellular fluid and prevents the entry of substances that may be neurotoxic. Disruption of the blood-brain barrier has been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, among others.

    The investigators' previous research showed that a critical player in blood-brain barrier function is Mfsd2a, a transmembrane protein found exclusively on the endothelial cells that line blood vessels on the barrier. Mfsd2a participates in lipid transport and is the sole means by which lysophospholipid DHA, the brain’s preferred form of DHA (a type of omega-3 fatty acid) is delivered to the brain.

    Using mice that carried a mutation that blocked Mfsd2a’s capacity to transport DHA, the investigators assessed blood-brain barrier function as well as caveolae formation and activity in the animals' brains. Then they compared the lipid composition of brain endothelial cells to lung epithelial cells, which lack Mfsd2a.

    They found that mice that lacked Mfsd2a function had leakier blood-brain barriers and greater caveolae formation and activity than normal mice. They also found that brain endothelial cells had higher lipid concentrations than lung epithelial cells. The most abundant lipid in the brain endothelial cells was DHA, which was found in concentrations that were two to five times higher.

    These findings suggest that Mfsd2a-mediated transport of lipids, particularly DHA, impairs caveolae activity, thereby preserving blood-brain integrity. Learn more about links between Mfsd2a, DHA, and brain health in this open-access peer-reviewed article by Dr. Rhonda Patrick..

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  • How precision nutrition may lower the risk of Alzheimer's disease in people with an APOE4 allele www.mdpi.com
    Nutrition Brain Alzheimer's Neurodegeneration Ketogenic Diet

    Abstract

    “The ApoE4 allele is the most well-studied genetic risk factor for Alzheimer’s disease, a condition that is increasing in prevalence and remains without a cure. Precision nutrition targeting metabolic pathways altered by ApoE4 provides a tool for the potential prevention of disease. However, no long-term human studies have been conducted to determine effective nutritional protocols for the prevention of Alzheimer’s disease in ApoE4 carriers. This may be because relatively little is yet known about the precise mechanisms by which the genetic variant confers an increased risk of dementia. Fortunately, recent research is beginning to shine a spotlight on these mechanisms. These new data open up the opportunity for speculation as to how carriers might ameliorate risk through lifestyle and nutrition. Herein, we review recent discoveries about how ApoE4 differentially impacts microglia and inflammatory pathways, astrocytes and lipid metabolism, pericytes and blood–brain barrier integrity, and insulin resistance and glucose metabolism. We use these data as a basis to speculate a precision nutrition approach for ApoE4 carriers, including a low-glycemic index diet with a ketogenic option, specific Mediterranean-style food choices, and a panel of seven nutritional supplements. Where possible, we integrate basic scientific mechanisms with human observational studies to create a more complete and convincing rationale for this precision nutrition approach. Until recent research discoveries can be translated into long-term human studies, a mechanism-informed practical clinical approach may be useful for clinicians and patients with ApoE4 to adopt a lifestyle and nutrition plan geared towards Alzheimer’s risk reduction.”

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  • Reduced expression of genes involved in integrity of blood-brain barrier, intestinal barrier in autism: 75% have reduced barrier-forming components www.sciencedaily.com
    Brain Microbiome Autism Intestinal Permeability Endotoxemia Blood-Brain Barrier

    From the article:

    The group analyzed postmortem cerebral cortex and cerebellum tissues from 33 individuals – 8 with ASD, 10 with schizophrenia and 15 healthy controls. Altered expression of genes associated with blood-brain-barrier integrity and function and with inflammation was detected in ASD tissue samples, supporting the hypothesis that an impaired blood-brain barrier associated with neuroinflammation contributes to ASD.

    In keeping with the hypothesis that the interplay within the gut-brain axis is a crucial component in the development of neurodevelopmental disorders, the group also analyzed intestinal epithelial tissue from 12 individuals with ASD and 9 without such disorders. That analysis revealed that 75 percent of the individuals affected by ASD had reduced expression of barrier-forming cellular components, compared with controls, and 66 percent showed a higher expression of molecules that increase intestinal permeability.

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  • Reservatrol strengthens tight-junction proteins in the blood-brain barrier and protects against oxidized LDL academic.oup.com
    Brain Cholesterol Resveratrol Polyphenol Endotoxemia

    Abstract

    “Cerebrovascular endothelial cells (CEC) comprise the blood-brain barrier (BBB). In a previous study, we showed that oxidized LDL (oxLDL) can induce apoptosis of mouse CEC. Resveratrol possesses chemopreventive potential. This study aimed to evaluate the effects of resveratrol on oxLDL-induced insults to mouse CEC and its possible mechanisms. Exposure of mouse CEC to 200 μmol/L oxLDL for 1 h did not cause cell death but significantly altered the permeability and transendothelial electrical resistance of the cell monolayer. However, resveratrol completely normalized such injury. As for the mechanisms, resveratrol completely protected oxLDL-induced disruption of F-actin and microtubule cytoskeletons as well as occludin and zona occludens-1 (ZO-1) tight junctions. The oxLDL-induced decreases in the mitochondrial membrane potential and intracellular ATP levels were normalized by resveratrol. Exposure of mouse CEC to 200 μmol/L oxLDL for 24 h elevated oxidative stress and simultaneously induced cell apoptosis. However, resveratrol partially protected against oxLDL-induced CEC apoptosis. The oxLDL-induced alterations in levels of Bcl-2, Bax, and cytochrome c were completely normalized by resveratrol. Consequently, resveratrol partially decreased oxLDL-induced activation of caspases-9 and -3. Therefore, in this study, we show that resveratrol can protect against oxLDL-induced damage of the BBB through protecting disruption of the tight junction structure and apoptotic insults to CEC.”

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  • Resveratrol reinforces the blood-brain barrier and reverses dysfunction due to diabetes www.sciencedaily.com
    Brain Resveratrol Endotoxemia

    “The largest nationwide clinical trial to study high-dose resveratrol long-term in people with mild to moderate Alzheimer’s disease found that a biomarker that declines when the disease progresses was stabilized in people who took the purified form of resveratrol. Resveratrol is a naturally occurring compound found in foods such as red grapes, raspberries, dark chocolate and some red wines.”

    Abstract “Resveratrol is a natural polyphenolic compound that activates nicotinamide adenosine dinucleotide-dependent deacetylase SIRT1. Resveratrol has recently been shown to exert potent antidiabetic actions when orally delivered to animal models of type 2 diabetes. However, the tissue(s) mediating these beneficial effects is unknown. Because SIRT1 is expressed in central nervous system (CNS) neurons known to control glucose and insulin homeostasis, we hypothesized that resveratrol antidiabetic effects are mediated by the brain. Here, we report that long-term intracerebroventricular infusion of resveratrol normalizes hyperglycemia and greatly improves hyperinsulinemia in diet-induced obese and diabetic mice. It is noteworthy that these effects are independent of changes in body weight, food intake, and circulating leptin levels. In addition, CNS resveratrol delivery improves hypothalamic nuclear factor-κB inflammatory signaling by reducing acetylated-RelA/p65 and total RelA/p65 protein contents, and inhibitor of nuclear factor-κB α and IκB kinase β mRNA levels. Furthermore, this treatment leads to reduced hepatic phosphoenolpyruvate carboxykinase 1 mRNA and protein levels and ameliorates pyruvate-induced hyperglycemia in this mouse model of type 2 diabetes. Collectively, our results unveiled a previously unrecognized key role for the CNS in mediating the antidiabetic actions of resveratrol.”

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  • Leaking of the blood-brain barrier disrupts healthy aging and memory www.sciencedaily.com
    Brain Alzheimer's Aging Endotoxemia

    Abstract:

    “The blood–brain barrier (BBB) protects the central nervous system (CNS) from unregulated exposure to the blood and its contents. The BBB also controls the blood-to-brain and brain-to-blood permeation of many substances, resulting in nourishment of the CNS, its homeostatic regulation and communication between the CNS and peripheral tissues. The cells forming the BBB communicate with cells of the brain and in the periphery. This highly regulated interface changes with healthy aging. Here, we review those changes, starting with morphology and disruption. Transporter changes include those for amyloid beta peptide, glucose and drugs. Brain fluid dynamics, pericyte health and basement membrane and glycocalyx compositions are all altered with healthy aging. Carrying the ApoE4 allele leads to an acceleration of most of the BBB’s age-related changes. We discuss how alterations in the BBB that occur with healthy aging reflect adaptation to the postreproductive phase of life and may affect vulnerability to age-associated diseases.”

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  • Increased permeability of the blood brain barrier www.sciencedaily.com
    Brain Intestinal Permeability Endotoxemia

    “Endothelial cells of blood vessels of the central nervous system (CNS) constitute blood-CNS barriers. Barrier properties are not intrinsic to these cells; rather they are induced and maintained by CNS microenvironment. Notably, the abluminal surfaces of CNS capillaries are ensheathed by pericytes and astrocytes. However, extrinsic factors from these perivascular cells that regulate barrier integrity are largely unknown. Here, we establish vitronectin, an extracellular matrix protein secreted by CNS pericytes, as a regulator of blood-CNS barrier function via interactions with its integrin receptor, α5, in endothelial cells. Genetic ablation of vitronectin or mutating vitronectin to prevent integrin binding, as well as endothelial-specific deletion of integrin α5, causes barrier leakage in mice. Furthermore, vitronectin-integrin α5 signaling maintains barrier integrity by actively inhibiting transcytosis in endothelial cells. These results demonstrate that signaling from perivascular cells to endothelial cells via ligand-receptor interactions is a key mechanism to regulate barrier permeability.”

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  • Oleic acid produced by cells in the brain (and found in olive oil) may be a key cell proliferation and neurogenesis signal www.sciencedaily.com
    Brain Neurogenesis

    Oleic acid produced in the brain promotes neurogenesis – the generation of new neurons.

    Oleic acid is a monounsaturated fatty acid produced in plants and is the primary fatty acid found in olive oil. Interestingly, oleic acid is also produced in the human brain. Findings from a recent study suggest that brain-derived oleic acid activates neural stem cells in the hippocampus, promoting neurogenesis – the generation of new neurons.

    The hippocampus is a small organ located within the brain’s medial temporal lobe. It is an important part of the limbic system (the region that regulates emotions) and plays critical roles in memory, learning, and spatial navigation. The neurons in the hippocampus are particularly vulnerable to amyloid-beta plaque accumulation, tau tangle formation, and subsequent atrophy – early indicators of Alzheimer’s disease.

    The investigators used spectroscopy, a research tool that uses light scatter to measure concentration, to look for the presence of monounsaturated fatty acids in neural progenitor cells. These cells differ from stem cells in that they can undergo only a limited number of replication cycles. They found that the progenitor cells contained several monounsaturated fatty acids, the most abundant of which was oleic acid. Treating the cells with a chemical that blocked the activity of enzymes involved in oleic acid production dramatically reduced the cells' survival.

    Next, they used spectroscopy to look for the presence of monounsaturated fatty acids in the brains of mice. They found an abundance of the fatty acids, especially oleic acid, in the dentate gyrus, the region of the hippocampus where neurogenesis occurs. Then, using homology modeling (a type of computer-based study technique) they observed that oleic acid bound to TLX, a protein in neural stem cells that regulates neurogenesis, switching on the protein’s activity and driving the production of new neurons.

    These findings suggest that oleic acid produced in the brain activates neurogenesis. Therapeutic modulation of TLX may be a means to counteract the effects of impaired neurogenesis in age-related cognitive decline, depression, Alzheimer’s disease, and other conditions. Brain-derived neurotropic factor, or BDNF, also promotes neurogenesis. Learn more about BDNF and the lifestyle behaviors that promote its production in our overview article.

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  • Mid-life long duration antibiotic use of >= two months linked to poorer scores in cognition, learning, working memory, and attention in later life www.sciencealert.com
    Brain Aging Microbiome Performance Memory Antibiotics Dementia

    Antibiotic use in midlife increases a person’s risk for neuropsychiatric diseases.

    Antibiotics are prescribed for a wide range of infectious diseases. In 2015, healthcare providers in the United States wrote nearly 270 million antibiotic prescriptions – more than 800 antibiotic prescriptions for every 1,000 people. Health experts estimate that 30 percent of these prescriptions were likely unnecessary. Findings from a new study suggest that antibiotic use in midlife increases a person’s risk for neuropsychiatric diseases.

    The study included approximately 15,000 midlife participants (average age, 55 years) enrolled in the Nurses’ Health Study II, an ongoing prospective cohort study of female nurses. The participants completed questionnaires regarding their general health, diet, lifestyle, and medication use during the previous four years, including antibiotic use and the reason for which the antibiotic was prescribed. The investigators categorized the participants' cumulative antibiotic use as none, one to 14 days, 15 days to two months, and two months or more. Participants also completed a battery of neuropsychological tests.

    The investigators found that participants who took antibiotics for at least two months over the previous four years were more likely to perform worse on neuropsychological tests than participants who did not take antibiotics. The influence of antibiotic use on neuropsychological test scores was roughly equivalent to three to four years of aging. These findings held true even after considering other factors that could influence cognitive function, including age and coexisting illnesses.

    These findings suggest that longer exposure to antibiotics in midlife negatively influences cognitive health, underscoring the importance of moderating antibiotic use in older adults. They also support findings from animal studies that suggest antibiotic use early in life alters neuropeptide signaling pathways that influence behavioral development. Learn more about the effects of antibiotic use in early life in this clip featuring Dr. Eran Elinav.

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  • Medium chain triglycerides (MCTs) improved cognition in patients with Alzheimer's disease. www.ncbi.nlm.nih.gov
    Brain Alzheimer's Neurodegeneration

    Medium-chain triglycerides improve cognitive function in Alzheimer’s disease.

    The brain relies heavily on glucose as its primary fuel, burning as much as 130 grams of glucose per day. However, glucose metabolism in the brain is impaired in Alzheimer’s disease, contributing to many of the disease’s symptoms. Findings from a recent study demonstrate that ketones derived from medium chain triglyceride metabolism may provide an alternative fuel source for the brain in the setting of Alzheimer’s disease.

    Ketones are molecules produced by the liver during the breakdown of fatty acids. Ketone production occurs during periods of low food intake (such as during fasting), carbohydrate-restrictive diets, starvation, or prolonged intense exercise. Humans produce three types of ketones: acetoacetate, beta-hydroxybutyrate, and acetone. Ketones are readily used as energy by a diverse array of cell types, including neurons, and some evidence suggests that ketones improve cognitive function.

    Medium-chain triglycerides (MCTs) are a class of saturated fats. They are composed of medium-length fatty acid chains (six to 12 carbons long) bound by a glycerol backbone. Medium-chain triglycerides occur naturally in coconut oil, palm oil, and butter, but they can also be synthesized in a laboratory or food processing setting and provided as dietary supplements.

    The randomized, placebo-controlled trial involved 20 adults between the ages of 53 and 84 years who had been diagnosed with Alzheimer’s disease. The investigators used a crossover design, which allows all participants to receive the same treatment, at different times. In this trial, half of the participants received an average of two tablespoons of MCTs daily for three months, while the other half received a comparable amount of olive oil for the same duration. Then the participants switched to the opposite treatment. Participants underwent cognitive testing before, during, and after the intervention. After completing both forms of the intervention, all the participants received MCTs for six months. The investigators collected the participants' demographic and health data, which included measures of blood lipids, fasting insulin, body mass index, and body fat composition.

    They found that 80 percent of the participants demonstrated improved or stable cognitive function while taking the MCTs. The greatest improvements were seen among participants who received MCTs last (providing them nine months of uninterrupted treatment) and among those who were older than 73 years.

    These findings suggest that long-term MCT intake stabilizes cognitive function in adults with Alzheimer’s disease, especially in mild to moderate disease. This was a small study, however, so larger studies are needed to confirm these findings.

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  • Milk May Exacerbate Multiple Sclerosis Symptoms www.sciencedaily.com
    Brain Multiple Sclerosis Autoimmunity

    Antibodies that destroy myelin in multiple sclerosis may cross-react with casein, a milk protein.

    Multiple sclerosis (MS) is a neurodegenerative and autoimmune disease caused when the immune system attacks myelin proteins on nerves, mistaking them for proteins produced by pathogens. The cause of this immune confusion is complex but may involve exposure to proteins found in cow’s milk, which anecdotally worsen MS symptoms for some patients. New research supports this anecdotal evidence, finding that MS autoantibodies cross-react with casein, the principal protein in cow’s milk.

    In order to create antibodies that react to new pathogens, B cells (a type of immune cells) use somatic hypermutation, a process during which they intentionally mutate regions of their DNA involved in antibody production. These rapid mutations are needed to increase antibody repertoire, the collection of an individual’s B cell receptor and antibody sequences; however, somatic hypermutation can result in the creation of autoantibodies, which bind to self-proteins produced by the body. While autoimmune B cells are usually destroyed shortly after creation, lingering autoimmune cells can proliferate and lead to diseases such as type 1 diabetes, rheumatoid arthritis, and MS. One reason autoantibodies persist is cross-reactivity with other proteins, such as those produced by pathogens or absorbed from the diet, especially in cases where gut leakiness increases the introduction of new proteins to the blood.

    The investigators gave one group of mice an injection of casein with adjuvants, which are compounds added to vaccines to increase the body’s antibody response. To compare casein to other milk proteins, they also immunized one group of mice with alpha-lactalbumin and another with beta-lactoglobulin, both whey proteins, for a total of three mouse groups. Changes in behavior and nerve degeneration were observed at 13, 20, or 40 days after immunization. The researchers also collected blood samples from 39 patients with MS and 23 patients with other neurological diseases in order to test for cross-reactivity of autoantibodies with casein.

    Mice immunized with casein exhibited a range of MS symptoms such as weakness and disorientation, while mice immunized with whey proteins did not. Immunization with casein led to a progressive increase in casein-reactive antibodies and deterioration of myelin in nerves of the lower spinal cord. The researchers found that casein-immunized mice produced autoantibodies that cross-react with myelin-associated glycoprotein (MAG), a protein produced by nerve cells called oligodendrocytes, which have a similar structure to casein. Finally, they found that 42 percent of participants with MS had casein-reactive antibodies compared to only 28 percent of participants with other neurological disorders.

    While it is not clear from these results what role dairy consumption plays in the development of MS, the authors suggest that some patients with MS may benefit from restricting dairy in their diet.

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  • Consumption of a fermented dairy beverage improves hippocampal-dependent relational memory in a randomized, controlled cross-over trial www.tandfonline.com
    Brain Memory Dairy

    Drinking kefir, a probiotic dairy beverage, improves memory.

    The community of microbes that comprise the gut microbiota act a bit like a sensory organ in the body, communicating information about the outside world to the brain and forming a gut-brain axis. Antibiotic and other medication use and changes in the diet can modulate the gut microbiota community in ways that reduce or increase the risk of neuropsychiatric illnesses such as depression. Findings of a recent report show that consuming a fermented dairy beverage may improve memory via changes in the gut-brain axis.

    The hypothalamic-pituitary-adrenal axis (i.e., gut-brain axis) is formed by neural and endocrine connections between the hypothalamis, a brain region that controls body temperature, hunger, and sleep; the pituitary gland, a endocrine organ in the brain that produces hormones; and the adrenal gland, which is located above the kidneys and produces hormones that regulate stress such as adrenaline and cortisol. This axis of stress control communicates directly with the hippocampus, the memory center of the brain, which helps the brain retain memories of stressful situations, but also contributes to the development of depression. Previous research shows that probiotics can reduced depression severity; however, additional research is necessary to understand the mechanisms of this relationship.

    The authors recruited 18 healthy adults and randomly assigned them to consume eight ounces of either kefir (i.e., a fermented dairy beverage with 12 strains of active bacteria) or low-fat lactose-free milk daily for four weeks. Participants completed questionnaires about their health, performed cognitive testing with electroencephalogram (EGG) measurement, and provided a fecal sample for the sequencing of the gut microbiome. After a washout period of about three weeks, participants switched to the opposite treatment and repeated the experiment.

    The authors found that Lactobascillus bacteria more than doubled following kefir consumption suggesting significant change in the gut microbial community. Participants consuming kefir performed better on two measures of memory called misplacement and object-location binding. The researchers did not observe changes in depression scores in either group.

    It’s important to note that more than 50 percent of participants in the study had a post-graduate degree, which could skew these results. Future studies in larger and more diverse populations are needed to better understand the effects of probiotics on the brain.

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  • Inflammatory injury from obesity is mediated by activation of TLR4 (but may be ameliorated by omega-3) www.sciencedaily.com
    Brain Obesity Omega-3 Inflammation Toll-Like Receptors Lipopolysaccharide

    Knocking out TLR4 in mice ameliorates obesity-associated inflammation, which may come as no surprise since increased circulation of LPS (a potent activator of TLR4) has been implicated in obesity due to associations with increased presence of LPS binding protein.

    While genetically knocking out TLR4 is probably not a practical solution to the inflammatory cascade associated with human obesity, which may also be a smoking gun in obesity-associated brain shrinkage and diminished cognition, dietary intake of omega-3 fatty acids EPA and DHA may at least be partly ameliorative (see review). Additionally, a study in breast cancer patients showed that 5 grams per day of EPA and DHA ultimately lead to hypermethylation (usually interpreted as suppressive) of TLR4.

    From the article:

    When a person consumes more calories than needed, the excess calories are stored in the form of triglycerides inside fat tissue, also known as white adipose tissue (WAT). Researchers know that in obese people, WAT becomes overworked, fat cells begin to die, and immune cells become activated. But the exact mechanism by which this inflammation occurs isn’t fully understood.

    […]

    After five months on a high-fat diet, the mice lacking Tlr4 had gained just as much weight, and just as much fat, as other mice on a high-fat diet. But the genetically engineered mice – with [fibro-inflammatory progenitors] that could no longer generate the same signals – no longer had high levels of inflammation. Instead, the levels of inflammatory molecules in their WAT were closer to the levels seen in mice on low-fat diets.

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  • Blocking toll-like receptor 4 with Naltrexone reduces alcohol seeking behavior in mice www.sciencedaily.com
    Brain Inflammation Alcohol Circadian Rhythm Behavior Toll-Like Receptors

    The circadian rhythm aspect of drug rewards: “Our body’s circadian rhythms affect the ‘reward’ signals we receive in the brain from drug-related behavior, and the peak time for this reward typically occurs during the evening, or dark phase. We wanted to test what the role of the brain’s immune system might have on that reward, and whether or not we could switch it off.”

    Using naltrexone to block TLR4 reduces alcohol behavior:

    The researchers focused their attention on the immune receptor Toll-like receptor 4 (TLR4). They administered the drug (+)-Naltrexone (pronounced: PLUS-NAL-TREX-OWN), which is known to block TLR4, to mice.

    “Our studies showed a significant reduction in alcohol drinking behavior by mice that had been given (+)-Naltrexone, specifically at night time when the reward for drug-related behavior is usually at its greatest,” Mr Jacobsen says.

    Interestingly and somewhat paradoxically, chronically activating TLR4 through genetic engineering-associated tricks also seems to reduce alcohol seeking in mice.

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  • TLR4 receptor involved in recognizing and triggering the innate immune system in response to bacteria may be involved in reinforcing binge drinking www.sciencedaily.com
    Brain Gut Alcohol Immune System Behavior Intestinal Permeability

    Genetic activation of TLR4 in the brain reduced binge drinking. What makes this so interesting is that alcohol consumption itself promotes intestinal permeability, which increases systemic activation of TLR4, potentially resulting in negative cardiovascular outcomes, among other things.

    From the article:

    One of the study’s most novel findings concerns TLR4’s important role in binge drinking. Science has traditionally considered TLR4 to be an innate immunity receptor involved with neuroinflammation in the brain. Scientists associated TLR4 with microglia, cells that support inflammatory responses in the brain. “What makes this finding particularly important for the field of neuroscience is that we’re showing that TLR4 plays a significant role in neurons, specifically, the neurons that are connected to the GABA receptor,” says Dr. June.

    To establish the connection between the GABA receptors, TLR4 and alcohol, the scientists manipulated this pathway in the binge drinking rodents. Dr. Aurelian was a pioneer in developing a method to inhibit gene expression, helping scientists to pinpoint the role of individual genes in the body. […] The scientists found that when they artificially stimulated the GABA receptors and TLR4 in order to simulate the good feelings binge drinkers feel when drinking alcohol, the rats lost interest in alcohol for two weeks after the procedure.

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  • Discovery highlights why women are more susceptible to Alzheimer's disease: follicle-stimulating hormone (FSH) may be a major pathogenic factor www.eurekalert.org
    Brain Alzheimer's Aging Neurodegeneration

    From the article:

    “During menopause, the serum concentration of FSH strongly increases, binding to the cognate FSH receptor on neurons and activating the C/EBPβ/AEP pathway. This results in Aβ and Tau pathologies, leading to the development of AD,” said Dr. Zaidi Mone, co-corresponding author of the study and a tenured professor at the Mount Sinai School of Medicine in New York.

    The researchers employed different methods to demonstrate this finding. Using ovariectomized mice, they used anti-FSH antibody treatment to block FSH and inactivate the C/EBPβ/AEP pathway. They also deleted FSH receptor (FSHR) expression in neurons to abolish the binding of FSH to FSHR in the hippocampus. Both of these methods alleviated pathology and cognitive dysfunction. In addition, knockdown of C/EBPβ in the AD mice model decreased AD pathologies.

    Besides working with female mice, the researchers also injected FSH into male mice and discovered that FSH promoted AD pathologies.

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  • Ketogenic diet and β-Hydroxybutyrate may improve disorders of epigenetic machinery via HDAC inhibition, reducing intellectual disability www.sciencedaily.com
    Brain Epigenetics Ketosis Intelligence HDAC Inhibitor Ketogenic Diet

    Ketogenic diet and beta-hydroxybutyrate improve gene transcription and reduce intellectual disability in Kabuki syndrome.

    Kabuki syndrome is a debilitating inherited disorder caused by mutations in two genes involved in the regulation of chromatin remodeling, one of the first steps in DNA transcription. Ketones such as beta-hydroxybutyrate have been shown to enhance DNA transcription and gene expression. Findings from one group of researchers show that a ketogenic diet can alleviate some of the neurological deficits of Kabuki syndrome and improve memory.

    Kabuki syndrome is named for the facial features common to people with the disorder, which looked similar to Kabuki theatre makeup to the Japanese scientists who first researched the disease. In addition to distinctive facial features, the syndrome causes a wide range of health problems such as heart defects, difficulty eating, weak muscle tone, immune deficiency, and intellectual disability. This wide range of severe health issues is explained by the fundamental importance of chromatin remodeling to the body’s functioning, which is impaired in those with Kabuki syndrome.

    Chromatin is the name for the coiled structure DNA forms within the cells of plants and animals, which looks a bit like a tangled telephone cord. This coiled structure prevents DNA from being opened and transcribed (the first step in gene expression and DNA replication) randomly. Chromatin is wrapped around histone proteins that open or close the chromatin, based on whether the histone has a chemical tag called an acetyl group attached or not. As DNA accumulates epigenetic changes over the lifespan, histones become resistant to acetylation, chromatin is harder to open, and gene expression slows. Histone deacetylase (HDAC) inhibitors, such as the ketone beta-hydroxybutyrate (BHB), are compounds that help release histones, open chromatin, prevent loss of gene expression with aging, and may even lengthen lifespan.

    The researchers used a strain of mice that have the same DNA mutations that cause Kabuki syndrome in humans and fed them either a normal diet or a ketogenic diet for two weeks. The researchers fed a third group of mice a normal diet and gave them three daily injections of BHB for two weeks. To assess memory and cognitive performance, mice completed a water maze, a sensitive measure of hippocampal function, which is closely related to memory. The researchers measured changes in gene expression, HDAC activity, and neurogenesis.

    Compared to a normal chow diet, a ketogenic diet increased the concentration of serum BHB, normalized acetylated histone levels, and increased the expression of several genes that are downregulated in Kabuki syndrome. These changes in gene expression enhanced multiple markers of neurogenesis and improved performance during the water maze test. Mice eating a normal diet that received daily BHB injections achieved similar serum BHB levels as mice eating a ketogenic diet and experienced the same gains in neurogenesis.

    This comprehensive study provides insight into the potential of ketogenic diets and supplemental BHB to improve deficits in gene expression in mice with a debilitating genetic disorder. Future research is needed in order to translate these insights into clinically useful information for humans.

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  • D-beta-hydroxybutyrate supplementation restored impaired brain function and protected against neurodegeneration in mouse model of Parkinson's disease www.sciencedaily.com
    Nutrition Brain Parkinson's Aging Ketosis Neurodegeneration

    From the article:

    Infusion of D-beta-hydroxybutyrate (D-beta-HB) to mice suffering from Parkinson disease restored impaired brain function and protected against neurodegeneration and motor skill abnormalities.

    […]

    Przedborski and colleagues administered the neurotoxin MPTP to mice, which caused dopaminergic neurodegeneration and deficits in the mitochondrial electron transport chain reminiscent of Parkinson disease. Using this model of disease, the authors showed that the infusion of the ketone body D-beta-HB restored mitochondrial respiration and protected against MPTP-induced neurodegeneration and motor deficits. The study supports a critical role for mitochondrial defect in Parkinson disease.

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  • Maintaining a lower systolic blood pressure (less than 120 mm Hg) may reduce the amount of white matter lesions, reducing risk of dementia www.sciencedaily.com
    Brain Aging Dementia Blood Pressure

    Maintaining a systolic blood pressure of 120 or less may protect against dementia and cognitive decline. Nearly two-thirds of adults living in the United States have hypertension (high blood pressure), defined as having a systolic pressure of 130 or higher or a diastolic pressure of 80 or higher. Hypertension damages small blood vessels in the eyes, kidneys, and other tissues, increasing the risk for disease and dysfunction. A 2019 study found that intensive blood pressure control in patients with hypertension reduces the risk of developing small blood vessel damage-related white matter lesions in the brain.

    Intensive blood pressure control is an aggressive treatment protocol for hypertension that seeks to achieve a target systolic blood pressure goal of 120 or less. This differs from standard treatment protocols, which stipulate that within three months of starting medication therapy to reduce high blood pressure, a patient’s target pressures (systolic and diastolic) should be less than 140/90. After three months, the target pressures should be less than 130/80.

    White matter lesions are areas in the brain that appear as intense white spots on magnetic resonance imaging (MRI) scans. They are often indicators of small blood vessel disease and are considered a risk factor for dementia.

    The study involved 670 adults (average age, 67 years) who had hypertension. Roughly half of the participants underwent intensive blood pressure control treatment, while the other half underwent standard treatment. The investigators performed MRI scans of all participants at the beginning of the intervention and again about four years later.

    They found that participants who underwent intensive blood pressure control had fewer white matter lesions in their brains compared to those who underwent the standard treatment. Interestingly, those who underwent intensive treatment exhibited greater brain volume losses than those who underwent standard treatment, but this difference was not statistically significant.

    These findings suggest that intensive blood pressure control reduces white matter lesions in the brains of people with hypertension and support findings from a related study that demonstrated that intensive blood pressure control may reduce the risk of adverse cognitive outcomes.

    Hypertension is highly preventable with lifestyle modifications that involve diet and exercise. For example, dietary components, such as potassium and magnesiumquercetin and vitamin D lower blood pressure. Aerobic exercise also lowers blood pressure. Learn about other beneficial effects of aerobic exercise in our overview article.

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  • Elevated blood pressure as low as 135/85 may result in enhanced brain aging: damage may build up over years, starting in a person's twenties www.sciencedaily.com
    Brain Heart Disease Dementia Blood Pressure

    Currently selected for this coming member’s digest by team member Melisa B.

    From the article:

    “Compared to a person with a high blood pressure of 135/85, someone with an optimal reading of 110/70 was found to have a brain age that appears more than six months younger by the time they reach middle age.”

    […]

    “By detecting the impact of increased blood pressure on the brain health of people in their 40s and older, we have to assume the effects of elevated blood pressure must build up over many years and could start in their 20s. This means that a young person’s brain is already vulnerable,” he said.

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  • Damage to the brain among elderly, known as white matter hyperintensities, prominent in people with history of subclinically elevated blood pressure www.sciencedaily.com
    Brain Dementia Blood Pressure

    From the article:

    The research, carried out by Dr Karolina Wartolowska, a clinical research fellow at the Centre for Prevention of Stroke and Dementia, University of Oxford, UK, looked for damage in the brain called “white matter hyperintensities” (WMH). These show up on MRI brain scans as brighter regions and they indicate damage to the small blood vessels in the brain that increases with age and blood pressure. WMH are associated with an increased risk of stroke, dementia, physical disabilities, depression and a decline in thinking abilities.

    Dr Wartolowska said: “Not all people develop these changes as they age, but they are present in more than 50% of patients over the age of 65 and most people over the age of 80 even without high blood pressure, but it is more likely to develop with higher blood pressure and more likely to become severe.”

    […]

    The researchers found that a higher load of WMH was strongly associated with current systolic blood pressure, but the strongest association was for past diastolic blood pressure, particularly when under the age of 50. Any increase in blood pressure, even below the usual treatment threshold of 140 mmHg for systolic and below 90 mmHg for diastolic, was linked to increased WMH, especially when people were taking medication to treat high blood pressure.*

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  • Red wine mitigates the negative neurological effects of high LDL cholesterol even without reducing its levels directly. www.tandfonline.com
    Brain Cholesterol Inflammation Alcohol

    Since the 1980’s, clinicians and researchers have been puzzled by the “French paradox”: the observation that residents of France have a surprisingly low incidence of cardiovascular disease given their high rates of smoking, intakes of saturated fat, and hypercholesterolemia (i.e. abnormally high serum levels of harmful low-density lipoprotein (LDL) cholesterol). A recent study now offers evidence that the negative health impacts of these common risk factors might be effectively mitigated by the French habit of regular red wine consumption.

    The authors of this study examined mice that had been genetically modified to lack LDL receptors – proteins crucial for removing LDLs from the bloodstream and initiating their degradation. This genetic modification, known as a “knock-out”, meant that the mice experienced a virtually life-long state of hypercholesterolemia, which served as the biological backdrop for an experiment on the potential health effects of wine consumption.

    At the age of three months (early mouse adulthood), animals were randomly assigned to receive 60 days of unlimited access to either plain tap water or red wine diluted to yield a 6% ethanol solution. This concentration ensured that the animals consumed the human equivalent of a 5-ounce glass of wine on a daily basis.

    When the researchers tested the mice on a variety of cognitive tasks, they discovered that the water-only group displayed learning and memory impairments characteristic of their poor lipid profiles. Their performance was particularly poor on a short-term memory test, where the animals turned out to be unable to recognize objects they had seen only an hour prior. Long-term memory retention was also compromised. In a test that required the animals to remember the location of an escape platform hidden in a tub of opaque water, the mice swam in the right direction only 20 percent of the time.

    Interestingly, wine-consuming mice were not impaired to the same degree. And while their plasma lipid profiles were no better compared to their water-drinking peers, they had substantially lower levels of several biomarkers of neuroinflammation, such as GFAP and lectin. The findings indicate that red wine compounds might help protect against the negative health outcomes of hypercholesterolemia by interfering with the associated inflammatory processes.

    Link to full study.

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  • Could the cure to alcoholism be a liver hormone modulated by aerobic exercise? FGF21 changes behavior of monkeys, reducing alcohol consumption by 50% newatlas.com
    Exercise Brain Behavior Addiction Aerobic FGF21

    From linked article:

    The researchers gave the monkeys a two-bottle choice between water and ethanol, and administered one group an analog of FGF21 to see what effect it had. Sure enough, the test monkeys drank 50 percent less alcohol than the control group. Similar tests in mice also saw a 50-percent reduction in alcohol consumption after being given either human FGF21 or an analog. Interestingly though, the mice and monkeys still chose the ethanol just as often as before, but they drank far less each time.

    Fibroblast growth factor 21 happens to be modulated by aerobic exercise:

    In a new study published in the scientific Journal of Clinical Investigation – Insight, the researchers show that cardio training on an exercise bike causes three times as large an increase in the production of the hormone FGF21 than strength training with weights. FGF21 has a lot of positive effects on metabolism.

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  • A mitochondrial link to depression: master regulator of mitochondrial biogenesis PGC-1 alpha protects mice from stress-induced depression www.sciencedaily.com
    Exercise Brain Depression Mitochondria

    From the article:

    It was known that the protein PGC-1a1 (pronounced PGC-1alpha1) increases in skeletal muscle with exercise, and mediates the beneficial muscle conditioning in connection with physical activity. In this study researchers used a genetically modified mouse with high levels of PGC-1a1 in skeletal muscle that shows many characteristics of well-trained muscles (even without exercising).

    These mice, and normal control mice, were exposed to a stressful environment, such as loud noises, flashing lights and reversed circadian rhythm at irregular intervals. After five weeks of mild stress, normal mice had developed depressive behaviour, whereas the genetically modified mice (with well-trained muscle characteristics) had no depressive symptoms.

    Eliminating the neurotoxic effects of kynurenine:

    The researchers discovered that mice with higher levels of PGC-1a1 in muscle also had higher levels of enzymes called KAT. KATs convert a substance formed during stress (kynurenine) into kynurenic acid, a substance that is not able to pass from the blood to the brain. The exact function of kynurenine is not known, but high levels of kynurenine can be measured in patients with mental illness.

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  • Exercise induces epigenetic changes in mice that enhance learning and brain function in their offspring www.sciencedaily.com
    Exercise Brain Epigenetics Memory Development

    From the article:

    In mice, the scientists showed that learning ability was passed onto the next generation by epigenetic inheritance. When Fischer and co-workers exposed mice to a stimulating environment in which they had plenty of exercise, their offspring also benefited: compared to the mice of a control group, they achieved better results in tests that evaluate learning ability. These rodents were also found to have improved synaptic plasticity in the hippocampus, a region of the brain important for learning

    Both mental and physical activity of the parents matter:

    The researchers also found that miRNA212 and miRNA132 accumulated in the brains and sperm of mice after physical and mental activity. It was previously known that these molecules stimulate the formation of synapses in the brain, thus improving learning ability. Through the sperm, they are transmitted to the next generation. “Presumably, they modify brain development in a very subtle manner improving the connection of neurons. This results in a cognitive advantage for the offspring,” says Fischer.

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  • Exercise may improve thinking skills and thicken areas of the brain in people as young as 20 www.sciencedaily.com
    Exercise Brain Aging Performance

    From the article:

    Researchers found that aerobic exercise increased thinking skills. From the beginning of the study to the end, those who did aerobic exercise improved their overall scores on executive function tests by 0.50 points, which was a statistically significant difference from those who did stretching and toning, who improved by 0.25 points. […] “Since a difference of 0.5 standard deviations is equivalent to 20 years of age-related difference in performance on these tests, the people who exercised were testing as if they were about 10 years younger at age 40 and about 20 years younger at age 60,” Stern said.

    Increased thickness of the outer layer of the brain in the left frontal area:

    “Since a difference of 0.5 standard deviations is equivalent to 20 years of age-related difference in performance on these tests, the people who exercised were testing as if they were about 10 years younger at age 40 and about 20 years younger at age 60,” Stern said.

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  • Rebalancing gut microbiome with butyrate lengthens survival in mouse model of ALS by repairing intestinal permeability www.sciencedaily.com
    Brain Aging Microbiome Neurodegeneration Butyrate Intestinal Permeability

    From the article:

    In a mouse model of ALS, the compound butyrate helped correct a gut microbiome imbalance and reduced gut leakiness – both symptoms of ALS. The treated mice lived also longer compared to mice that weren’t given butyrate.

    […]

    When the researchers fed the ALS-prone mice butyrate in their water, starting when the mice were 35 to 42 days old, the mice showed a restored gut microbiome profile and improved gut integrity. Butyrate-treated mice also showed improved neuromuscular function and delayed onset of ALS symptoms. Treated mice showed symptoms at 150 days old compared to control mice at about 110 days. Treated mice also lived an average 38 days longer than mice not given butyrate.

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  • Gene enhancers activated by exercise are hotspots of inter-individual variation and linked to cognitive abilities www.sciencedaily.com
    Exercise Brain Epigenetics Aging Aerobic

    From the article:

    The scientists discovered that after completing the endurance training program, the structure of many enhancers in the skeletal muscle of the young men had been altered. By connecting the enhancers to genetic databases, they discovered that many of the regulated enhancers have already been identified as hotspots of genetic variation between individuals – hotspots that have been associated with human disease.

    The scientists speculate that the beneficial effects of exercise on organs distant from muscle, like the brain, may largely be mediated by regulating the secretion of muscle factors. In particular, they found that exercise remodels enhancer activity in skeletal muscle that are linked to cognitive abilities, which opens for the identification of exercise training-induced secreted muscle factors targeting the brain.

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  • A high-polyphenol diet is protective against age-related brain shrinkage. www.eurekalert.org
    Brain Alzheimer's Obesity Aging Green Tea Nuts Dementia Urolithin A

    “The effect of diet on age-related brain atrophy is largely unproven.

    This 18-month clinical trial longitudinally measured brain structure volumes by magnetic-resonance-imaging…Abdominally obese/dyslipidemic participants were randomly assigned to (1)-healthy dietary guidelines (HDG), (2)-Mediterranean (MED) diet, or (3)-Green-MED diet (MED diet higher in polyphenols and lower in red/processed meat). All subjects received free gym memberships and physical activity guidance. Both MED groups consumed 28g/day walnuts (+440 mg/d polyphenols). The Green-MED group consumed green-tea (3-4 cups/day) and Mankai (Wolffia-globosa strain, 100g frozen-cubes/day) green shake (+800mg/day polyphenols).

    Compared to younger participants, atrophy was accelerated among those ≥ 50 years. In subjects ≥50years, HOC decline and LVV expansion were attenuated in both MED groups, with the best outcomes among Green-MED diet participants, as compared to HDG. Similar patterns were observed among younger subjects. Improved insulin sensitivity over the trial was the strongest parameter associated with brain atrophy attenuation (p<0.05). Greater Mankai, green-tea and walnuts intake and less red and processed meat were significantly and independently associated with reduced HOC decline (p<0.05). Elevated urinary levels of the Mankai-derived polyphenols: urolithin-A (r = 0.24;p = 0.013) and tyrosol (r = 0.26;p = 0.007) were significantly associated with lower HOC decline.

    A Green-MED, high-polyphenol diet, rich in Mankai, green tea and walnuts and low in red/processed meat is potentially neuroprotective for age-related brain atrophy."

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  • Exercise reverses aspects of brain aging: improvements in executive function, mental flexibility, verbal fluency, and blood flow to the brain neurosciencenews.com
    Exercise Brain Aging Aerobic

    Aging drives an array of physiological, functional, and mental changes in the human body. It is the primary risk factor for many chronic diseases in humans, including cancer, Alzheimer’s disease, and cardiovascular disease. Findings from a 2020 study suggest that exercise reverses some of the harmful effects of aging on the brain.

    Scientists have identified strong links between regular physical exercise and brain health. Some of the mechanisms that drive the beneficial effects of exercise on the brain include increases in brain volume and connectivity, improved blood flow, enhanced synaptic plasticity, and increased neurogenesis – the formation of new neurons.

    The intervention study involved 206 healthy, cognitively intact middle-aged and older adults (average age, 66 years) with low physical activity levels. The participants engaged in a supervised aerobic exercise program three days per week, gradually increasing from 20 to 40 minutes over a period of six months. They also completed an unsupervised exercise session one day per week during the six-month period. The authors of the study assessed the participants' cognitive performance, cerebrovascular function, and overall fitness on three separate occasions over a period of 12 months.

    After completing the six months of exercise, the authors of the study noted that the study participants improved by nearly 6 percent on measures of working memory, flexible thinking, and self-control. They improved by nearly 2.5 percent on tests of verbal fluency, comparable to abilities seen in person five years younger. Blood flow to the brain increased by nearly 3 percent, suggesting that cerebrovascular function is a critical aspect of maintaining or improving memory and verbal skills.

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  • Leg exercise may be critical to brain: leg suspension reduces neural stem cells in subventricular zone by 70% compared to controls (animal study) www.sciencedaily.com
    Exercise Brain Stem Cells

    From the article:

    The study involved restricting mice from using their hind legs, but not their front legs, over a period of 28 days. The mice continued to eat and groom normally and did not exhibit stress. At the end of the trial, the researchers examined an area of the brain called the sub-ventricular zone, which in many mammals has the role of maintaining nerve cell health. It is also the area where neural stem cells produce new neurons.

    Limiting physical activity decreased the number of neural stem cells by 70 percent compared to a control group of mice, which were allowed to roam. Furthermore, both neurons and oligodendrocytes – specialized cells that support and insulate nerve cells – didn’t fully mature when exercise was severely reduced.

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  • Treadmill running at 80% maximal aerobic capacity for 1 hour 5 days per week enhanced learning and vascularization of the motor cortex (primate study) www.sciencedaily.com
    Exercise Brain Aerobic

    From the article:

    “We found that monkeys who exercised regularly at an intensity that would improve fitness in middle-aged people learned to do tests of cognitive function faster and had greater blood volume in the brain’s motor cortex than their sedentary counterparts,” Dr. Cameron said. “This suggests people who exercise are getting similar benefits.” For the study, the researchers trained adult female cynomolgus monkeys to run on a human-sized treadmill at 80 percent of their individual maximal aerobic capacity for one hour each day, five days per week, for five months.

    […]

    “Monkeys that exercised learned to remove the well covers twice as quickly as control animals,” Dr. Cameron said. “Also, they were more engaged in the tasks and made more attempts to get the rewards, but they also made more mistakes.

    […]

    When the researchers examined tissue samples from the brain’s motor cortex, they found that mature monkeys that ran had greater vascular volume than middle-aged runners or sedentary animals. But those blood flow changes reversed in monkeys that were sedentary after exercising for five months.

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  • Six months of daily aerobic exercise directly impacts tests of executive function, mental flexibility, self-correction, and verbal fluency www.sciencedaily.com
    Exercise Brain Aging Memory Aerobic

    From the article:

    Participants were enrolled in a supervised aerobic exercise program held three days a week. As they progressed through the program, they increased their workout from an average of 20 minutes a day to an average of at least 40 minutes. In addition, people were asked to work out on their own once a week.

    Researchers found that after six months of exercise, participants improved by 5.7% on tests of executive function, which includes mental flexibility and self-correction. Verbal fluency, which tests how quickly you can retrieve information, increased by 2.4%.

    […]

    Before and after six months of aerobic activity, the participants' average peak blood flow to the brain was measured using ultrasound. Blood flow rose from an average of 51.3 centimeters per second (cm/sec) to an average of 52.7 cm/sec, a 2.8% increase. The increase in blood flow with exercise was associated with a number of modest but significant improvements in aspects of thinking that usually decline as we age, Poulin said.

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  • Exercise preserves connections in the brain, providing protection against Alzheimer's disease.
    Exercise Brain Aging

    A growing body of evidence indicates that exercise supports cognitive health throughout the lifespan, even into one’s later years. Scientists don’t fully understand the mechanisms that drive the beneficial effects of exercise, but some studies suggest that it increases brain volume, while others suggest that it reduces the brain’s toxic burden. Findings from a recent study suggest that exercise maintains synapses in the brains of older adults.

    Synapses are junctions between neighboring neurons, where the exchange of electrical signals and neuronal communication occurs. Synaptic formation and integrity are necessary for the establishment and maintenance of the brain’s neural networks and the precision of its circuitry. The loss of synapses promotes the collapse of neural networks important for memory and cognition and drive the dementia associated with Alzheimer’s disease. Key players in synaptic integrity are synaptic proteins, which play critical roles in neurotransmission and neuronal development.

    The investigators drew on data from the Rush Memory and Aging Project, an ongoing study of aging and Alzheimer’s disease among older adults. More than 400 older adults participated in the study. They wore activity monitors to track their movement and exercise throughout the day for up to 10 days. They also agreed to donate their brains upon their death for postmortem evaluation, during which the investigators measured the presence of synaptic proteins in the participants' brain tissue.

    They found that older adults who exercised regularly had higher levels of synaptic proteins in their brains. The proteins were present in multiple brain regions, including areas involved in memory and cognitive function, and were highest when activity levels were measured within two years of death, suggesting that without sufficient exercise, the proteins diminished over time.

    These findings suggest that exercise preserves synaptic integrity via enhanced production of synaptic proteins, potentially providing protection against Alzheimer’s disease. Learn how exercise affects other aspects of brain health in this episode featuring Dr. Giselle Petzinger.

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  • Meditation improves the error detection capacity of the brain. www.sciencedaily.com
    Brain Meditation

    Meditation is a form of mental training geared toward improving a person’s core neurocognitive function, such as regulation of attention and emotion. Open monitoring meditation, often referred to as “being present,” trains a person to engage in non-judgmental attention to present-moment experiences. Findings from a 2019 study suggest that open monitoring meditation improves a neurocognitive function called error monitoring.

    Error monitoring is the process by which the brain detects and responds to mistakes. It reflects core cognitive control processes that underlie emotional and behavioral regulation and plays key roles in learning, academic achievement, and work performance.

    The study involved 212 healthy female college students (average age, 19 years) who had never practiced meditation before. Half of the participants engaged in a 20-minute open monitoring meditation exercise, while the other half listened to an audio lecture. The investigators measured the participants' brain activity in both activities via electroencephalography (EEG). After completion of their respective activities, the participants took a computerized test to gauge distraction and performance.

    The EEGs revealed that brain activity related to conscious error detection increased in the participants who participated in the meditation. No changes in error detection were noted in the participants who listened to the audio lecture.

    These findings suggest that open monitoring meditation enhances the brain’s capacity to detect and pay attention to mistakes, potentially reducing the number of errors a person makes. Learn about other health benefits of meditation in this episode featuring Dr. Rhonda Patrick.

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  • Just one sugar-sweetened beverage per week impairs executive function in children. www.eatthis.com
    Brain Sugar Blood Sugar

    Sugar-sweetened beverage consumption in the United States has decreased in recent decades, hopefully translating into lower rates of obesity and cardiovascular disease, both associated with excess sugar consumption. Although the cardiometabolic effects of added sugars in adults have been well-documented, the effects of sugar sweetened beverages on brain function, especially in children, is under-investigated. Findings of a new report show an association between sugar-sweetened beverage consumption and poorer cognitive performance in children.

    Executive function refers to a set of high-level cognitive skills, such as complex reasoning, goal-oriented activity, and self-regulation, that begin development during gestation and continue throughout childhood. Previous research has demonstrated that excess sugar consumption causes neuroinflammation, decreased hippocampal function, and poorer spatial learning ability in adolescent rats, but not adult rats. While it is plausible that excess sugar consumption causes similar effects in children, this area is under-investigated, especially in less developed countries such as China.

    The researchers recruited more than 6,000 children (ages, 6 to 12 years) who were enrolled at one of five participating school districts in Guangzhou, China. Parents of these children completed questionnaires about their child’s sugar-sweetened beverage (e.g., soda, fruit juice, energy drinks) consumption, executive function (e.g., emotion regulation, organizing, memory), and other demographics and lifestyle information (e.g., socioeconomic status, parental education, parental smoking status, exercise habits). The researchers categorized children as consuming zero, one, or two or more eight ounce servings of sugar-sweetened beverages per week.

    Compared to non-consumers, children who consumed even one serving of sugar-sweetened beverages per week had worse scores on all executive functioning subscales including behavior regulation and metacognition. This trend was even stronger in children consuming two or more servings per week, with a 45 percent increased chance of poor behavior regulation and 70 percent increased chance of poor metacognition compared to non-consumers. These relationships were not altered when taking sex, age, and BMI into account.

    In this large observational study, consumption of just one serving of sugar-sweetened beverages per week was associated with worse executive function in children. The authors noted that interventional trials are needed to establish the causal mechanisms of this relationship.

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  • Colorful compounds in berries promote brain and heart health. www.mdpi.com
    Nutrition Brain Heart Disease Polyphenol

    Berries are a colorful and nutritious food containing many types of bioactive compounds, including anthocyanins, a type of polyphenol with blue/purple pigment. Anthocyanins from berries such as blueberries, black raspberries, chokeberries, and bilberries are recognized for their ability to protect against cardiovascular and neurodegenerative diseases. Findings of a recent systematic review provide robust evidence demonstrating the beneficial effects of anthocyanins on cognitive performance and cardiovascular disease risk factors.

    Cognitive performance refers to a set of mental skills such as attention, memory, psychomotor speed, and executive function that develop through early adulthood and then decline in old age. As the world population ages, cognitive impairment is a growing public health concern that requires targeted strategies for prevention. Impaired vascular function, a factor that contributes to poor brain health and cognitive performance with age, may be modifiable with diet and lifestyle changes. Previous research has demonstrated that eating blueberries improves vascular function (measured with flow mediated dilation) in healthy men; but further research is needed to understand the molecular mechanisms.

    Polyphenols are a large class of bioactive compounds found in fruits, vegetables, teas, coffee, wine, and olive oil with antioxidant properties because of their many phenol rings. Due to their special cyclized electron structure, phenols capture and neutralize oxygen radicals and reflect light at unique wavelengths, giving them vibrant color. A previous systematic review of research on blueberries found good evidence to support their ability to improve memory, executive function, and psychomotor function in adults with mild cognitive impairment; however, less research has focused on total anthocyanins in the diet.

    The authors searched for studies investigating the six most anthocyanin-rich fruits (i.e., blackcurrant, black raspberry, blueberry, bilberry, chokeberry, and elderberry). They selected all randomized, placebo-controlled intervention studies in humans that investigated at least one cardiometabolic or cognitive performance parameter for inclusion in their analysis. Although methods of data collection used among the studies widely varied, the authors extracted data from their selected studies and combined it into clusters for comparison.

    The authors of the review investigated the effects of berry anthocyanin supplementation on memory in 14 studies with mostly older adult participants, revealing improved memory, especially verbal memory, and symptoms of mild cognitive impairment. In young and middle-aged adults, multiple studies found improvements in attention and psychomotor speed with anthocyanin supplementation. The research revealed that short-term berry supplementation was sufficient to produce benefits on attention and psychomotor speed, but long-term supplementation was best for memory.

    All studies that measured flow mediated dilation, the most accurate measure of vascular function, found an improvement following anthocyanin supplementation except for one study in smokers. Long-term berry supplementation also lowered blood pressure in adults at high risk for cardiometabolic disease, but not healthy adults, indicating that individual characteristics alter a person’s response to anthocyanin supplementation.

    This large systematic review provides robust evidence for the beneficial effects of berry anthocyanins on multiple markers of cognitive and cardiovascular performance.

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  • The brain can remember and resurrect immune responses to previous infections. www.scientificamerican.com
    Brain Immune System

    The brain’s inner workings have traditionally been viewed as separate from “unconscious” physiological functions like immunity. Yet, recent research has uncovered a surprising degree of reciprocal brain-immune system interaction. For example, biomarkers of peripheral immunity influence brain aging and cognition, and dopamine-rich reward circuits in the brain influence systemic antibacterial activity in immune cells. A recent study now reveals that specific brain cells store memories of the body’s past experiences with infections, potentially reawakening previous immune responses.

    The researchers first measured brain activity in a group of mice that had inflammatory bowel disease. Their measurements revealed that the bowel inflammation and its associated immune response generated a broad pattern of activity across several regions of the brain, especially the insular cortex, a region considered crucial for receiving and processing information about internal bodily states and immune system activities.

    Then, to test whether the pattern of neuronal activity in the insular cortex represented a true memory of bowel inflammation, they examined how the mice reacted when the insular neurons were reactivated four weeks after the animals' recovery from illness. The result was a near-perfect revival of the original immune response to bowel inflammation, including a surge of white blood cells to the colon, heightened activation of a range of T-cells specialized for sensing and attacking pathogens, and a spike in pro-inflammatory molecules such as interleukins and tumor necrosis factor-alpha.

    The brain-induced immune event exhibited two features that indicated it was a form of recollection. First, it was exclusively located in the colon, suggesting a relatively precise “memory” of bowel inflammation rather than a generic signal for immune defense. Second, a repeated experience with simulated bowel disease caused the insular cortex to generate a new and largely non-overlapping pattern of immune-triggering activity. This indicates that the insular cortex is capable of “remembering” distinct episodes of the body’s encounters with disease.

    This study provides some of the first causal evidence that brain cells can form memories of past immune reactions – a property that may have evolved to help bodily tissues become faster and more precise in how they tackle future infections. While the mechanisms of these neuro-immune interactions are not fully understood, the interactions offer the potential for targeted insular brain stimulation to treat severe autoimmune and inflammatory health conditions.

    Link to full publication.

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  • Loneliness is associated with a less diverse microbiota, a marker of disease. www.inverse.com
    Brain Gut

    Social support is a necessary resource for maintaining physical and mental health. Conversely, loneliness is associated with depression, poor sleep, impaired cognitive function, and early death. Findings of a new study show a relationship between the gut microbiota and feelings of wisdom, compassion, and social support.

    The gut microbiota is composed of bacteria and other microorganisms that are unique to each individual. A microbiota with high alpha-diversity, meaning a greater number of microbial species, supports health and reduces the risk of diseases such as inflammatory bowel disease and liver disease. Scientists don’t fully understand how gut microbiota diversity relates to social support.

    The investigators analyzed data from 184 participants between the ages of 21 and 100 years who were taking part in a larger study about aging. Participants completed a phone interview during which they answered questions about their social habits, health, and wellbeing. They also provided a fecal sample for sequencing of bacterial DNA in their gut microbiota.

    The data revealed a significant statistical relationship among alpha-diversity and loneliness, wisdom, social support, compassion, and social engagement. Individuals with low alpha-diversity reported higher levels of loneliness and lower levels of all positive social variables. These relationships remained significant even when taking age and body mass index (a proxy for body fat) into account. The researchers found no relationship between alpha-diversity and sex, physical health, or depression.

    These results are the first to show an association between low alpha-diversity and loneliness. Although the researchers found no association between low alpha-diversity and poor mental and physical health in this study, future studies are needed to explore this relationship further. This research is especially important given that loneliness has sharply increased during the COVID-19 pandemic.

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  • Estrogen may provide protection against Alzheimer's disease. medicalxpress.com
    Brain Estrogen

    Scientists have long known that estrogen, the primary female sex hormone, exerts protective effects on multiple organ systems. For example, estrogen helps maintain healthy blood lipid levels, reduces the risk of cardiovascular disease, and promotes bone health. Findings from a recent study suggest that estrogen protects against age-related cognitive decline and Alzheimer’s disease.

    Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive decline and memory impairment. The disease disproportionally affects women, and scientists have identified distinct sex-related differences in Alzheimer’s disease symptoms, progression, biomarkers, and risk factors. Interestingly, the pathological hallmarks of Alzheimer’s disease begin to appear 10 to 20 years before the onset of symptoms – roughly coinciding with the period of menopause in women.

    The study involved 99 women and 29 men (average ages, 52 years) who were cognitively normal. The women provided information about their reproductive histories, such as when they began menstruating, how many pregnancies they had, when they experienced menopause, and whether they had used hormonal contraceptives or hormone replacement therapy. Both women and men underwent memory testing and brain scans.

    The scans revealed that the women who were peri- or postmenopausal had less gray matter volume in the temporal cortex, an area of the brain vulnerable to the effects of Alzheimer’s disease. Women who were premenopausal or had longer estrogen exposure due to their reproductive histories were more likely to have greater gray matter volumes. Exposure to estrogen did not influence performance on the memory tests directly, but participants with greater gray matter volume tended to perform better than those with lower volume.

    These findings suggest that estrogen exposure exerts protective effects on brain health and illuminate the need for sex-specific research on Alzheimer’s disease pathology and therapies. This was a small study, however, and only identified associations between estrogen exposure and brain health, not causes.

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  • Methyl donor supplements negate harmful effects of high-sugar diet. apple.news
    Brain Depression Anxiety

    Depression and anxiety are neuropsychiatric diseases characterized by neurological dysfunction and poor mental health. Oxidative stress, which is caused by an imbalance in the concentration of reactive oxygen species and antioxidant compounds, may be one driver of neurological damage in the development of depression and anxiety. Findings of a new report demonstrate the ability of methyl donor supplementation to reduce oxidative stress in the brain and relieve depression and anxiety symptoms in rats eating a high-sugar diet.

    Methyl donors (e.g., choline, betaine, folate, vitamin B12) are nutrients that provide a methyl group (one carbon and three hydrogen molecules) for a series of chemical reactions in the body. Methyl donors interact with the methyl carrier, S-adenosyl-L-methionine (SAM) and methylation enzymes to complete the transfer of a methyl group from the donor to a target protein, lipid, or nucleic acid. Methylation of nucleic acids in DNA and ribonucleic acids in RNA is necessary for epigenetic modifications and gene expression. Good dietary sources of methyl donors include egg yolks and soy foods (high in choline); whole grains (high in betaine); green vegetables (high in folate); and meat, dairy, and fortified products (high in vitamin B12).

    Methyl groups may also have antioxidant properties that protect the body from oxidative damage due to environmental stress, such as a high sugar diet, and emotional stress. Previous research has demonstrated the ability of methyl donor supplementation to reduce the metabolic and neuropsychiatric impairments caused by a high sugar diet in rats.

    The investigators fed 21 female rats a standard chow diet with either tap water (7 rats) or drinking water with 23 percent fructose added (equivalent to twice the sugar concentration of most sodas)(14 rats). After 10 weeks, the investigators gave half of the rats in the fructose group methyl donor supplements (i.e., choline, betaine, folate, and vitamin B12). The rats continued the study for an additional eight weeks. The researchers measured the effects of fructose and methyl donors on metabolism, behavior, and brain health.

    A high-fructose diet caused increased weight gain, fasting glucose and triglycerides, and anxiety and depression behaviors compared to a standard diet. A high-fructose diet also increased oxidative damage and lipid peroxidation in the neurons of the hippocampus, a key brain region damaged by depression and anxiety. After eight weeks of methyl donor supplementation, this hippocampal damage was reversed, reducing depression and anxiety behavior. Methyl donor supplementation also normalized glucose, triglyceride, and cholesterol levels among rats consuming a high-fructose diet.

    These results demonstrate the efficacy of methyl donor supplementation to reduce or reverse the promotion of obesity, metabolic disease, and depression and anxiety on a high-fructose diet in rats.

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  • Maternal body weight influences risk of ADHD and obesity in offspring. apple.news
    Brain Obesity Pregnancy ADHD Genetics

    A woman’s body weight before and during pregnancy can have profound health effects on both mother and child. Women with obesity are at greater risk for developing pregnancy complications that can impair infant neurodevelopment, such as gestational diabetes, preeclampsia, preterm birth, and birth trauma. Findings from a new study suggest that maternal obesity contributes to attention deficit hyperactivity disorder (ADHD) and obesity in offspring.

    ADHD is a neuro-behavioral condition characterized by inattention and/or hyperactive or impulsive behavior that interferes with functioning, learning, or development. Obesity is characterized as having excessive body fat – typically defined as having greater than 25 percent body fat for males and greater than 33 percent body fat for females.

    The study included nearly 3,000 Finnish women and their offspring (~9,400 children). The authors of the study collected information about the children’s behavior and attention span from mothers and teachers. They gathered anthropometric data to determine the mothers' and children’s body mass index (BMI), a proxy for body fatness. They used Mendelian randomization and polygenic risk scores to assess risk for ADHD and/or obesity. Mendelian randomization is a research method that provides evidence of links between modifiable risk factors and disease based on genetic variants within a population. A polygenic risk score estimates a person’s genetic propensity for developing a trait or disease.

    They found that children whose mothers had a high BMI were more likely to develop ADHD, independent of genetic makeup. The Mendelian randomization analysis identified a bidirectional link between developing ADHD and obesity-related traits, suggesting that certain genetic variations may predispose children to both ADHD and obesity concurrently. The polygenic risk score revealed evidence for genetic overlap between having ADHD and greater BMI.

    These finding suggest that both genetic and prenatal environmental factors influence the likelihood that a woman’s child will develop ADHD and obesity. They also underscore the importance of maintaining a healthy maternal body weight before and during pregnancy.

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  • Maternal diabetes causes birth defects by increasing cellular aging. apple.news
    Brain Aging Diabetes Pregnancy

    Neural tube defects (e.g., spina bifida, hydranencephaly) are a group of birth defects caused by incomplete development of the outer layers of the brain or spinal cord. Prenatal folate supplementation prevents an estimated 70 percent of neural tube defects, but additional therapies are needed. A recent report describes the relationship between maternal diabetes and abnormal cell aging in the fetal nervous system in mice.

    Previous research has demonstrated a relationship between maternal diabetes and the incidence of neural tube defects in mice; however, the mechanisms that drive this relationship are unknown. High blood glucose levels cause oxidative damage and promote cellular senescence, a state in which cells are not metabolically active and do not reproduce. Aging cells accumulate damage over time and become senescent. In adults, an excess of senescent cells can promote inflammation and disease. In the developing fetus, senescence is vital for tissue remodeling and the building of limbs and organs. However, inappropriate senescence may lead to abnormal development.

    The investigators used multiple mouse models in their study. In a first experiment, they used a strain of mice that develop diabetes and compared them to wild-type mice that are not predisposed to any disease. They injected pregnant females from both groups with either rapamycin, a compound that slows cellular aging by inhibiting the enzyme mTOR, or a placebo. In a second experiment, they used diabetic and non-diabetic strains of knockout mice, whose genomes do not contain the gene FoxO3a, a regulator of aging that may slow cellular senescence.

    Maternal diabetes increased the abundance of biomarkers of cellular senescence and DNA damage in the lining of the brain in offspring. Pregnant diabetic mice that were exposed to rapamycin had offspring with lower levels of senescence biomarkers and fewer neural tube defects compared to placebo. Offspring from FoxO3a knockout mice experienced the same decrease in senescence biomarkers and neural tube defect rates as rapamycin-treated mice.

    These results elucidate the mechanisms by which maternal diabetes can cause birth defects through metabolic changes that accelerate aging. Learn more about the role of cellular senescence in aging in this episode featuring Dr. Judith Campisi.

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  • Whole-body hyperthermia activates muscle hormone irisin and increases neuroprotective factors. www.sciencedirect.com
    Exercise Brain Muscle Sauna BDNF Neurodegeneration

    Exposure to high heat while sauna bathing causes mild hyperthermia – an increase in the body’s core temperature – that induces a thermoregulatory response to restore homeostasis and condition the body for future heat stressors. These adaptations to high temperatures involve increased production of brain derived neurotrophic factor (BDNF), a promoter of neuroplasticity, and irisin, a biomarker of exercise. Findings of a new report demonstrate that whole-body hyperthermia increases BDNF and irisin in healthy young adults.

    Whole-body hyperthermia is a therapeutic strategy used to treat various diseases, including cancer and depression. Previous research has shown that use of a hyperthermia chamber increases BDNF to a greater extent than light intensity exercise. Some research has suggested that BDNF production is stimulated by irisin, a hormone secreted from muscle in response to exercise. Irisin may mediate some of the beneficial effects of exercise and sauna use in humans, but additional research is needed.

    The authors recruited 20 male participants (average age, 22 years) and assessed their baseline heat tolerance using a hyperthermia protocol. Participants reclined in a hyperthermia chamber while the researchers increased the temperature of the chamber by 50 degrees F every ten minutes until the participant reached their personal heat threshold. Next, participants completed ten hyperthermia sessions tailored to their baseline conditioning, during which the hyperthermia chamber was set to a temperature of 150 to 175 degrees F. Following a three-week wash-out period, they completed ten sham treatments over two weeks, during which the hyperthermia chamber was set to a temperature of 75 to 77 degrees F.

    Participants had an average core body temperature of 102 degrees F at the end of each whole-body hyperthermia treatment. Following ten whole-body hyperthermia treatments, participants had a significant increase in circulating irisin levels (6.3 micrograms per milliliter) compared to their baseline levels (5.0 micrograms per milliliter) and compared to their irisin levels following the sham treatment (5.4 micrograms per milliliter). Whole-body hyperthermia treatment also significantly increased BDNF levels (28.3 picograms per liter) compared to baseline (25.9 picograms per liter).

    In healthy young adults, ten whole-body hyperthermia significantly increased irisin and BDNF levels. The authors noted that future studies should explore the effects of whole-body hyperthermia on adipose tissue, which also produces irisin.

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  • Irisin, a muscle hormone, mediates the neuroprotective effects of exercise. www.massgeneral.org
    Exercise Brain Alzheimer's Aging Hormones Neurodegeneration

    Aging causes brain changes that impair cognitive function, even in people who do not have Alzheimer’s disease or dementia. However, lifestyle factors like diet and exercise have significant influence over the rate of cognitive decline. Previous research has shown that exercise improves brain health and cognitive function during aging. A new report details the role of the muscle hormone irisin in the neuroprotective effects of exercise

    Irisin, a type of myokine, is a hormone secreted from muscle in response to exercise. Previous research has shown that irisin may mediate some of the beneficial effects of exercise on the brain by stimulating the production of brain-derived neurotrophic factor (BDNF), a growth factor that increases neuroplasticity. Irisin is a fragment of the prohormone FNDC5, which is attached to the membranes of muscle cells. During exercise, irisin is cleaved from FNDC5 and circulates throughout the body to induce adaptations to exercise.

    The authors used mice of varying ages who lack the genes necessary to produce FNDC5, called knock-outs, and genetically-normal mice, called wild-type. Both groups of mice completed exercise testing to measure balance, grip strength, endurance, and motor coordination; a water maze test to measure spatial learning ability and memory; and an open field test to measure locomotor activity levels, anxiety, and willingness to explore. In order to study the effects of irisin supplementation, the investigators conducted a second experiment in which they administered exogenous (i.e., made outside the body) irisin to a strain of mice who develop an Alzherimer’s-like dementia at an early age due to loss of FNDC5 function. The investigators measured structural and psychological changes in the brain throughout both experiments.

    Both knock-out and wild-type mice exercised the same amount during testing. However, unlike the wild-type mice, knock-out mice did not show exercise-induced improvements in spatial learning and memory. Aged knock-out mice had more cognitive decline than wild-type mice and were less likely to prefer novel objects, a behavior associated with loss of function in the hippocampus, the brain region most associated with memory loss in dementia. Indeed, aged knock-out mice showed abnormal neuronal activation patterns in the dentate gyrus, a structure within the hippocampus that contributes to memory formation.

    In contrast to knock-out mice and sedentary wild-type mice, wild-type mice who exercised had increased dendritic complexity and length in the dentate gyrus. This demonstrates the ability of exercise to improve neuronal structure and function in brain areas associated with memory through mechanisms involving irisin. Regular injections with exogenous irisin significantly improved performance on spatial learning and memory tasks in mice with Alzheimer’s-like dementia compared to untreated mice. These improvements may have been caused by dampening of overactive glial activity, leading to reduced inflammation.

    Taken together, these data suggest that irisin is essential for mediating the beneficial effects of exercise on cognitive function. The authors concluded that these data also demonstrate the efficacy of exogenous irisin administration in regulating cognitive function in mice with Alzheimer’s-like dementia, providing support for future use of irisin therapies in humans with dementia.

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  • Folate reduces risk for Alzheimer’s disease. www.frontiersin.org
    Brain Alzheimer's Micronutrients Folate Neurodegeneration

    Alzheimer’s disease, the most common type of neurodegenerative disease in older adults, causes a progressive deterioration of cognitive function. Recent research indicates that folate (vitamin B9) deficiency may play a role in Alzheimer’s pathology along with other micronutrients, such as vitamin A. A recent systematic review and meta-analysis reports that folate deficiency increases the risk for Alzheimer’s disease.

    Folate is an essential nutrient used by the body to create new DNA and RNA and to metabolize amino acids, all of which are necessary for cell division. Good sources of folate include legumes, such as peanuts and chickpeas, and green vegetables such as spinach and asparagus. Previous research has shown that folate supplementation improves cognitive function in older adults through mechanisms that are not well-understood, but likely involve reduced inflammation. Because dose, population characteristics, and testing methods often vary among clinical trials, coming to a consensus about the efficacy of an investigational treatment presents challenges; however, review articles can be a valuable way to combine and report existing data in a new and helpful way. This study is a systematic review and meta-analysis, meaning that the authors searched existing literature for studies related to folate and Alzherimer’s disease, collected studies based on a set of criteria meant to select for high-quality design, and then combined the data and reanalyzed it.

    The authors selected 59 studies that met their criteria for high-quality design. In a sample of more than 2,000 participants from a collection of case-control studies, participants with folate deficiency (less than 13.5 nanomoles per liter) were more than twice as likely to develop Alzheimer’s disease compared to participants with normal folate status (greater than 13.5 nanomoles per liter). Likewise, data from a collection of five cohort studies revealed that participants with folate deficiency were 88 percent more likely to develop Alzheimer’s disease compared to individuals with sufficient folate status. Finally, in a sample of 11 cohort studies, participants who consumed less than the recommended dietary allowance (400 micrograms) were 70 percent more likely to develop Alzheimer’s disease than those who consumed 400 micrograms of folate per day or more.

    This review of the evidence supports a relationship between folate intake and serum folate concentration in reducing risk for developing Alzheimer’s disease. Future studies should utilize an interventional design to investigate the mechanisms of folate in Alzheimer’s pathology.

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  • Stimulant medications increase willingness to expend effort, not ability. www.sciencedaily.com
    Brain ADHD Dopamine

    Executive function refers to a set of cognitive abilities that facilitate control over voluntary behaviors, including attention control, working memory, and cognitive flexibility. While executive functions are critical for complex tasks such as planning, they are also mentally taxing. Without sufficient motivation, people with poor executive function may struggle to meet goals. Researchers report their findings that dopamine signaling is responsible for the effects of Ritalin and other stimulant medications on motivation and executive function.

    Dopamine is one of the most abundant neurotransmitters in the brain and is involved in reward-motivated behavior, learning, and memory. Activities that provide a reward (e.g., food, money) increase dopamine levels, causing a sensation of pleasure that enhances learning by deeply encoding memories related to rewarding activities. Motivation to complete a task is based, in part, on whether a task is judged to provide sufficient pleasure relative to the cost of its required effort. Capacity to synthesize dopamine varies from person to person; however, lower dopamine levels in key brain areas are associated with attention deficit hyperactivity disorder (ADHD), substance use disorders, and Parkinson’s disease. Drugs such as methylphenidate (i.e., Ritalin), a medication used to treat ADHD, and sulpiride, a medication used to treat schizophrenia and depression, interact with dopamine receptors in the brain and can increase motivation.

    The authors recruited 50 healthy adults (ages, 18 to 43 years). Participants completed a test called a cognitive effort-discounting paradigm. In this test, participants are asked how much money they would want to receive in exchange for completing tasks of varying difficulty. The authors measured the estimated effort cost as the amount of money necessary to make participants willing to perform a cognitively difficult working memory task. Participants completed effort-discounting tasks under the influence of 20 milligrams of methylphenidate, 400 milligrams of sulpiride, or a placebo on three separate testing days. The researchers used a positron emission tomography (PET) scan to measure dopamine synthesis capacity in the caudate nucleus, a brain region responsible for reward-based learning. Finally, the researchers used a statistical model based on the effort-discounting task to further explore the effects of methylphenidate and sulpiride on motivation.

    While on the placebo treatment, participants’ willingness to expend cognitive effort increased as their baseline dopamine synthesis capacity increased. Notably, while performance on the working memory task decreased with difficulty, there was no relationship between task performance and dopamine levels. Both methylphenidate and sulpiride increased willingness to expend cognitive effort, but only in participants with low baseline dopamine synthesis capacity. Using their computer model, the investigators found that methylphenidate increased feelings of reward while sulpiride decreased effort cost. Further, they found that the cost-benefit analysis involved in the decision to expend effort occurs early in the decision-making process and can be measured by patterns in gaze (focusing on a reward or cost of a task) during cognitive testing. While higher baseline dopamine synthesis capacity and drug administration did not affect gaze patterns directy, higher dopamine levels strengthened the impact of gaze and attention to the benefits versus the costs of a decision.

    These findings indicate that Ritalin and other attention-enhancing drugs work by increasing willingness to attempt cognitively-difficult tasks, not the ability.

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  • Beige fat protects against dementia by reducing visceral-like properties of subcutaneous fat www.sciencedaily.com
    Brain Dementia Cold Stress Visceral Fat

    The color of fat tissue – white, brown, or beige – dictates the role the tissue plays in the body. Whereas white fat is involved in lipid storage and the release of free fatty acids for energy, brown fat is involved primarily in thermogenesis – the production of heat. Beige fat, which is typically co-located with white fat, can exhibit either storage or thermogenic properties, depending on environmental conditions. It also exerts anti-inflammatory properties via induction of interleukin 4, an anti-inflammatory molecule. White fat can convert to beige fat, a process known as “beiging.” Findings described in a recent report suggest that beige fat mediates the neuroprotective effects of subcutaneous fat.

    Subcutaneous fat, which is composed of both white and beige fat, is stored just beneath the skin. Commonly associated with a “pear” shape, it may protect against dementia. Visceral fat, on the other hand, is composed of white fat. It is stored in the abdominal cavity close to internal organs such as the liver, pancreas, and intestines. An excess of visceral fat, often referred to as central obesity or abdominal obesity, is commonly associated with an “apple” shape and an increased risk for chronic disease, including dementia.

    The authors of the report conducted a two-part study using a type of mouse genetically modified to lack the gene that promotes beiging. Without beiging, subcutaneous fat behaves more like visceral fat.

    In the first part of the study, they fed either a low-fat or high-fat diet to the genetically modified mice and normal mice for one month. They tested the animals' cognitive function and measured markers of inflammation and immune activation. Both groups of mice became obese on the high-fat diet, but cognitive tests revealed that the mice without beige fat showed signs of early cognitive impairment while the normal mice did not. The mice without beige fat also exhibited rapid, robust inflammatory responses to the high-fat diet, including activation of microglial cells (a type of immune cell found in the brain). Microglia activation promotes inflammation, harms brain health, and contributes to dementia.

    In the second part of the study, the authors transplanted subcutaneous fat from young, lean healthy mice into the abdominal areas of the obese, cognitively impaired mice. The recipient mice experienced improvements in memory and synaptic plasticity – the ability to form new connections between neurons.

    These findings suggest that beige fat drives the neuroprotective and anti-inflammatory effects of subcutaneous fat in mice. A growing body of evidence suggests that cold exposure promotes beiging of white fat. Learn more about the health effects of cold exposure in our overview article.

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  • Fecal microbiota transplantation from young mice reverses aging effects. www.sciencedaily.com
    Brain Aging Microbiome Immune System Microbes

    Declines in brain function are common with age owing to metabolic and immune alterations that include changes to the gut microbiota, the community of microorganisms that inhabit the intestines. While a diverse microbial community with many species of beneficial bacteria is associated with improved nutrition and reduced inflammation, older adults (especially residents of long-term care facilities) have perturbations in microbiota composition that increase the risk for cognitive decline and frailty. Findings of a report released this month show that fecal microbiota transplantation from young to aged mice reverses age-associated cognitive impairment.

    Fecal microbiota transplantation is a therapy in which microbes are isolated from the stool of a donor, processed, filtered, and administered to a recipient by nasogastric tube or enema. Previous research demonstrates the efficacy of fecal microbiota transplantation in treating infection with Clostridium difficile, a hospital-acquired infection that is difficult to treat with antibiotics, and a growing list of other diseases such as inflammatory bowel disease, metabolic syndrome, neurodevelopmental disorders (e.g., autism), and autoimmune diseases. Fecal microbiota transplantation improves health partially by increasing microbiota alpha diversity, meaning the number of species in an individual’s microbiota, also called “richess.” A microbiota with high richness is more likely to contain key beneficial species, such as those that produce neuroprotective short chain fatty acids.

    Given the wide range of diseases associated with gastrointestinal microbiota composition, its effects on aging are an area of intense interest. Prior investigations have demonstrated that transfer of the fecal microbiota from aged mice to young mice alters immunity, neurogenesis, and cognition; however, the consequence of fecal transplantation from young mice to aged mice is unknown.

    The investigators performed their experiment using young and aged male mice. They assigned aged mice to receive a fecal microbiota transplant from either a young mouse (the experimental group) or aged mouse (the control group). For further comparison, the researchers also assigned a group of young mice to receive a fecal microbiota transplant from another young mouse. Mice received the fecal microbiota transplant treatments once per day for three days, then twice weekly for four weeks. The mice completed a battery of tests to assess cognitive function. The researchers collected fecal samples in order to sequence the DNA of the microbiota and blood samples in order to measure hormones, cytokines, and other immune markers before and after the four weeks of treatment. Finally, they analyzed changes to gene expression and metabolism in the hippocampus, the brain region most-associated with age-related cognitive decline.

    At baseline, young and aged mice had distinctly different microbiota composition. Following four weeks of microbiota transplantation, young mice, aged mice receiving a young transplant, and aged mice receiving an aged transplant all had similar microbiota composition. Aged mice tended to have more over-reactive T cells, dendritic cells, and macrophages, especially in the lymph nodes that line the intestines. Aged mice also showed enlargement of microglia (the predominant immune cells in the brain), a common feature of neurodegenerative diseases. Microbiota transplantation from young mice reversed these age-related effects on brain and peripheral immunity. Amino acid metabolism in the hippocampus, which is necessary for neurotransmission and cognition, was impaired in aged mice, but restored following microbiota transplantation from young mice. Finally, the improved hippocampal metabolism in aged mice that received a young microbiota transplant translated to increased learning and long-term memory and reduced anxiety-related behaviors compared to aged mice receiving an aged microbiota transplant.

    These results reveal the potential benefits of fecal microbiota transplantation from young donors as a therapy to promote healthy aging.

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  • High caffeine intake increases a person's risk for developing dementia. www.sciencedaily.com
    Brain Coffee

    Epidemiological studies have identified links between coffee consumption and a variety of health outcomes. For instance, evidence suggests that drinking five to six cups of coffee a day reduces the risk of developing type 2 diabetes, while drinking three to five cups may reduce the risk of developing Alzheimer’s disease and dementia, compared to drinking none at all. A new study suggests that high caffeinated coffee consumption increases a person’s risk for developing dementia.

    The authors of the study drew on data from more 390,000 people enrolled in the UK Biobank study who were tracked over a period of eight to 12 years. Looking at individuals’ neurological diagnoses, the researchers found that while drinking two to four cups of coffee was associated with lower odds of developing dementia compared to drinking no coffee or exclusively decaffeinated coffee, consuming more than six cups of caffeinated coffee per day markedly increased those odds. The greater risk associated with high coffee consumption was present even when researchers statistically accounted for a variety of demographic factors such as water intake, exercise, sleep quality, stress, and body mass index. The effect also held up equally in men and women, as well as across different age groups.

    Further interesting observations emerged when the researchers examined brain scans of more than 17,500 of the study’s participants. The scans revealed that participants who drank six or more cups per day exhibited the lowest average brain volumes – an effect that was not seen in those who drank decaffeinated coffee, suggesting that the effects were driven by caffeine.

    One of the mechanisms that may drive the harmful effects of caffeine on the brain is caffeine’s blockade of the brain’s adenosine A2 receptors, which have been found to play a crucial role in enabling a subregion of the hippocampus (a structure involved in memory formation) to undergo plasticity and learning. In dampening the A2 receptor signal, caffeine might reduce the formation of new connections and potentially dampen levels of neuronal activity to a point where some connections may be eliminated. Importantly, however, research studies in this field are frequently carried out with young mouse brains, and further research across the entire lifespan is needed.

    These findings demonstrate that high caffeine consumption (defined as drinking more than six cups a day) may contribute to brain shrinkage and have a detrimental impact on neurological function. Caffeine consumption also influences sleep quality, which in turn influences brain health. Learn more about how caffeine affects sleep in this clip featuring Dr. Matthew Walker.

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  • Psilocybin, the active ingredient of "magic mushrooms," triggers rapid and lasting growth of new connections in the brain.
    Brain Mushroom Psychedelic LSD

    Psilocybin is a bioactive psychedelic compound present in certain varieties of mushrooms, commonly referred to as “magic” mushrooms. With clinical trials finding psilocybin treatment to be effective at reducing symptoms of treatment-resistant depression and obsessive compulsive disorder, increasingly more attention is being drawn to the potential mental health benefits of the compound. Findings from a recent study indicate that a single dose of psilocybin triggers a tangible and lasting proliferation of new neuronal connections in the mouse brain, improving brain plasticity.

    In the first phase of their study, the researchers set out to identify a dose of psilocybin that was sufficient to trigger behavioral indicators of mice having a psychedelic-like experience. This involved injecting 82 mice with five doses of psilocybin or a saline solution (of 0, 0.25, 0.5, 1, and 2 milligrams per kilogram of bodyweight) and pinpointing the minimal dose of the drug that reliably caused the animals to twitch their heads. Then, after providing the animals a “psychedelic” dose of one milligram per kilogram of bodyweight, the researchers examined whether psilocybin had an influence on the neurons of the rodents’ frontal cortex – an area of the mammalian brain heavily involved in higher-level cognition, imagination, and decision-making. Their focus fell primarily on the neurons’ dendritic spines: tiny mushroom-like protrusions of membrane that act as neuronal connections by receiving signals and passing them on as electrical impulses.

    To track these miniscule anatomical structures using a microscope, the researchers used genetically modified mice whose frontal cortex neurons (spines included) produced a glowing green fluorescent protein known as GFP. All mice began with receiving two microscopy sessions during which the researchers quantified baseline densities of dendritic spines in a tiny section of their frontal cortex. The animals were then randomly allocated to receive either a single dose of psilocybin or a control saline injection, after which the researchers quantified their spine densities on five more occasions (days 1, 3, 5, 7, and 34), blinded to whether the mice had received the active compound or saline.

    Tracking spine densities this way revealed that a single dose of psilocybin reliably induced a significant increase in the formation of new spines, which peaked at a 12 percent increase one week after exposure. A proportion of these new connections persisted 34 days after drug exposure. Interestingly, the effect was more pronounced in female animals, although whether this has any therapeutic implications remains to be seen.

    This study provides anatomical evidence that psilocybin is capable of stimulating new and lasting connections in the brain – an occurrence that may contribute to the drug’s ability to change mental state both in the short and longer terms. As recent studies report that psychedelic compounds promote mTOR signaling and protein synthesis to stimulate and support the production of new cellular machinery (e.g., dendritic spines), scientists are on the cusp of understanding the biological mechanisms and therapeutic potential of these compounds.

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  • COVID-19 illness is linked with impaired cognitive function even months after recovery. www.sciencedaily.com
    Brain Memory COVID-19

    Researchers and clinicians are growing increasingly concerned about the possibility of COVID-19 having a persistent impact on health that extends far beyond recovery from acute illness. In particular, anecdotal reports of former patients experiencing depression, “brain fog,” and difficulty finding the right words in conversation even months later appear to point to a potential long-term impact on cognition. A recent large-scale study offers evidence that COVID-19 promotes long-term cognitive deficits, even among those who experience the mildest form of the disease.

    The study recruited a representative cohort of 81,337 UK participants (average age, 46 years) to take part in a citizen science project known as the Great British Intelligence Test, a widely promoted free opportunity for people to identify their cognitive strengths. Participants performed a series of clinically validated online tasks assessing their emotional processing abilities, as well as cognitive skills such as attention, problem solving, and working memory. Scores from this latter group of tests were pooled to extract a composite score of global cognitive ability for each participant.

    After completing the cognitive tasks, participants were asked to provide some details about their experiences with COVID-19 – information that the researchers went on to use to build a predictive model of their global cognitive and emotional processing abilities.

    Their analysis revealed that clinically confirmed cases of COVID-19 infection were associated with significant cognitive deficits even nine months following infection (the longest period recorded in the study). This was particularly evident in complex tasks that required participants to reason, plan ahead, and solve problems using analogies, although the researchers also observed a general slowing of reaction times across all tasks.

    The scale of this cognitive impairment depended on the severity of respiratory symptoms. People who had severe cases of COVID-19 that required hospitalization and ventilation exhibited the greatest cognitive decline, surpassing the average decline observed in former stroke victims, as well as the mean cognitive difference between groups that differed by 10 years of age.

    Perhaps most surprisingly, the researchers found a significant degree of cognitive decline even in mild cases of COVID-19 who remained at home for the duration of their illness. These individuals performed below what would have been expected if they had not contracted the infection, roughly equivalent to 3.5 IQ points in a classic intelligence test.

    This study offers evidence that COVID-19 infection might have long-term health implications far beyond respiratory symptoms and that recovery may be associated with tangible impairments in certain aspects of higher cognitive function. It remains to be explored whether these deficits remain in the longer term.

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  • Greater muscle strength reduces depression risk. www.psypost.org
    Exercise Brain Depression Muscle IL-6

    Depression is characterized by mood alterations, such as increased sadness and irritability, and physiological changes, such as decreased sleep, appetite, and sexual desire. Previous research has reported a relationship between increased muscle strength and lower depression risk in older adults. Findings of a recent study detail the relationship between muscle strength and depression risk in young adults.

    Cytokines are proteins that participate in cell-signaling. Pro-inflammatory cytokines are increased in depression and contribute to the dysfunction of neurotransmission, hippocampal neurogenesis, and stress-related nervous system activation. Skeletal muscle cells secrete a number of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-8, and IL-15. A previous study demonstrated a relationship between lower levels of inflammation in adolescents with increased muscle strength and decreased body fat, but the study did not measure depression risk.

    The authors included 600 female participants without depression (average age, 19 years) in their analysis who were part of a larger observational study of physical fitness and health in Chinese college students. Participants completed a survey to measure depression symptoms and a physical exam including the use of a dynamometer to measure grip strength, a proxy for total skeletal muscle strength. The authors collected these measures at baseline and at a one-year follow-up. They classified participants into one of four categories based on the amount of grip strength they gained over the one-year study period.

    At the one-year time point, about 11 percent of participants reported depressive symptoms. Participants who gained the most grip strength over the one-year study period had a 66 percent lower risk of depression compared to participants who gained the least grip strength. Participants with the greatest gains in grip strength tended to be younger and smoke less at baseline than participants with the least gains in grip strength. Finally, gains in grip strength were significantly related to body mass index (BMI) at baseline. Underweight, defined as a BMI less than 18.5, was more common in participants with the lowest gains in grip strength (43 percent), while overweight, defined as a BMI greater than 25, was more common in participants with the greatest gains in grip strength (23 percent).

    The authors concluded that increased grip strength is associated with a lower risk of depressive symptoms in young adults.

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  • Exercise restores cognitive losses caused by sleep deprivation. www.sciencedirect.com
    Exercise Brain Sleep

    Chronic sleep deprivation, a risk factor for cardiovascular and Alzheimer’s diseases, is common among adults in industrialized nations, with many reporting less than seven hours of sleep each night during the workweek. Acute sleep deprivation impairs cognitive function, working memory, attention, and executive function, increasing the rate of mistakes made while driving, at work, and at home. A recent report details the effects of aerobic exercise on cognitive function following a night of sleep deprivation.

    Sleep deprivation has been shown to decrease brain oxygen saturation, contributing to cognitive impairment. However, previous research has demonstrated that aerobic exercise increases blood flow to the prefrontal cortex, activating key brain regions that improve cognitive function. Enhanced blood flow to the brain during exercise increases oxygen saturation in brain tissue and improves energy metabolism.

    In this study, the researchers recruited 12 participants (average age, 21 years) and measured their baseline maximum aerobic capacity while riding a stationary bicycle. On a separate study visit, participants completed cognitive testing and answered questionnaires before and after cycling for 20 minutes at 60 percent of their maximum aerobic capacity. Participants wore an electrode cap on their heads during exercise to measure electrical activity in the brain. They completed this study visit twice in random order, once after a full night of rest and once following a night of total sleep deprivation.

    Sleep-deprived participants reported feeling sleepier and performed significantly worse on cognitive tests prior to exercise. Following exercise, both sleepiness and cognitive function were improved in both groups, although cognitive scores were still comparatively worse in the sleep-deprived group. Under both rested and sleep-deprived conditions, blood flow to the prefrontal cortex increased within 12 minutes of initiating exercise and was maintained until the end of exercise. However, the researchers did not find a relationship between oxygenation levels and cognitive function, so whether exercise-induced brain oxygenation had a beneficial effect on cognitive function is unclear.

    The authors concluded that exercise corrects the cognitive impairment induced by sleep deprivation, although future research is needed to identify the best exercise protocol to maximize the benefits on brain oxygenation following sleep deprivation.

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  • Creatine intake improves cognitive performance in older adults. link.springer.com
    Brain Aging

    Cognitive decline is a personally challenging issue that degrades the quality of life for those affected. It is also a growing public health burden, with one in nine adults aged 65 years and older living with some level of cognitive impairment. Previous research has identified dietary components that reduce age-related cognitive impairment, including vitamin E, folate, and vitamin D. Authors of a new report investigated the effects of creatine on cognitive function in older adults.

    Creatine is a compound found primarily in the brain and muscle that is involved with the production of energy in the form of adenosine triphosphate (ATP). Creatine is obtained in the diet from red meat, poultry, fish, and seafood and is also available as a dietary supplement. In older adults, metabolic dysfunction decreases cellular energy, potentially contributing to cognitive decline. One meta-analysis found that dietary creatine improves aspects of cognitive function in young and older healthy adults.

    The authors of the current study analyzed data from more than 1,300 participants (average age, 71 years) in the National Health and Nutrition Examination Survey (NHANES), a long-term study collecting lifestyle and health data from people living in the United States. Participants completed cognitive testing and a 24-hour dietary recall during an interview with NHANES staff. The researchers analyzed the dietary data for foods containing creatine and calculated each participant’s estimated daily creatine intake. This assessment did not include supplemental creatine.

    Participants with higher dietary creatine intake tended to have higher cognitive scores, even after taking into account other nutrition factors and socioeconomic status. Participants in the top 50 percent of creatine intake consumed more than 0.95 grams of creatine per day, the amount in about 14 ounces of cooked beef or fish. These participants performed better on cognitive testing than those in the bottom 50 percent.

    These findings suggest creatine from food may be protective against age-related cognitive decline. Future research is needed to determine a dose of creatine that improves cognition without damaging kidney health, which is a concern for older adult populations.

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  • Spermidine supplementation improves memory performance in older adults with subjective cognitive decline. pubmed.ncbi.nlm.nih.gov
    Brain Alzheimer's Autophagy Dementia Supplements

    Spermidine is a polyamine compound that may increase health span due to its ability to induce autophagy, the process by which the body removes damaged and dysfunctional cells. In animal models, spermidine supplementation has been shown to prevent memory loss. Findings from a recent report detail the first experiment exploring the effects of spermidine supplementation on memory in older adults without dementia.

    Episodic memory, which records specific events, situations, and experiences, declines with age, but this loss may be impeded by certain lifestyle interventions, such as caloric restriction. The effects of spermidine in the body mimic caloric restriction, making it a promising therapy for the reversal of memory loss. Previous research demonstrates the ability of spermidine supplementation to restore memory performance in fruit flies; however, the effects of spermidine supplementation on memory performance in humans are unknown.

    The authors recruited 30 adults (aged 60 to 80 years) with subjective cognitive decline, a condition associated with objective cognitive decline and Alzheimer’s disease. They assigned half of the participants to consume a capsule containing 750 milligrams of a spermidine-rich plant extract containing 1.2 milligrams of spermidine daily for three months, while the other half consumed a placebo supplement. Participants completed memory assessments and other cognitive testing before and after the supplement period.

    Participants consuming the spermidine supplement had moderately enhanced memory performance after three months compared to those who took the placebo. In particular, permidine supplementation enhanced mnemonic discrimination, the ability to differentiate between new and previously encountered items. There was no difference in other cognitive functions between groups.

    The authors concluded that spermidine supplementation may be an effective treatment for slowing cognitive decline in older adults with subjective cognitive impairment. They noted that this was a small pilot trial and that larger clinical trials are needed to expand on these results.

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  • Mushroom consumption is associated with a reduced risk of cognitive impairment in older adults with dementia. www.sciencedaily.com
    Brain Mushroom Dementia

    Mild cognitive impairment is an intermediary stage between normal cognitive functioning and dementia and may be treatable with diet and lifestyle interventions. Mushrooms contain a number of bioactive compounds, such as hericenones and erinacines, that increase nerve growth factor production and ergothione, an antioxidant and cytoprotective compound. One group of researchers examined the relationship between mushroom consumption and mild cognitive impairment in older adults.

    Previous research has shown that mushroom intake improved cognitive performance among Norwegian participants (ages 70 to 74 years). Another epidemiological study in Japanese participants (ages 65 years and older) found that mushroom consumption of at least three times per week or more was associated with a 19 percent reduced risk of dementia. However, the effect of mushroom consumption on the risk of mild cognitive impairment is unknown.

    The authors reviewed data from over 600 participants without dementia (ages 60 years and older) from a study in Singapore aiming to identify dietary factors that are associated with healthy aging. Participants provided data regarding demographics, lifestyle, diet, health history, cognitive function, and psychological well being, among others. The researchers interviewed participants to assess their mushroom intake and measured participants’ cognitive function using a standardized questionnaire.

    Participants who consumed greater than two servings of mushrooms per week (1.5 cups of cooked mushrooms, about 300 grams) were 43 percent less likely to have mild cognitive impairment than those who consumed mushrooms less than once per week. This association was independent of age, sex, education, cigarette smoking, alcohol consumption, hypertension, diabetes, heart disease, stroke, physical activities, and social activities. Participants with mild cognitive impairment were more likely to have hypertension and diabetes and were less active in social activities.

    The results of this cross-sectional study support the potential of mushroom consumption in delaying the development of cognitive decline. The authors noted that a strength of their study was their accounting of lifestyle and health factors.

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  • Spending time in nature improves brain health. www.washingtonpost.com
    Brain Mental Health

    Roughly half of the world’s population lives in urban areas, far removed from the natural environment. Evidence indicates that people who live in urban areas are at greater risk for mental health disorders, such as depression. Findings from a new study suggest that walking in nature reduces ruminative thinking and decreases activity in parts of the brain associated with mental illness.

    Ruminative thinking – dwelling on ideas (especially stressors) to excess – is a common feature of mental illness. Rumination can set in motion a cascade of hormonal and physiological responses that harm mental and physical health. A major player in the body’s response to rumination is a biological pathway that starts in the brain’s hypothalamus with the release of corticotrophin-releasing hormone, which drives the stress hormone system and has a direct effect on many parts of the body, including the brain, gut, and DNA.

    Spending time in nature is associated with a variety of beneficial effects on mental and physical health. For example, some research indicates that walking in forested areas, sometimes referred to as “forest bathing,” improves immune function, likely due to beneficial bioactive compounds produced by trees and inhaled by walkers. Other research has identified dose-dependent improvements in health following natural experiences.

    The study involved 38 mentally healthy men and women living in a large urban area. Half of the participants took a 90-minute walk in a natural area where native plants, animals, and birds were in abundance. The other half took a 90-minute walk in an urban area where there were busy streets and heavy traffic. To rule out any physiological effects of exercise on brain health and function, both groups wore monitors to measure their heart rate and respirations. After their respective walks, participants underwent magnetic resonance imaging (MRI) studies of their brains, with emphasis on the subgenual prefrontal cortex, an area of the brain involved in emotional regulation and reward mechanisms. They also completed a questionnaire in which they rated their ruminative tendencies.

    The MRI studies revealed that after the participants walked in a natural area, their subgenual prefrontal cortex showed less activity. Those who walked in the urban area showed no changes in this region of the brain. Participants who walked in the natural area also reported less ruminative thinking after the walk, but those who walked in the urban area did not. The monitors revealed that the walks were equal in distance and exerted no physiological effects on the walkers.

    These findings suggest that spending time in the natural environment benefits brain health and reduces ruminative thinking, underscoring the importance of public health measures to increase natural spaces within urban areas. If natural areas are not easily accessible, meditation offers another means of reducing ruminative thinking. Learn more about the benefits of meditation in this episode featuring Dr. Rhonda Patrick.

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  • Omega-3 supplementation improves cognitive performance in cognitively healthy older adults with coronary artery disease. academic.oup.com
    Brain Heart Disease Omega-3 Supplements

    Dementia is a large and growing health concern facing older adults, with approximately 15 to 20 percent of people aged 65 years and older living with mild cognitive impairment. Omega-3 fatty acids have benefits for those with mild cognitive impairment and coronary artery disease, a risk factor for dementia because it restricts blood flow to the brain. Findings of a recent report demonstrate the effects of omega-3 supplementation on cognitive decline in cognitively healthy older adults with coronary artery disease.

    The omega-3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) protect the aging brain by decreasing oxidative stress and inflammation and increasing neurogenesis. Dietary consumption of omega-3 rich foods such as fish is associated with a decreased risk of Alzheimer’s disease, while low blood levels of DHA are associated with smaller brain volume, a hallmark of cognitive decline. To date, there have been few studies measuring the impact of long-term omega-3 supplementation on cognitive function in adults without cognitive impairment or dementia.

    The researchers enrolled 285 adults (average age, 63 years) who had stable coronary artery disease and were taking cholesterol-lowering statin medication. They assigned half of the participants to consume an EPA and DHA supplement (approximately 3 grams of omega-3 fatty acids total) for 30 months while the other half consumed no supplement. Participants completed a battery of cognitive tests at baseline, 12 months, and 30 months, measuring global cognition, language, verbal fluency, visual-motor coordination, psychomotor speed, and memory.

    After 30 months of omega-3 supplementation, participants had significantly better scores for verbal fluency, language, and memory than participants who did not supplement. Participants who supplemented also performed significantly better on two measures of visual-motor coordination. These improvements were measurable at just 12 months of supplementation.

    The investigators concluded that combined EPA and DHA supplementation improved cognition in cognitively healthy older adults with coronary artery disease. These results demonstrate the ability of omega-3 fatty acids to protect brain health even in those with coronary artery disease, a risk factor for dementia.

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  • Spermidine improves cognitive function in humans. www.cell.com
    Brain Autophagy

    Age-related changes in the brain drive cognitive impairment, which in turn alters memory formation and promotes mitochondrial dysfunction. A recent study demonstrates that spermidine improves cognitive function in humans.

    Spermidine is a dietary compound found in a number of foods, including wheat germ, cauliflower, broccoli, mushrooms, amaranth, a variety of cheeses (especially aged cheeses), and soybean products, such as natto. First identified in semen, spermidine demonstrates anti-aging properties in animal studies, likely due to its capacity to induce autophagy – the process by which the body clears dead and damaged cells. Human studies have demonstrated an association between dietary spermidine intake and increased survival..

    The authors of the study investigated the effects of spermidine supplementation in various models of aging. They fed aged mice spermidine in their drinking water and measured the compound’s appearance in the animals' brains. The compound appeared in brain tissue within one week of administration and continued to accrue to roughly one-third of bloodstream levels. Spermidine altered protein synthesis in the animals' brains via its actions on hypusine, an amino acid that is essential for the function of ELF5A, a protein that plays roles in mammalian protein production. Mice that received spermidine exhibited improvements in spontaneous behavior, exploration, maze completion, and other measures of cognitive function.

    The authors also fed fruit flies spermidine and found that the compound improved mitochondrial function and reduced age-induced memory impairments. These improvements were mediated by Atg7, PINK, and parkin – proteins that play key roles in autophagy and mitophagy.

    Then the authors reviewed epidemiological data from food frequency questionnaires and cognitive tests completed by participants in the Bruneck Study, a prospective cohort study of adults living in Bruneck, Italy. They found that higher intake of spermidine-rich foods was associated with greater cognitive function in aging.

    These findings suggest that dietary spermidine exerts neuroprotective effects in several model of aging, likely due to the compound’s effects on mitochondrial health. Dietary interventions that promote spermidine-rich foods may be useful in slowing cognitive decline in humans.

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  • Lutein and zeaxanthin supplementation improves visual processing in younger healthy adults. journals.plos.org
    Brain Eyes Carotenoids

    Cognitive function, including complex executive functions like working memory and basic functions like sensory processing, progressively declines with age. While executive function loss is highly variable and easily measurable in older adult populations, younger adults usually perform at a level consistent with their peers, which makes studying cognitive decline in younger adults difficult. In a 2014 report, researchers measured visual processing ability in young adults before and after supplementation with lutein and zeaxanthin.

    Visual processing refers to the brain’s ability to utilize and interpret visual information. Because visual processing utilizes similar brain architecture as more complex tasks such as working memory, it is a useful measure in assessing brain health and cognitive decline.

    Lutein and zeaxanthin are carotenoid pigments found in foods that accumulate in the retina and throughout the brain and perform light-absorbing, antioxidant, and anti-inflammatory functions. Animal research has demonstrated that the density of these pigments in the eye is a good indicator of their density in the brain, providing researchers a non-invasive means to measure the relationship between pigmentation and cognitive function. Higher pigment density in the eye[has been associated with better cognitive performance and visual processing speed in older adults with or without cognitive decline.

    Researchers measured the baseline visual processing speed and retinal concentration of lutein and zeaxanthin in healthy young adults (average age, 22 years). They assigned participants to consume either placebo, zeaxanthin only (20 milligrams), or a combination of zeaxanthin (26 milligrams), lutein (8 milligrams), and mixed omega-3 fatty acids (190 milligrams) per day for four months. They measured retina pigmentation and visual processing speed again following the intervention.

    The authors reported a moderate, yet statistically significant, relationship between baseline retinal pigment levels and visual processing speed. Following the intervention, both supplement groups demonstrated a significant increase in retinal pigmentation compared to placebo. Finally, participants in the supplement groups also performed 12 percent better on the critical flicker fusion test and decreased visual motor reaction time by 10 percent, two measures of visual processing.

    The authors conclude that lutein and zeaxanthin supplementation may be an effective way to increase visual processing speed, even in young healthy adults.

    Link to full study.

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  • Excess sugar intake in early life impairs memory in adulthood via changes in the gut microbiota. www.sciencedaily.com
    Brain Diet Microbiome Memory Development

    A healthy gut microbiota is important for cognitive function at any age, but especially during development. Poor dietary quality in early life (i.e., consuming excess sugar) negatively impacts the composition of the gut microbiota and impairs cognitive functioning; however, the mechanisms that drive these changes are unclear. Authors of a new report detail the functional relationship between detrimental gut microbes and hippocampal memory in rats exposed to excess sugar during adolescence.

    Germ-free mice, which are born and raised in a sterile environment, demonstrate impaired brain development compared to mice with a normal gut microbiota. This suggests that microbiota composition in early life may impact cognitive function in adulthood. Dietary strategies that minimize sugar intake may improve microbiota quality and maximize developmental potential in children and adolescents.

    The investigators conducted a two-part experiment in rats. In the first experiment, they fed sugar-sweetened water or plain water to juvenile rats for 11 weeks. They sequenced bacterial DNA from the rats' fecal samples to measure changes in the gut microbiota. In the second experiment, the researchers treated juvenile rats with antibiotics or a placebo for seven days. Then they treated one half of the antibiotic group with a bacterial culture of Parabacteroides distasonis and Parabacteroides johnsonii, while the other half received a placebo. In both experiments, rats completed a series of tests to measure memory function in adulthood. Finally, the researchers measured gene expression in the hippocampus, one the major memory centers of the brain.

    Adult sugar-fed rats exhibited impaired performance on memory tasks associated with the hippocampus, but not other memory centers. The authors discovered that sugar consumption led to an increase in Parabacteroides bacteria in the gut that correlated with impaired hippocampal function. When antibiotic-treated rats were given Parabacteroides distasonis and Parabacteroides johnsonii as a supplement in adolescence, they exhibited similar deficits in memory performance in adulthood as sugar-fed rats. Sugar consumption altered the expression of genes associated with neurotransmitter signaling, while Parabacteroides treatment altered genes associated with metabolic function, neurodegenerative disease, and dopamine signaling.

    The authors of this comprehensive report concluded that early-life dietary factors like sugar consumption impact brain development and may impair memory via changes in the gut microbiota.

    Link to full study.

    Learn more about sugar and its effects on the brain and body in this podcast featuring Dr. Rhonda Patrick.

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  • Omega-3 fatty acid supplementation improves cognitive function in adults without dementia. academic.oup.com
    Brain Omega-3

    Diets rich in omega-3 fatty acids have been shown to decrease the risk of Alzheimer’s disease. A growing number of studies have also demonstrated the benefits of omega-3 supplementation in adults with dementia. Authors of a recent report investigated the effects of omega-3 supplementation in adults without cognitive decline.

    Both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the two main forms of omega-3 fatty acids, suppress inflammation, regulate neurogenesis, decrease oxidative stress, and protect the aging brain. Previous research has demonstrated the ability to preserve white and gray matter volume in the brain.

    Older adults (average age, 63 years) with stable coronary artery disease who were taking statin medication participated in this trial. Researchers assigned half of the participants to consume 1.9 grams of EPA and 1.5 grams of DHA per day for 30 months while the other half took no supplement. Participants completed a battery of five neuropsychological tests at baseline, 12 months, and 30 months.

    Participants in the EPA + DHA group performed statistically significantly better in multiple cognitive domains including verbal fluency, language, memory, psychomotor speed and attention, and visual-motor coordination, compared to the group that took no supplement. This benefit was seen after 12 months of supplementation and remained significant after 30 months.

    The authors noted that the high dose and length of supplementation were strengths of their study. They concluded that omega-3s should be recommended for cognitively healthy adults to prevent or delay cognitive decline.

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  • Decreased brain derived neurotrophic factor, physical activity, and brain volume are associated with greater memory impairment. www.nature.com
    Brain Aging BDNF

    Brain derived neurotrophic factor (BDNF) is a growth factor associated with decreased risk of dementia and improved cognitive function in humans. While BDNF promotes brain cell growth plasticity, its precursor form, called proBDNF, has the opposite effect, promoting cell death. The authors of a recent report investigated the relationship between blood levels of pro-BDNF and memory loss.

    The effects of Alzheimer’s disease on the brain can be observed 10 to15 years before the onset of dementia, which presents the opportunity for early detection. Even though BDNF is known to cross the blood-brain barrier, whether blood levels of BDNF are reflective of BDNF activity in the brain is unclear. Establishing blood biomarkers of dementia risk provides the ability for early intervention.

    The authors recruited 256 older adults (average age, 68 years) without dementia. They analyzed magnetic resonance imaging (MRI) scans of the participants’ brains and measured blood levels of BDNF and proBDNF. Participants completed questionnaires to measure memory and physical activity habits.

    The investigators reported that increased age and decreased physical activity were associated with poorer memory performance. MRI findings showed decreased volume in the hippocampus, the region of the brain associated with memory, in those with worse memory scores. Finally, the authors reported that decreased blood levels of BDNF, but not pro-BDNF, were associated with worse memory performance.

    These results echo earlier findings that exercise is associated with greater BDNF activity and better memory performance. The authors conclude the measuring blood levels of BDNF may be an effective strategy for early detection of dementia.

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  • Omega-3 fatty acids protect the brain from the harms of air pollution. n.neurology.org
    Brain Omega-3

    Robust evidence indicates that omega-3 fatty acids play critical roles in maintaining optimal human health, potentially conferring protection against heart disease, stroke, cancer, and other conditions. A new study demonstrates that dietary consumption of omega-3 fatty acids may help protect the brain from damage associated with exposure to particulate matter in air pollution.

    Particulate matter is a mixture of solid particles and liquid droplets. It is present in fine inhalable particles, with diameters that are generally 2.5 micrograms or less. Exposure to air pollution promotes oxidative stress and increases the risk of developing many chronic diseases, including cardiovascular disease, cancer, hypertension, and diabetes. Evidence indicates that global air pollution shortens people’s lives on a scale greater than warfare, other forms of violence, parasitic infection, and more.

    The investigation involved 1,315 women (average age, 70 years) whose brain volumes had been assessed using structural brain magnetic resonance imaging (MRI) as part of a previous observational study. The authors of the current study estimated the women’s average exposure to particulate matter over a three-year period, based on the women’s addresses prior to the MRI. They measured the women’s dietary intake of omega-3 fatty acids and non-fried fish via food frequency questionnaires and measured the omega-3 fatty content in the women’s red blood cells.

    They found that higher intake of omega-3 fatty acids corresponded with higher red blood cell levels of omega-3s. In turn, the women with higher levels of omega-3 fatty acids in their red blood cells had greater white matter and hippocampus volumes. Women who lived in areas with high levels of particulate air pollution had lower brain volumes, but these effects were attenuated with higher intake of omega-3 fatty acids and non-fried fish.

    These findings suggest that omega-3 fatty acids confer protection against potential neurotoxic effects of air pollution on white matter volumes.

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  • Neurological effects of COVID-19 still evident six months after recovery. www.scientificamerican.com
    Brain COVID-19

    COVID-19 primarily manifests as a respiratory illness, but cardiovascular, gastrointestinal, and neurological symptoms have been reported in some cases. Although most of these symptoms are acute and resolve within a few weeks, many people experience long-term complications of the illness, a phenomenon referred to as “post-COVID-19 syndrome. A recent report describes the long-term neurological effects of COVID-19.

    Mounting evidence indicates that COVID-19 affects the neurological system. A previous report found that the range of acute neurological symptoms associated with COVID-19 included psychoses, delirium, encephalitis, strokes, and Guillain-Barré syndrome. Other evidence suggests that COVID-19 affects speech. A case report describes a woman who manifested stuttering and word-finding difficulties during her COVID-19 illness. A recent lay article described the occurrence of stutter several weeks after recovering from COVID-19. Neuroscientists posit that the inflammatory response that accompanies COVID-19 perturbs the brain neurocircuitry that controls speech.

    The most recent study investigating neurological phenomena associated with COVID-19 involved 165 people (average age, 65 years) who had been hospitalized for the illness and had recovered. Six months after discharge from the hospital, the patients were assessed for long-term neurological symptoms.

    The assessments revealed that more than one-third of the patients experienced long-term neurological abnormalities after COVID-19 illness. The most common complaints were fatigue, memory and attention problems, sleep disorders, and muscle pains. Others included depression, anxiety, visual disturbances, impaired sense of smell, and tingling or numbness. The patients who reported having cognitive deficits were more likely to have experienced worse respiratory symptoms and required longer hospitalization than those without cognitive problems.

    These findings suggest that COVID-19 is associated with a wide range of neurological disorders and many of these disorders manifest long after the original infection. The authors noted that since their study excluded patients with pre-existing neurological disorders, their findings might underestimate the full burden of neurological symptoms associated with COVID-19.

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  • Exercise in middle age improves cerebrovascular health later in life. www.aan.com
    Exercise Brain

    For optimal health, adults of all ages should engage in at least 150 minutes of moderate intensity physical exercise or at least 75 minutes of vigorous intensity physical exercise each week, or an equivalent combination of both. Findings from a new study show that engaging in moderate-to-vigorous intensity exercise in middle age improves cerebrovascular health later in life.

    The study involved an ethnically and racially diverse group of more than 1,600 adults (average age, 54 years). The authors of the study assessed the participants' moderate-to-vigorous intensity exercise levels based on interviews at the beginning of the study (when they were in middle age) and 25 years later. They classified the participants' exercise levels as none, low, middle, or high. The participants underwent magnetic resonance imaging studies to assess cerebrovascular health and measure white and gray matter volumes.

    Roughly one-third (39 percent) of the participants were classified as having moderate-to-vigorous intensity exercise levels during mid-life, and one-third (34 percent) were classified as having low levels. Those who had high exercise levels (about two-and-a-half hours per week) had greater intact white matter volume but not gray matter in late-life. Those who exercised more were 32 percent less likely to have experienced a lacunar infarct (a type of stroke) compared to those who engaged in no exercise.

    These findings suggest that exercise in middle age throughout older age is protective for the brain and underscore public health messaging for people of all ages to engage in more physical activity.

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  • Suppressing thoughts facilitates removal of information from working memory. www.eurekalert.org
    Brain

    Working memory is a limited capacity storage mechanism that allows the brain to store information in the short-term. It facilitates learning and execution of everyday tasks. Findings from a new study suggest that the removal of information from working memory requires active suppression.

    Most people can only hold three or four thoughts in working memory; eventually old information (thoughts) needs to be removed to make room for new ones. The inability to remove old thoughts from working memory is a characteristic of many mental health disorders, including depression, anxiety, compulsive disorder, and post-traumatic stress disorder. Previous work by the authors of the current study identified three distinct strategies for thought removal: replacement of the thought with another, suppression of the thought, and clearing the mind of all thoughts.

    The authors of the current study combined machine learning and neuroimaging to observe how the brain responded to removal of old information from working memory in 60 healthy volunteers. The participants underwent functional magnetic resonance imaging while storing information in their working memory and again while performing strategies to remove that information.

    The imaging studies revealed that replacing and clearing thoughts work by shifting the brain’s focus. This action deactivates the thoughts' neural representation in the brain but leaves the information intact. Suppressing thoughts, however, deletes them, freeing up working memory capacity to take in other information.

    These findings suggest that thought suppression is beneficial for freeing up space in working memory, which has relevance not only for mental health, but also for learning and productivity.

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  • Sulforaphane protects the brain during stroke via hormetic preconditioning. www.sciencedirect.com
    Brain Sulforaphane Stroke NRF2

    Stroke is one of the leading causes of death and disability worldwide, claiming the lives of roughly 5 million people and leaving another 5 million permanently disabled every year. A 2013 study demonstrated that sulforaphane protects the brain during ischemic stroke via hormetic preconditioning.

    Ischemic stroke occurs when blood flow to the brain is reduced or interrupted, starving neurons of oxygen and nutrients. Neuronal death occurs in the immediate area of a stroke within the first few hours of the incident, but nearby cells can be rescued with appropriate therapies. Heme oxygenase-1 (HO-1), an antioxidant enzyme, attenuates neuronal injury. Nrf2, a protein that regulates the expression of antioxidant and stress response proteins, induces HO-1 expression.

    The authors of the study gave mice sulforaphane (5 milligrams per kilogram of body weight) or corn oil with saline via injection. After the mice experienced a stroke, the authors measured the animals' Nrf2 and HO-1 gene expression and assessed behavioral changes, blood-brain barrier integrity, and neurological deficits.

    The mice that received sulforaphane treatment showed increased HO-1 expression, reduced blood-brain barrier damage, and fewer neurological deficits than mice that received the corn oil/saline. Levels of peroxynitrite, a short-lived reactive oxygen species associated with cell death, increased in the mice, suggesting that hormetic preconditioning mediated the protection sulforaphane provided against stroke.

    These findings suggest that dietary or supplemental interventions (such as sulforaphane) that precondition the brain against injury offer promise as strategies to reduce complications associated with stroke.

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  • A pilot trial finds sulforaphane treatment increases glutathione levels in the brain. www.karger.com
    Brain Sulforaphane Glutathione NRF2 Moringa

    Cellular damage incurred by oxidative stress underlies the pathophysiology of many chronic health disorders, including neuropsychiatric conditions such as schizophrenia. Glutathione, an antioxidant compound produced by the body’s cells, helps prevent damage from oxidative stress. Evidence from a 2018 study suggests that sulforaphane increases glutathione in the brain.

    Scientists typically rely on magnetic resonance spectrometry (MRS) for measuring glutathione levels in brain tissue. Evidence suggests MRS is inadequate, however, and often yields inconsistent results across studies. These inconsistencies have prompted some investigators to explore the reliability of glutathione level measurements in blood as an indicator of oxidative stress-associated brain changes.

    The pilot clinical study involved nine healthy adults. Eight of the participants were between the ages of 21 and 26 years; one was 56 years old. Each of the participants took 100 micromoles of sulforaphane (from a standardized broccoli sprout extract) by mouth every morning for one week. The authors of the study collected urine and blood specimens from the participants and performed MRS scans on their brains prior to the first dose of sulforaphane and within four hours of the final dose.

    At the end of the week-long study, the participants' blood cell glutathione levels increased 32 percent. The MRS scans revealed similar increases in the thalamus, a region of the brain involved in information processing and a key player in schizophrenia. These observations were consistent regardless of age, sex, or race of the participants.

    These findings suggest that sulforaphane shows promise as a therapeutic strategy for modulating oxidative stress in the brain, an underlying feature of schizophrenia. Some evidence that moringin, an isothiocyanate compound derived from moringa, may be useful in treating some of the symptoms of schizophrenia. Watch this clip in which Dr. Jed Fahey describes the health benefits associated with moringin and discusses the chemical structure differences between it and sulforaphane.

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  • Obesity impairs brain neuroplasticity, increasing the risk for dementia and cognitive decline. www.unisa.edu.au
    Brain Obesity

    Having obesity increases a person’s risk for developing many chronic diseases, including dementia. The global prevalence of obesity is approximately 13 percent. A recent study suggests that obesity impairs brain neuroplasticity.

    Neuroplasticity, the brain’s capacity to reorganize itself in response to changes in its environment, is critical during periods of learning, psychological stress, and trauma. Some evidence suggests that obesity impairs neuroplasticity. People with dementia and Alzheimer’s disease often have impaired neuroplasticity.

    The study involved 30 young adults, 14 of whom had obesity and 16 of whom had healthy body weights. The authors of the study measured the participants' brain plasticity using a technique called theta burst transcranial magnetic stimulation (cTBS) – a procedure involving repeated pulses of electrical stimulation. They applied cTBS to the motor cortex of the participants' brains (an area responsible for the planning, control, and execution of voluntary movements) to briefly suppress excitability, a nerve’s capacity to produce an action potential.

    They found that cTBS suppressed cortical excitability in the participants in the healthy weight group but not among those in the obese group, suggesting impaired neuroplasticity among those with obesity.

    The authors of the study suggested that the reduced neuroplasticity observed among the obese participants might be due to inflammation, a common feature in obesity and a key driver in many chronic diseases. However, they also posited that the impairments were due to reduced levels of brain-derived neurotrophic factor (BDNF) – a cell signaling protein that plays key roles in a number of signaling pathways. BDNF levels and signaling are often decreased in the setting of obesity, but exercise increases BDNF levels.

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  • Humans' ability to read arose from other mechanisms that were "repurposed" for this unique skill set. news.mit.edu
    Brain

    The ability to recognize and assign meaning to shapes and symbols – known as orthographic processing – is unique to humans, a skill acquired relatively recently in human history. Scientists believe that orthographic processing was not a newly developed skill; rather, it built on neuronal mechanisms already in use. Findings from a new study demonstrate that a part of the brain called the inferotemporal cortex facilitates orthographic processing.

    The inferotemporal cortex is a region of the brain located on the underside of the temporal lobe, the part of the brain closest to the ear. It plays critical roles in the visual processing and visual recognition of objects.

    The authors of the study recorded the activity of hundreds of neurons in V4 (a region of the visual cortex) and the inferior temporal cortex of monkeys while the animals viewed images of letters, words, and non-word letter combinations. The authors used a special computerized model to predict whether the monkeys' brain activity was associated with a word or a non-word. Monkeys are good models for understanding aspects of human visual processing because they share similar behaviors and underlying brain mechanisms with humans.

    They found that the inferotemporal cortex of the monkeys could accurately extract explicit representations of written letters and words, suggesting that this region of the monkeys' brains acts as a sort of precursor to orthographic processing. These findings suggest that humans' ability to read arose from other mechanisms that were “repurposed” for this unique skillset.

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  • Suicidal behavior linked to Val66Met genetic variant which reduces BDNF activity www.sciencedaily.com
    Brain Depression Behavior BDNF

    From the article:

    After pooling results from 11 previous studies and adding their own study data involving people with schizophrenia, CAMH scientists confirmed that among people with a psychiatric diagnosis, those with the methionine (“met”) variation of the gene had a higher risk of suicidal behaviour compared to those with the valine variation.

    […]

    “Our findings may lead to the testing and development of treatments that target this gene in order to help prevent suicide,” says Dr. James Kennedy, director of CAMH’s Neuroscience Research Department. “In the future, if other researchers can replicate and extend our findings, then genetic testing may be possible to help identify people at increased risk for suicide.”

    As the low-functioning BDNF met variation is a risk factor for suicidal behaviour, it may also be possible to develop a compound to increase BDNF functioning, Dr. Kennedy says.

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  • A loss of BDNF, as a result of viral strategy, may be responsible for a type of dementia that occurs in 30 percent of untreated HIV-positive patients www.sciencedaily.com
    Brain HIV Dementia BDNF

    From the article:

    The research team found that even though HIV does not infect neurons, it tries to stop the brain from producing a protein growth factor – mature brain derived neurotrophic factor (mature BDNF) – that Mocchetti says acts like “food” for brain neurons.

    […]

    Mocchetti believes that HIV stops production of mature BDNF because that protein interferes with the ability of the virus to attack other brain cells. It does this through the potent gp120 envelope protein that sticks out from the viral shell – the same protein that hooks on to brain macrophages and microglial cells to infect them. “In earlier experiments, when we dumped gp120 into neuronal tissue culture, there was a 30-40 percent loss of neurons overnight. That makes gp120 a remarkable neurotoxin.”

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  • The combination of tobacco and alcohol may exacerbate deleterious effects in memory region: increased oxidative stress in hippocampus, less BDNF www.sciencedaily.com
    Brain Alcohol Memory Tobacco BDNF

    From the article:

    The researchers treated rats with alcohol, tobacco smoke or both twice a day for 28 days and then compared their brains with control animals that didn’t receive either substance. They found that the combined alcohol and smoking treatment increased the level of reactive oxygen species in the hippocampus compared with control animals or rats given tobacco smoke alone. In all of the brain areas studied, combined alcohol and smoking increased the levels of specific pro-inflammatory cytokines more than either treatment alone.

    Reduced levels of BDNF, another harbinger of bad news:

    And in the striatum and frontal cortex, rats with both treatments showed lower levels of brain-derived neurotrophic factor, a growth factor that helps existing neurons survive and stimulates the growth of new ones. These results suggest that alcoholics who smoke could be at additional risk for neural damage, the researchers say.

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  • 20-minute transcranial direct current stimulation sessions shown to enhance maze performance, memory, brain plasticity in rodent model of Alzheimer's www.sciencedaily.com
    Brain Alzheimer's BDNF Neurodegeneration

    From the article:

    After exposing the mice to single 20-minute tDCS sessions, the researchers saw signs of improved memory and brain plasticity (the ability to form new connections between neurons when learning new information), which lasted at least a week. This intellectual boost was demonstrated by the enhanced performance of the mice during tests requiring them to navigate a water maze and distinguish between known and unknown objects.

    This effect depended on increased production of BDNF:

    More important, the researchers identified the actual molecular trigger behind the bolstered memory and plasticity–increased production of BDNF, a protein essential to brain growth. BDNF, which stands for “brain-derived neurotrophic factor,” is synthesized naturally by neurons and is crucial to neuronal development and specialization.

    “While the technique and behavioral effects of tDCS are not new,” said ONR Global Associate Director Dr. Monique Beaudoin, “Dr. Grassi’s work is the first to describe BDNF as a mechanism for the behavioral changes that occur after tDCS treatment. This is an exciting and growing research area of great interest to ONR.”

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  • BDNF variant may mediate degree of brain benefits from exercise. www.sciencedaily.com
    Exercise Brain Memory ADHD BDNF

    Exercise improves cognitive function and reduces the risk neurodegenerative diseases such as Alzheimer’s disease. Some of these benefits are mediated by brain-derived neurotrophic factor (BDNF). Findings from a 2012 study showed that regular exercise improved cognitive function and increased BDNF levels, but a genetic variant in BDNF influenced the degree of these effects.

    BDNF is a protein that acts on neurons in the central and peripheral nervous systems. A single-nucleotide polymorphism (SNP) in the gene that encodes BDNF causes a substitution of the amino acid valine (Val) by methionine (Met) in the BDNF protein. This genetic variant, known as Val66Met, alters exercise-driven release of BDNF and affects learning, memory, and emotion.

    The intervention study involved 75 sedentary, healthy, young adults between the ages of 18 and 35 years. The participants took memory tests and mental health surveys before and after engaging in their randomly assigned respective activities: no exercise; four weeks of exercise with exercise and a test on the last day; four weeks of exercise, without exercise on the final test day; or a single bout of exercise on the last test day.

    The participants who engaged in exercise showed improvements in memory and experienced lower levels of perceived stress, but only if they exercised for four weeks including the final day of testing. Participants who engaged in a single bout of exercise showed no changes in memory performance and demonstrated higher perceived stress levels. The authors of the study noted improvements in the participants' memory only if they did not carry the Val66Met variant, suggesting that the associated reduction in BDNF release attenuated some of the cognitive benefits of exercise. They also noted that the improvements in cognitive function were not correlated to improvements in mental health.

    These findings suggest that the variable effects of exercise on brain function are related to a genetic variant that influences the production of BDNF.

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  • Omega-3 fatty acids in fish may protect the brain from damage due to air pollution. www.sciencedaily.com
    Nutrition Brain Omega-3

    Omega-3 fatty acids are essential for human health. Evidence demonstrates that omega-3 fatty acids may also be beneficial against heart disease, stroke, cancer, and other conditions. A new study demonstrates that dietary consumption of omega-3 fatty acids in fish may help protect the brain from damage induced by particulate matter in air pollution.

    Particulate matter is a mixture of solid particles and liquid droplets. It is present in fine inhalable particles, with diameters that are generally 2.5 micrograms or less. Some evidence suggests that exposure to particulate air pollutants accelerates aging.

    The observational study involved more than 1,300 women between the ages of 65 and 80 years who were dementia-free at the time of enrollment. The authors of the study determined the approximate levels of particulate matter to which the women were exposed over a three-year period based on their addresses. They measured omega-3 fatty acid concentrations in the women’s red blood cells and measured brain white matter volume in the women’s brains via imaging studies. The women completed questionnaires about their weekly dietary intake of baked or broiled seafood or fish.

    The brain imaging studies revealed that particulate matter exposure was associated with white matter and hippocampal volume losses. These losses were particularly noticeable among women with the lowest levels of omega-3s in their red blood cells.

    The findings from this study indicate that dietary intake of fish rich in omega-3 fatty acids may be protective against brain losses associated with air pollutant exposure. Another dietary compound that might offer protection from air pollutant is sulforaphane, a bioactive compound derived from cruciferous vegetables. Watch this clip in which sulforaphane expert Dr. Jed Fahey describes how sulforaphane provides protection from benzene, a carcinogenic compound present in air pollution.

    Read more
  • Omega-3 DHA intake increases hypothalamic neurogenesis in mice. diabetes.diabetesjournals.org
    Brain Obesity Omega-3 BDNF

    Saturated fatty acid intake induces inflammation in the hypothalamus that can eventually lead to apoptosis of hypothalamic neurons and subsequent loss of the control of caloric intake and energy expenditure. The overall health of hypothalamic neurons requires their regular renewal, a process known as neurogenesis, which is impaired in obesity. Findings from a 2016 study showed that docosahexaenoic acid (DHA), a type of polyunsaturated fatty acid (PUFA), increased hypothalamic neurogenesis in mice.

    DHA is an omega-3 fatty acid found in the human brain and the meat of fatty fish. DHA plays a key role in the development of eye and nerve tissues and is essential for normal brain function in humans.

    The authors of the study conducted a six-protocol study in mice. They fed the mice a high-fat diet for eight weeks and then fed them diets containing varying concentrations and types of fats, including flaxseed oil and DHA. They also injected DHA or BDNF, a growth factor involved in neurogenesis, into the brains of the mice.

    Mice that ate the DHA-containing diet showed improvements in body mass, glucose metabolism, activity levels, and response to leptin, a hormone involved in appetite control. Both the DHA-containing diet and the injected DHA increased levels of hypothalamic neurogenesis at rates similar to or superior to those observed with BDNF.

    These findings suggest that dietary intake of PUFAs such as DHA show promise as a strategy to ameliorate hypothalamic neuronal losses associated with obesity.

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  • Dance intervention increased brain volume and plasma BDNF levels in older adults. pubmed.ncbi.nlm.nih.gov
    Brain BDNF

    Aging alters many features of brain structure and function. Emerging evidence indicates that these alterations are avoidable, however. Findings from a 2018 study demonstrate that dancing counteracts the harmful effects of aging on the human brain.

    Previous research has demonstrated that dancing simultaneously challenges sensory, motor, and cognitive aspects of brain function. Dancing is comparable to other forms of exercise in terms of cardiovascular demands, but it differs in terms of coordinative and cognitive demands.

    The authors of the study randomized 38 adults between the ages of 63 and 80 years to participate in one of two six-month-long exercise programs. Half of the participants engaged in active but repetitive exercises such as cycling and weight training, and the other half engaged in dancing. Both groups participated in their respective activities twice a week for 90 minutes. The authors of the study collected blood samples, performed cognitive and physical fitness assessments, and conducted imaging studies to determine the participants' responses to the interventions.

    The participants who engaged in the dance intervention showed marked improvements in brain volume in several regions of their brains compared to the other group, especially in the cingulate cortex, insula, corpus callosum and sensorimotor cortex, areas responsible for emotion, learning, memory, self-awareness, and voluntary movement. Both groups showed improvements in attention and spatial memory, but dancing increased the participants' plasma BDNF levels. BDNF is a growth factor that plays key roles in neuroplasticity, the brain’s capacity to reorganize itself in response to changes in its environment.

    These findings suggest that dance is superior to other forms of active exercise in terms of brain benefits. Exercise intervention programs geared toward older adults show promise as a means to forestall the harmful effects of aging on the brain.

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  • Fish oil omega-3 normalizes BDNF levels in the hippocampus and improves cognitive function in animal model of traumatic brain injury www.liebertpub.com
    Brain Omega-3 Tissue Repair BDNF TBI

    From the publication:

    Our finding that supplementation of omega-3 fatty acids normalizes the protein levels of BDNF after TBI suggests that BDNF mediates the beneficial effects of omega-3 fatty acids on cognitive function.

    […]

    It is notable that fish oil supplementation increased BDNF but did not affect cognitive function in intact rats. It is possible that slight changes in BDNF may not significantly affect cognition under normal conditions. It seems likely, however, that under pathological weakness small decreases in BDNF can be a factor to further deteriorate cognitive function. This eventual possibility emphasizes the necessity to use therapeutic means, such as dietary supplementation of fish oil, to maintain normal levels of BDNF under challenging conditions.

    Mitigation of oxidative stress as a mechanism of increased BDNF:

    It has been shown that TBI can result in cumulative ROS, which may be associated with reduction of BDNF. Thus, DHA may help to counteract elevated levels of ROS with subsequent effects on the action of BDNF on synaptic plasticity and cognition after TBI.

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  • BDNF genetic variant Val66met found in ~30% of the population is associated with up to 20% worse performance on driving test www.sciencedaily.com
    Brain Genetics BDNF

    From the article:

    People with a particular gene variant performed more than 20 percent worse on a driving test than people without it – and a follow-up test a few days later yielded similar results. About 30 percent of Americans have the variant.

    Often there are benefits and trade-offs when it comes to genetics:

    The gene variant isn’t always bad, though. Studies have found that people with it maintain their usual mental sharpness longer than those without it when neurodegenerative diseases such as Parkinson’s, Huntington’s and multiple sclerosis are present.

    “It’s as if nature is trying to determine the best approach,” Cramer said. “If you want to learn a new skill or have had a stroke and need to regenerate brain cells, there’s evidence that having the variant is not good. But if you’ve got a disease that affects cognitive function, there’s evidence it can act in your favor. The variant brings a different balance between flexibility and stability.”

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  • Carriers of a common BDNF genetic variant demonstrate more rapid decline from Alzheimer's disease. www.sciencedaily.com
    Brain Alzheimer's Genetics BDNF Neurodegeneration

    BDNF plays critical roles in many aspects of cognitive function, including learning and memory formation. A single-nucleotide polymorphism (SNP) in the gene that encodes BDNF causes a substitution of the amino acid valine (Val) by methionine (Met) in a specific region of the DNA where the gene is located. Evidence suggests that carrying the Met allele (Met/Met or Val/Met genotype) is associated with lower BDNF expression.. A 2017 study found that amyloid-beta burden impaired BDNF-related learning and memory.

    Amyloid-beta is a toxic 42-amino acid peptide that aggregates and forms plaques in the brain with age. Amyloid-beta is associated with Alzheimer’s disease, a progressive neurodegenerative disease that can occur in middle or old age and is the most common cause of dementia.

    The study involved more than 1,000 adults (approximately 55 years at the beginning of the study) who were enrolled in a larger study of Alzheimer’s disease. Nearly 65 percent of the participants were at high risk for developing Alzheimer’s disease, having at least one parent diagnosed with the condition. Each of the participants underwent cognitive assessment and BDNF genotyping five times over a period of four to 11 years. In addition, a small cohort of participants underwent imaging studies to assess amyloid-beta burden.

    The genotyping revealed that approximately one-third of the participants were carriers of the Met-66 allele. Compared to Val/Val carriers, Met-66 carriers showed steeper declines in cognitive function. In addition, Met-66 carriers with greater amyloid-beta burden showed an even greater cognitive decline, likely due to lower BDNF expression. These findings suggest that a SNP in the gene for BDNF influences cognitive health and could serve as a therapeutic target against Alzheimer’s disease.

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  • From the blood to the brain: BDNF-producing blood cells travels to the hypothalamus in adults, regulating and suppressing appetite [animal research] www.sciencedaily.com
    Brain Obesity BDNF

    From the article:

    We knew that blood cells produced BDNF,“[…] "We didn’t know why it was produced in blood cells.”

    Dr. Hiroshi Urabe and Dr. Hideto Kojima, current and former postdoctoral fellows in Chan’s laboratory respectively, looked for BDNF in the brains of mice who had not been fed for about 24 hours. The bone marrow-derived cells had been marked with a fluorescent protein that showed up on microscopy. To their surprise, they found cells producing BDNF in a part of the brain’s hypothalamus called the paraventricular nucleus.

    “We knew that in embryonic development, some blood cells do go to the brain and become microglial cells,” said Chan. […]“This is the first time we have shown that this happens in adulthood. Blood cells can go to one part of the brain and become physically changed to become microglial-like cells.”

    A new way to affect appetite and obesity?

    When normal bone marrow cells that produce BDNF are injected into the third ventricle (a fluid-filled cavity in the brain) of mice that lack BDNF, they no longer have the urge to overeat, said Chan.

    All in all, the studies represent a new mechanism by which these bone-marrow derived cells control feeding through BDNF and could provide a new avenue to attack obesity, said Chan.

    He and his colleagues hypothesize that the bone marrow cells that produce BDNF fine tune the appetite response, although a host of different appetite-controlling hormones produced by the regular nerve cells in the hypothalamus do the lion’s share of the work.

    Read more
  • BDNF mimetic 7,8-dihydroxyflavone protects neurons against cell death. www.sciencedaily.com
    Brain Parkinson's BDNF Stroke

    BDNF’s neuroprotective capacity suggests that it could be useful in preventing or treating neurodegenerative diseases. Circumventing problems with BDNF’s delivery, half-life, and other limitations has proven challenging. A 2010 study found that 7,8-dihydroxyflavone, a BDNF mimetic, exerted neuroprotective qualities similar to those of BDNF.

    7,8-dihydroxyflavone is a type of flavonoid compound present in a variety of plants. Flavonoids exert antioxidant and anti-inflammatory effects, among others. Some evidence indicates that 7,8-dihydroxyflavone might be useful in reversing the damage associated with lead poisoning in children.

    The authors of the study screened 2,000 bioactive compounds to gauge their ability to protect rodent and human neurons from apoptosis and identified five compounds, including 7,8-dihydroxyflavone, that showed potential in protecting the cells. Then they treated the cells with BDNF and the various compounds and deprived the cells of oxygen and glucose.

    They found that none of the compounds was as effective as 7,8-dihydroxyflavone in protecting the cells from apoptosis. In fact, 7,8-dihydroxyflavone was even more protective than BDNF. They also found that 7,8-dihydroxyflavone exerted its protective qualities by activating a receptor called TrkB, to which BDNF binds. They replicated their findings in an in vivo study of mice, indicating that 7,8-dihydroxyflavone enhances neuronal survival.

    These findings demonstrate that flavonoid compounds that mimic the effects of BDNF show potential as therapeutics against neurodegenerative diseases.

    Read more
  • Plasma levels of BDNF lower in women with history of suicide attempts. www.sciencedaily.com
    Brain Depression BDNF

    Suicide is a major public health concern, claiming the lives of nearly 800,000 people worldwide each year. A history of a suicide attempt is a robust predictor of a future attempt. Findings from a 2017 study suggest that plasma levels of BDNF are a marker for suicidality.

    BDNF is a protein that plays critical roles in the creation and functioning of neurons and the ability of synapses to strengthen or weaken over time. Low BDNF levels are associated with an increased risk for depression.

    The participants in the study included 34 women with a history of suicide attempt and 39 without (average age, 33 years). The women were matched based on age, ethnicity, family income, body mass index, and cigarette smoking history. The authors of the study assessed the women’s mental health history and current status and took blood samples to determine BDNF levels.

    Thirty (88 percent) of the women who had attempted suicide had a lifetime history of major depressive disorder. Of these, 14 (40 percent) met the criteria for current major depressive disorder. The women with a history of suicide attempt had lower levels of BDNF than women without a history of suicide – a difference that was maintained even after taking into account other potential psychiatric or demographic factors. The authors of the study posited that lower BDNF levels represent a trait-like biochemical indicator of suicide risk and might be relevant for suicide prevention.

    Other biochemical indicators of suicide have been identified, as well. For example, markers of accelerated extrinsic aging have been observed in the blood of suicide completers. Age acceleration is a phenomenon that occurs when an individual’s epigenetic age exceeds their chronological age. Learn more about epigenetic aging in this overview article.

    Read more
  • BDNF genetic variant predicts success in alcohol dependence treatment. www.sciencedaily.com
    Brain Alcohol Genetics Addiction BDNF

    Alcohol dependence is a complex disorder that increases a person’s risk of death from all causes. Findings from a 2009 study suggest that variations in certain genes can impact the likelihood of relapsing following treatment.

    BDNF is involved in neuronal growth and survival, as well as influencing neurotransmitters – chemical signals from the nervous system. Low BDNF levels have been linked to the development of depression, anxiety, and alcohol dependence.

    Previous research has demonstrated that alcohol dependence has a genetic component. The current study investigated whether common variations in certain genes would have an effect on post-treatment relapse.

    The prospective study involved 154 participants who met the criteria for alcohol dependence and were admitted to a treatment facility. The patients provided blood samples for genetic analysis and completed self-assessment questionnaires about depression, hopelessness, impulsivity, and the severity of their alcohol use. The authors followed up with participants for approximately one year to assess whether they had relapsed. Relapse was defined as any drinking during the observation period, with heavy drinking considered as more than four drinks per day for more than four consecutive days. During the follow-up period, 59 (48 percent) participants relapsed, with 48 returning to heavy drinking. The average time to relapse was 218 days.

    The authors tested a genetic variant that resides in the BDNF gene, known as Val66Met. They observed that participants with the Val form of this gene were more likely to relapse compared to those with the Met version. Participants with two copies of the Val allele – one from each parent – had higher rates of relapse and shorter times to relapse when compared to carriers of at least one Met allele.

    These findings suggest that BDNF influences a person’s ability to remain abstinent following treatment for alcohol dependence. With further evaluation, these findings may help clinicians to identify people at increased risk for post-treatment relapse and tailor their care plans.

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  • Bipolar disorder patients experience generalized impaired cellular resilience and broad reductions in BDNF that may contribute to the disease www.sciencedaily.com
    Brain Depression Stress BDNF

    From the article:

    Effective neuronal plasticity also depends on neurotrophins, which are regulatory factors that promote development and survival of brain cells. Brain-derived neurotrophic factor (BDNF) is the neurotrophin mostly found in the brain. It has been extensively investigated in bipolar disorder patients and has been suggested as a hallmark of bipolar disorder. Indeed, some studies have shown that the levels of BDNF in the serum of bipolar disorder patients are reduced whenever patients undergo a period of depression, hypomania, or mania. Other studies have shown that regardless of mood state, bipolar disorder patients present reduced levels of BDNF. Overall, changes in BDNF levels seem to be a characteristic found in bipolar disorder patients that may contribute to the pathophysiology of the disease.

    Immediate early genes:

    Immediate early genes (IEGs) are a class of genes that respond very rapidly to environmental stimuli, and that includes stress. IEGs respond to a stressor by activating other genes that lead to neuronal plasticity, the ability of brain cells to change in form and function in response to changes in the environment. Ultimately, it is the process of neuronal plasticity that gives the brain the ability to learn from and adapt to new experiences.

    One type of protein produced by IEGs is the so-called Early Growth Response (EGR) proteins, which translate environmental influence into long-term changes in the brain. These proteins are found throughout the brain and are highly produced in response to environmental changes such as stressful stimuli and sleep deprivation. Without the action played out by these proteins, brain cells and the brain itself cannot appropriately respond to the many stimuli that are constantly received from the environment.

    […]

    in a previous study done by the group in 2016, one type of IEG gene known as EGR3, that normally responds to environmental events and stressful stimuli, was found repressed in the brain of bipolar disorder patients, suggesting that when facing a stressor, the EGR3 in bipolar disorder patients does not respond to the stimulus appropriately. Indeed, bipolar disorder patients are highly prone to stress and have more difficulties dealing with stress or adapting to it if compared to healthy individuals. What the research group is now suggesting is that both EGR3 and BDNF may each play a critical role in the impaired cellular resilience seen in bipolar disorder, and that each of these two genes may affect each other’s expression in the cell. “We believe that the reduced level of BDNF that has been extensively observed in bipolar disorder patients is caused by the fact that EGR3 is repressed in the brain of bipolar disorder patients. The two molecules are interconnected in a regulatory pathway that is disrupted in bipolar disorder patients,”

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  • Decreased exposure to air pollution associated with improved cognitive development and increases BDNF levels in children. www.sciencedaily.com
    Brain Development Pollution BDNF

    Exposure to air pollutants is associated with an increased risk of developing many health disorders, including heart disease, stroke, chronic obstructive pulmonary disease, lung cancer, and acute respiratory infections. Some evidence suggests that exposure to air pollution can impair neurological development in children. A 2014 study showed that reducing exposure to polycyclic aromatic hydrocarbons (PAHs) was associated with improved cognitive development and increased BDNF levels in children.

    Polycyclic aromatic hydrocarbons are produced during the combustion of coal, oil, gasoline, trash, tobacco, and wood. High-temperature cooking, such as grilling, promotes the formation of PAHs in meat and other foods. PAHs promote the formation of DNA adducts – covalent modifications of DNA that can drive carcinogenesis.

    The study involved two cohorts of mother-child pairs who lived near a coal plant in China. One cohort of pairs was made up of 150 women who were pregnant while the coal power plant was operational and the other was made up of 158 women who were pregnant after it closed. None of the women smoked, and they all lived within 2.5 kilometers (about 1.5 miles) from the coal plant.

    The authors of the study analyzed BDNF levels and their relationship to adduct formation and developmental outcomes in the two cohorts. They collected umbilical cord blood and maternal blood samples and measured the amount of DNA adducts in the samples. They also measured plasma levels of BDNF. When the children reached the age of two years, they underwent standardized testing that assessed motor, adaptive, language, and social development.

    The children who were born to women who were pregnant after the plant closed had lower levels of PAH-DNA adducts, higher concentrations of BDNF, and higher developmental scores than those who were born to women who were pregnant when the plant was operational. Higher BDNF levels were associated with developmental scores. The findings suggest that reducing exposure to air pollutants during pregnancy lowers levels of PAH-DNA adducts and increases BDNF levels in infants.

    Interestingly, clinical trials have demonstrated that sulforaphane, a compound derived from cruciferous vegetables (especially broccoli sprouts), can reduce the harmful effects of exposure to air pollutants (including PAHs) in humans. Sulforaphane works by switching on the activity of the body’s in-house detoxication pathways. Learn more about sulforaphane in this podcast featuring Dr. Jed Fahey.

    Read more
  • Women with a BDNF genetic variant experience fewer negative cognitive effects during chemotherapy. www.sciencedaily.com
    Brain Cancer Dementia BDNF

    Chemotherapy-associated cognitive impairment is a side-effect of chemotherapy in which people experience difficulties with concentration, decision making, and memory. Findings from a 2015 study suggest that women with a BDNF gene variation experience fewer cognitive problems during chemotherapy compared to those without this variation.

    BDNF is a growth factor that is involved in the growth and repair of neurons. BDNF is expressed in the prefrontal cortex and hippocampus regions of the brain, which are involved in executive function, learning, and memory. A common variation in the BDNF gene called a single nucleotide polymorphism, or SNP, can alter how the BDNF protein functions. The SNP, known as Val66Met, results in the amino acid valine being replaced with methionine in the BDNF protein. Researchers have studied how the Val66Met SNP affects various aspects of cognition.

    Previous research has demonstrated that women with breast cancer who were treated with chemotherapy experienced varying levels of cognitive decline. The current study investigated whether genetics, particularly variations in the BDNF gene, might make a person more susceptible to experiencing these effects.

    The prospective cohort study involved 145 women (average age, 51 years) with early-stage breast cancer who were scheduled to receive chemotherapy. The authors of the study evaluated the participants' cognitive function using neuropsychological tools before, during, and at the end of chemotherapy treatment. Also, the researchers determined which version of the BDNF gene each participant possessed. If a patient’s test score during or at the end of treatment was 15 percent lower than baseline, they were considered to have cognitive impairment.

    The authors observed that 54 women experienced cognitive impairment after treatment; however, those with the Met allele had fewer problems with verbal fluency and multitasking compared to those with the Val allele, particularly in older participants. This information may allow for early interventions in preventing cognitive impairment during chemotherapy.

    These findings suggest that women may differ in their susceptibility to chemotherapy-associated cognitive impairment depending on which version of the BDNF gene they carry. Further research is required to confirm these findings, and brain imaging studies are needed to determine if these findings are the result of changes in brain anatomy.

    Read more
  • Restoration of BDNF-mediated signaling as a potential therapeutic strategy against Huntington's disease. www.sciencedaily.com
    Brain BDNF Neurodegeneration

    Huntington’s disease is a progressive neurodegenerative disorder characterized by uncontrolled movements, speech problems, personality changes, and dementia. The disease is caused by a single genetic mutation, called a CAG repeat, that drives abnormal protein folding and aggregation of the huntingtin protein and subsequent death of striatal neurons. Findings from a 2010 study demonstrate that modulating pathways involved in BDNF-mediated signaling shows promise as a therapeutic against Huntington’s disease.

    Evidence suggests that normal huntingtin promotes the expression of BDNF, but mutated huntingtin impairs it. Striatal neurons need BDNF for their normal function and survival. A critical component in BDNF’s actions on striatal cells is a receptor called TrkB, to which BDNF binds. Levels of TrkB are diminished in Huntington’s disease.

    The authors of the in vitro cell study investigated the effects of BDNF administration on mutant huntingtin. They found that altered cell-signaling in the Ras/MAPK/ERK1/2 pathway in cells expressing mutant huntingtin drove the loss of TrkB receptors, increased striatal cells' sensitivity to oxidative damage, and promoted cell death. These findings suggest that identifying ways to modulate the Ras/MAPK/ERK1/2 pathway and restore BDNF-related signaling shows promise as a therapeutic strategy against Huntington’s disease.

    Read more
  • BDNF genetic variant influences response to exposure therapy among people with PTSD. www.sciencedaily.com
    Brain Behavior Anxiety BDNF

    Exposure therapy is a type of cognitive behavioral therapy commonly used to treat people with posttraumatic stress disorder (PTSD). Some evidence suggests that BDNF mediates the response to exposure therapy, which can vary among people. A 2013 study demonstrated that genetic differences in BDNF expression influences how well a person responds to exposure therapy.

    A single-nucleotide polymorphism (SNP) in the region of the DNA that encodes BDNF causes a substitution of the amino acid valine (Val) by methionine (Met) in the BDNF protein. Evidence suggests that carriers of the Met allele (Met/Met or Val/Met genotype) have reduced hippocampal function, poor episodic memory, and decreased exercise-induced secretion of BDNF.

    The study involved 55 people between the ages of 18 and 65 years who had previously participated in an eight-week exposure therapy program. The participants provided DNA (via saliva samples) for BDNF genotyping.

    The genotyping revealed that 30 participants carried the Val/Val BDNF allele, and 25 participants carried the Met-66 allele. Carriers of the Met-66 allele showed a poorer response to exposure therapy than carriers of the Val/Val allele, suggesting that the SNP influenced BDNF expression and subsequent response to cognitive behavioral therapy.

    Read more
  • Low BDNF during pregnancy is associated with depression during pregnancy and subsequent low fetal birth weight. www.sciencedaily.com
    Brain Pregnancy Development BDNF

    Depression is the most common form of mental health condition worldwide, affecting more than 322 million people. The disorder affects women disproportionately and is particularly common during pregnancy. Findings from a 2017 study demonstrated that serum levels of BDNF drop considerably during pregnancy, potentially increasing a woman’s risk for depression.

    BDNF modulates synaptic plasticity and long-term potentiation – critical aspects of memory storage and brain function. Low BDNF levels are associated with increased risk for depression00181-1/fulltext?cc=y=).

    The study involved 139 healthy pregnant women (77 Blacks and 62 whites) who were assessed three times during their pregnancies (once during each trimester) and again at four to 11 weeks postpartum. The authors of the study measured the participants' BDNF and cortisol levels via blood samples, gathered demographic data, and conducted psychosocial assessments. They reviewed the women’s medical records to determine their infants' birth weights.

    The results of their assessments indicated that the women’s BDNF levels dropped considerably over the course of their pregnancies but rebounded during the postpartum period. In general, Black women had higher BDNF levels and lower cortisol levels than white women during pregnancy and postpartum. Lower levels of BDNF during the second and third trimesters were associated with higher risk for depression and lower birthweight babies, regardless of race.

    Interestingly, these findings contradict those of an earlier study in rats and humans. However, the authors of the current study suggested that the conflicting findings may have been due to differences in assays used to measure BDNF.

    Evidence indicates that exercise increases BDNF. Exercise is generally considered safe for pregnant women and may be a way to prevent some of the changes in mood that occur during pregnancy.

    Read more
  • Preclinical evidence suggests BDNF may be a potent interventional tool in Alzheimer's and brain aging by directly improving learning and memory www.sciencedaily.com
    Exercise Brain Alzheimer's Aging Memory BDNF

    From the article:

    For these experiments, the researchers injected the BDNF gene or protein in a series of cell culture and animal models, including transgenic mouse models of Alzheimer’s disease; aged rats; rats with induced damage to the entorhinal cortex; aged rhesus monkeys, and monkeys with entorhinal cortex damage.

    In each case, when compared with control groups not treated with BDNF, the treated animals demonstrated significant improvement in the performance of a variety of learning and memory tests. Notably, the brains of the treated animals also exhibited restored BDNF gene expression, enhanced cell size, improved cell signaling, and activation of function in neurons that would otherwise have degenerated, compared to untreated animals. These benefits extended to the degenerating hippocampus where short-term memory is processed, one of the first regions of the brain to suffer damage in Alzheimer’s disease.

    […]

    “In this series of studies, we have shown that BDNF targets the cortical cells themselves, preventing their death, stimulating their function, and improving learning and memory. Thus, BDNF treatment can potentially provide long-lasting protection by slowing, or even stopping disease progression in the cortical regions that receive treatment.”

    Read more
  • Brain-derived neurotrophic factor may be able to disrupt cocaine-seeking when applied directly to the nucleus accumbens in the brain [animal research] www.sciencedaily.com
    Brain Behavior Addiction BDNF

    From the article:

    Cocaine relapse was significantly reduced in a preclinical model when brain-derived neurotropic factor (BDNF) was applied to the nucleus accumbens deep in the brain immediately before cocaine-seeking behavior, report investigators at the Medical University of South Carolina (MUSC) in an article published online in June 2018 by Addiction Biology.

    […]

    While other research groups have studied how BDNF administration affects drug self-administration and relapse, no one has looked at what happens if BDNF is given immediately before relapse.

    Since low serum BDNF levels are seen in cocaine-dependent patients compared to non-addicts, the MUSC researchers sought to better understand the connection between BDNF and cocaine relapse. The nucleus accumbens was selected as the focal point for BDNF administration since it is a central component of the brain reward circuit.

    “An important aspect of this study is that while others have shown that BDNF is important for establishing the state of addiction, we find that can also be used to reverse addiction,” says Peter Kalivas, Ph.D., professor and chair in the Department of Neuroscience. “This exemplifies that the primary effect of BDNF is to promote changes in the brain, and that this capacity to change the brain contributes to how people get addicted, but also can be harnessed to remove brain pathologies such as drug addiction.”

    The findings reported in Addiction Biology are the first to show that applying BDNF to the nucleus accumbens immediately before the reinstatement phase, when the rats are once again seeking cocaine due to cue exposure, greatly reduces relapse.

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  • Depressed or blocked BDNF activity has an interesting side-effect in rodents: increased aggression and social dominance seeking www.sciencedaily.com
    Brain Behavior BDNF

    From the article:

    A/Prof. Je’s team generated transgenic mice in which the TrkB receptor was removed specifically in the GABAergic interneurons in the area of the brain regulating emotional and social behaviour, known as the corticolimbic system. The transgenic mice exhibited unusual aggressive behaviour when housed together with normal mice. To understand the origin of this behaviour, the team conducted behavioural tests. They found that the mice were not being aggressive to protect their territory. They were also not being aggressive because they were stronger; the transgenic mice were injured more than other mice during acts of aggression. Instead, their aggressive behaviour was a result of increased fighting for status and dominance over other mice in the group.

    The researchers found that due to the loss of BDNF-TrkB, GABA-ergic interneurons in these transgenic mice supplied weaker inhibition to surrounding excitatory cells, which became overactive. They proceeded to shut down excitatory neurons in a specific area of the transgenic mice brains, which re-established the “excitatory/inhibitory” balance and which “instantaneously reversed the abnormal social dominance,” says Duke-NUS post-doctoral research fellow Dr. Shawn Pang Hao Tan, who was the first author of the paper.

    Read more
  • BDNF response in obese subjects is better under in high-intensity conditions rather than moderate-intensity: addressing cognitive dysfunction in obese www.sciencedaily.com
    Exercise Brain Obesity Aerobic BDNF Lactate

    From the article:

    Results of study, published in the journal Experimental Biology and Medicine, show that the BDNF response to acute high-intensity interval exercise was greater than continuous moderate-intensity exercise in obese subjects when compared to normal-weight subjects. Similarly, although acute high-intensity interval exercise induced greater blood lactate and plasma cortisol levels than continuous moderate-intensity exercise, obese subjects produced less blood lactate, but showed no difference in cortisol than normal-weight subjects.

    These findings suggest that acute high-intensity interval exercise may be a more effective protocol to upregulate BDNF expression in an obese population, independent of increased lactate and cortisol levels.

    Read more
  • Six weeks of 20-minute high-intensity interval training significantly improves "high-interference" memory, large fitness gains associated w/ more BDNF www.sciencedaily.com
    Brain Performance Memory Aerobic BDNF

    From the article:

    Scientists have found that six weeks of intense exercise – short bouts of interval training over the course of 20 minutes – showed significant improvements in what is known as high-interference memory, which, for example, allows us to distinguish our car from another of the same make and model.

    […]

    They also found that participants who experienced greater fitness gains also experienced greater increases in brain-derived neurotrophic factor (BDNF), a protein that supports the growth, function and survival of brain cells.

    “Improvements in this type of memory from exercise might help to explain the previously established link between aerobic exercise and better academic performance,” says Jennifer Heisz, an assistant professor in the Department of Kinesiology at McMaster and lead author of the study.

    Read more
  • Neonatal brain damage decreased by ~50% when a triglyceride lipid emulsion containing omega-3 DHA was injected within two hours of ischemic stroke www.sciencedaily.com
    Brain Omega-3 Stroke

    Animal research.

    From the article:

    The study compared the effectiveness of emulsions with two omega-3 fatty acids – DHA and eicosapentaenoic acid (EPA) – as well as optimal doses and therapeutic window. The researchers found that DHA provided protection while EPA did not. The therapeutic window ranged from 90 minutes prior to several hours after with the optimal window for treatment 0 – 2 hours.

    Prior work:

    Dr. Bazan’s group at the LSU Health Sciences Center New Orleans Neuroscience Center of Excellence has increasingly shown that DHA is a potentially powerful treatment for stroke for nearly ten years. His study published in 2011 found DHA triggered production of Neuroprotectin D1 (NPD1), a naturally occurring neuroprotective molecule in the brain derived from DHA and discovered by Dr. Bazan. Not only did DHA treatment salvage stroke-damaged brain tissue that would have died, its repair mechanisms rendered some areas indistinguishable from normal tissue by 7 days.

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  • Brain-derived neurotrophic factor levels reveal overall severity of traumatic brain injuries -- sharp reductions in TBI after injury predict outcomes www.sciencedaily.com
    Brain BDNF

    From the article:

    Korley and collaborators around the country wanted to know if a blood test could better predict which patients would have ongoing brain injury-related problems, to provide better treatment for them. So they measured the levels of three proteins that they suspected play a role in brain cell activity in more than 300 patients with a TBI and 150 patients without brain injuries. Then, they followed those with a TBI for the next six months.

    Levels of one protein, called brain-derived neurotrophic factor (BDNF), taken within 24 hours of someone’s head injury, could predict the severity of a TBI and how a patient would fare, they found. While healthy people averaged 60 nanograms per milliliter of BDNF in their bloodstreams, patients with brain injuries had less than one-third of that amount, averaging less than 20 nanograms per milliliter, and those with the most severe TBIs had even lower levels, around 4 nanograms per milliliter. Moreover, patients with high levels of BDNF had mostly recovered from their injuries six months later. But in patients with the lowest levels of BDNF, symptoms still lingered at follow-up. The results suggest that a test for BDNF levels, administered in the emergency room, could help stratify patients.

    Read more
  • Every other day fasting in mice protected brain from neurotoxic injury, prior work showing enhanced BDNF www.sciencedaily.com
    Brain Fasting BDNF

    From the article:

    Mice on these three diets were given a neurotoxin called kainate, which damages nerve cells in a brain region called the hippocampus that is critical for learning and memory. (In humans, nerve cells in the hippocampus are destroyed by Alzheimer’s disease). Dr. Mattson’s team found that nerve cells of the meal-skipping mice were more resistant to neurotoxin injury or death than nerve cells of the mice on either of the other diets.

    […]

    Previous studies by Dr. Mattson and his colleagues suggested that nerve cells in the brains of rodents on a meal-skipping diet are more resistant to dysfunction and death in experimental models of stroke and other neurological disorders including Parkinson’s, Alzheimer’s and Huntington’s diseases. Dr. Mattson also has found that meal-skipping diets can stimulate brain cells in mice to produce a protein called brain-derived neurotrophic factor (BDNF) that promotes the survival and growth of nerve cells.

    Read more
  • Neural plasticity induced in visual cortex by cycling may improve recovery from amblyopia ("lazy eye") — previously thought untreatable in adults
    Exercise Brain Eyes Aerobic

    From the article:

    Lunghi and Sale put 20 adults through this test twice; in one deprivation test, participants with one eye patched watched a movie while relaxing in a chair. In the other test, participants with one eye patched exercised on a stationary bike for ten-minute intervals during the movie. The results were clear: brain plasticity was enhanced by the exercise.

    “We found that if, during the two hours of eye patching, the subject intermittently cycles, the perceptual effect of eye patching on binocular rivalry is stronger compared to a condition in which, during the two hours of patching, the subject watches a movie while sitting on a chair. That is, after physical activity, the eye that was patched is strongly potentiated, indicating increased levels of brain plasticity.”

    Read more
  • Beta-hydroxybutyrate, a ketone, increases brain-derived neurotrophic factor expression: relevance for neurodegenerative disease www.sciencedaily.com
    Exercise Brain Alzheimer's Diet Ketosis BDNF HDAC Inhibitor

    β-hydroxybutyrate production consequent to exercise induces within the muscle the activities of a key promoter involved in the production of brain-derived neurotrophic factor.

    From the article:

    Studies have shown that BDNF levels in the brains of people with Alzheimer’s or Huntington’s disease are, on average, half that of people without either brain-damaging disease.

    Among the key findings of the current study was that a ketone, a chemical naturally produced in the liver called beta-hydroxybutyrate (DBHB), triggers biological reactions that activate the BDNF gene to produce more of its protein. DBHB has long been known to build up in the body and brain with exercise. Ketones are “by-product” chemicals made when animals break down fat as an alternative energy source after having drained more readily available sugar stores during exercise.

    Specifically, Chao says, the researchers found that DBHB prevents other proteins in the brain known as histone deacetylase complexes, or HDACs, from suppressing BDNF production by altering the environment of the BDNF gene.

    Read more
  • Environmental enrichment alone produces browning of fat and enhanced weight control not accountable by exercise alone [animal study]
    Brain Obesity Memory Fat BDNF Thermogenesis

    From the article:

    “Up to now the only known approach to inducing brown fat has been through exposure to chronic cold. Our research reveals a novel way of doing this without cold exposure. We show that animals living in an enriched environment become lean and resistant to diet-induced obesity, even in the presence of unlimited food.”

    […]

    The current study used a similarly designed environment, with 15-20 mice housed in large containers equipped with running wheels, tunnels, huts, wood toys, a maze, and nesting material, in addition to unlimited food and water.

    Key findings include the following:

    • Enriched animals showed a significant reduction in abdominal white fat mass (49 percent less than controls).

    • Exercise (running in a wheel) alone did not account for the changes in body composition and metabolism of enriched animals.

    • Fed a high fat diet (45 percent fat), enriched animals gained 29 percent less weight than control mice and remained lean, with no change in food intake. Enriched animals also had a higher body temperature, suggesting that greater energy output, not suppressed appetite, led to the resistance to obesity.

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  • Increases in brain-derived neurotrophic factor from aerobic exercise associated with appetite suppression, weight loss, and improved blood pressure www.sciencedaily.com
    Exercise Brain Obesity Blood Pressure Aerobic Weight Loss BDNF

    From the article:

    The team evaluated blood levels of BDNF before and after a three-month program of aerobic exercise in 15 overweight or obese men and women. The seven men and eight women, ages 26 to 51, worked out on a treadmill and bicycle. They were asked about their calorie intake and told to continue eating their usual number of calories. The participants were unaware that one of the study’s objectives was to evaluate changes in food intake.

    At the end of the study, the subjects had decreased BMI, waist circumference, and blood pressure, the data showed. They also reported consuming fewer calories than at the beginning of the study. Over the three months, BDNF levels greatly increased. This higher the concentration of BDNF, the less the subject’s intake of calories and the greater the weight loss, Araya said.

    Thus, it is possible that increases in BDNF suppress appetite, she said. They did not test appetite suppression directly, but some past studies have shown that aerobic exercise suppresses appetite.

    Read more
  • Increased visceral fat impairs cognition through chronic microglial activation mediated by IL-1 beta release [animal research] www.sciencedaily.com
    Brain Inflammation Memory Fat Dementia Weight Loss NLRP3 Visceral Fat

    Scientists find that visceral fat, a type of adipose tissue that produces high levels of inflammatory signals known as adipokines, impair learning and memory in mice by setting off an inflammatory cascade mediated by the release of IL-1 beta, which crosses the blood-brain barrier leading to chronic activation of microglia.

    From the article:

    “We have identified a specific signal that is generated in visceral fat, released into the blood that gets through the blood brain barrier and into the brain where it activates microglia and impairs cognition.”

    Visceral fat as the ring leader:

    They looked further and found that just transplanting the visceral fat caused essentially the same impact as obesity resulting from a high-fat diet, including significantly increasing brain levels of interleukin-1 beta and activating microglia. Mice missing interleukin-1 beta’s receptor on the microglia also were protected from these brain ravages.

    […]

    To measure cognitive ability, the scientists looked at mice’s ability to navigate a water maze after 12 weeks on a high- or low-fat diet. They found it took the normal, or wild type, mice consuming the higher fat diet as well as the visceral transplant recipients with NLRP3 intact longer to negotiate the water maze. In fact, while they could reach a platform they could see, they had trouble finding one beneath the water’s surface that they had been taught to find. Mice with the interleukin-1 receptor knocked out, could find it just fine, Stranahan says.

    The high-fat diet, transplant mice also had weaker connections, or synapses, between neurons involved in learning and memory. Mice on a high-fat diet but missing NLRP3 were spared these changes, like mice on a low-fat diet.

    Read more
  • Greater BDNF expression in brain tied to up to 50% slower decline in memory in older people (for those in top decile of expression) www.sciencedaily.com
    Brain Alzheimer's Memory Dementia BDNF

    A study of BDNF gene expression in post-mortem brain tissue found that BDNF may provide a buffer against dementia, particularly when higher expression is found in the context of the classical Alzheimer’s brain pathology of amyloid-beta plaques and tau tangles.

    From the article:

    For the study, 535 people with an average age of 81 were followed until death, for an average of six years. They took yearly tests of their thinking and memory skills, and after death, a neurologist reviewed their records and determined whether they had dementia, some memory and thinking problems called mild cognitive impairment or no thinking and memory problems. Autopsies were conducted on their brains after death, and the amount of protein from BDNF gene expression in the brain was then measured.

    […]

    The rate of cognitive decline was about 50 percent slower for those in the highest 10 percent of protein from BDNF gene expression compared to the lowest 10 percent. The effect of plaques and tangles in the brain on cognitive decline was reduced for people with high levels of BDNF. In the people with the highest amount of Alzheimer’s disease hallmarks in their brains, cognitive decline was about 40 percent slower for people with the highest amount of protein from BDNF gene expression compared to those with the lowest amount.

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  • Recovery sleep after a period of sleep deprivation restores hippocampal activity but not the ability to form memories. www.nature.com
    Brain Sleep

    Sleep facilitates the storage of new information in the hippocampus – the region of the brain responsible for the formation and consolidation of short-term memories. Poor sleep, however, inhibits the brain’s ability to form memories. Findings from a new study demonstrate that two nights of recovery sleep after a period of sleep deprivation restores hippocampal activity but not the ability to form memories.

    Sleep deprivation increases a person’s risk of developing many chronic illnesses, including cardiovascular disease, kidney dysfunction, hypertension, diabetes, stroke, obesity, and depression. More than a third of all adults living in the United States report having poor sleep habits.

    The study involved 39 healthy adults who participated in a controlled in-laboratory sleep protocol. Each of the participants experienced one night of sleep deprivation followed by two consecutive nights of recovery sleep. The authors of the study used standard recognition tests to assess the participants' ability to form memories at baseline and every day thereafter. They used functional magnetic resonance imaging (fMRI) to assess the participants' hippocampal functional connectivity at baseline, after sleep deprivation, and after recovery sleep.

    After a single night of sleep deprivation, the participants' memory performance was markedly worse. Similarly, the fMRIs revealed that the participants' hippocampal connectivity was impaired in several regions of the brain associated with memory formation.

    After two nights of recovery sleep, hippocampal connectivity was restored, but memory performance was still impaired. These findings suggest that a person needs more than two nights of recovery sleep to restore memory function after just one night of sleep loss.

    Other studies have demonstrated the effects of sleep deprivation on academic performance. Watch this clip in which sleep expert Dr. Matthew Walker describes the role that sleep plays in learning and new memory formation.

    Read more
  • Blood levels of docosahexaenoic acid, a type of omega-3 fatty acid, predict how well children concentrate and learn. www.sciencedaily.com
    Brain Omega-3 Development

    Nutrition is essential for a child’s development and lifelong health. Early nutritional shortfalls are associated with impaired neurological development and growth. Findings from a new study indicate that blood levels of docosahexaenoic acid (DHA), a type of omega-3 fatty acid, predict how well children concentrate and learn.

    Omega-3 fatty acids are essential for human health. DHA is an omega-3 fatty acid found in the human brain and the meat of fatty fish. It plays a key role in the development of eye and nerve tissues and is essential for normal brain function in humans. Dietary sources of DHA include krill oil, salmon and (especially the roe), flying fish, and pollock.

    The randomized controlled study involved 362 children between the ages of seven and nine years who had below-average reading skills, with most of the children reading at levels about 18 months younger than their chronological ages. Each of the children took either 600 milligrams of supplemental DHA per day or a placebo for 16 weeks. At the end of the study period, the authors of the study assessed the children for changes in reading, working memory, and behavior, including attention deficit-hyperactivity disorder, based on performance and teacher and parental assessments.

    Although the authors of the study didn’t observe improvements in reading scores in the supplemented group as a whole, they did see small improvements among those who were reading at the lowest levels. Children reading at the 20th percentile gained nearly a month in terms of reading age level. Those reading at the 10th percentile gained nearly two months – roughly a 50 percent improvement above what would normally be expected. The parents reported improvements in behavior, but the teachers did not. Supplementation did not affect the children’s working memory.

    These findings suggest that supplemental DHA provides an effective means to improve reading and behavior in children with poor reading skills.

    Read more
  • Cardiorespiratory fitness and body composition influence brain health. www.eurekalert.org
    Exercise Brain Obesity

    A growing body of research demonstrates that exercise has beneficial effects on brain health. N-acetyl aspartic acid (NAA) is a compound found in the central nervous system that serves as a biomarker of neuronal health and energy production. Findings from a new study indicate that lower body fat and higher cardiorespiratory fitness are positively correlated with NAA levels.

    Cardiorespiratory fitness is a measure of the body’s ability to deliver oxygen to skeletal muscles during sustained physical activity. It is commonly measured by VO2 max, a person’s maximum rate of oxygen consumption while under maximal physical stress. Cardiorespiratory fitness is linked with lower body fat composition.

    The study involved 290 healthy young adults (average age, 24 years). Each of the participants' body composition and cardiorespiratory fitness were assessed. Then the participants underwent magnetic resonance spectroscopy (MRS) to assess their NAA levels.

    The MRS scans revealed that participants with less body fat and higher levels of cardiorespiratory fitness had higher levels of NAA in the white matter of their brains. This association was driven primarily by a participant’s whole-body total percent fat, suggesting that body fat might have negative effects on brain health. Exercise exerts a wide range of beneficial effects on brain health. Watch this podcast featuring Dr. Rhonda Patrick in which she describes how exercise might be useful in treating or reducing the risk of depression.

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  • Vitamin C status important for fetal hippocampal development: deficiency leads to a 10-15 percent reduction www.sciencedaily.com
    Brain Vitamin C Memory Pregnancy Development

    According to animal research, even mild vitamin C deficiency may impact fetal hippocampal development, a part of the brain crucial for learning and memory.

    From the article:

    “Even marginal vitamin C deficiency in the mother stunts the fetal hippocampus, the important memory centre, by 10-15 per cent, preventing the brain from optimal development,” says Professor Jens Lykkesfeldt.

    […]

    “People with low economic status who eat poorly – and perhaps also smoke – often suffer from vitamin C deficiency. Comparatively speaking, their children risk being born with a poorly developed memory potential. These children may encounter learning problems, and seen in a societal context, history repeats itself because these children find it more difficult to escape the environment into which they are born,” says Jens Lykkesfeldt.

    From an earlier study’s press release:

    Guinea pigs subjected to moderate vitamin C deficiency have 30 per cent less hippocampal neurones and markedly worse spatial memory than guinea pigs given a normal diet. […] The highest concentration of vitamin C is found in the neurons of the brain and in case of a low intake of vitamin C, the remaining vitamin is retained in the brain to secure this organ.

    Vitamin C deficiency is widespread and may impact early development:

    In some areas in the world, vitamin C deficiency is very common – population studies in Brazil and Mexico have shown that 30 to 40 per cent of the pregnant women have too low levels of vitamin C, and the low level is also found in their foetuses and new-born babies.

    Read more
  • Exercise improved cognitive function in overweight children. www.sciencedaily.com
    Exercise Brain Intelligence Aerobic

    Exercise benefits many aspects of cognitive function. Evidence suggests that children who engage in physical activity typically perform better in school. Findings from a 2011 study showed that exercise improved cognitive function in overweight children.

    The intervention study involved 171 sedentary, overweight children between the ages of 7 and 11 years old. The authors of the study enrolled the children into one of three programs: a “low dose” 20-minute exercise program, a “high-dose” 40-minute exercise program, or a control (sedentary) program. The exercise programs were provided on school days only, for approximately three months. None of the children received any additional tutoring beyond their normal lessons. At the end of the intervention, the children took standardized cognition and achievement tests. Twenty of the children underwent functional MRI (fMRI) testing.

    The results of the standardized tests demonstrated that exercise improved the children’s cognitive function in a dose-dependent manner. Intelligence scores increased among the children in the exercising groups, especially among those in the high dose (40-minute) group, whose scores increased approximately 3.8 points. No improvements were observed among those in the control group.

    Analysis of the fMRIs revealed that the exercising children exhibited higher levels of activity in their prefrontal cortex, an area of the brain associated with complex thinking, decision making, and social behavior – indicators of improved cognitive skills.

    These findings suggest that exercise can benefit children’s cognitive performance and underscore the importance of physical activity programs in schools.

    Read more
  • High-dose injections of vitamin C reduced tumor weight and growth rate by about 50% in mouse models of brain, ovarian, and pancreatic cancer www.sciencedaily.com
    Brain Cancer Vitamin C

    From the article:

    High-dose injections of vitamin C, also known as ascorbate or ascorbic acid, reduced tumor weight and growth rate by about 50 percent in mouse models of brain, ovarian and pancreatic cancers, researchers report in the Proceedings of the National Academy of Sciences. The researchers traced ascorbate’s anti-cancer effect to the formation of hydrogen peroxide in the extracellular fluid surrounding the tumors. Normal cells were unaffected.

    Intravenous administration as a crucial differentiator:

    “Clinical and pharmacokinetic studies conducted in the past 12 years showed that oral ascorbate levels in plasma and tissue are tightly controlled. In the case series, ascorbate was given orally and intravenously, but in the trials ascorbate was just given orally. It was not realized at the time that only injected ascorbate might deliver the concentrations needed to see an anti-tumor effect,” said Levine

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  • Abnormal striatal function may be a promising biomarker for diagnosis and evaluating treatment efficacy in schizophrenia www.eurekalert.org
    Brain Schizophrenia

    The researchers showed, for the first time, that striatal dysfunction was effective in distinguishing schizophrenia patients and that such dysfunction was also responsible for poorer antipsychotic response. This may be an important tool for objectively diagnosing and treatment response rather than the current approach, which primarily relies on the “softer” endpoint of patient behavior.

    From the article:

    The researchers showed, for the first time, that striatal dysfunction was effective in distinguishing schizophrenia patients and that such dysfunction was also responsible for poorer antipsychotic response.

    Based on the newly developed biomarker, the researchers extended their research to other neuropsychiatric disorders. They showed that individuals with bipolar disorder also showed striatal dysfunction that overlapped with the dysfunction associated with schizophrenia.

    Read more
  • Brain aging emerges in the late 40's but dietary ketosis increases overall brain activity and stabilizes functional networks. news.stonybrook.edu
    Brain Aging Ketosis Insulin Time-Restricted Eating Carbohydrates Ketogenic Diet

    Insulin resistance and poor blood glucose control – defining characteristics of type 2 diabetes – drive changes associated with brain aging and cognitive decline. A growing body of evidence suggests that dementia is the manifestation of insulin resistance and altered metabolism in the brain. A recent study suggests that dietary patterns that promote ketosis improve brain metabolism and function.

    Ketosis is a metabolic state that results in the body’s production and use of ketones (byproducts of fatty acid metabolism). It occurs under conditions of fasting, starvation, and low carbohydrate intake. Ketones induce physiological and metabolic responses to promote brain health.

    The study had multiple components. First, the authors of the study investigated the time course of human brain aging. Using functional MRI (fMRI) data from more than 900 people between the ages of 18 and 88 years, they determined that neural network stability is a biomarker of brain aging, and the loss of network stability manifests as early as the fifth decade of life (average age, 47 years). They found that the greatest changes in the brain occur around the age of 60 years.

    Then they performed fMRI scans on 12 young adults (average age, 28 years) to assess how different energy sources – glucose versus ketones – alter brain function. Each participant underwent three scans under different dietary conditions: a normal diet without fasting, a normal diet with overnight fasting, or a ketogenic diet for one week. They performed fMRI scans on 30 young adults (average age 29 years) 30 minutes after they took an oral bolus of either glucose or ketones or after following their normal diet with overnight fasting. The authors of the study measured the participants' blood glucose and ketone levels before and after each of the scans.

    The fMRI scans revealed that ketones increased overall brain activity and stabilized functional networks, but glucose had the opposite effect, regardless of whether the ketones were produced endogenously or supplied from exogenous sources. These findings suggest that dietary interventions that increase ketone production may be useful in mitigating the harmful effects of glucose on the brain.

    Certain dietary patterns promote ketosis. For example, the Ketoflex 12/3 diet, a form of time-restrictive eating that limits the period during which a person eats to a 12-hour window at least three hours before bedtime, promotes the production of ketones. Watch this clip in which Dr. Dale Bredesen describes this novel dietary protocol and how it improves cognitive function.

    Read more
  • Consuming diet drinks along with carbohydrates may have negative effects on the brain and metabolic health. www.inverse.com
    Brain Insulin Carbohydrates Weight Loss

    Low-calorie sweeteners – also known as non-nutritive sweeteners, artificial sweeteners, or sugar substitutes – contain few, if any, calories but deliver a greater intensity of sweetness than sweeteners with calories. They are ubiquitous in the Western diet, appearing in beverages, baked goods, frozen desserts, chewing gum, and many other foods. A new study demonstrates that consuming low-calorie sweeteners in tandem with carbohydrate-rich foods alters brain function and impairs metabolism.

    The health effects of consuming low-calorie sweeteners are not well understood. Whereas some evidence suggests that substituting sugar-sweetened beverages with low-calorie sweeteners can aid in weight loss, other studies suggest that low-calorie sweeteners may contribute to weight gain and diabetes risk, especially in men.

    This study involved 45 healthy adults who did not regularly consume low-calorie sweeteners. Over a period of 10 days, each of the participants drank seven 12-ounce beverages that contained sucralose (a low-calorie sweetener), sugar, or a combination of sucralose and maltodextrin (a polysaccharide produced from grain starch). Before and after the study period, participants underwent oral glucose tolerance tests, sensory tests, and neuroimaging to assess insulin sensitivity, taste perception, and brain response to taste, respectively.

    The authors of the study found that drinking the beverage sweetened with the sucralose-maltodextrin combination reduced the participants' insulin sensitivity and altered their brain responses to sweet tastes. These findings suggest that consuming low-calorie sweeteners while eating or drinking high carbohydrate foods or beverages may have negative effects on metabolism.

    Read more
  • Excess visceral fat promotes inflammation and drives cognitive decline. www.eurekalert.org
    Brain Obesity Depression Neurons Protein Metabolic Syndrome NLRP3 Visceral Fat

    Visceral fat – body fat that is stored in the abdominal cavity in close proximity to important internal organs such as the liver, pancreas, and intestines – plays a central role in the interrelationship between obesity and systemic inflammation. Excess visceral fat, often referred to as central or abdominal obesity, is a strong predictor of age-related cognitive decline. A new study in mice demonstrates that having excess visceral fat may impair cognition by activating the NLRP3 inflammasome and promoting the release of interleukin-1 beta (IL-1β).

    Inflammasomes are large, intracellular complexes that detect and respond to internal and external threats. Activation of inflammasomes has been implicated in a host of inflammatory disorders. Cryopyrin, also known as NLRP3, is a protein that drives the formation and activation of the NLRP3 inflammasome.

    Interleukin-1 beta is a proinflammatory protein present in many cells. NLRP3 inflammasome-driven release of IL-1β activates microglia, the brain’s resident immune cells. Microglia serve an essential role in maintaining brain microenvironment homeostasis. Acute activation of microglia modulates inflammation and neurotoxicity, but chronic activation promotes brain inflammation and harm.

    The authors of the study first determined that mice lacking the gene for NLRP3 did not experience visceral fat-induced brain inflammation and cognitive decline. They also determined that when visceral fat from normal, obese mice was transplanted into these mice, they exhibited higher levels of IL-1β in their hippocampus, an area of the brain associated with memory (in particular, the consolidation of short-term memories to long-term memories), learning, and spatial navigation.

    To understand the effects of IL-1β on brain function, the authors of the study fed the mice a high- or low-fat diet for 12 weeks and then assessed the animals' capacity to navigate a water maze. The mice that ate the higher-fat diet experienced greater difficulties negotiating the water maze, compared to those that ate the lower-fat diet. Examination of the animals' brains revealed that the mice that ate the high-fat diet (as well as those that received the fat transplants) had weaker synapses between the neurons involved in learning and memory.

    These findings suggest that chronic inflammation driven by excess visceral fat may contribute to cognitive decline by promoting the release of IL-1β and increasing inflammation. Inflammation drives other aspects of brain dysfunction, including those associated with depression. Watch this clip in which Dr. Charles Raison discusses how a pro-inflammatory environment can contribute to the risk of depression.

    Read more
  • Brain tissue levels of iron during adolescence influence cognitive abilities. massivesci.com
    Brain Development Iron Neurons

    As many as 10 million people living in the United States have low iron levels. Findings from a new study suggest that iron levels in the basal ganglia region of the brain during youth influence cognitive ability.

    Iron is an essential nutrient that plays critical roles in many facets of brain function, including cellular respiration, neurotransmitter synthesis, and myelination – a process essential to nerve cell transmission and cognitive development. Iron can be obtained in the diet from both animal and plant sources.

    The basal ganglia comprise clusters of neurons located deep within the cerebral hemispheres, at the base of the forebrain and the top of the midbrain. They participate in a wide range of cognitive, motor, and emotive functions.

    The longitudinal study involved more than 800 young people between the ages of 8 and 26 years old who were enrolled in the Philadelphia Neurodevelopment Cohort study. The participants underwent neuroimaging scans up to three times during the study period to quantify iron levels in four regions (caudate, putamen, nucleus accumbens, and globus pallidus) of their basal ganglia. They also completed cognitive performance tests to assess executive control, complex cognition, episodic memory, social cognition, and motor speed.

    The imaging scans revealed that iron levels increased over time in all four regions of the basal ganglia, with the greatest concentrations present in the globus pallidus and putamen, areas that regulate voluntary movement and learning. Higher iron concentrations in the putamen, in particular, were related to higher cognitive abilities among the participants. The accumulation of iron in these regions occurred earlier in females.

    These findings highlight the importance of proper nutrition during development and suggest that iron supplementation may be beneficial, especially during adolescence.

    Read more
  • Alcohol and cigarettes may accelerate brain aging. www.inverse.com
    Brain Aging Alcohol Tobacco Dairy Intelligence

    How well (and how quickly) we age depends on a confluence of genetic, environmental, and lifestyle factors. Some lifestyle behaviors, such as alcohol consumption and cigarette smoking, elicit harmful effects on multiple body systems that can accumulate over time to modulate aging. A new study demonstrates that alcohol consumption and cigarette smoking accelerate brain aging, in particular.

    Research indicates that smoking cigarettes alters multiple structural aspects of the brain. For example, smokers tend to have less gray matter density and volume in the frontal, occipital, and temporal lobes – areas related to a wide range of brain function. Similarly, heavy alcohol use is associated with reduced gray and white matter volumes in the medial-prefrontal and orbitofrontal cortices.

    The authors of the study assessed relative brain age, a comparative measure of brain aging between people of the same chronological age, to determine if a person’s brain is aging at a different rate relative to their peers. The study was based on analysis of brain-imaging data collected from more than 17,000 UK Biobank participants who were of European ancestry and were cognitively normal. After determining the participants' relative brain age, they studied the association of relative brain age with cigarette smoking, alcohol consumption, and genetic variants.

    They found that regular (daily or nearly daily) cigarette smoking or alcohol consumption increased relative brain aging. Every gram of alcohol (~20 grams in 1 fluid ounce) consumed per day was linked to one week of accelerated brain aging and each year spent smoking one pack of cigarettes per day was linked to 11 days of accelerated brain aging.

    These increases in brain aging were associated with poor cognitive function and declines in fluid intelligence, the ability to creatively solve problems without prior knowledge or learning. They also identified two single nucleotide polymorphisms associated with accelerated brain aging.

    While it is important to note that the effect of alcohol on brain aging was only seen in daily or almost daily drinkers, these findings provide useful insights into how cigarette smoking and alcohol consumption influence brain aging and highlight the need for future research to fully elucidate the factors associated with how the brain ages.

    Read more
  • High and low exercise intensity elicit different effects on brain function. www.iospress.nl
    Exercise Brain Depression Lactate

    An abundance of scientific data demonstrates that regular exercise improves overall physical health. Findings from a new study demonstrate how different exercise intensities influence brain function.

    The study involved 22 young men (average age, 27 years) who exercised regularly. Each of the men completed questionnaires and underwent tests to assess their mood, mental health, and cognitive function. Then the men engaged in either low or high intensity exercise (relative to each individual’s fitness level) on a treadmill for 30 minutes, with the two exercise periods separated by several days. The low-intensity exercise was performed at 35 percent under the lactate threshold (the point at which an increase in blood lactate concentration of 0.4 mmol/l above the baseline is observed). The high-intensity exercise was performed at 20 percent above the lactate threshold.

    Although both forms of exercise improved the men’s reported moods, resting state functional magnetic resonance imaging provided insights into how the different exercise intensities influenced brain function. Whereas low-intensity exercise activated brain networks involved in cognition control and attention processing, high-intensity exercise activated networks involved in mood.

    These findings support other data indicating that exercise benefits brain health and suggest that exercise may be a promising modality for use in improving cognitive function and in treating mood disorders.

    Read more
  • Preliminary findings suggest that women taking oral contraceptives have a smaller hypothalamus. www.livescience.com
    Brain

    More than 150 million women worldwide rely on oral contraceptives to prevent pregnancy. Findings presented last month at the Radiological Society of North America’s annual meeting demonstrate that oral contraceptive use is associated with smaller hypothalamus volume.

    The hypothalamus is a region of the forebrain located below the thalamus. It coordinates both the autonomic nervous system and pituitary gland activity, controlling body temperature, thirst, hunger, and other homeostatic systems, and is involved in sleep and emotional activity.

    The study involved 50 healthy young women who were taking oral contraceptives. Each of the women underwent an MRI to assess structural changes in their brains. The MRI results showed that the hypothalamus volumes of the women who were taking oral contraceptives were approximately 6 percent lower women not taking oral contraceptives. Overall brain size was not affected, however.

    This was a small preliminary study with very preliminary findings. Larger studies are needed to confirm this association.

    Read more
  • Boys whose mothers were overweight or obese during pregnancy scored 5 or more points lower on IQ tests at age 7. www.sciencedaily.com
    Brain Obesity Pregnancy Intelligence

    Many factors influence a child’s growth and development, including parenting styles, environmental exposures, socioeconomic status, and maternal health. Maternal obesity, in particular, drives inflammatory, hormonal, and metabolic dysfunction that may adversely affect a developing fetus. Findings from a new study indicate that boys born to obese women perform poorly in measures of motor skills and intelligence compared to children born to healthy weight women.

    The study involved 368 children born to low-income African American or Dominican women living in the United States. The children underwent motor skill and intelligence testing at the ages of 3 and 7 years, respectively. The women were weighed before and during their pregnancies.

    Boys born to women who were overweight or obese during pregnancy scored poorly on motor skills tests at age 3. Similarly, boys whose mothers were overweight or obese during pregnancy scored 5 or more points lower on intelligence tests, compared to boys whose mothers were a healthy weight. Girls did not exhibit differences in motor skills or intelligence. Interestingly, a nurturing home environment modulated some, but not all, of the negative effects of maternal obesity on development.

    Although this was a prospective study and causation cannot be established, these findings point to the importance of maternal nutritional status before and during pregnancy. Unfortunately, this study did not control for important confounders such as diet during pregnancy or whether mothers breastfed their sons. Breastfeeding has been linked to intelligence in children.

    It is noteworthy that the negative effects of maternal obesity were only found in boys and not girls. Other studies have shown that exposure to lead or fluoride in-utero has a negative effect on intelligence in boys. It seems as though boys are particularly vulnerable during fetal development.

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  • Higher cardiorespiratory fitness associated with increases in gray matter volume. newsnetwork.mayoclinic.org
    Exercise Brain Aging Neurons

    Cardiorespiratory fitness is a measure of the body’s ability to deliver oxygen to skeletal muscles during sustained physical activity. Findings from a new study suggest that higher cardiorespiratory fitness may increase the brain’s gray matter.

    Gray matter contains the cell bodies, dendrites, and axon terminals of neurons in the brain. Loss of gray matter is associated with cognitive decline and memory loss – hallmarks of dementia. Physical inactivity promotes gray matter losses and is a major risk factor for dementia.

    The new study involved more than 2,100 adults between the ages of 21 and 84 years living in Germany. The authors of the study assessed the participants' cardiorespiratory fitness based on peak oxygen uptake during exercise on a stationary bike. They also measured the participants' gray matter and total brain volume using magnetic resonance imaging (MRI).

    The MRI analysis revealed that for a single standard deviation increase in peak oxygen uptake, gray matter volume increased by more than 5 cubic centimeters in regions associated with emotion, memory encoding, learning, and decision making. These findings suggest that physical activity that promotes cardiorespiratory fitness might be a means to prevent dementia associated with gray matter losses.

    Sauna bathing is an exercise mimetic and promotes many of the cardiovascular benefits associated with exercise. Dr. Rhonda Patrick describes some of these effects in this podcast.

    Read more
  • More abdominal fat drives loss of fluid intelligence whereas more muscle mass protects against loss. www.sciencedaily.com
    Brain Fat Muscle Protein Intelligence Weight Loss

    Fluid intelligence – the ability to creatively solve problems without prior knowledge or learning – declines with age, often as early as the third decade of life. Evidence from a new study suggests that body composition influences declines in fluid intelligence, and these declines may be related to immune system activation.

    Body composition describes an individual’s body fat and lean mass. Excess body fat promotes systemic inflammation (which can promote neuroinflammation) and drives immune-related inflammatory processes. Lean muscle mass, however, may be protective against inflammation.

    The study involved more than 4,400 middle-aged and older men and women living in the United Kingdom. The participants' body composition, cognitive function, blood leukocytes (white blood cells), and variables such as age, education level, and socioeconomic status were measured every other year for a period of six years.

    The authors of the study found that higher levels of body fat, especially abdominal fat, were associated with greater losses of fluid intelligence. The losses appeared to be related to sex-specific increases in blood leukocyte counts and inflammation, as evidenced by higher levels of C-reactive protein.

    These findings point to the importance of maintaining a healthy body weight throughout life as a strategy to reduce or prevent cognitive decline.

    Read more
  • Depression and suicide linked to air pollution www.theguardian.com
    Brain Depression Behavior Pollution

    Air pollution contains a myriad of toxic substances. Exposure to air pollutants is associated with poor health outcomes and increased risk of disease. Findings from a recent review and meta-analysis suggest that high concentrations of particulate matter in air pollution may increase the risk of developing depression.

    Depression is the most common mental health disorder worldwide, affecting approximately 322 million people – more than 4 percent of the global population. Between 2005 and 2015, rates of depression increased by more than 18 percent, and public health experts predict that by the year 2020, depression likely will rank second in the global burden of disease.

    Particulate matter in air pollution is a mixture of solid particles and liquid droplets. Some evidence suggests that exposure to particulate air pollutants accelerates aging.

    The authors of the review conducted a meta-analysis of 14 studies involving more than 680,000 participants living in North America, Europe, and Asia. They found that as concentrations of particulate matter increased, the risk of depression and suicide increased. Specifically, for every 10 microgram per cubic meter increase in particulate matter that is 2.5 microns or less in width, the risk of depression increased by 19 percent and risk of suicide increased by 5 percent.

    The mechanisms that drive these links may be related to increased oxidative stress and neuroinflammation as a consequence of exposure to air pollutants. These findings point to the need for improving air quality and monitoring at-risk groups living in areas where air quality is poor.

    Read more
  • Yoga increases the volume of a brain region involved in learning and memory and changes several brain regions involved in emotional regulation. www.sciencedaily.com
    Brain Depression Vegetarian Aerobic Breathing Technique

    The benefits of physical activity, especially aerobic exercise such as running, swimming, or cycling, have positive effects on brain health and function. A recent review suggests that yoga has similar effects on the brain.

    Yoga is an ancient Indian practice that engages the mind and body through physical poses, breathing techniques, and meditation. It incorporates aspects of mindfulness not commonly present in other forms of exercise.

    The authors of the review focused on 11 cross-sectional, longitudinal, or intervention studies examining the effects of yoga on the brain’s structures, function, and blood flow based on MRI, functional MRI, and SPECT (single-photon emission computed tomography). They found that yoga had beneficial effects on the hippocampus, amygdala, prefrontal cortex, cingulate cortex, and the default mode network. These areas of the brain play critical roles in memory processing, emotional control, and decision making.

    The authors identified a few confounders in their review. People who practice yoga are more likely to be physically active, non-obese, and well-educated. They are also more likely to follow vegetarian or plant-based diets. These lifestyle behaviors have been shown to have beneficial effects on brain health.

    Overall, however, the findings from this review suggest that exercise interventions like yoga may be a useful strategy to mitigate age-related changes within the brain associated with memory loss and cognitive decline.

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  • IQs of children whose mothers consumed fish during pregnancy nearly 5 to 10 points higher than those of children whose mothers did not eat fish. www.nytimes.com
    Brain Omega-3 Pregnancy Vitamin A Intelligence

    A pregnant woman’s diet has considerable impact on her child’s health and development. Findings from two recent reviews suggest that maternal consumption of fish and seafood improves children’s performance on intelligence tests.

    According to the Dietary Guidelines for Americans 2015-2020, seafood is a broad term that includes both fresh and saltwater fishes (such as salmon, tuna, trout, and tilapia) and shellfish (such as shrimp, crab, and oysters). Dietary intake of seafood provides many vitamins, minerals, and essential fatty acids that play key roles in a child’s neurocognitive development during pregnancy and early life. Seafood also contains mercury, a neurotoxicant. Questions remain about whether seafood consumption impairs neurocognitive development in pregnancy and childhood.

    The authors of the review analyzed data from randomized controlled trials, prospective cohort studies, or case-control studies involving pregnant women and their children, including 29 studies of more than 102,000 mother-child pairs and 15 studies of more than 25,000 children under the age of 18 years. They found that even low intake of seafood – about four ounces per week – improved neurocognitive development among children. These improvements were manifested in an average increase of 7.7 points on intelligence tests. In addition, no negative neurocognitive outcomes were reported, even with high seafood intake, despite possible higher mercury exposure to mercury.

    These findings have relevance for public health recommendations regarding dietary seafood intake among pregnant women and children.

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  • Obese adolescents have decreased white matter in a brain region that connects the right and left hemispheres of the brain (compared to healthy teens). www.sciencedaily.com
    Brain Obesity Inflammation Insulin

    Obese adolescents have decreased white matter in a brain region that connects the right and left hemispheres of the brain (compared to healthy teens). These changes correlated with markers of inflammation and insulin resistance.

    Approximately 20 percent of teens living in the United States are obese. Obesity negatively affects multiple organ systems, including the nervous system. Findings from a new study indicate that the white matter in the brains of obese teens is lower than that of healthy teens.

    Obesity is associated with chronic low-grade inflammation, which can drive many disease processes. A specialized magnetic resonance imaging technique, called diffusion tensor imaging (DTI), can measure this inflammation in the brain.

    A study involving 59 obese adolescents and 61 normal weight adolescents between the ages of 12 and 16 years used DTI to measure damage to the white matter in the teens' brains. The imaging results revealed that areas of the corpus callosum, a bundle of nerve fibers that connects the left and right hemispheres of the brain, as well as areas of the middle orbitofrontal gyrus, an area responsible for emotional control and reward circuits, were diminished in the obese teens' brains. Damage in these areas was correlated with altered levels of insulin, inflammatory markers, and leptin, a key regulator of appetite, and insulin.

    Future research with DTI imaging techniques may reveal whether these changes in the structure of obese teens' brains are reversible.

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  • Gut bacteria may alter the aging process of the human brain through the production of butyrate www.sciencedaily.com
    Brain Gut Aging Microbiome Neuron Fatty Liver Neurons Neurogenesis Butyrate

    The gut microbiota is a complex and dynamic population of microorganisms that is subject to change throughout an individual’s lifespan in response to the aging process. Findings from a new study demonstrate that altering the gut microbial population may alter the aging process of the human brain.

    The authors of the study transplanted gut microbiota samples from healthy young or old mice into young germ­-free mice. Eight weeks after the transplant, the mice that received microbial samples from the old mice demonstrated increased neurogenesis – the process of forming new neurons – in the hippocampus region of their brains.

    Further analysis revealed that these mice also had larger numbers of butyrate-producing microbes in their colons. Butyrate, a short-chain fatty acid, is produced during bacterial fermentation in the human colon and has wide-ranging effects on human physiology. In this study, butyrate was associated with an increase in growth factors and subsequent activation of key longevity signaling pathways in the livers of the recipient mice. When butyrate alone was given to the recipient mice it promoted neurogenesis, as well.

    The findings from this study may have relevance for dietary interventions to maintain or improve brain health.

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  • 12 weeks of high-intensity interval training improves memory by 30% in older adults between the ages of 60 and 88. www.sciencedaily.com
    Exercise Brain Aging Memory Dementia Aerobic

    Cognitive decline and associated memory loss are common features of aging, affecting approximately 16 million people living in the United States. A recent study found that high-intensity interval training improves memory in older adults.

    The study involved 64 sedentary older adults between the ages of 60 and 88 years who were randomized to participate in 12 weeks of high-intensity interval training, moderate continuous training, or stretching (which served as the control group). Each of the participants' memory and executive functions were assessed before the training began.

    The participants in the high-intensity group performed four intervals of high-intensity exercise on a treadmill for four minutes, followed by a period of recovery. The participants in the moderate continuous group performed a single set of moderate-intensity aerobic exercise for approximately 50 minutes.

    At the end of the study period, participants who engaged in high-intensity exercise performed better on memory tests than those who engaged in moderate continuous training or stretching only. The participants who saw the greatest fitness gains also saw the greatest memory improvements. Both high-intensity interval and moderate continuous exercise improved executive function in the participants.

    These findings suggest that aerobic exercise, especially if it includes high-intensity interval training, has the potential to enhance memory in older adults.

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  • Inflammation may play a causal role in diminishing certain cognitive functions. www.birmingham.ac.uk
    Brain Inflammation Depression Protein

    Inflammation is a critical element of the body’s immune response that involves the activity of immune cells, cell-signaling proteins, and pro-inflammatory factors. Chronic inflammation, which occurs on the cellular level in response to toxins or other stressors, is implicated in the development of many chronic illnesses, including cancer, cardiovascular disease, and diabetes. Findings from a new study indicate that inflammation may be a factor in the “brain fog” that commonly accompanies chronic illness.

    The double-blinded placebo-controlled study involved 20 young men (average age, 24 years) who were injected with either a typhoid vaccine or saline. The purpose of the vaccine was to induce mild, transient inflammation, which was confirmed by the participants' blood levels of interleukin-6, a pro-inflammatory molecule.

    Six hours after the participants received their injection, three measures of their brain activity – alerting, orienting, and executive control – were assessed via electroencephalogram (EEG). The EEG results indicated that the participants' capacity for staying alert in preparation for a task was diminished post-vaccine but their other brain activities were unaffected. These findings point to a causal link between inflammation and diminished brain function and may explain why people who suffer from chronic disease often complain of difficulty concentrating or carrying out tasks.

    Interestingly, other studies have used methods similar to those used in this study to show that inflammation plays a causal role in depression. To learn more about the role of inflammation in depression, check out the FMF topic page on depression. Read the whole article or skip to the section on inflammation.

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  • Waves of Fluid Bathe the Sleeping Brain, Perhaps to Clear Waste www.the-scientist.com
    Brain Alzheimer's Sleep Neurons Protein

    The glymphatic system – a vast arrangement of cerebrospinal fluid-filled cavities surrounding the small blood vessels in the brain – facilitates the removal of proteins and metabolites from the central nervous system. During sleep, these interstitial spaces increase by more than 60 percent. A new study demonstrates that large quantities of cerebrospinal fluid flow through these spaces in a rhythmic fashion during deep sleep to remove waste.

    The study involved 13 young, healthy men and women whose neuronal activity, blood levels, and cerebrospinal fluid (CSF) flow were measured during sleep. As the study subjects slept, a large wave of CSF flowed through their brains roughly every 20 seconds, preceded by changes in brain neuronal activity and blood flow.

    Poor sleep – which would impair glymphatic function – has been linked to a variety of neurodegenerative diseases. For example, disruption in deep sleep is highly pronounced in people with Alzheimer’s disease and typically precedes diagnosis.

    Glymphatic activation has also been shown to play a key role in the transport of biomarkers of traumatic brain injury (TBI). In particular, cerebrospinal fluid-mediated removal of tau protein in the brain via glymphatic routes is crucial for limiting secondary neuronal damage following traumatic brain injury. Unfortunately, some types of TBI impair glymphatic function and may be one reason why people with TBI are at a higher risk for neurodegenerative diseases.

    Taken together, these data suggest that sleep – especially deep sleep – is not only important for the prevention of Alzheimer’s disease but also may be key in the treatment of TBI.

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  • Human longevity was associated with decreased levels of genes involved in neural overactivity. www.nature.com
    Brain Aging Stress Protein

    Healthy brain activity is achieved by maintaining a balance between neural excitation and inhibition. Impairment in this balance is related to many neurological and neurodegenerative disorders, including epilepsy, autism, Parkinson’s, Alzheimer’s, and schizophrenia. In Caenorhabditis elegans, a model organism for studying both the nervous system and aging, neural excitation increases with age and age-related cognitive decline, but lifespan increases with inhibition. A recent study demonstrates that extended longevity in humans is associated with lower levels of genes related to neural excitation.

    The multi-arm study focused on three organisms: C. elegans, humans, and mice. The authors of the study found that global inhibition of neural excitation increased the lifespan of C. elegans. RNA sequencing and microarray analysis of human genes revealed that long-lived people (older than 85 years) have higher levels of REST, a gene-silencing transcription factor that downregulates neural excitation-related genes. In addition, they found that mice that are deficient in REST exhibit higher levels of neural excitation. REST and lower levels of neural excitation activate FOXO1, a longevity-associated transcription factor in mammals, suggesting that REST regulates a conserved mechanism of aging.

    The authors of the study suggested that REST activation and subsequent reduction of excitatory neural activity may be a means to slow aging in humans.

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  • A mid-day nap 3x per week in children ages 10-12 was associated with a 7.6% increase in academic performance, elevated mood, improved behavior. penntoday.upenn.edu
    Brain Sleep Behavior Development

    A mid-day nap at least 3x per week in children ages 10-12 was associated with a 7.6% increase in academic performance, elevated mood, improved self-control, and fewer behavioral problems.

    This study was conducted in 3,000 school children in China where napping continues through elementary and middle school, even into adulthood. It is well known that napping is critical for intellectual development and emotional regulation in infants and toddlers so it is not too surprising that naps may be beneficial for older children as well.

    Additionally, many school children remain drowsy throughout the day as a consequence of early school start times. The authors of this study propose an interesting potential “middle ground” solution to the early start times; mid-day naps at school.

    This study was not a randomized controlled trial which is necessary to establish causation. Still, I think almost every parent would agree that naps make happier and healthier children.

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  • Obesity can break down our protective blood brain barrier resulting in problems with learning and memory: overactivity of adenosine in obesity www.sciencedaily.com
    Brain Alzheimer's Obesity Diabetes Coffee Insulin Blood Sugar Blood-Brain Barrier Lipopolysaccharide

    Diet-induced insulin resistance caused blood vessels to become leaky which impaired blood and oxygen flow to a brain region involved in learning and memory (animal evidence).

    Obesity and insulin resistance are associated with a leaky blood-brain barrier. This new animal study found that a high-sugar combined with a high-fat diet caused shrinkage of the tight junctions between endothelial cells that make up the blood-brain barrier and actual holes in those cells.

    Obesity is known to increase toll-like receptor activation through a variety of mechanisms. One of the mechanisms is through through associated increases of circulating of lipopolysaccharide. Another mechanism is the leaking of fatty acids from fatty acids, triggering toll-like receptors through the recognition of damage-associated molecular patterns (DAMPs). (See “obesity” section of toll-like receptor article.)

    Furthermore, LPS challenge in animal studies induces microglia in the brain to attack and damage the blood-brain barrier.

    Blocking adenosine may play a role in preventing impairment of the blood-brain barrier by diet-induced obesity

    However, adenosine, which helps us sleep and helps regulate our blood pressure and is blocked by caffeine may play a role in preventing some of the damaging effects obesity has on the blood-brain barrier, which promotes dementia.

    From the article:

    They knew that chronic activation of the receptor Adora2a [an adenosine receptor] on the endothelial cells that line this important barrier in our brain can let factors from the blood enter the brain and affect the function of our neurons.

    Now Medical College of Georgia scientists have shown that when they block Adora2a in a model of diet-induced obesity, this important barrier function is maintained.

    […]

    In the brain, adenosine is a neurotransmitter that helps us sleep and helps regulate our blood pressure; in the body it’s also a component of the cell fuel adenosine triphosphate, or ATP. Adenosine also activates receptors Adora1a and Adora2a on endothelial cells, which normally supports healthy relationships between brain activity and blood flow.

    Problems arise with chronic activation, particularly in the brain, which is what happens with obesity, says Stranahan.

    People who have obesity and diabetes have higher rates of cognitive impairment as they age and most of the related structural changes are in the hippocampus, a center of learning and memory and Stranahan’s focus of study. Fat is a source of inflammation and there is evidence that reducing chronic inflammation in the brain helps prevent obesity-related memory loss.

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  • A new study shows that even 80-year-olds can grow new neurons in the hippocampus region of the brain, but this process is decreased in people with AD. www.the-scientist.com
    Brain Alzheimer's Neurons

    A new study shows that even 80-year-olds can grow new neurons in the hippocampus region of the brain, but this process is decreased in people with Alzheimer’s disease.

    The process of growing new neurons is called neurogenesis and it is highly active during brain development but whether it occurs in adults has been unclear. An animal study published last year had shed some doubt on adult neurogenesis claiming it does not occur.

    A new study using cutting-edge techniques looked at human samples and provided pretty solid evidence of neurogenesis in adult humans. It also found that in tissue samples from people with Alzheimer’s disease, neurogenesis was dramatically diminished. This is in line with brain imaging studies showing brain atrophy in the hippocampus brain region in Alzheimer’s disease patients.

    One of the major regulators of neurogenesis is the growth factor BDNF. Studies have shown 30 minutes of exercise can increase BDNF in humans. BDNF is able to cross the blood-brain barrier and promote the growth of new neurons.

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  • Animal study demonstrates fungus C. albicans can cross the blood-brain barrier and may promote neurodegenerative disease, such as Alzheimer's www.sciencedaily.com
    Brain Alzheimer's Parkinson's Aging Microbiome Blood-Brain Barrier

    A common type of fungus, Candida albicans, was shown to cross the blood-brain barrier and trigger an inflammatory response in the brain that results in memory impairment (mouse study).

    These findings raise the possibility that fungal infections may play a role in the development of chronic neurodegenerative disorders, such as Alzheimer’s disease. Dr. Dale Bredesen talks about this is the recent podcast episode I did with him.

    Check that out here: https://www.foundmyfitness.com/episodes/dale-bredesen

    From the article:

    “We thought that yeast would not enter the brain, but it does,” Corry said. “In the brain, the yeast triggered the activity of microglia, a resident type of immune cell. The cells became very active ‘eating and digesting’ the yeast. They also produced a number of molecules that mediated an inflammatory response leading to the capture of the yeasts inside a granule-type structure inside the brain. We called it fungus-induced glial granuloma, or FIGG.”

    The mice cleared the yeast infection in about 10 days; however, the microglia remained active and the FIGGs persisted well past this point, out to at least day 21. Intriguingly, as the FIGGs formed, amyloid precursor proteins accumulated within the periphery and amyloid beta molecules built up around yeast cells captured at the center of FIGGs. These amyloid molecules are typically found in plaques that are the trademark of Alzheimer’s disease. […] Intriguingly, as the FIGGs formed, amyloid precursor proteins accumulated within the periphery and amyloid beta molecules built up around yeast cells captured at the center of FIGGs. These amyloid molecules are typically found in plaques that are the trademark of Alzheimer’s disease.

    […]

    “The results prompted us to consider the possibility that in some cases, fungi also could be involved in the development of chronic neurodegenerative disorders, such as Alzheimer’s, Parkinson’s and multiple sclerosis. We are currently exploring this possibility.”

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  • Two randomized placebo-controlled trials found that supplementation with omega-3 fatty acids (1.2 g/day) improved mood, cognitive functioning. www.ncbi.nlm.nih.gov
    Brain Omega-3 Behavior

    Two randomized placebo-controlled trials found that supplementation with omega-3 fatty acids (1.2 g/day) improved mood, cognitive functioning and reduced psychosis in high-risk adolescents compared to placebo.

    The finding that treatment with fish oil may prevent or at least delay the onset of psychotic disorder gives hope that there may be alternatives to antipsychotics for the first psychotic episode. Omega-3 fatty acids have been shown to be very safe even when used in relatively high doses, and except for gastrointestinal symptoms like fishy eructation, they are free of clinically relevant adverse effects. They have the advantage of excellent tolerability, public acceptance, relatively low costs, and benefits for general health.

    Second study: http://journals.sagepub.com/doi/10.1177/070674371305800705

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  • Betaine reduces β-amyloid-induced paralysis in an Alzheimer model of Caenorhabditis elegans | Genes & Nutrition | Full Text genesandnutrition.biomedcentral.com
    Brain Alzheimer's Neuron Neurons Homocysteine

    Full Title: Betaine reduces β-amyloid-induced paralysis through activation of cystathionine-β-synthase in an Alzheimer model of Caenorhabditis elegans

    Betaine at a concentration of 100 μM was able to reduce homocysteine levels in the presence and absence of 1 mM homocysteine. Simultaneously, betaine both reduced normal paralysis rates in the absence of homocysteine and increased paralysis rates triggered by addition of homocysteine. Knockdown of cystathionine-β-synthase using RNA interference both increased homocysteine levels and paralysis. Additionally, it prevented the reducing effects of betaine on homocysteine levels and paralysis.

    Our studies show that betaine is able to reduce homocysteine levels and β-amyloid-induced toxicity in a C. elegans model for Alzheimer’s disease. This effect is independent of the remethylation pathway but requires the transsulfuration pathway mediated by cystathionine-β-synthase.

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  • A high-fat diet promotes depression-like behavior in mice by suppressing hypothalamic PKA signaling papers.ssrn.com
    Brain Obesity Depression Saturated Fat Protein

    Obesity is associated with an increased risk of depression. The aim of the present study was to investigate whether obesity is a causative factor for the development of depression and what is the molecular pathway(s) that link these two disorders. Using lipidomic and transcriptomic methods we identified a mechanism that links exposure to a high-fat diet (HFD) in mice with alterations in hypothalamic function that lead to depression. Consumption of an HFD selectively induced accumulation of palmitic acid in the hypothalamus, suppressed the 3´, 5´-cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, and increased the concentration of free-fatty acid receptor 1 (FFAR1). Deficiency of phosphodiesterase 4A (PDE4A), an enzyme that degrades cAMP and modulates stimulatory regulative G-protein (Gs)-coupled G protein-coupled receptor signaling, protected animals either from genetic- or dietary induced depression phenotype.

    These findings suggest that dietary intake of saturated fats disrupts hypothalamic functions by suppressing cAMP/PKA signaling through activation of PDE4A. FFAR1 inhibition and/or an increase of cAMP signaling in the hypothalamus could offer potential therapeutic targets to counteract the effects of dietary or genetically induced obesity on depression.

    https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3188483

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  • Food Additives Causing Harm, Reforms Urgently Needed, AAP Says www.medscape.com
    Brain Cancer Gut Hormones Pregnancy Neurotransmitter Insulin

    The Worst Offenders:

    The statement addresses 2 broad categories of additives: direct and indirect. Indirect additives refers to substances in “food contact materials,” such as “adhesives, dyes, coatings, paper, paperboard, plastic, and other polymers,” the authors of the policy statement explain. Direct food additives include chemicals such as colorings, flavorings, and preservatives added to food during processing. Within those two categories the authors identified six types of additives of most concern, based on accumulating evidence summarized in the report and in an accompanying press release:

    Bisphenols: Used to manufacture plastic containers and food and beverage cans, these compounds have been associated with endocrine and neurodevelopmental disruption and obesogenic activity, with alterations in the timing of puberty, reduced fertility, and impaired neurological and immunological development. One bisphenol, bisphenol A, has already been banned from baby bottles and sippy cups.

Phthalates: As components of plastic wrap and plastic tubing and containers, phthalates similarly have been implicated in endocrine disruption and obesogenic activity. "A robust literature" shows that these chemicals adversely affect male sexual development, may contribute to childhood obesity and insulin resistance, and may also contribute to cardiovascular disease.

Perfluoroalkyl chemicals: These chemicals are used in the manufacture of greaseproof paper and cardboard packaging. They have been associated with immunosuppression, endocrine disruption such as impaired thyroid function, and decreased birth weight.

Perchlorate: Often added to plastic packaging for dry foods to control static electricity, perchlorate has been shown to disrupt production of thyroid hormone, with implications for subsequent cognitive function. Of particular concern is exposure among pregnant women, "given that the developing fetus is entirely reliant on the maternal thyroid hormone during the first trimester of pregnancy," the authors write in the technical report. They suggest that perchlorate "may be contributing to the increase in neonatal hypothyroidism and other thyroid system perturbations that have been documented in the United States."

Nitrates and nitrites: As direct food additives, these compounds are used as preservatives and color enhancers in cured and processed meats, fish, and cheese. There has been "longstanding concern" over their use, the authors write, because of an association with cancers of the nervous and gastrointestinal systems, and methemoglobinemia in infants. They were classified as "probable human carcinogens" in 2006 by the International Agency for Research on Cancer.

Artificial food colors: Often added to products that appeal to children, such as juice drinks, artificial food colors have been associated in some studies with an increased risk for attention-deficit hyperactivity disorder. Although their mechanisms of action are not yet completely understood, and the research "should be interpreted with caution," the authors recommend "a thorough reassessment" of artificial food colors to ensure they are safe.
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  • Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1 papers.ssrn.com
    Brain Aging Circadian Rhythm Neuron Glutathione Neurons Protein

    Abstract

    Circadian clock dysfunction is a common symptom of aging and neurodegenerative diseases, though its impact on brain health is poorly understood. Astrocyte activation occurs in response to diverse insults, and plays a critical role in brain health and disease. We report that the core clock protein BMAL1 regulates astrogliosis in a synergistic manner via a cell-autonomous mechanism, and via a lesser non-cell-autonomous signal from neurons. Astrocyte-specific Bmal1 deletion induces astrocyte activation in vitro and in vivo, mediated in part by suppression of glutathione-s-transferase signaling. Functionally, loss of Bmal1 in astrocytes promotes neuronal death in vitro. Our results demonstrate that the core clock protein BMAL1 regulates astrocyte activation and function in vivo, elucidating a novel mechanism by which the circadian clock could influence many aspects of brain function and neurologic disease.

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  • Exercise for cognitive brain health in aging | Neurology Clinical Practice cp.neurology.org
    Exercise Brain Aging Aerobic

    Abstract:

    Purpose of review - We systematically appraised randomized controlled trials proposing exercise to influence cognition in older adults to (1) assess the methodologic quality using Cochrane criteria; (2) describe various exercise dose measures and assess their relationship with improved cognitive performance; and (3) identify consistent patterns of reported effects on cognition.

    Recent findings: There was overall good methodologic quality in all 98 included studies. The assessment of the relationship between improved cognition and various measures of exercise dose (session duration, weekly minutes, frequency, total weeks, and total hours) revealed a significant correlation with total hours. Improvements in global cognition, processing speed/attention, and executive function were most stable and consistent.

    Summary: We found that exercising for at least 52 hours [over the course of 6 months is the minimum amount needed] is associated with improved cognitive performance in older adults with and without cognitive impairment. Exercise modes supported by evidence are aerobic, resistance (strength) training, mind–body exercises, or combinations of these interventions.

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  • Maternal sugar consumption, particularly from sugar-sweetened beverages, was associated with poorer childhood cognition including non-verbal abilities www.sciencedaily.com
    Brain Depression Pregnancy Development Sugar Intelligence

    Maternal sugar consumption, particularly from sugar-sweetened beverages, was associated with poorer childhood cognition including non-verbal abilities to solve novel problems, poorer verbal memory, poorer fine motor, and poorer visual-spatial/visual-motor abilities in childhood.

    The study also found that substituting diet soda for sugar-sweetened soda during pregnancy was also linked to negative effects. However, children’s fruit consumption (but not fruit juice) had beneficial effects and was associated with higher cognitive scores.

    As with any observational study, it is difficult to establish causation. However, the data was adjusted for a variety of other health and socioeconomic factors which does strengthen the data.

    Here is the long list of the health/lifestyle factors that the data were adjusted for: maternal age, pre-pregnancy BMI, parity, education, smoking status during pregnancy, maternal prenatal fish intake (the mean of the first and second trimesters), household income at enrollment, and the child’s sex and race/ethnicity,child’s birth weight, maternal marital status, intelligence, depression during pregnancy, pre-pregnancy physical activity levels, Western or prudent dietary pattern (calculated without fruits and sugar beverages), breastfeeding duration, paternal age and education, and HOME-SF score.

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  • UDP-glucuronosyltransferases (UGTs) of the blood-brain barrier: their role in drug metabolism and detoxication www.frontiersin.org
    Brain Sulforaphane Dopamine

    [Abstract]

    UDP-glucuronosyltransferases (UGTs) form a multigenic family of membrane-bound enzymes expressed in various tissues, including brain. They catalyze the formation of β-D-glucuronides from structurally unrelated substances (drugs, other xenobiotics, as well as endogenous compounds) by the linkage of glucuronic acid from the high energy donor, UDP-α-D-glucuronic acid.

    In brain, UGTs actively participate to the overall protection of the tissue against the intrusion of potentially harmful lipophilic substances that are metabolized as hydrophilic glucuronides. These metabolites are generally inactive, except for important pharmacologically glucuronides such as morphine-6-glucuronide. UGTs are mainly expressed in endothelial cells and astrocytes of the blood brain barrier (BBB). They are also associated to brain interfaces devoid of BBB, such as circumventricular organ, pineal gland, pituitary gland and neuro-olfactory tissues.

    Beside their key-role as a detoxication barrier, UGTs play a role in the steady-state of endogenous compounds, like steroids or dopamine (DA) that participate to the function of the brain. UGT isoforms of family 1A, 2A, 2B and 3A are expressed in brain tissues to various levels and are known to present distinct but overlapping substrate specificity. The importance of these enzyme species with regard to the formation of toxic, pharmacologically or physiologically relevant glucuronides in the brain will be discussed.

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  • Reaction time and mood were improved in young individuals that consumed blackcurrant berry drink with 500 mg of polyphenols compared to placebo. www.tandfonline.com
    Brain Diet Vitamin A Polyphenol

    Reaction time and mood were improved in young individuals that consumed blackcurrant berry drink with 500 mg of polyphenols compared to placebo in a small pilot randomized controlled trial. EEG data also showed the blackcurrant drink changed brainwave activity.

    This was a small trial with a crossover study design, which means each person serves as their own control. Both the blackcurrant drink and the placebo drink had 6.98 g of sugar (glucose +fructose). They also both had the same amount of vitamin C…the only difference was that the placebo drink lacked the 500 mg of polyphenols.

    Conclusions cannot be made from this trial alone since it was a small pilot trial. However, there is a growing body of clinical trials showing polyphenols positively affect brain function in both young and old individuals.

    I understand that it would not be possible to make a placebo drink if the whole fruit was used…but I think it is better to consume the berries with the fiber which changes the way sugar is metabolized and also has benefits for the gut microbiome.

    More reading: https://www.ncbi.nlm.nih.gov/pubmed/26690214?dopt=Abstract

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  • Only 30% of pregnant women in New Zealand meet the international recommendations for DHA of 200mg per day. www.massey.ac.nz
    Brain Omega-3 Pregnancy

    Only 30% of pregnant women in New Zealand meet the international recommendations for DHA of 200mg per day. The mean intake in Western society is ~135 mg/d::dose per day (~2 servings of fish/mo). The American Heart Association recommends that adults consume 500 mg/d::dose per day of EPA and DHA (~2-3 servings/wk or ~8 oz of fish/wk). However, Many pregnant women are afraid of eating fish because of mercury…but a 2015 American Journal of Clinical Nutrition study showed that eating omega-3 fatty acids from fish actually protects the brain from the toxic effects of mercury even in the developing fetus (which is the most susceptible to mercury effects). Atlantic salmon, sockeye salmon, sardines, oysters, and tilapia are all low on the mercury scale and have 2 micrograms of mercury per 4 ounces cooked. Whereas albacore tuna has 40 micrograms of mercury per 4 ounces cooked and swordfish has 147 micrograms of mercury per serving.

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  • Traumatic brain injury (TBI) can nearly double a person's risk for dementia. www.newscientist.com
    Brain Alzheimer's

    Several studies have now shown that TBI can start an inflammatory cascade in the brain that leads to a much higher risk of dementia and Alzheimer’s disease. People with the apoE4 allele, which is the highest known risk factor for Alzheimer’s disease besides age, are twice as likely to get Alzheimer’s disease than those without apoE4. When people with the apoE4 allele undergo TBI their Alzheimer’s risk climbs to 10-fold! For those individuals with the apoE4 allele, it may be prudent to avoid playing sports that raise the risk of TBI such at football. There are many diet and lifestyle factors that can lower a person’s risk for Alzheimer’s particularly if they have the apoE4 allele including diet high in vegetables, fruit and wild salmon, good sleep, low alcohol intake, and no smoking. I’ll be talking more about Alzheimer’s disease and apoE4 soon…I am submitting a paper for publication on this topic and will be sharing my work very soon!

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  • Brain inflammation found to be 30% higher in people suffering with obsessive-compulsive disorder. www.eurekalert.org
    Brain Omega-3 Inflammation Depression Immune System Anxiety Iron

    There’s very good evidence for systemic inflammation being implicated in mental disorders more generally, but also depression specifically. See the FoundMyFitness video entitled “The Underlying Mechanisms of Depression” to learn about some of the interesting experiments establishing the connection between immune dysfunction and symptoms of depression.

    This study, however, seems to suggest that people with obsessive-compulsive disorder actively have 30% higher brain-related inflammation.

    FTA:

    A chemical dye measured the activity of immune cells called microglia, which are active in inflammation, in six brain areas that play a role in OCD. In people with OCD, inflammation was 32 per cent higher on average in these regions. Inflammation was greater in some people with OCD as compared to others, which could reflect variability in the biology of the illness. […] Another notable finding from the current study - a connection between resisting compulsions and brain inflammation - provides one indicator. At least nine out of 10 people with OCD carry out compulsions, the actions or rituals that people do to try to reduce their obsessions. In the study, people who experienced the greatest stress or anxiety when they tried to avoid acting out their compulsions also had the highest levels of inflammation in one brain area. This stress response could also help pinpoint who may best benefit from this type of treatment.

    In light of the fact that we now know the body’s immune system is afforded direct access to the brain via a network of lymphatic vessels in the meninges, it puts managing systemic inflammation in a whole new light.

    While we may be a long way away from finding a “cure” for people suffering from these disorders, it does make multi-pronged inflammation reduction approaches that much more appealing.

    This could possibly include…

    … and yes, possibly targetted drugs as well. The point is, by establishing inflammation as a missing link in these disorders it opens up a lot of different possible “treatments” that might have a cumulative effect! Interesting times.

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  • Consumption of broccoli sprouts during late gestation & lactation confers protection against developmental delay induced by maternal inflammation. www.sciencedirect.com
    Nutrition Brain Diet Development Sulforaphane Protein Lipopolysaccharide

    This is an interesting rodent study. The problem is, however, broccoli sprouts are not usually advisable for women that are pregnant because they can be a source of foodborne illness. If proven safe, however, it seems (at the surface) plausible that there could be ways to reduce the risk of in the future. Perhaps through supplementation?

    FTA:

    Methods: Pregnant Long-Evans rats were administered i.p. Injections of saline (100 μl) or lipopolysaccharide (LPS, 200 μg/kg), every 12 h on embryonic day (E) 19 and 20. In the treatment groups, dams were supplemented with 200 mg/day of dried BrSp from E14 until postnatal day 21. Pups underwent a series of neurodevelopmental reflex tests from postnatal day 3–21 followed by neuropathological analyses.

    Note: LPS elicits a strong immune response.

    Results: Pups born from the LPS group were significantly growth restricted (p < 0.001) and delayed in hindlimb placing (p < 0.05), cliff avoidance (p < 0.05), and gait (p < 0.001) compared to controls. […] Dietary supplementation with [broccoli sprouts] to offspring exposed to LPS had increased birth weights (p < 0.001), were no longer delayed in acquiring hindlimb placing, cliff avoidance, gait, and posture, and groomed less compared to LPS alone pups (p < 0.01). Histological analyses revealed that LPS pups had reduced myelin basic protein compared to controls.

    The discussion had some interesting things to say about why mitigating the fetal inflammatory response is a big deal:

    An important recognized antepartum risk factor is the systemic fetal inflammatory response (FIR) [3], which is associated with a four-fold increase in the risk of developing [cerebral palsy]. Both clinical and experimental studies have provided strong evidence supporting the association between FIR and brain injury leading to [cerebral palsy].

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  • Sulforaphane reduces circulating lead by almost 2/3rds and improve memory-related water maze task in lead-exposed mice. www.sciencedirect.com
    Fulltext Brain Alzheimer's Memory Environment Sulforaphane Vitamin A NRF2

    This study shows some pretty interesting things in terms of a dramatic ability to (apparently) decrease lead status in the blood and seems to also really improve memory performance and reduce oxidative stress (from the lead) in the brain. It’s really pretty impressive, especially in light of the fact that, according to this paper, the neurotoxic effects are associated with amyloid beta production. This makes it plausibly relevant in the context of Alzheimer’s.

    FTA:

    “Compared with the normal saline and [corn oil-treated] groups, the lead level in the blood of sulforaphane and SFN + Vitamin E group had a significant decrease. In water maze test, the mice treated with sulforaphane or/and Vitamin E performed better than mice of the normal saline and corn oil groups. In addition, a remarkable decrease in MDA (malondialdehyde) level was found in mice treated with sulforaphane or/and vitamin E than those in normal saline and corn oil groups.”

    Not stated explicitly so far as I could tell in the article, but the figure 2 makes it look like lead content in the blood is reduced by almost 2/3rds. According to figure 6, MDA in the hippocampus, a marker for oxidative status, rises by approximately half of what the lead-exposed non-SFN group did (normal saline). In other words: more oxidative stress than control in the hippocampus, but not as much as lead without sulforaphane. It’s almost like they got half the lead exposure, if the dose-response was linear. Similarly, actual memory function was dramatically improved (measured by maze task) relative to non-sulforaphane group… but still lagged control by a little bit.

    Altogether interesting study!

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  • People that consumed 2 sugary drinks a day are more likely to have poorer memory and smaller overall brain volume. www.sciencedaily.com
    Brain Alzheimer's Inflammation Dementia Sugar Blood Sugar

    People that drank two or more sugary beverages of any kind per day were more likely to have poorer memory, smaller overall brain volume, and a significantly smaller hippocampus. Researchers also found that higher intake of diet soda, at least one per day, was associated with smaller brain volume.

    In a second study, researchers looked at whether participants had suffered a stroke or been diagnosed with dementia due to Alzheimer’s disease. Interestingly, there was no association between sugary beverage intake and stroke or dementia. But people who drank at least one diet soda per day were nearly 3 times as likely to develop stroke and dementia.

    While no of this data proves causation, there is a growing body of research showing that excess refined sugar does increase inflammation which crosses the blood-brain barrier and acceleration brain aging. Regarding the diet soda, there have been studies linking artificial sweeteners to disruption of the gut microbiome which also causes inflammation which can lead to brain aging.

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  • Daily tea consumption (green, black or oolong) was associated with a 50% reduced risk of cognitive decline. www.sciencedaily.com
    Brain Alzheimer's Aging Depression Dementia Caffeine Antioxidant Dairy

    Daily tea consumption (green, black or oolong) was associated with a 50% reduced risk of cognitive decline and a 86% lower risk in people genetically predisposed (ApoE4 gene) for Alzheimer’s disease.

    The mechanism for the cognitive benefit is unclear and may include catechins, theaflavins, thearubigins and L-theanine which are all anti-inflammatory and have antioxidant activity. However, caffeine itself cannot be ruled out as a contributing factor as well.

    While this data is an association and does not prove causation, the data was adjusted for many different factors that affect health and it still found the 50% and 86% reductions. The health factors that were adjusted for in the analysis included age, gender, education, smoking, alcohol consumption, body mass index, hypertension, diabetes, heart diseases, stroke, depression, ApoE4, physical activity, social and productive activities, vegetable and fruit consumption, fish consumption, and daily coffee consumption.

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  • Whole Coffee Fruit Concentrate – Amping Up Growth Hormone for Brain Cells - See more at: http://www.drperlmutter.com/coffee-fruit-concentrate-and-brai www.drperlmutter.com
    Brain Neuron Neurons

    But now there is even more excitement in terms of BDNF. A novel nutritional supplement, whole coffee fruit concentrate, has recently been shown to have a dramatic effect, in humans, in terms of raising BDNF. In a recent report in Food and Nutrition Sciences, researchers demonstrated how whole coffee fruit concentrate (WCFC) affected BDNF levels in humans. The study involved 20 young adults (25-35 years) who were asked to consume whole coffee fruit concentrate powder followed by blood evaluations of their BDNF levels. Remarkably, BDNF levels actually doubled in those individuals taking the whole coffee fruit concentrate in comparison to those who were given coffee or a placebo. - See more at: http://www.drperlmutter.com/coffee-fruit-concentrate-and-brain-cells/#sthash.g9l4Ss72.dpuf

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  • Supplemental probiotics for 12 weeks improved cognition in Alzheimer's patients & also lowered inflammatory markers. www.sciencedaily.com
    Brain Alzheimer's Gut Microbiome Inflammation Probiotics Behavior Insulin Triglycerides Dopamine Norepinephrine Acetylcholine

    The probiotics also lowered triglycerides, VLDL, and markers of insulin resistance. There was no cognitive improvement in the placebo group.

    The participants took 2 billion Bifidobacterium bacteria per day, which is a pretty small quantity of probiotics. It is likely that the probiotics are working through multiple mechanisms such as lowering inflammation and increasing neurotransmitters. Other studies have shown that gut bacteria are able to modulate the levels of GABA, norepinephrine, serotonin, dopamine, and acetylcholine through the gut-brain axis.

    I spoke with the gut experts, Drs. Justin and Erica Sonnenburg, about the importance of the gut microbiome in human health and the various foods (ie. fermentable fiber and other prebiotics) that provide our gut bacteria with the food they need to thrive. Here is the interview (also available on iTunes and Sticher): https://www.youtube.com/watch?v=gOZcbNw7sng

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  • heat-shock protein response in the brains of both young and aged rats supplemented with blueberry extract www.neurobiologyofaging.org
    Brain Neuron Neurons Antioxidant Protein

    (From Life Extension.com/magazine) In a 2005 article published in the journal Neurobiology of Aging, Rachel Galli and her colleagues, also based at Tufts, reported discovering a specific mechanism by which blueberries help reverse the neurological aging process.16 The Galli study—which included Drs. Joseph and Shukitt-Hale as co-investigators—sought to measure the heat-shock protein response in the brains of both young and aged rats supplemented with blueberry extract compared to a control group of aged rats. A protective mechanism produced in the brains of most animals (and humans), heat-shock proteins fight free radicals and inflammation-inducing agents, acting similarly to antioxidants to support healthy brain tissues. As people age, however, their ability to generate heat-shock proteins in sufficient quantity declines,17 sometimes dramatically. The Tufts researchers sought to determine whether blueberries could help restore the heat-shock protein response in rats.16

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  • Fasting-like diet kills autoimmune cells & replaced them with healthy cells & improved symptoms in MS patients. www.sciencedaily.com
    Brain Fasting Immune System Multiple Sclerosis Autophagy Dairy Autoimmunity Ketogenic Diet

    This fasting-like diet also promotes regeneration of the myelin in mice with multiple sclerosis. In human patients with multiple sclerosis, the fasting-like diet led to improvements in symptoms if followed by a Mediterranean diet or a ketogenic diet.

    Here is the fasting-like diet that humans were given: Day 1 – pre-fasting followed by Day 2-8 – very low calorie diet. Day 1-prefasting consists of an 800 kcal (about 40% of normal caloric intake similar to mouse Day1 FMD) monodiet (fruit, rice, or potatoes) by preference of individuals. On the following day patients were recommended to use an oral laxative, Natrium Sulfuricum (20-40 g). FMD consisted of 100 ml vegetable broth or vegetable juice with 1tablespoon of linseed oil 3 times daily, plus additional calorie-free liquids. The daily calorie intake was predefined with 200 – 350 kcal (10-18% of normal caloric intake similar to mouse Day 2-3 FMD). Patients were advised to drink 2-3 L of unsweetened fluids each day (water, and herbal teas) and to use an enema if tolerated. After the 7-day fasting period solid foods were stepwise reintroduced for three days, starting with a steamed apple at day 8. After the fasting and refeeding period a normocaloric, plant-based Mediterranean diet was maintained until study end.

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  • Gastrodin promotes the secretion of brain-derived neurotrophic factor in the injured spinal cord www.ncbi.nlm.nih.gov
    Brain Aging

    Abstract: Gastrodin, an active component of tall gastrodia tuber, is widely used in the treatment of dizziness, paralysis, epilepsy, stroke and dementia, and exhibits a neuroprotective effect. A rat model of spinal cord injury was established using Allen’s method, and gastrodin was administered via the subarachnoid cavity and by intraperitoneal injection for 7 days. Results show that gastrodin promoted the secretion of brain-derived neurotrophic factor in rats with spinal cord injury. After gastrodin treatment, the maximum angle of the inclined plane test, and the Basso, Beattie and Bresnahan scores increased. Moreover, gastrodin improved neural tissue recovery in the injured spinal cord. These results demonstrate that gastrodin promotes the secretion of brain-derived neurotrophic factor, contributes to the recovery of neurological function, and protects neural cells against injury.

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  • New 20-page report on cryotherapy just released! Cold shock boosts norepinephrine up to 5-fold & increase type of immune cell that kills tumor cells. www.foundmyfitness.com
    Exercise Brain Alzheimer's Aging Metabolism Inflammation Memory Immune System Norepinephrine Protein

    This 20-page report explains how cold shock is a type of hormesis, which is a description of a type of stress that, in the right doses, is enough to shock the body and kick off adaptive processes and response mechanisms that are hardwired into our genes, and, once on, are able to create a resilience that actually exceeds what was needed to counter the initial stimuli. Rhonda discusses how cold exposure increases norepinephrine up to 5-fold in the brain and what the temperature and duration needed to do this are, how norepinephrine has an effect on mood, vigilance, focus, and attention, how cold exposure increases cold shock proteins including one in the brain that repairs damaged synapses and in muscle prevents atrophy, how cold-induced norepinephrine lowers inflammation and pain by decreasing the levels of 3 inflammatory mediators, how chronic cold shock may increase immune cell numbers and particularly a type of immune cell that kills cancer cells, how cold exposure increases metabolic rate, the number of mitochondria, and the burning of fat, what the effects of different cold exposure temperatures and timing are on athletic performance, recovery time, and muscle mass, and the differences between various types of cold shock modalities, including cold water immersion and whole body cryotherapy.

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  • Pomegranate is metabolized by gut bacteria to produce anti-inflammatory compound Urolithin A that prevents brain plaques. www.sciencedaily.com
    Nutrition Brain Alzheimer's Aging Inflammation Blood-Brain Barrier Urolithin A

    Computational studies suggest urolithin A crosses the blood-brain barrier.

    From the article:

    Alzheimer’s disease is associated with ß-amyloid (Aß) fibrillation, a process in which amyloid proteins in the brain form clumps. To fight the formation of these fibrils, however, a molecule would have to cross the blood-brain barrier – a series of cell junctions that prevent certain substances from entering the brain. In previous work, the researchers showed that a pomegranate extract has anti-Alzheimer’s effects in animals, but they did not identify the compounds responsible.

    […]

    Computational studies found that polyphenols could not cross the blood-brain barrier, but that urolithins could. Urolithins are anti-inflammatory and neuroprotective compounds that are formed when ellagitannins, a type of polyphenol, are metabolized by gut bacteria. The researchers then showed that urolithins reduced Aß fibrillation levels in vitro.

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  • Traumatic brain injury disrupts the brain's waste removal system, allowing toxic proteins to accumulate in the brain. www.sciencedaily.com
    Brain Alzheimer's Parkinson's Performance Concussion Protein Neurodegeneration Blood-Brain Barrier

    From the article:

    The new research focuses on the impact that traumatic brain injury has on the glymphatic system. It has been long observed that the protein tau plays an important role in the long-term damage sustained by the brain after a trauma. Tau helps stabilize the fibers, or axons, that nerve cells send out to communicate with their neighbors.

    However, during trauma, large numbers of these proteins are shaken free from the axons to drift in the space between the brain’s cells. Once unmoored from nerve cells, these sticky proteins are attracted to each other and, over time, form increasingly larger “tangles” that can become toxic to brain function.

    Under normal circumstances, the glymphatic system is able to clear stray tau from the brain. However, when the researchers studied the brains of mice with traumatic brain injury, they found that the trauma damaged the glymphatic system, specifically the ability of astrocytes – a support cell found in the brain – to regulate the cleaning process.

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  • Known alcohol-dependence gene Nf1 gene linked to GABA neurotransmitter. Mice with this functional gene steadily increase alcohol after withdrawal. www.sciencedaily.com
    Brain Alcohol Neurotransmitter

    FTA:

    The team tested several behavioral models, including a model in which mice escalate alcohol drinking after repeated withdrawal periods, to study the effects of partially deleting Nf1. In this experiment, which simulated the transition to excessive drinking that is associated with alcohol dependence in humans, they found that mice with functional Nf1 genes steadily increased their ethanol intake starting after just one episode of withdrawal. Conversely, mice with a partially deleted Nf1 gene showed no increase in alcohol consumption.

    Looks like the authors of this paper may be looking at epigenetic roles next?

    The team sees the new findings as “pieces to the puzzle.” Sanna believes future research should focus on exactly how Nf1 regulates the GABA system and how gene expression may be altered during early development.

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  • The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system journals.cambridge.org
    Abstract Brain Depression Stress Behavior Mental Health Cannabinoid Dairy

    Cannabidiol (CBD), the main non-psychotomimetic component of the plant Cannabis sativa, exerts therapeutically promising effects on human mental health such as inhibition of psychosis, anxiety and depression. However, the mechanistic bases of CBD action are unclear. Here we investigate the potential involvement of hippocampal neurogenesis in the anxiolytic effect of CBD in mice subjected to 14 d chronic unpredictable stress (CUS). Repeated administration of CBD (30 mg/kg i.p., 2 h after each daily stressor) increased hippocampal progenitor proliferation and neurogenesis in wild-type mice. Ganciclovir administration to GFAP-thymidine kinase (GFAP-TK) transgenic mice, which express thymidine kinase in adult neural progenitor cells, abrogated CBD-induced hippocampal neurogenesis. CBD administration prevented the anxiogenic effect of CUS in wild type but not in GFAP-TK mice as evidenced in the novelty suppressed feeding test and the elevated plus maze. This anxiolytic effect of CBD involved the participation of the CB1 cannabinoid receptor, as CBD administration increased hippocampal anandamide levels and administration of the CB1–selective antagonist AM251 prevented CBD actions. Studies conducted with hippocampal progenitor cells in culture showed that CBD promotes progenitor proliferation and cell cycle progression and mimics the proliferative effect of CB1 and CB2 cannabinoid receptor activation. Moreover, antagonists of these two receptors or endocannabinoid depletion by fatty acid amide hydrolase overexpression prevented CBD-induced cell proliferation. These findings support that the anxiolytic effect of chronic CBD administration in stressed mice depends on its proneurogenic action in the adult hippocampus by facilitating endocannabinoid-mediated signalling.

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  • The reason old folk sleep less found: neurons responsible for regulating sleep patterns in "ventrolateral preoptic nucleus" die off www.huffingtonpost.com
    Brain Aging Sleep Neurons

    The method by which this area was found to be critical is particularly interesting.

    FTA:

    Saper analyzed a dataset of almost 1,000 subjects who had entered into a memory and aging study back in 1997, when they were all healthy 65-year-olds. As part of the study, they had all agreed to wear a small watch-sized device on their wrists for about 7 to 10 days, every two years, that would record all their movements. Upon their deaths, their brains were donated to science, so research could continue.

    Saper chose 45 brains to examine, based on whether or not the ventrolateral preoptic nucleus was still intact. First he stained the brain in order to find the cluster of neurons, which were located in a similar part of the human brain as the rats' brains.

    Then he linked the neurons found in the brain to the rest-activity behavior data collected in that person’s final year of life. He found that the fewer neurons one had, the more sleep fragmentation that person experienced in the last year of life. Brains with the largest amount of neurons (over 6,000) belonged to people with longer, uninterrupted sleep.

    Another key finding from the study: The link between fewer neurons and less sleep was even more pronounced in people who had died with Alzheimer’s disease.

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