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Alzheimer's

Episodes

coffee

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

Posted on June 9th 2025 (21 days)

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

rhonda
Premium

Q&A #70 with Dr. Rhonda Patrick (5/3/25)

Posted on May 15th 2025 (about 2 months)

Dr. Rhonda Patrick discusses cancer prevention, linoleic acid, shingles vaccine and dementia, creatine's kidney effects, and shares her overnight oats recipe.

vitamin d

Why Vitamin D Deficiency Accelerates Brain Aging

Posted on May 13th 2025 (about 2 months)

Dr. Rhonda Patrick discusses a study that found vitamin D supplementation was associated with a 40% lower risk of dementia.

Topic Pages

  • Alcohol

    Chronic ethanol exposure exacerbates amyloid-β aggregation and tau hyperphosphorylation via oxidative stress and neuroinflammatory cascades, accelerating Alzheimer’s pathology.

  • Blood-brain barrier

    Alzheimer's disease-associated cerebrovascular amyloid and inflammation disrupt blood–brain barrier tight junctions, impeding amyloid-β clearance and accelerating neurodegeneration.

  • Brain-derived neurotrophic factor (BDNF)

    Alzheimer’s amyloid-β and hyperphosphorylated tau suppress BDNF transcription, weakening TrkB signaling, synaptic maintenance, and cognition.

  • Choline

    Alzheimer’s neuropathology decreases choline acetyltransferase, reducing acetylcholine synthesis and weakening neuronal cholinergic transmission.

  • Melatonin

    Melatonin scavenges ROS and inhibits amyloid-β aggregation and tau hyperphosphorylation, attenuating Alzheimer’s neurodegenerative cascades.

  • Polyphenol-rich diets and neurodegeneration (glycemic control)
    stub

    Polyphenols enhance neuronal insulin signaling and antioxidant defenses, lowering hyperglycemia-driven tau phosphorylation and amyloid-beta aggregation in Alzheimer’s.

  • Resveratrol

    Resveratrol activates SIRT1, promoting amyloid-β degradation and reducing tau hyperphosphorylation and neuroinflammation in Alzheimer’s models.

  • Salmon roe

    Salmon roe contains unfertilized salmon oocytes rich in omega-3 fatty acids, phosvitin, phospholipids, astaxanthin, and high-quality protein.

  • Sauna

    Sauna-induced passive hyperthermia upregulates heat-shock proteins, enhances cerebrovascular function, and dampens neuroinflammation, hypothesized mechanisms mitigating Alzheimer's neurodegeneration.

  • Small vessel disease

    Cerebral small vessel disease exacerbates Alzheimer's pathology via impaired perfusion, blood-brain barrier leakage, and reduced amyloid-β clearance.

News & Publications

  • High intake of naturally occurring nitrates from vegetables halves the pace of brain changes linked to Alzheimer's, especially among those at high genetic risk. www.sciencedirect.com
    Alzheimer's Diet

    Nitrates from vegetables—especially leafy greens and beets—are generally beneficial, due to their synergistic effects with antioxidants and other protective compounds. In contrast, nitrates in processed meats can form harmful byproducts during cooking or digestion and are linked to higher risks of chronic disease. A recent study found that people who eat more nitrate from vegetables show fewer signs of early brain changes associated with Alzheimer’s.

    Researchers analyzed data from more than 500 cognitively healthy older adults living in Australia. They estimated nitrate intake from food frequency questionnaires. They tracked the participants' brain health over 10 years using two types of brain scans: one to detect beta-amyloid buildup—a hallmark of Alzheimer's—and one to monitor brain shrinkage. They used statistical models to determine whether nitrate intake from different food sources affected brain changes, and whether results differed by sex or by presence of the APOE4 gene variant, which increases Alzheimer’s risk.

    Among women who carried the APOE4 gene variant, those with the highest intake of plant-sourced nitrate accumulated beta-amyloid at about half the rate of those with lower intakes. They also experienced slower shrinkage of the right hippocampus, a region critical for memory. Moderate plant nitrate intake also appeared protective in men with the gene variant and those without it, but the patterns varied depending on sex and genetic risk.

    These findings suggest that nitrate from vegetables helps protect brain health in older adults, particularly those at higher genetic risk for Alzheimer’s disease. The link appeared strongest for markers of beta-amyloid buildup and was less consistent for brain volume loss. Learn about other lifestyle strategies for reducing Alzheimer’s disease risk in this episode featuring Dr. Dale Bredesen.

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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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  • 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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  • 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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  • 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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  • Supplemental vitamin D is linked to a 40% lower risk of Alzheimer's in cognitively healthy older adults. alz-journals.onlinelibrary.wiley.com
    Vitamin D Alzheimer's Aging Dementia Supplements

    As the global population ages and the risk of Alzheimer’s disease increases, identifying lifestyle factors that may prevent or forestall the disease is becoming increasingly important. A recent study found that people who take vitamin D supplements are 40% less likely to develop Alzheimer’s than those who don’t supplement.

    The study involved more than 12,000 cognitively healthy older adults. Researchers gathered information about the participants' vitamin D supplementation practices and whether they developed Alzheimer’s over 10 years.

    They found that participants who took any form of supplemental vitamin D (D2, D3, or D3 with calcium) had a 40% lower risk of developing Alzheimer’s than non-supplementers. This effect was more robust in women, those with normal cognition, and people without the APOE4 gene (a risk factor for Alzheimer’s).

    These findings suggest that supplemental vitamin D protects against Alzheimer’s. However, this was an observational study, so other factors might have influenced the participants' Alzheimer’s risk. For example, those who took supplemental vitamin D had higher education than those who didn’t. Research suggests that higher educational attainment is associated with a lower risk of Alzheimer’s.

    Nevertheless, vitamin D is essential for human health, and most people living in the U.S. have low vitamin D levels, potentially driving the growing number of Alzheimer’s cases. Learn more about vitamin D’s effects on the brain in this episode featuring Dr. Rhonda Patrick.

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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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • 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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  • Smoking accelerates cognitive decline by 17% over a decade. www.eurekalert.org
    Exercise Alzheimer's Alcohol Dementia

    Smoking has numerous harmful effects on health, including increased risks of lung cancer, heart disease, and stroke. Evidence indicates smoking also contributes to cognitive decline, affecting memory and fluency. A recent study found that smoking accelerates cognitive decline by as much as 17% over time.

    Researchers examined data from more than 32,000 cognitively healthy adults aged 50 to 104 from 14 European countries. They grouped participants according to whether they smoked, engaged in regular exercise, were socially active, and drank moderately—defined as less than or equal to two alcoholic drinks per day for men or one drink per day for women. Then, they analyzed the effects of lifestyle on memory and fluency decline over 10 years.

    They found that non-smokers maintained relatively stable memory and fluency scores over the 10 years. However, smokers experienced up to 17 percent greater decline in memory and up to 16 percent greater decline in fluency, even after considering other factors that influence cognitive aging, including age at baseline, gender, country, education, wealth, and chronic conditions. Interestingly, healthy lifestyle behaviors offset some of the risks associated with smoking, with smokers who exercised, socialized, and drank moderately exhibiting cognitive declines comparable to non-smokers.

    These findings suggest that smoking markedly increases cognitive decline, increasing the risk for Alzheimer’s disease and other forms of dementia. Quitting smoking can be challenging, but mindfulness techniques can help. Learn more about mindfulness in this clip featuring Dr. Ashley Mason.

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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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  • Intensive lifestyle modification that includes diet, exercise, and stress management improves cognitive function and slows disease progression in older adults with mild cognitive impairment while also reversing biomarkers of Alzheimer's disease. link.springer.com
    Exercise Alzheimer's Diet Omega-3 Probiotics Stress Meditation Magnesium Dementia Supplements

    Mild cognitive impairment is often a precursor to Alzheimer’s disease, marking the initial stages of cognitive decline that precede more severe dementia. Evidence suggests lifestyle factors mediate the progression of mild cognitive impairment. A recent study found that intensive lifestyle modification improves cognitive and functional performance and slows disease progression in older adults with mild cognitive impairment.

    Researchers conducted a randomized controlled trial involving 49 participants aged 45-90 with mild cognitive impairment or early dementia due to Alzheimer’s disease. Half of the participants received the usual care, while the other half received a 20-week intensive lifestyle intervention. The researchers assessed the participants' cognitive and functional performance and measured plasma biomarkers associated with Alzheimer’s before and after the intervention.

    They found that participants in the intervention group showed considerable improvements in cognition and function compared to the control group. In addition, Aβ42/40 ratios increased in the intervention group but decreased in the control group.

    The Aβ42/40 ratio is a measure of the relative levels of two forms of amyloid-beta protein (Aβ42 and Aβ40) in the blood or cerebrospinal fluid. It is a biomarker used to assess the presence and progression of Alzheimer’s disease. Lower ratios typically indicate higher levels of brain amyloid-beta plaques, a hallmark of the disease. An increase in the Aβ42/40 ratio, as observed in the intervention group, suggests a potential reversal or slowing of amyloid-beta plaque accumulation, indicating an improvement in disease pathology.

    These findings suggest that intensive lifestyle modification has profound effects on Alzheimer’s disease progression in older adults with mild cognitive impairment. FoundMyFitness has a wealth of information about the various components used in this intensive protocol, which included:

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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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  • 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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  • Higher vitamin D levels are linked to 18 percent lower dementia risk in older adults with prediabetes. pubmed.ncbi.nlm.nih.gov
    Vitamin D Alzheimer's Diabetes Genetics Dementia

    Lifestyle and nutritional factors influence the risk of dementia, particularly among people with prediabetes – a condition characterized by elevated blood sugar levels that are not high enough to be classified as diabetes. A recent study found that higher vitamin D levels may reduce the risk of developing dementia in older adults with prediabetes.

    Researchers drew on data collected from a large cohort of more than 34,000 older adults enrolled in the UK Biobank, all of whom had prediabetes but did not have dementia at the start of the study. They measured the participants' blood vitamin D levels and monitored them for the development of dementia, including Alzheimer’s disease and vascular dementia, for approximately 12 years. Their analysis also considered genetic variations that could influence the relationship between vitamin D levels and dementia risk.

    They found that participants with higher blood vitamin D levels were 18 percent less likely to develop any type of dementia, with similar findings for Alzheimer’s disease and vascular dementia. The protective effect of vitamin D was particularly robust in participants who did not carry polymorphisms (genetic variants) related to the vitamin D receptor, highlighting a potential interaction between genetics and vitamin D levels in dementia risk.

    These findings suggest that maintaining adequate levels of vitamin D benefits brain health, especially in older adults with prediabetes, a group at elevated risk for dementia. They add to the growing body of evidence supporting the importance of vitamin D for overall health and emphasize the need for further research to understand the mechanisms behind its protective effects on the brain. Learn more about vitamin D in our comprehensive overview article.

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  • A ketogenic diet restores long-term potentiation, a crucial mechanism for learning and memory, to healthy levels in mice prone to Alzheimer's-like symptoms, implicating ketone bodies as potential therapeutic agents. www.ucdavis.edu
    Alzheimer's Diet Aging Ketosis Memory Dementia Ketogenic Diet

    A ketogenic diet – a high-fat, low-carbohydrate dietary pattern – offers potential benefits in various health contexts, including weight management and seizure control. Some evidence suggests that the ketogenic diet is beneficial in preventing or treating neurodegenerative diseases, such as Alzheimer’s and dementia. A recent study in older mice found that a ketogenic diet improves memory functions and increases lifespan.

    Researchers compared the effects of a seven-month ketogenic diet to a standard diet in mice prone to developing Alzheimer’s-like symptoms. They examined the hippocampal region of the animals' brains, a crucial area for memory and learning, to gauge the diet’s effects on synaptic plasticity – the brain’s ability to form and reorganize synaptic connections, especially in response to learning or new experiences.

    They found that mice on the ketogenic diet experienced restoration of their long-term potentiation – a measure of synaptic strength and a fundamental mechanism for learning and memory – to levels comparable to healthy mice. They attributed this restoration to the marked elevation of beta-hydroxybutyrate (BHB), a ketone body produced during the ketogenic diet. They also found that the diet triggered enhancements in several key pathways and molecules associated with synaptic plasticity, including notable increases in specific enzymes and brain-derived neurotrophic factor (BDNF), particularly in female mice.

    BDNF is crucial for cognitive functions, providing support for neuronal survival, growth, and differentiation and enhancing learning and memory by strengthening and creating synaptic pathways. Elevated BDNF levels correlate with better cognitive performance, whereas its deficiency is linked to various mental and neurodegenerative disorders, highlighting its significance in brain health. Learn more about BDNF in our overview article.

    These findings suggest that a ketogenic diet ameliorates memory impairments and bolsters neuronal health in an Alzheimer’s mouse model, primarily through the action of BHB and its enhancement of synaptic plasticity. Learn more about beta-hydroxybutyrate in our overview article.

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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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  • 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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  • 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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  • 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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  • Poor oral health may triple Alzheimer's disease risk. www.brainandlife.org
    Alzheimer's Dementia Dental

    Oral health is intricately linked to overall well-being, with emerging research identifying associations between poor oral health and an increased risk of many chronic diseases, including cardiovascular disease, diabetes, and cancer. A recent study found that oral diseases associated with tooth loss more than tripled the risk of developing Alzheimer’s disease.

    Researchers assessed Alzheimer’s disease risk among more than 32 million people. They categorized the participants as having normal or poor oral health and assessed serum biomarkers associated with Alzheimer’s, including blood glucose, lipids, and C-reactive protein (a marker of inflammation).

    They found that more than 1.2 million participants had poor oral health, while the remainder had normal oral health. Those with poor oral health were more than twice as likely to develop Alzheimer’s disease than those with normal oral health, regardless of age, gender, or serum biomarkers. Those with oral conditions associated with tooth loss were more than three times more likely to develop Alzheimer’s.

    The findings from this large epidemiological study suggest that poor oral health markedly increases a person’s risk for developing Alzheimer’s disease. In vitro research further supports these findings, demonstrating 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. And research in mice shows that oral bacteria over-stimulate microglia, impairing their ability to eliminate amyloid-beta, a harmful protein linked to Alzheimer’s.

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  • Dementia cases could surpass previous estimates by 40 percent, highlighting the need for prevention. medicalxpress.com
    Alzheimer's Aging Dementia

    Nearly 50 million people worldwide live with Alzheimer’s disease or another form of dementia — a number projected to triple in the coming decades. However, a recent study suggests the number could be even higher, as much as 40 percent more than previous estimates.

    Researchers analyzed data from the English Longitudinal Study of Ageing, a long-term study of older adults living in England and Wales. They identified dementia cases from among more than 90,000 people. Then, they analyzed how dementia incidence changed over time based on age, sex, and education.

    They found that dementia incidence decreased by 28.8 percent between 2002 and 2008 and then increased by 25.2 percent between 2008 and 2016 (nearly 3 percent per year). People with lower educational attainment experienced a slower decline in dementia during 2002-2008 and a more rapid increase after 2008, demonstrating growing disparities. The researchers predicted that if dementia incidence continues to rise at the same pace observed from 2008 to 2016, the number of people living with dementia will roughly double by 2040.

    These findings suggest that the number of people with dementia will be markedly higher in the coming decades. Evidence suggests lifestyle factors influence a person’s dementia risk. Learn how sauna use, exercise, sleep, and dietary components, such as omega-3 fatty acids and sulforaphane exert robust anti-aging effects on the brain, potentially preventing or forestalling dementia.

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  • Lifelong choline supplementation provides a potential shield against Alzheimer's disease in mice. www.ncbi.nlm.nih.gov
    Nutrition Alzheimer's Diet Aging Micronutrients Neurotransmitter Acetylcholine

    Choline, an essential nutrient found in eggs, meat, fish, beans, and nuts, supports the production of acetylcholine, a neurotransmitter involved in neurogenesis, synapse formation, learning, and memory. Most people living in the US 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. A 2019 study in mice found that lifelong choline supplementation prevented Alzheimer’s disease and preserved cognitive function.

    Researchers fed mice susceptible to developing Alzheimer’s disease a regular diet or a diet supplemented with choline from early life to old age. When the mice reached the age of 10 months, the researchers assessed the animals' memory function and examined their brain tissue.

    They found that mice that received lifelong choline supplementation had better spatial memory and fewer amyloid-beta plaques in their brains than those on a regular diet. They also found that the mechanisms driving these effects were related to reduced amyloid-beta peptide synthesis, a dampened microglia inflammatory response, and downregulation of the alpha-7 nicotinic acetylcholine and sigma-1 receptors, both of which are critical for various neurological processes.

    These findings suggest that lifelong choline supplementation mitigates Alzheimer’s disease pathology and maintains cognitive function in mice susceptible to the disease. Other research showed that mice that ate a choline-poor diet had higher brain levels of amyloid-beta and tau – two proteins implicated in the pathogenesis of Alzheimer’s disease – than those that ate a choline-rich diet. The mice that ate a choline-poor diet also gained weight, showed signs of altered metabolism, liver damage, and enlarged hearts, and performed poorly on motor skills tests.

    More than 55 million people worldwide live with Alzheimer’s disease. Learn more about the disease and how to prevent it in this episode featuring Dr. Dale Bredesen.

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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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  • 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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  • 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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  • 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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  • 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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  • Greater lean muscle mass linked to a 12 percent reduction in Alzheimer's disease risk, suggesting exercise can play a critical role in prevention. medicalxpress.com
    Alzheimer's Genetics Muscle

    A growing body of evidence links excess body fat to an increased risk for Alzheimer’s disease, likely due to several factors, including heightened inflammation, insulin resistance, and elevated levels of amyloid-beta (a pathological hallmark of the disease) in fat tissue. A recent study found that greater lean muscle mass reduced the risk for Alzheimer’s disease by 12 percent.

    Using Mendelian randomization techniques, researchers analyzed health data and cognitive performance of more than a million people with or without Alzheimer’s disease. Mendelian randomization is a research method that provides evidence of links between modifiable risk factors and disease based on genetic variants within a population. They calculated the participants' muscle mass based on genetic factors, often referred to as genetic proxies.

    They found that people with greater genetically proxied lean muscle mass in the arms and legs were 12 percent less likely to develop Alzheimer’s disease, even when accounting for genetic factors that may influence risk. They also demonstrated better cognitive performance.

    These findings suggest that lean muscle mass protects against Alzheimer’s disease. However, the researchers noted that whether increasing lean muscle mass can reverse the pathology of Alzheimer’s disease in people with preclinical disease or mild cognitive impairment is unclear. Learn how resistance training helps build and maintain lean muscle mass in this clip featuring Dr. Brad Schoenfeld.

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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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  • Blocking the body's antiviral immune response holds promise for Alzheimer's disease prevention. medicalxpress.com
    Alzheimer's Aging Immune System Virus

    The immune system plays important, and sometimes surprising, roles in brain health. A new study in mice found that blocking components of the antiviral immune response may make the brain more resilient to the effects of abnormal tau – potentially preventing Alzheimer’s disease and other forms of dementia.

    Tau is a protein found in the brain. Abnormal tau can form aggregates called tau tangles – one of the defining characteristics of Alzheimer’s disease – activating antiviral response pathways and interfering with normal brain function and cognition.

    Researchers studied the effects of exposure to abnormal tau on microglia, the brain’s resident immune cells. They found that when microglia were exposed to abnormal tau, the mitochondria became “leaky,” releasing their DNA into the cellular fluid. The immune system inappropriately interpreted the leaked DNA as a viral attack, triggering an immune response that promoted the release of type-I interferon, a cytokine that drives the antiviral immune response. Interrupting the pathways involved in this response restored normal brain function.

    These findings suggest that suppressing the inappropriate immune response to abnormal tau exposure could provide a means to prevent or treat the tau-associated pathologies common in Alzheimer’s disease and dementia. Learn about other strategies to reduce the risk of Alzheimer’s disease in this episode featuring Dr. Dale Bredesen.

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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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  • 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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  • 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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  • Choline deficiency may increase the risk of Alzheimer's disease by promoting the formation of amyloid-beta and tau. www.sciencedaily.com
    Nutrition Alzheimer's Memory Blood-Brain Barrier

    A new study in mice shows that choline deficiency increases the risk of Alzheimer’s disease. Researchers fed mice that are predisposed to Alzheimer’s disease either a choline-rich or choline-poor diet for seven months, starting in midlife until late life. They subjected the mice to motor and memory skills tests, and then they examined the animals' brains and other organs.

    They found that mice that ate a choline-poor diet had higher brain levels of amyloid-beta and tau – two proteins implicated in the pathogenesis of Alzheimer’s disease – than those that ate a choline-rich diet. The mice that ate a choline-poor diet also gained weight, showed signs of altered metabolism, liver damage, and enlarged hearts, and performed poorly on motor skills tests.

    Choline is an essential nutrient that supports the production of acetylcholine, a neurotransmitter involved in neurogenesis, synapse formation, learning, and memory. 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.

    These findings suggest that choline deficiency increases the risk of Alzheimer’s disease and damages vital organs in mice. For a tasty way to get more choline into your diet, try this low-carb, choline-rich lemon tart.

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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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  • 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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  • 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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  • Newly identified APOE4 gene variant cuts Alzheimer's disease risk – rather than increasing it. jamanetwork.com
    Alzheimer's Genetics Dementia

    People who carry a newly identified variant of the APOE4 gene are more than 50 percent less likely to develop Alzheimer’s disease than non-carriers, a new study shows. Carriers of an APOE3 variant are more than 60 percent less likely to develop the disease.

    Researchers analyzed the genetic makeup of more than 544,000 people. The participants included people who had been diagnosed with Alzheimer’s disease, those with a first-degree relative who had the disease, and those who were healthy.

    The researchers found that two rare variants reduced the participants' risk of developing Alzheimer’s disease. Carriers of an APOE4 variant called R251G were 56 percent less likely to develop the disease, and carriers of an APOE3 variant called V236E were 63 percent less likely.

    APOE is a protein involved in lipid transport. There are three known forms of the APOE gene that influence Alzheimer’s disease risk: APOE2, APOE3, and APOE4. APOE4 is the primary genetic risk factor for Alzheimer’s disease. Having one APOE4 allele typically increases a person’s Alzheimer’s disease risk as much as threefold; carrying two APOE4 alleles typically increases a person’s risk as much as 15-fold. However, this newly identified sub-type of APOE4 markedly alters that risk and adds complexity to discussions about the role of genetics in Alzheimer’s disease.

    These findings suggest that some variants of the APOE gene may be protective against Alzheimer’s disease. Although genetics play key roles in Alzheimer’s disease risk, lifestyle does, too. Eating a healthy diet, exercising, meditating, and sauna use may forestall or even prevent the onset of the disease. Learn more about preventing Alzheimer’s disease in this episode featuring Dr. Dale Bredesen.

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  • Green tea catechins, resveratrol, curcumin and metformin reduced amyloid plaque formation in herpes-induced Alzheimer's disease tissue models. (2022) neurosciencenews.com
    Alzheimer's Green Tea Curcumin Resveratrol Metformin

    From the article:

    They have tested 21 different compounds in Alzheimer’s-afflicted neural cells in the lab, measuring the compounds’ effect on the growth of sticky beta amyloid plaques. These plaques develop in the brains of people with Alzheimer’s.

    […]

    The initial screening was done in simpler models, and compounds that had a positive effect were then tested in the 3D neural tissue model. That model is created using a nonreactive silk sponge seeded with human skin cells that, through genetic reprogramming, are converted into neural stem cell progenitors.

    Those cells grow and populate the sponge, “which allows for 3D network formation of neurons similar to what you’d see in the human brain,” Cairns says.

    The initial screen found five compounds had “really robust prevention of these plaques,” she says. In addition to the green tea compounds and resveratrol, they found curcumin from turmeric, the diabetic medication Metformin, and a compound called citicoline prevented plaques from forming and did not have anti-viral effects.

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  • New type of blood test may detect a hidden toxin behind Alzheimer's disease years before patients show symptoms of memory loss or confusion. (2022) www.sciencealert.com
    Alzheimer's Diagnostics

    From the article:

    Researchers at the University of Washington (UW) created the novel blood test. It’s designed to pick up on a molecular precursor in the blood that can cause proteins to irregularly fold and clump in the brain, ultimately forming amyloid beta (Aβ) plaques.

    Aβ plaques are a famous hallmark of Alzheimer’s disease, but their role in cognitive decline is uncertain. Historically, these extracellular plaques have been considered an early trigger of neuron dysfunction and loss, ultimately leading to cognitive decline.

    But recent studies have shown that Aβ plaques are only present in a third of Alzheimer’s patients, and sometimes, they are present in the brains of people who experience no cognitive deficits.

    In other words, extracellular Aβ plaques in the brain aren’t necessarily toxic in and of themselves, but they might stem from notoriously difficult-to-detect molecular toxins.

    These toxins are essentially the functional versions of the Aβ found within cells. They are known as ‘toxic Aβ oligomers’, and some scientists think they could subtly damage neurons from afar, somehow predisposing the cells to extracellular plaques and clumps.

    Scientists are still figuring out the details, but the hypothesis has led UW researchers to make an impressively accurate soluble oligomer binding assay, nicknamed SOBA.

    Researchers first tested SOBA on 310 participants' blood plasma. Some participants showed mild cognitive impairment or Alzheimer’s disease, while others were in good cognitive health.

    By measuring toxic Aβ oligomers in the blood plasma, SOBA picked out all 53 participants with Alzheimer’s who were later confirmed to have the disease post-mortem.

    Meanwhile, in the control group, SOBA detected oligomers in the blood plasma samples of 11 individuals. Ten of these participants were later diagnosed with mild cognitive impairment or Alzheimer’s.

    […]

    Misfolding proteins also seem to be associated with Parkinson’s disease, type II diabetes, and Lewy body dementia, which means SOBA could one day be tweaked to pick up early markers of these other illnesses.

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  • Estrogen may improve memory and promote neuron repair and function, while progesterone alone may adversely affect memory, rodent studies suggest(2004) www.sciencedaily.com
    Alzheimer's Hormones Memory Estrogen Neurons

    From the article:

    Cyclic administration of estrogen might be inferior to continuous or no administration in terms of improving memory functions.

    Researchers removed the ovaries of 32 middle-aged mice before starting them on various courses of HT lasting three months. A continuous group received estrogen injections daily, a cyclical group was administered estrogen every four days, and a control group received daily injections with no estrogen.

    After three months, the mice underwent a variety of cognitive tests. […] Mice were tested every day for two weeks for both spatial reference memory (long-term memory for information that did not change during the test session) and working memory (short-term memory for information that changed in each trial).

    Mice on the cyclical regimen made more reference and working memory errors than control mice. The cyclical group also made more reference memory errors than mice receiving continuous estrogen.

    Another test focused on object recognition, a type of nonspatial memory. […] Because mice have a natural tendency to explore novel objects, mice with good memory for the original objects should spend more time examining the new object. Again, mice in the control and continuous groups outperformed the cyclical HT mice.

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    Estrogen may promote neuron repair and improve neuronal function.

    Other researchers studied the effects of continuous versus no administration of HT. Investigators removed the ovaries of mice aged 8 to 12 weeks and either treated them with continuous estrogen for 47 days or did not treat them with estrogen. Researchers then sacrificed the mice at different time periods after estrogen exposure (at 5, 14, 28, and 47 day intervals) and examined them for the production of the proteins associated with neuron repair and the formation of contacts between neurons.

    […]

    After five days on estrogen, the estrogen-treated mice produced more of the proteins important for repair and neuronal function. However, with prolonged, continuous estrogen treatment, this effect diminished, and by day 47 the estrogen-treated mice were similar to the non-estrogen-treated mice in levels of the repair proteins. In addition, at the end of the experiment, mice that did not receive estrogen showed an elevation of a brain protein associated with the negative aspects of brain aging, while estrogen-treated mice did not.

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    Progesterone may be detrimental to learning and increase short-term memory deficits in aged rats.

    Thirty rats were used in the study. Ten rats kept their ovaries, and twenty rats had their ovaries removed. The ovariectomized rats were then divided into two groups: those receiving progesterone and a control group that did not receive progesterone.

    As in the Yale study, a water maze was used to test working and reference memory. The maze difficulty was changed at increasing rates, forcing the rats to remember greater amounts of information. The rats receiving progesterone exhibited deficiencies in learning and remembering the maze. In addition, rats treated with progesterone also showed problems remembering many items of information, while untreated rats were able to successfully remember the items.

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    Progesterone may inhibit neuroprotective effects of estrogen

    In the first experiment, levels of beta-amyloid protein were evaluated after a six-week period of hormone treatment. Higher levels of beta-amyloid protein were observed in the hormone-depleted rats compared with control animals. The group receiving estrogen did not experience an increase in levels of beta-amyloid. For the rats receiving the combination of estrogen and progesterone, although progesterone failed to decrease beta-amyloid levels, it did not alter the ability of the estrogen treatment to reduce beta-amyloid levels.

    In the second study, rats were treated with a mild dose of neurotoxin after two weeks of hormone treatment. The hormone-depleted rats experienced the greatest amount of neuronal death. In estrogen-treated rats a protective effective against neuronal death was observed, while rats treated with estrogen and progesterone in combination did exhibit neuronal death, suggesting that progesterone inhibited the neuroprotective action of estrogen in this model.

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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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  • 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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  • Estradiol given to women with mild to moderate Alzheimer's disease improved their memory by up to 35% and attention skills by 20%. (2001) www.sciencedaily.com
    Alzheimer's Hormones Memory Estrogen

    From the article:

    Asthana noted differences between the current study and those that found no memory-enhancing effect. Asthana’s study used estradiol, a type of estrogen that has been shown to have an effect on the brain. Other studies used a compound that contains low doses of estradiol along with other forms of estrogen that have not been proven to have an effect on the brain, he said. Also, the largest study finding no effect included only women who had hysterectomies. “We don’t know enough yet about how a hysterectomy versus no hysterectomy can affect the brain’s response to estrogen,” he said.

    In the current study, the women were given a variety of tests to measure their attention skills, recent verbal memory, recent visual memory and semantic memory, or the ability to name common items from pictures.

    The women receiving estrogen improved their performance on an attention test by 20 percent more than the women receiving a placebo. Those receiving estrogen also improved on some of the tests of recent verbal and visual memory by 35 and 30 percent more than those receiving a placebo. On the test of semantic memory, those taking estrogen performed 10 percent better than those taking a placebo.

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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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  • 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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  • 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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  • High testosterone levels may increase the risk for aggression, hallucinations and other acting-out behaviors in men with Alzheimer's. (2014) www.sciencedaily.com
    Alzheimer's Hormones Testosterone

    From the article:

    Studies have found that having lower testosterone levels increased the risk for developing Alzheimer’s disease, said Dr. James Hall, Professor of Psychiatry and Behavioral Health.

    “But once someone already has Alzheimer’s, higher levels of testosterone are related to acting-out behaviors,” he said. “Those behaviors, such as agitation and delusions, occur at some point in at least 70 percent of Alzheimer’s patients.”

    […]

    For the study, 87 elderly men with mild to moderate Alzheimer’s disease were evaluated. Dr. Hall found the likelihood of having hallucinations was 5.5 times greater for the men with higher levels of testosterone than those with lower levels.

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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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  • Patients undergoing testosterone-lowering therapy for prostate cancer had an 88% increased risk of Alzheimer's risk. (2015) www.sciencedaily.com
    Alzheimer's Cancer Hormones Diabetes Testosterone Prostate Cardiovascular

    From the article:

    Using two different methods of statistical analysis, the team showed that the ADT [androgen deprivation therapy] group, compared to the control group, had significantly more Alzheimer’s diagnoses in the years following the initiation of androgen-lowering therapy. By the most sophisticated measure, members of the ADT [androgen deprivation therapy] group were about 88 percent more likely to get Alzheimer’s during the follow-up period.

    The analyses also suggested a “dose-response effect.” The longer individuals underwent ADT the greater their risk of Alzheimer’s disease, they found. The longer-duration ADT patients also had more than double the Alzheimer’s risk of non-ADT controls.

    […]

    How low testosterone would lead to increased Alzheimer’s risk isn’t precisely known, but there is some evidence that testosterone has a general protective effect on brain cells, so that lowering testosterone would leave the brain less able to resist the processes leading to Alzheimer’s dementia. Studies in mice and in humans also have suggested that lower testosterone levels may allow greater production of the Alzheimer’s protein amyloid beta. Moreover, low testosterone may increase Alzheimer’s risk indirectly, by promoting conditions such as diabetes and atherosclerosis that are known to predispose to Alzheimer’s.

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  • In men with Alzheimer's disease, free testosterone levels were about half those of healthy men. (2004) www.sciencedaily.com
    Alzheimer's Aging Hormones Memory Testosterone Lactate

    From the article:

    Dr. Resnick, Scott Moffat, Ph.D., and their colleagues evaluated the testosterone levels of 574 men, ages 32 to 87, who participated in the Baltimore Longitudinal Study of Aging (BLSA). The investigators examined free and total testosterone levels-measured over an average of 19 years-in relationship to subsequent diagnosis of AD. Based on physical, neurological and neuropsychological exams, 54 of the 574 men were diagnosed with AD.

    The research team found that for every 50 percent increase in the free testosterone index in the bloodstream, there was about a 26 percent decrease in the risk of developing AD. Although overall free testosterone levels fell over time, these levels dropped more precipitously in those men who later developed AD. In fact, at the end of the study, men who were diagnosed with AD, on average, had about half the levels of circulating free testosterone as men who didn’t develop the disease. In some cases, the drop-offs in free testosterone levels associated with AD were detected up to a decade before diagnosis.

    Previously, Dr. Resnick and her colleagues found that older men with high levels of circulating free testosterone have better visual and verbal memory and perform spatial tasks more adeptly than their peers.

    “It is quite possible that circulating free testosterone has a broad range of influences on the aging brain,” Dr. Resnick said.

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  • Testosterone replacement therapy may help improve the quality of life for deficient elderly men with mild cases of Alzheimer's disease. (2005) www.sciencedaily.com
    Alzheimer's Hormones Testosterone

    From the article:

    “For the patients with AD, the testosterone-treated group had significantly greater improvements in the scores on the caregiver version of the quality-of-life scale,” the researchers report. “No significant treatment group differences were detected in the cognitive scores at end of study, although numerically greater improvement or less decline on measures of visuospatial functions was demonstrated with testosterone treatment compared with placebo. In the healthy control group, a nonsignificant trend toward greater improvement in self-rated quality of life was observed in the testosterone-treated group compared with placebo treatment. No difference between the treatment groups was detected in the remaining outcome measures.”

    “In conclusion, the present results should be considered preliminary and do not warrant routine treatment of AD and healthy control men with testosterone. Future studies with larger sample sizes are needed before clinical decisions regarding testosterone therapy can be rationally based. For men with compromised quality of life, as reflected on the type of measure employed in this study, and who suffer from low serum T [testosterone] levels, testosterone therapy may be a reasonable consideration.”

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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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  • 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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  • 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 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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  • 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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  • Getting a flu shot reduced the development Alzheimer's by 40 percent. medicalxpress.com
    Alzheimer's Vaccine

    Background: Prior studies have found a reduced risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions. However, the effect of influenza vaccination on Alzheimer’s disease (AD) risk in a general cohort of older US adults has not been characterized.

    Objective: To compare the risk of incident AD between patients with and without prior influenza vaccination in a large US claims database.

    Methods: Deidentified claims data spanning September 1, 2009 through August 31, 2019 were used. Eligible patients were free of dementia during the 6-year look-back period and≥65 years old by the start of follow-up. Propensity-score matching (PSM) was used to create flu-vaccinated and flu-unvaccinated cohorts with similar baseline demographics, medication usage, and comorbidities. Relative risk (RR) and absolute risk reduction (ARR) were estimated to assess the effect of influenza vaccination on AD risk during the 4-year follow-up.

    Results: From the unmatched sample of eligible patients (n = 2,356,479), PSM produced a sample of 935,887 flu–vaccinated-unvaccinated matched pairs. The matched sample was 73.7 (SD, 8.7) years of age and 56.9% female, with median follow-up of 46 (IQR, 29–48) months; 5.1% (n = 47,889) of the flu-vaccinated patients and 8.5% (n = 79,630) of the flu-unvaccinated patients developed AD during follow-up. The RR was 0.60 (95% CI, 0.59–0.61) and ARR was 0.034 (95% CI, 0.033–0.035), corresponding to a number needed to treat of 29.4.

    Conclusion: This study demonstrates that influenza vaccination is associated with reduced AD risk in a nationwide sample of US adults aged 65 and older.

    https://content.iospress.com/articles/journal-of-alzheimers-disease/jad220361

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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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  • Study shows people with a high omega-3 DHA level in their blood are at 49% lower risk of Alzheimer’s www.eurekalert.org
    Alzheimer's Omega-3

    Higher DHA concentrations cut Alzheimer’s disease risk by half.

    Docosahexaenoic acid (DHA) is an omega-3 fatty acid found in krill oil and the meat and roe of salmon, flying fish, and pollock. When consumed in the diet (or obtained from dietary supplements), DHA preferentially accumulates in the human brain, where it plays essential roles in normal brain function. Findings from a recent study suggest that higher concentrations of DHA in red blood cells protect against Alzheimer’s disease.

    The concentration of omega-3 fatty acids in red blood cells, referred to as the “omega-3 index,” is an indicator of long-term omega-3 exposure, analogous to the HbA1c test for long-term blood glucose concentrations. In general, people who have high blood concentrations – an omega-3 index of about 8 to 12 percent – are far less likely to die from all causes of premature death than those with lower concentrations.

    The investigators drew on data collected in the Framingham Offspring Cohort study, an ongoing study of the effects of lifestyle risk factors on cardiovascular, neurological, and other types of disease outcomes across three generations of participants. Their investigation, which involved nearly 1,500 adults (65 years and older) who did not have dementia, examined whether red blood cell concentrations of DHA influenced the participants' Alzheimer’s disease risk, especially those who carried the APOE4 gene, the primary genetic risk factor for the disease. They categorized the DHA concentrations across five levels and tracked the participants' health for seven years.

    They found that participants whose red blood cell DHA concentrations were in the top fifth were roughly half as likely to develop Alzheimer’s disease during the follow-up period than those in the lowest fifth. This protective effect of DHA translated to nearly five years of life free of Alzheimer’s disease. Higher DHA concentrations conferred more than seven years of protection for participants with the APOE4 gene, suggesting that promoting DHA intake among this susceptible group could have marked effects on their neurological health.

    These findings suggest that higher concentrations of DHA, a type of omega-3 fatty acid, protect against Alzheimer’s disease, especially among carriers of the APOE4 gene. Learn more about the beneficial health effects of omega-3s in this episode featuring Dr. Bill Harris. And for more information about how DHA influences Alzheimer’s disease risk, check out this open-access, peer-reviewed article by Dr. Rhonda Patrick.

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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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  • 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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  • 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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  • 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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  • 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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  • 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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  • Processes contributing to cancer may reduce risk of Alzheimer's disease, according to post-mortem analysis www.the-scientist.com
    Alzheimer's Cancer Aging Neurodegeneration

    From the article:

    Thanks to those data, which showed participants with cancer had fewer hallmarks of Alzheimer’s disease in their brains as well as a reduced likelihood of neurodegenerative symptoms during their lifetimes, lead study author Erin Abner, a University of Kentucky epidemiologist and aging researcher and her team were able to offer the clearest picture yet of a molecular mechanism that seems to link the two diseases.

    “The connection is becoming more and more apparent,” New York University cancer researcher Eva Hernando-Monge, who didn’t work on the study, tells The Scientist.

    They investigated cancer deaths for traces of Alzheimer’s:

    As cohort members passed away, the team autopsied their brains to look for biomarkers associated with Alzheimer’s disease, including structures such as neurofibrillary tangles and neuritic plaques. They also noted when someone carried the APOE ε4 allele, a known genetic risk factor for the neurodegenerative condition.

    […]

    The analysis revealed “less Alzheimer’s pathology in the people who had cancer, both amyloid and tau,” Abner says. “We also saw evidence [that] another amyloid pathology—cerebral amyloid angiopathy, which is amyloid aggregation in blood vessel walls—was lower.

    Mechanisms of the cancer-Alzheimer’s anti-relationship:

    Processes related to cell growth and survival, as well as the production of specific molecules including the antistress response protein vimentin and the enzyme carbonic anhydrase, are all upregulated in cancer, he finds. Alzheimer’s occurs when these processes and proteins are downregulated.

    Another review, published in Molecular Psychiatry in 2021, identifies the proteins p53 and PIN1 as implicated in both cancer and Alzheimer’s. PIN1 overexpression is associated with myriad cancers, but its absence is linked to the formation of the Alzheimer’s biomarkers tracked in the Brain study. Meanwhile, p53 has a well-established anticancer role, but can also contribute to neurodegenerative disease.

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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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  • 50% of all dementias and Alzheimers may start with leaky blood-brain barrier www.sciencedaily.com
    Alzheimer's Aging Inflammation Dementia Blood-Brain Barrier Lipopolysaccharide

    From the article:

    “Many scientists have focused their Alzheimer’s disease research on the buildup of toxic amyloid and tau proteins in the brain, but this study and others from my lab show that the problem starts earlier – with leaky blood vessels in the brain,” said Berislav Zlokovic, senior author of the study

    Reducing fibrinogen that enters the brain through leaky gatekeeping may be important for preventing decline:

    Fibrinogen develops blood clots so wounds can heal. When gatekeeper cells are compromised, an unhealthy amount of fibrinogen slinks into the brain and causes white matter and brain structures, including axons (nerve fibers) and oligodendrocytes (cells that produces myelin), to die.

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  • People with more severe leakage of blood-brain barrier have worse memory problems, potentially a separate or very early process in Alzheimer's disease www.sciencedaily.com
    Alzheimer's Memory Blood-Brain Barrier

    From the article:

    USC’s five-year study, which involved 161 older adults, showed that people with the worst memory problems also had the most leakage in their brain’s blood vessels – regardless of whether abnormal proteins amyloid and tau were present.

    “The fact that we’re seeing the blood vessels leaking, independent of tau and independent of amyloid, when people have cognitive impairment on a mild level, suggests it could be a totally separate process or a very early process,” said senior author Berislav Zlokovic, director of the Zilkha Neurogenetic Institute at the Keck School of Medicine of USC. “That was surprising that this blood-brain barrier breakdown is occurring independently.”

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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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  • 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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  • 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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  • Loss of Neurons, Not Lack of Sleep, Makes Alzheimer’s Patients Drowsy neurosciencenews.com
    Alzheimer's

    Neuron losses in the brain promote daytime sleepiness in Alzheimer’s disease.

    Scientists have long believed that poor nighttime sleep drives the daytime sleepiness often experienced by people with Alzheimer’s disease. However, findings from a recent study suggest that the loss of wake-promoting neurons in the brain promotes daytime sleepiness in people with Alzheimer’s disease.

    During nighttime sleep, the brain activates the glymphatic system, a self-cleaning process that rids the brain of toxic products, including amyloid-beta and tau tangles. Poor sleep promotes the accumulation of these products, which in turn, promotes poor sleep, creating a vicious cycle that affects brain health. Amyloid-beta accumulation and tau tangle formation are the primary pathological hallmarks of Alzheimer’s disease.

    The investigators recruited 33 people with Alzheimer’s disease, 20 people with progressive supranuclear palsy (a rare neurological disorder that affects balance, movement, vision, speech and swallowing), and 32 healthy people to participate in the study. They assessed the participants' brain activity using electroencephalography and assessed their sleep quality using polysomnography. Upon the participants' deaths, the investigators examined the participants' brains for neuronal changes and the presence of amyloid-beta or tau.

    They found that people with Alzheimer’s disease exhibited an increased desire to sleep and exhibited fewer wake-promoting neurons in their brains, promoting daytime sleepiness. Conversely, people with progressive supranuclear palsy had a decreased desire to sleep and exhibited fewer sleep-promoting neurons, robbing them of the ability to fall asleep and causing sleep deprivation. The dominant toxic protein in the participants' brains was tau.

    These findings suggest that neuronal losses in the brains of people with neurodegenerative disorders contributes to sleep irregularities, and these losses are due to tau accumulation. Learn more about the role of sleep in neurodegenerative disorders in this clip featuring Dr. Matt Walker.

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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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  • 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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  • Altered central and blood glutathione in Alzheimer’s disease and mild cognitive impairment. alzres.biomedcentral.com
    Alzheimer's Glutathione

    People with Alzheimer’s disease or mild cognitive impairment have low glutathione levels. Oxidative stress is a biological phenomenon that manifests when highly reactive molecules produced during metabolism accumulate in the body, damaging DNA and cells and driving a wide of range of chronic diseases, including Alzheimer’s disease and mild cognitive impairment. The body produces antioxidant molecules to counter the effects of oxidative stress, but its capacity to produce the molecules varies based on a person’s lifestyle and overall health. A recent meta-analysis reveals that people with Alzheimer’s disease and mild cognitive impairment have low brain and blood levels of the antioxidant molecule glutathione.

    Glutathione is a potent antioxidant compound produced in the body’s tissues, particularly those that experience high levels of oxidative stress, such as the eyes, liver, and brain. Glutathione scavenges harmful reactive molecules, thereby preventing damage from oxidative stress, but evidence suggests glutathione levels decrease with aging, contributing to many aging-related diseases.

    The authors analyzed data from studies in which researchers measured glutathione levels in the brains (eight studies) or blood (33 studies) of people with Alzheimer’s disease or mild cognitive impairment and compared those levels to healthy people. They conducted a sub-analysis of the data collected in the brain studies that used an advanced measurement technique called MEGA-PRESS, which may be more accurate than traditional techniques.

    They found that when using traditional measurement techniques, researchers did not observe differences in brain glutathione levels among people with Alzheimer’s disease or mild cognitive impairment versus healthy people. However, when researchers used the MEGA-PRESS technique, brain glutathione levels were indeed lower in people with Alzheimer’s disease or mild cognitive impairment. The data also revealed lower blood glutathione levels in both Alzheimer’s disease and mild cognitive impairment, compared to healthy people.

    These findings suggest that people with Alzheimer’s disease or mild cognitive impairment have lower levels of glutathione in their brains and blood. Interestingly, some dietary compounds or lifestyle behaviors may increase endogenous glutathione production. For example, evidence suggests that sulforaphane, a bioactive compound derived from broccoli and broccoli sprouts, increases glutathione in the brain. In addition, sauna use, which induces mild hyperthermia, increases the production of heat shock proteins, which are involved in glutathione maintenance and activity.

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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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  • Defensive compounds in plants may protect against Alzheimer's disease. pubs.rsc.org
    Nutrition Alzheimer's

    Amyloid-beta is a toxic protein that aggregates (clumps together) and forms plaques in the brain with age. Amyloid-beta aggregation is associated with Alzheimer’s disease, a progressive neurodegenerative disease that causes dementia. Findings from a recent study suggest that defensive compounds present in plants protect against amyloid-beta aggregation in an animal model of Alzheimer’s disease.

    Plants produce vast arsenals of defensive compounds to protect them from pathogenic attack and herbivore consumption. Evidence suggests that these compounds exert protective effects in humans, reducing the risk of many acute and chronic diseases. Scientists have identified thousands of plant defensive compounds that may benefit human health; perhaps the best known of these include sulforaphane, curcumin, and resveratrol.

    The study investigators performed an in vitro assay to gauge the capacity of nine plant defensive compounds (five flavones and four [tyrosols])https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571782/) to prevent amyloid-beta aggregation. They found that two of the flavone compounds, scutellarein and baicalein (which are found in plants in the mint family), reduced amyloid-beta aggregation as much as 90 percent, and two of the tyrosol compounds, hydroxytyrosol and hydroxytyrosol acetate (which are found in olives and olive oil), reduced aggregation as much as 100 percent. Then the investigators gave hydroxytyrosol to worms that tend to develop a condition like Alzheimer’s disease and found that the compound reduced amyloid-beta aggregation in the worms' brains by 43 percent.

    These findings demonstrate that plant defensive compounds scutellarein, baicalein, hydroxytyrosol, and hydroxytyrosol acetate inhibit amyloid-beta aggregation and show promise as candidates to prevent and/or treat Alzheimer’s disease. Evidence indicates that sulforaphane shows similar promise, as it impairs amyloid-beta production and improves learning and memory

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  • Brain’s own immune cells "infect" healthy neurons with Alzheimer-linked beta-amyloid protein. www.nature.com
    Alzheimer's Immune System

    Alzheimer’s disease is a common neurodegenerative disorder affecting an estimated 24 million older adults worldwide. Researchers believe the disease is caused by toxic levels of beta-amyloid protein aggregates in the brain that impair neuronal function and trigger cognitive decline. While this process is partly under the influence of genes, studies also indicate links between Alzheimer’s and external factors such as head injury. Findings from a new study shed new light on this link, suggesting that events such as head trauma and stroke accelerate Alzheimer’s disease by activating one of the brain’s major immune cells and triggering an infection-like spread of amyloid-beta tangles to previously unaffected tissues.

    The researchers conducted their experiments in mice genetically engineered to carry five mutations associated with Alzheimer’s disease. While these mutations lead to brain beta-amyloid aggregations and cognitive impairments at an early age, the team uncovered that even genetically healthy brain tissue could accumulate these aggregations if implanted into the brains of these mutant mice.

    To better understand this infection-like phenomenon, the researchers examined whether the mutant brain cells of the host might import beta-amyloid particles by migrating into the transplanted tissue or making connections with its neurons. Tracking them under a microscope offered no support for this hypothesis. Instead, the team uncovered a mass migration into the implanted tissue of microglia, the main immune cells of the nervous system, specialized for scouting brain tissue for signs of injury or pathogen invasion and clearing out cellular debris.

    One possible reason for this migration is that microglia are drawn to wounds. Indeed, the microglia were particularly concentrated around the edges of the transplant and exhibited similar migrations to tiny brain lesions that the researchers generated using lasers. However, in moving from the genetically diseased to healthy tissue, the microglia dumped large numbers of beta-amyloid particles previously picked up from the degenerating host brain tissue.

    The results offer an updated picture of Alzheimer’s disease progression where the brain’s own immune cells inadvertently drive the spread of pathogenic beta-amyloid aggregations – an effect that might be aggravated by brain injury events and inflammation. While scientists are uncertain why contaminated microglia engage in this “dumping” practice, targeting the cells' activity as a way of interfering with the neurodegenerative process provides promising research opportunities.

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  • Novel amyloid-beta vaccine reduces Alzheimer’s-like dementia in mice. www.sciencedaily.com
    Alzheimer's Vaccine

    Alzheimer’s disease is a neurodegenerative disease characterized by aggregates of misfolded proteins such as amyloid-beta and tau in the brain. Previous research has attempted to use amyloid-beta vaccines to stall or reverse the progression of Alzherimer’s disease; however, these trials failed to produce a vaccine that was effective and safe00023-6/fulltext). A study released this week has identified a new target for Alzheimer’s disease vaccines that may succeed in clearing amyloid-beta plaques.

    Amyloid-beta is a small, 36-43 amino acid protein that is cleaved from a larger amyloid precursor protein in the brain. After being cleaved, the small amyloid-beta protein can become misfolded, lose its function, and form oligomers, which are aggregate protein structures with many repeating identical units. Some of the amino acids on one end of the amyloid-beta structure fold over, creating a hairpin structure and contributing to plaque formation. Previous research has suggested the hairpin site is an effective target for preventing aggregation; however, no vaccine has yet been developed that exploits this molecular pattern.

    The authors designed a peptide that is a portion of the amyloid-beta protein containing 14 amino acids that are cyclized to form a stable pseudo hairpin structure. They inoculated healthy mice with the cyclized peptide and measured the antibody response. Next, they immunized mice who exhibit Alzheimer’s-like dementia and measured the effect on amyloid-beta plaques in the brain. They also measured cognitive function and hippocampal volume, which both decline with Alzherimer’s disease.

    The authors found that healthy mice had a robust immune response to immunization and produced antibodies specific to the pseudo hairpin protein they designed. In mice who develop Alheimer’s-like dementia, immunization significantly reduced the amount of amyloid-beta plaques in regions of the brain such as the cerebral cortex, hippocampus, and thalamus. These regions also exhibited increased glucose metabolism following immunization, indicating better metabolic health in the brain. Finally, immunization increased the number of neurons in the hippocampus, the brain region most associated with learning memory. Immunized mice with greater hippocampal volume performed better on learning and memory tasks.

    Immunization with the novel pseudo hairpin structure reversed amyloid-beta aggregation in the brain and improved brain health and cognitive performance in mice. This exciting research may contribute to the development of Alzheimer’s disease vaccines in humans.

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  • Hypertension in mid-life reduces brain volume and increases risk of dementia. neurosciencenews.com
    Alzheimer's Dementia Blood Pressure Stroke

    Many people develop hypertension (high blood pressure) with age, putting them at risk of cardiovascular disease, chronic kidney disease, retinal damage, and stroke. Hypertension is also a risk factor for Alzheimer’s disease and dementia, due to damage caused by years of vessel injury, microbleeds, and lesions. Authors of a recent study report that hypertension diagnosed in early or midlife, but not late life, is a predictor of dementia.

    Because hypertension damages the delicate small blood vessels of the heart, kidneys, eyes, brain, and other organs, it is a risk factor for a wide range of chronic diseases. Previous research has shown that hypertension, by restricting blood flow, reduces brain volume in key areas associated with dementia, such as the prefrontal cortex and hippocampus. As the number of young adults with hypertension increases to an estimated 1.6 billion globally by 2025, research on the risks of hypertension in earlier life are needed.

    The authors collected data from more than 135,000 participants with hypertension and 135,000 matched control participants without hypertension from the United Kingdom Biobank, a long-term study of United Kingdom citizens. The researchers categorized participants into four categories: younger than 35 years; 35 to 44 years; 45 to 54 years; and 55 to 64 years. They used magnetic resonance imaging data to measure brain volume, and hospital records, death records, and self-reports to assess dementia status. Participants in the study provided data at a baseline appointment between 2006 and 2010 and at a follow-up appointment between 2014 and 2021.

    Participants diagnosed with hypertension at any age had smaller brain volume than their matched control participant without hypertension. Participants diagnosed earlier in life had the greatest reductions, with participants diagnosed between ages 35 and 44 exhibiting a 0.8 percent loss in volume and participants before age 35 exhibiting a 1.2 percent loss. Specifically, hypertension was associated with loss of peripheral cortical gray matter, brain tissue necessary for higher brain functions such as learning, memory, and attention. Participants diagnosed with hypertension between ages 35 and 44 were at a 61 percent higher risk of dementia than the matched control participants without hypertension.

    The authors concluded that hypertension diagnosed in early mid life, but not late life, is associated with decreased brain volume and increased risk of dementia. Lifestyle strategies that reduce blood pressure, such as exercise, sauna use, dietary modification, and stress management, may reduce dementia risk.

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  • Omega-3 fatty acids slow memory loss in people with Alzheimer's disease. apple.news
    Nutrition Alzheimer's Omega-3 Neurodegeneration

    Omega-3 fatty acids are essential for human health. They participate in pathways involved in the biosynthesis of hormones that regulate blood clotting, contraction and relaxation of artery walls, and inflammation. They have been shown to help prevent heart disease and stroke; may help control lupus, eczema, and rheumatoid arthritis; and may play protective roles in cancer and other conditions. Findings from a new study suggest that omega-3 fatty acids slow cognitive decline in Alzheimer’s disease.

    Alzheimer’s disease is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline. The primary risk factor for Alzheimer’s disease is aging, with risk roughly doubling every five years after the age of 65 years. Nutritional status also plays key roles in Alzheimer’s disease risk and pathology. The intervention study involved 33 people who had been diagnosed with Alzheimer’s disease. Approximately half of the participants took a supplement providing 2.3 grams of omega-3 fatty acids daily for six months; the other half took a placebo. All participants took the Mini Mental State Examination (MMSE), a widely accepted measure of memory and cognitive function, before and after the intervention. The study investigators collected cerebrospinal fluid samples before and after the intervention to measure several biomarkers associated with neurodegenerative diseases and inflammation, including amyloid beta proteins, tau, interleukin 6, chitinase-3-like protein 1 (YKL-40), and neurofilament light (NfL). YKL-40 is associated with neuroinflammation, and NfL is associated with damage to the axons of nerves in brain white matter.

    The MMSE scores of the participants who took the omega-3 fatty acid supplements remained stable over the six-month intervention, decreasing by only 0.06 points, but the scores of those who took the placebo decreased by two points. The two groups' biomarkers were similar at the beginning of the intervention, but YKL-40 and NfL increased slightly in the group that received the omega-3 fatty acid supplement, indicating a possible increase in neurodegeneration and inflammatory responses. However, the increase in the two biomarkers did not correlate with the participants' MMSE scores.

    These findings suggest that omega-3 fatty acids help maintain memory and cognitive function in older adults with Alzheimer’s disease. This was a very small study, however, and further research is needed to confirm any protective effects of omega-3 fatty acid intake in Alzheimer’s disease.

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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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  • Eating processed meat increases risk for dementia, but eating unprocessed meat might be protective. academic.oup.com
    Alzheimer's Dementia

    Dementia is a broad term that includes Alzheimer’s disease, vascular dementia, and other forms of the condition. It is characterized by the loss of memory, language, problem-solving skills, and/or other aspects of cognitive function. Approximately 50 million people worldwide have dementia. A recent study investigated links between meat consumption and dementia risk.

    Meat is rich in several essential nutrients, including protein, iron, zinc, and vitamin B12. Findings from epidemiological studies suggest that diets high in red and processed meats increase a person’s risk for type 2 diabetes, cardiovascular disease, cancer (particularly colorectal cancer), and all causes of premature death.

    The present study involved more than 493,000 adults enrolled in the UK Biobank, a biomedical database containing health information about people living in the United Kingdom. The participants completed a food frequency questionnaire in which they provided answers about their meat consumption, to include processed meat, unprocessed poultry, and unprocessed red meat (beef, lamb, and pork). The authors of the study defined “processed meat” as bacon, ham, sausages, meat pies, kebabs, burgers, and chicken nuggets.

    They found that eating unprocessed red meat was linked with a lower risk of dementia and Alzheimer’s disease, whereas eating processed meat was linked with higher risk. They did not identify any associations between poultry consumption and dementia risk. Each additional 50-gram per day increment in unprocessed red meat intake decreased their risk for all causes of dementia by 19 percent and decreased their risk for Alzheimer’s disease by 30 percent. In contrast, each additional 25-gram per day increment in processed meat intake increased a person’s risk for all types of dementia by 44 percent and increased their risk for Alzheimer’s disease by 52 percent.

    High levels of protein and iron in unprocessed red meat may partially explain the link between unprocessed meat intake and lower risk of dementia. Adequate protein intake has been linked with lower dementia risk in older adults, and iron is necessary for many aspect of brain health, including the production of neurotransmitters and myelin. On the other hand, processed meat contains nitrites and N-nitroso compounds, which may promote oxidative stress, lipid peroxidation, and activation of proinflammatory cytokines or other mechanisms potentially involved in the development of dementia.

    These findings suggest that eating processed meat increases a person’s risk for developing dementia but eating unprocessed meat does not. They also underscore the importance of distinguishing between processed and unprocessed meat in nutrition studies. This was a large, well-designed prospective study that accounted for multiple confounding factors, including age, gender, ethnicity, socioeconomic status, educational level, BMI, physical activity level, smoking status, typical sleep duration, stroke history, family history of dementia, and dietary factors (including consumption of vegetables, fruits, fish, tea, coffee, and alcohol).

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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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  • Inadequate sleep increases a person's risk of developing Alzheimer's disease and dementia. neurosciencenews.com
    Alzheimer's Sleep Dementia

    Sleep is essential for human health. Not getting enough sleep or having poor, fragmented sleep increases a person’s risk of developing many chronic illnesses, including cardiovascular disease, hypertension, diabetes, stroke, obesity, and depression. Findings from a new study suggest that inadequate sleep increases a person’s risk of developing Alzheimer’s disease and dementia.

    Alzheimer’s disease and dementia are age-related disorders characterized by memory loss, cognitive decline, and behavioral changes. Nearly 50 million people are living with Alzheimer’s disease or a related dementia worldwide, a number expected to triple by the year 2050.

    The authors of the study drew on data from the National Health and Aging Trends Study, an on-going longitudinal study of adults living in the United States who are over the age of 65 years. More than 2,800 participants (average age, 76 years) completed questionnaires about their sleep quality, including time to sleep onset, sleep duration, and snoring. The authors collected information about the participants' cognitive health or death from any cause for up to five years after completion of the questionnaires.

    They found that participants who reported getting fewer than five hours of sleep per night were twice as likely to develop dementia compared to those who had seven to eight hours of sleep per night. Taking a long time to fall asleep (more than 30 minutes) increased the risk of dementia 45 percent. The authors also found that getting fewer than five hours of sleep per night, daytime sleepiness, and regular napping increased the risk of all causes of premature death.

    These findings indicate that short sleep duration and sleep-associated problems among older adults increase the risk of developing dementia and dying prematurely. The research of sleep expert Dr. Matthew Walker focuses on identifying certain windows of vulnerability during a person’s life when interventions might improve sleep quality to prevent or delay age-related cognitive decline. Learn more in this clip.

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  • Restoring immune cell metabolism reduces inflammation and slows cognitive decline in mice www.the-scientist.com
    Alzheimer's

    Aging involves the collective physiological, functional, and mental changes that accrue in a biological organism over time. A key driver of aging is inflammation, which affects multiple organs, including the brain. Findings from a new study demonstrate that altering prostaglandin E2 signaling in macrophages reduces inflammation and slows cognitive decline in mice.

    Macrophages are a type of immune cell. They are key players in the initiation, maintenance, and resolution of inflammation.

    Prostaglandin E2 is an important mediator of inflammation, angiogenesis, cell survival, and proliferation. It is produced via the enzymatic conversion of arachidonic acid, a type of fatty acid. Binding of prostaglandin E2 to its receptors on immune cells alters glucose metabolism in the cells and drives inflammation. Prostaglandin E2 levels increase with age and in the setting of neurodegenerative disease.

    The investigators first studied peripheral blood mononuclear cells collected from young (less than 35 years) and old (greater than 65 years) human donors to better understand how prostaglandin E2 signaling affected macrophage energy production. They found that prostaglandin E2 reduced glycolysis (the breakdown of glucose) and impaired mitochondrial oxygen use. The primary receptor that mediated these effects was the EP2 receptor, which was present in higher quantities in the macrophages of old donors. Then they treated the cells with an inhibitor to block the EP2 receptor and found that the alterations in energy production reversed.

    Next, the investigators studied mice that are predisposed to have Alzheimer’s disease. They treated the animals with EP2 receptor inhibitors or deactivated their EP2 gene. They found that in both situations the macrophages had better energy production, and the mice had lower levels of inflammation and cognitive decline.

    These findings suggest that inhibition of immune-related processes that promote inflammation restores immune cell energy production and slows cognitive decline in mice. Learn more about the role of inflammation in cognitive decline in this episode featuring Dr. Dale Bredesen.

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  • Hydrogen sulfide protects against Alzheimer's disease by preventing tau tangle formation. www.eurekalert.org
    Alzheimer's

    Abnormal aggregates of tau, a protein found in the brain, are one of the defining characteristics of Alzheimer’s disease. These aggregates, known as tau tangles, inhibit normal brain function. The degree of cognitive impairment in Alzheimer’s disease is correlated with their presence. Findings from a new study suggest that hydrogen sulfide prevents tau tangle formation by inhibiting tau phosphorylation.

    Hydrogen sulfide is a naturally occurring gas, notable for its strong odor of rotten eggs. Exposure to hydrogen sulfide can cause irritation to the eyes and respiratory system. Hydrogen sulfide is also produced in the body’s tissues. Sometimes referred to as a gasotransmitter, it serves as a signaling molecule and actively participates in regulation of a wide range of physiological functions, including inflammation and cell death. Evidence suggests that hydrogen sulfide inhibits free radical reactions in aging and age-related neurodegenerative diseases. Hydrogen sulfide signaling is impaired with aging.

    Tau phosphorylation is a chemical modification facilitated by the activity of several enzymes, including glycogen synthase kinase 3-beta (GSK3-beta). Hyperactive GSK3-beta promotes abnormal tau phosphorylation and subsequent tangle formation.

    The investigators used a mouse model of Alzheimer’s disease to study the effects of hydrogen sulfide on the brain. They injected the mice with hydrogen sulfide daily for 12 weeks and then subjected the mice to various cognitive and motor tests. They also conducted biochemical experiments to gauge the effects of hydrogen sulfide on GSK3-beta.

    The tests revealed that the mice treated with hydrogen sulfide performed 50 percent better on the tests than mice that did not receive the treatment. The biochemical experiments revealed that a chemical modification of GSK3-beta called sulfhydration inhibits tau phosphorylation. However, under conditions of low hydrogen sulfide levels, GSK3-beta is disproportionately attracted to tau, promoting hyperphosphorylation and tau tangle formation.

    These findings suggest that strategies to improve hydrogen sulfide status in the brain show promise as a treatment for Alzheimer’s disease.

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  • Dietary patterns that include cheese and wine may promote cognitive health. www.research.iastate.edu
    Alzheimer's Aging Dementia

    Fluid intelligence – the ability to creatively solve problems without prior knowledge or learning – declines with age. Greater losses of fluid intelligence are associated with increased risk of Alzheimer’s disease. Findings from a recent study suggest that dietary factors protect against fluid intelligence losses.

    Nutrition plays critical roles in maintaining cognitive health. Evidence indicates that adherence to dietary patterns that include fruits, vegetables, nuts, and olive oil reduces the risk of developing Alzheimer’s disease. People who carry gene variants that increase their risk of Alzheimer’s disease may benefit from consuming foods that are rich in DHA, a type of omega-3 fatty acid.

    The study involved nearly 1,800 people between the ages of 46 and 77 years who were enrolled in the UK Biobank Prospective Study. The participants completed three fluid intelligence tests over a period of several years to assess their ability to creatively solve problems without prior knowledge or learning. They also completed food frequency questionnaires regarding their dietary intake.

    The authors of the study found that daily cheese consumption provided the most protection against age-related fluid intelligence losses. They also found that alcohol consumption, especially red wine, provided protection. Eating lamb was associated with better cognitive performance but eating other types of red meat was not. In general, eating too much salt promoted cognitive decline, especially among high-risk groups.

    These findings suggest that dietary modifications can promote cognitive health in aging. One mechanism that may drive these benefits is autophagy, a cellular recycling program that is crucial in maintaining neuronal health. Caloric restriction mimetics, such as spermidine (present in aged cheese) and resveratrol (present in red wine), “trick” cells into inducing autophagy even in the setting of sufficient nutrient levels. Watch Dr. Guido Kroemer describe the autophagy-inducing effects of calorie restriction mimetics such as spermidine and resveratrol.

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  • Sulforaphane inhibits enzyme involved in amyloid-beta production. www.mdpi.com
    Nutrition Alzheimer's Sulforaphane NRF2

    Amyloid-beta is a toxic 42-amino acid peptide that clumps and forms plaques in the brain with age. Amyloid-beta is associated with Alzheimer’s disease, a progressive neurodegenerative disease and the most common cause of dementia. Findings from a new study demonstrate that sulforaphane impairs BACE1, an enzyme involved in the production of amyloid-beta.

    BACE1, or beta site amyloid precursor protein cleaving enzyme 1, is produced primarily in the central nervous system. People with Alzheimer’s disease often have high levels of BACE1 in their brains.

    The authors of the study set out to evaluate sulforaphane’s capacity to inhibit BACE1. They used fluorescence resonance energy transfer analysis to determine the enzyme’s activity and then calculated its kinetics. They assessed sulforaphane’s enzyme selectivity in the presence of several other enzymes and compared its effects to those of resveratrol and quercetin, bioactive compounds that exert beneficial effects on human health.

    They found that sulforaphane was six times more effective against BACE1 compared to resveratrol and quercetin. Sulforaphane demonstrated high affinity for BACE1 and had few off-target effects, suggesting that sulforaphane shows promise as a candidate to reduce the activity of BACE1, potentially playing a role in preventing Alzheimer’s disease.

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  • Vitamin D deficiency exacerbates inflammation and Alzheimer's pathology in mice. pubmed.ncbi.nlm.nih.gov
    Vitamin D Alzheimer's

    Currently selected for this coming member’s digest by team member Melisa B.

    Adequate exercise is one of the most effective lifestyle interventions to improve aging, but many people, especially older adults, can find it difficult to exercise. In a study published this month, researchers tested the effects of resveratrol as an adjuvant therapy to exercise for older adults with physical limitations.

    The word “adjuvant” has roots in Latin that mean “helping toward.” Adjuvant therapies are add-ons that may improve the effectiveness of other interventions. Resveratrol is known to activate mitochondria through a protein called PGC-1α, the master regulator of mitochondrial biogenesis. Therefore, resveratrol may boost the benefits of exercise by enhancing mitochondrial adaptation in skeletal muscle.

    The purpose of this randomized controlled pilot study was to determine the safety and feasibility of chronic exercise combined with resveratrol supplementation. The investigators split a group of 60 adults (average age, 71 years) with physical limitations into three groups. All three groups completed supervised walking and whole-body resistance training twice weekly for 12 weeks. One group took 500 milligrams of resveratrol daily, another took 1,000 milligrams of resveratrol daily, and the third group took a placebo. The participants completed a battery of physical function tests and gave blood so the researchers could measure markers of cardiovascular risk.

    On average, participants completed 82 percent of their exercise sessions and took 85 percent of their resveratrol doses, indicating that the intervention was acceptable for most participants. The rate of adverse events was similar between groups with an average of nine events, indicating that the intervention was safe. Pilot studies are not designed to evaluate the effect of the study intervention on health; however, the authors reported some promising early results. Participants in the 1,000 milligram group exhibited a clinically-significant increase of 449 meters in their 6-minute walk test and increased levels of citrate synthase, a common marker of mitochondrial volume.

    The authors are planning a large-scale clinical trial to build on these preliminary results.

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  • Nanoparticles in air pollution accumulate in the brains of young adults: A common denominator in neurodegenerative disease? www.sciencedaily.com
    Alzheimer's Parkinson's Development Pollution

    Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative conditions in older adults, affecting a combined 36 million people worldwide. Evidence suggests that exposure to air pollution increases the risk of developing these diseases. Findings from a recent study demonstrate that particulate matter in air pollution accumulates in the brains of young adults and may serve as a common denominator in the pathophysiology of AD and PD.

    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. Ultrafine particles less than 1 microgram in diameter, referred to as nanoparticles, are often enriched in highly reactive metals such as iron, aluminum, titanium, and others. They may serve as catalysts for reactive oxygen species formation and promote protein misfolding and aggregation. Nanoparticles in air pollution are not regulated and carry many health risks. They are also present in food additives and food packaging materials.

    The authors of the study documented biomarkers of AD and PD present in brainstem samples taken during the autopsies of 186 healthy children and young adults (age range, 11 months to 27 years) living in the metro area of Mexico City, a region known for its high levels of air pollution. They also conducted magnetic remanence studies to quantify the presence of metal-rich nanoparticles in the brainstem samples. Finally, using high resolution scanning and transmission electron microscopy and energy-dispersive X ray analysis, they identified the composition, location, size, and shape of nanoparticles in the substantia nigra region of a randomly chosen single sample taken from the larger group. Damage to the substantia nigra is a hallmark of PD.

    They found that all of the brainstem samples contained iron-, aluminum-, and titanium-rich nanoparticles. The quantity of nanoparticles varied among the brain samples, likely due to the level and duration of exposure. The authors posited that these nanoparticles could have been acquired via both oral and respiratory routes from food sources and airborne exposures, respectively. Damage to the mitochondria, endoplasmic reticulum, and neuromelanin in the single brainstem sample correlated with the presence of iron-, aluminum-, and titanium-rich nanoparticles.

    These findings suggest that exposure to nanoparticles is pervasive, with evidence confirmed as early as 11 months of age. Such exposures may put people living in urban areas where high levels of air pollutants are present at greater risk for developing AD and PD.

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  • Commonly prescribed drugs linked to increased risk of Alzheimer's disease. www.sciencedaily.com
    Alzheimer's

    Alzheimer’s disease is a neurodegenerative disorder characterized by progressive memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. The major genetic risk factor for Alzheimer’s disease is a variant in the apolipoprotein E (APOE) gene called apolipoprotein E4 (APOE4). Findings from a new study suggest that use of anticholinergic drugs increases the risk of cognitive decline, especially among those who are APOE4 carriers.

    Anticholinergic drugs are a widely prescribed class of drugs that work by blocking the activity of acetylcholine, a neurotransmitter. They are used to treat a wide range of conditions, including respiratory disorders, Parkinson’s disease, dizziness, allergies, and incontinence, among others.

    The study included nearly 700 cognitively normal adults who were enrolled in the Alzheimer’s Disease Neuroimaging Initiative study. Participants provided information regarding regular (at least once a week for more than six months) use of anticholinergic drugs. The authors of the study assessed the participants' progression from normal cognitive function to mild cognitive impairment over a 10-year period and noted rates of decline in memory, executive function, and language. They also investigated whether participants who carried the APOE4 gene were at greater risk for decline.

    Participants who took anticholinergic drugs were 42 percent more likely to progress to mild cognitive impairment during the 10-year period compared with participants who did not take the drugs. Participants who took the drugs and were APOE4 carriers had a more than twofold greater risk of decline.

    These findings suggest that commonly prescribed anticholinergic drugs increase the risk of cognitive decline, especially among adults who carry the APOE4 gene. Careful consideration of drug choice among older adults is advised.

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  • Long-term poor sleep predicts amyloid-beta deposition in the brain. www.the-scientist.com
    Alzheimer's Sleep

    Sleep disruption is linked with the pathophysiology of Alzheimer’s disease, with characteristic changes in sleep emerging early in life, well before the clinical onset of the disease. A key player in the development of Alzheimer’s disease is amyloid-beta. Insufficient sleep increases the production of amyloid-beta, and amyloid-beta deposition, in turn, impairs sleep in a vicious, self-perpetuating loop. Findings from a new study demonstrate that chronic poor sleep predicts the degree of amyloid-beta deposition in the brain.

    The study involved 32 older adults (average age, 73 years) who were cognitively intact. The authors of the study analyzed the participants' sleep patterns at the beginning of the four-year study. At periodic intervals throughout the study, the authors measured the participants' cognitive function and performed positron emission tomography (PET) scans to check for the presence of amyloid-beta in the participants' brains.

    They found that most of the participants already had some amyloid-beta accumulation in their brains, but this was not surprising, considering the participants' ages. They also found that participants who had less slow wave sleep and poor sleep efficiency were more likely to have faster accumulation of amyloid-beta.

    These findings demonstrate that objective markers of sleep could forecast the rate of amyloid-beta deposition in the human brain.

    Read more
  • New blood test diagnoses Alzheimer's disease decades before symptoms manifest. www.eurekalert.org
    Alzheimer's

    Alzheimer’s disease is a neurodegenerative disorder characterized by progressive memory loss, cognitive decline, and behavioral changes. Roughly 50 million people have Alzheimer’s disease worldwide. Researchers have developed a blood test that measures phospho-tau217 (p-tau217), a type of tau protein, and may be useful in diagnosing Alzheimer’s disease as early as 20 years before symptoms manifest.

    Tau is a protein that clumps together and forms tangles inside neurons in the brains of people with Alzheimer’s disease. When tau tangles form, the system for transporting mitochondria, lipids, and cellular metabolites is disrupted. As a result, cellular energy is reduced, and new synapse formation is halted, resulting in impaired memory, a hallmark of Alzheimer’s disease. Typically, the presence of tau tangles is determined during autopsy, but it can be observed via PET imaging studies in living persons.

    The study involved more than 1,400 people from three cross-sectional cohorts. Some of the participants were cognitively impaired, while others were not. The three cohorts provided data from clinical, neuropathological, imaging, cerebrospinal fluid, blood-based biomarker, and genetic assessments.

    The authors of the study found that the p-tau217 blood test distinguished the presence of Alzheimer’s disease from other neurodegenerative diseases better than currently used biomarkers and equally as well as imaging studies. The test identified early signs of Alzheimer’s disease in people who were genetically predisposed to the condition as much as 20 years before the onset of symptoms. These findings suggest that a simple blood test could accurately diagnose Alzheimer’s disease early in its pathology, potentially providing strategies to delay or prevent the disease.

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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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  • 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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  • 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.”

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  • 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.

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  • 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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  • Six months of aerobic exercise improved brain glucose metabolism, improved executive function, & increased cardiorespiratory fitness in older adults. www.sciencedaily.com
    Exercise Alzheimer's Aerobic

    An abundance of scientific evidence demonstrates that exercise benefits physical health and improves cognitive function in people of all ages. A new study has found that aerobic exercise improves brain glucose metabolism and executive function in older adults who are at risk for Alzheimer’s disease.

    Impaired brain glucose uptake and metabolism are pathological hallmarks of Alzheimer’s disease, and their manifestation typically precedes the onset of clinical symptoms. Impaired brain glucose uptake also plays a causal role in tau tangle formation, another hallmark of Alzheimer’s disease.

    Executive function involves higher-level cognitive skills that include working memory, flexible thinking, and self-control. A person who experiences loss of executive function may have problems with planning, organization, flexible thinking, social behavior, decision making, emotional control, and concentration.

    The randomized, controlled, exercise intervention involved 23 cognitively normal, sedentary adults between the ages of 45 and 80 years old who had a family history or genetic risk for Alzheimer’s disease. Eleven of the participants engaged in a moderate-intensity exercise program in which they walked on a treadmill three times per week for 26 weeks. The remaining participants made no changes to their physical activity levels.

    At the end of the study, the participants who engaged in the exercise program experienced improved cardiorespiratory fitness and improved brain glucose metabolism in the posterior cingulate cortex region of their brains. They also spent less time engaged in sedentary activities compared to those who did not change their activity levels. Furthermore, the adults who exercised demonstrated improvements in their executive functioning. Other recent research suggests that aerobic exercise, especially if it includes high-intensity interval training, has the potential to enhance memory in older adults.

    Taken together, these findings suggest that lifestyle modifications that include exercise may be beneficial in improving cognitive function in people at high risk for Alzheimer’s disease. Interestingly, sauna use mimics the effects of exercise and may be useful in reducing Alzheimer’s disease risk. Learn more in this clip featuring sauna expert Dr. Jari Laukanen.

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  • Lithium may halt progression of Alzheimer’s disease. www.mcgill.ca
    Alzheimer's Depression Salt

    Alzheimer’s disease is a neurodegenerative disorder characterized by progressive memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. It is the most common form of dementia, affecting nearly 50 million people worldwide. One of the primary pathological hallmarks of Alzheimer’s disease is the progressive accumulation of amyloid-beta plaques in the brain. A new study in a mouse model of Alzheimer’s disease demonstrates that low-dose lithium may halt the progression of the disease by decreasing amyloid-beta plaque accumulation.

    Lithium is a drug commonly used to treat bipolar disorder and drug-resistant depression. A microdose form of lithium, called NP03, consists of lithium encapsulated in a water-in-oil microemulsion. It is absorbed in the mouth to facilitate uptake and increase bioavailability. NP03 delivers doses of lithium that are up to 400 times lower than typical formulations.

    The study involved transgenic mice that develop Alzheimer’s disease and its characteristic amyloid-beta plaque formation and cognitive impairments. The authors of the study gave the mice NP03 (40 micrograms of lithium per kilogram of body weight) five times a week for 12 weeks, to span the timeframe in which the mice would have amyloid-beta accumulation. They assessed the animals' ability to perform memory tasks and then measured levels of amyloid-beta and proinflammatory molecules in the animals' brains.

    They found that NP03 improved cognitive performance, reduced amyloid-beta burden, and reduced markers of neuroinflammation and cellular oxidative stress in the mice. These findings suggest that a microdose lithium formulation may be beneficial in reducing amyloid-beta burden in the later stages of Alzheimer’s disease progression.

    Read more
  • Disrupted glucose metabolism may be a major contributing factor to Alzheimer's disease. jamanetwork.com
    Alzheimer's

    Impaired glucose metabolism is a defining characteristic of type 2 diabetes. People who have type 2 diabetes have a markedly higher risk of developing Alzheimer’s disease. Impaired glucose uptake and metabolism in the brain are pathological hallmarks of Alzheimer’s disease. Their manifestation precedes the onset of clinical symptoms. Impaired brain glucose uptake also plays a causal role in tau tangle formation.

    Emerging evidence presented at a recent meeting of the Society for Neuroscience suggests that impaired glucose metabolism may be a causal factor in the pathogenesis of Alzheimer’s disease. In fact, some researchers have even suggested that Alzheimer’s disease is “type 3 diabetes.” A summary of the evidence presented and links to more than a dozen studies supporting these conclusions can be found in this perspective.

    Read more
  • One night of sleep deprivation in healthy young men caused increased blood levels of tau, a protein that forms tangles in the brain. www.eurekalert.org
    Alzheimer's Sleep Neurons Protein

    Sleep disruption is intrinsically linked with Alzheimer’s disease and its pathophysiology, with characteristic changes in sleep emerging early in life, well before the clinical onset of the disease. A key player in the development of Alzheimer’s disease is amyloid-beta. Insufficient sleep increases the production of amyloid-beta, and amyloid-beta deposition, in turn, impairs sleep in a vicious, self-perpetuating loop. Findings from a new study demonstrate that sleep deprivation also increases blood levels of tau, a protein found in the brain.

    Tau is a microtubule-bound protein that forms the neurofibrillary “tau tangles” associated with Alzheimer’s disease. Tau tangles disrupt the transport of metabolites, lipids, and mitochondria across a neuron to the synapse where neurotransmission occurs. Diminished slow-wave sleep is associated with higher levels of tau in the brain. Elevated tau is a sign of Alzheimer’s disease and has been linked to cognitive decline.

    The two-condition crossover study involved 15 healthy young men who were randomized to regimens of either two nights of consecutive sleep or one night of sleep followed by one night of sleep deprivation. Following the one night of sleep deprivation, participants' blood levels of tau increased approximately 17 percent, compared to an approximately 2 percent increase following the night of sleep. Other biomarkers of Alzheimer’s disease-associated proteins were unchanged. While tau tangle formation in neurons can disrupt normal function, it is unclear what elevated blood levels of tau protein mean. Future studies are needed to elucidate this finding.

    Watch this clip featuring Dr. Matthew Walker in which he describes current research focused on identifying age-related sleep deprivation vulnerability windows for prevention of Alzheimer’s disease.

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  • Hyperbaric oxygen therapy demonstrates efficacy in treating symptoms of Alzheimer's disease. www.sciencedaily.com
    Alzheimer's

    Alzheimer’s disease is a progressive neurodegenerative disorder characterized by memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. Global altered brain metabolism typically precedes the onset of clinical symptoms in Alzheimer’s disease. Evidence from a recent case study indicates that hyperbaric oxygen therapy may benefit brain metabolism in patients with Alzheimer’s disease.

    Hyperbaric oxygen therapy involves exposure to 100 percent oxygen at greater than normal pressure. It is commonly used to treat wounds and other medical conditions in which hypoxia is an underlying factor. The mechanisms by which hyperbaric oxygen therapy works involve epigenetic modulation of gene expression to mediate factors that drive disease and inflammation.

    The case study involved a 58-year-old woman with early-onset, rapidly progressing Alzheimer’s disease. After receiving 40 hyperbaric treatments over a period of nine weeks, the patient reported improvements in memory, concentration, sleep, conversation, appetite, general mood, and physical function. PET imaging one month after the patient’s treatment concluded showed as much as 38 percent improvement in brain metabolism. Long-term treatment (22 months) and pharmaceutical treatment elicited continued patient improvements.

    Read more
  • A vaccine developed to prevent tuberculosis, now also used to treat bladder cancer, reduced the incidence of Alzheimer’s disease four-fold. journals.plos.org
    Alzheimer's Vaccine

    Alzheimer’s disease is a neurodegenerative disorder characterized by progressive memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. It is the most common form of dementia, affecting nearly 50 million people worldwide. Findings from a recent study suggest that the bacillus Calmette-Guérin vaccine, originally developed to provide immunity against tuberculosis and now widely used to treat bladder cancer, may be useful in reducing the incidence of Alzheimer’s disease in bladder cancer patients.

    A critical element of Alzheimer’s disease pathogenesis is neuroinflammation. Previous research has shown that BCG vaccination triggers an immune response that increases systemic IL-2 levels which, in turn, increases the population of neuroprotective T-reg cells. BCG also increases anti-inflammatory cytokines in the brain, thereby reducing neuroinflammation.

    The new study involved 1,371 patients (average age, 68 years) with bladder cancer who received various agents as intravesical chemotherapy. Of these patients, 878 received BCG treatment. After a median of eight years of follow-up, those who received the BCG intravesical therapy exhibited a four-fold reduction in the risk of developing Alzheimer’s disease. These findings suggest that BCG vaccine treatment might be useful in preventing Alzheimer’s disease.

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  • Increasing gamma rhythm activity in the brain can affect the pathology and symptoms of Alzheimer’s disease picower.mit.edu
    Alzheimer's Neurons

    Alzheimer’s disease is a neurodegenerative disorder characterized by progressive memory loss, spatial disorientation, cognitive dysfunction, and behavioral changes. It is the most common form of dementia, affecting nearly 50 million people worldwide. The primary pathological hallmarks of Alzheimer’s disease include amyloid-beta plaques and tau tangles. Abnormal electrical activity in the brain can worsen the condition. A recent review describes findings from two rodent studies suggesting that stimulating gamma waves in the brain may reverse the pathology and symptoms of Alzheimer’s disease.

    During wakefulness and periods of REM sleep, the human brain exhibits spontaneous rhythmical activity in the form of fast-moving gamma waves. These waves are evoked by intense attention, conditioned responses, tasks requiring fine movements, or sensory stimuli.

    The studies utilized mice that were predisposed to Alzheimer’s disease. These mice often exhibit diminished gamma wave activity. The authors of the studies exposed the mice to visual and auditory stimuli that were designed to promote gamma wave activity.

    Following exposure to visual stimuli alone, the mice exhibited reduced amyloid burden and structural changes in the microglial cells in the visual cortex of their brains. These structural changes were consistent with increased phagocytic capacity, which is crucial for the clearance of apoptotic or necrotic cells and the removal of amyloid-beta. Exposure to auditory stimuli alone had similar effects on microglial activity and amyloid burden in the auditory cortex of the mice’s brains, but the mice also exhibited improved performance on several hippocampal-dependent tasks and improved brain vasculature.

    When the mice were exposed to combined auditory and visual stimuli to promote gamma wave activity, the amyloid burden was reduced throughout the neocortex, the area of the brain that processes sensory, motor, language, emotional, and associative information. In addition, the microglia in several regions of the brain exhibited a clustering pattern around the amyloid plaques that facilitated clearance.

    These findings suggest that non-invasive techniques that promote gamma wave activity in the brain may be useful in treating people with Alzheimer’s disease.

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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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  • A 28% lower risk of dementia and better cognition was associated with a high intake of dietary phosphatidylcholine mainly from eggs and meat in men. www.sciencedaily.com
    Alzheimer's Omega-3 Dementia Acetylcholine Neurons

    A 28% lower risk of dementia and better scores on tests for memory and linguistic abilities was associated with a high intake of dietary phosphatidylcholine mainly from eggs and meat in men.

    Choline is an important precursor to the neurotransmitter acetylcholine which plays an important role in cognition. Phosphatidylcholine is a very important component of cell membranes that make up neurons and also combines with the omega-3 fatty acid DHA to form lysophosphatidylcholine DHA which is transported across the blood-brain barrier. I published a paper last year on the important role DHA in phosphatidylcholine form plays in preventing Alzheimer’s disease particularly in people genetically predisposed to the disease.

    This new study was an observational study so causation cannot be established. Future clinical trials need to be done before definitive conclusions can be made.

    Link to my study on DHA and Alzheimer’s disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338661/

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  • higher acid-sphingomyelinase associated with disease progression in Alzheimer's www.ncbi.nlm.nih.gov
    Alzheimer's Parkinson's Mental Health Cannabinoid Neurotransmitter Dementia

    “Pharmacological restoration of ASM to the normal range improves pathology in AD mice The ASM-mediated lysosomal/autophagic dysfunction in AD prompted us to examine possible therapeutic implications of this pathway. To decrease ASM in APP/PS1 mice, we undertook pharmacological inhibition using amitriptyline-hydrochloride (AMI) for 4 mo (Fig. 9 A). AMI is a known inhibitor of ASM that can cross the blood–brain barrier. At 9 mo of age, AMI-treated APP/PS1 mice exhibited decreased ASM activity compared with vehicle-treated mice (Fig. 9 B). Other sphingolipid metabolites were not changed (Fig. 9 C). Aβ levels were decreased in the AMI-treated APP/PS1 mice compared with the nontreated littermates.”

    “ASM activity is known to be increased by environmental stress and in various diseases, and is elevated in AD patients (He and Schuchman, 2012). One downstream consequence of increased ASM is elevated ceramide, contributing to cell death, inflammation, and other common disease findings. Although elevated ASM is known to occur in AD, the cellular mechanisms that link ASM and AD have not been fully characterized. The data presented here suggest a previously unknown role of ASM in the down-regulation of lysosomal biogenesis and inhibition of lysosome-dependent autophagic proteolysis. The findings also establish proof of concept for ASM inhibitor therapy in AD.”

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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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  • Time-restricted eating, a ketogenic diet, and exercise improved cognitive function and markers of metabolism in a woman with ApoE4 and Alzheimer's . www.sciencedirect.com
    Alzheimer's Ketosis Fasting Insulin Triglycerides Time-Restricted Eating Metabolic Syndrome Ketogenic Diet

    Time-restricted eating (TRE), a ketogenic diet, and exercise improved cognitive function and markers of metabolism including triglycerides, VLDL, and HbA1c in a 71-year-old woman with ApoE4 that has mild Alzheimer’s disease and metabolic syndrome (case study).

    This is an interesting proof of principle study showing that implementing a nutrition protocol purposed at raising plasma ketones through fasting (TRE) a ketogenic diet and physical exercises can compensate for insulin resistance and the ApoE4 gene in a mild Alzheimer’s patient experiencing cognitive impairment.

    The APOE4 gene is the largest risk factor for Alzheimer’s disease besides age itself.

    To learn more check out this episode highlight of Dr. Dale Bredesen talking about time-restricted eating and a ketogenic diet in the context of Alzheimer’s disease in people with and without ApoE4.

    Episode: https://youtu.be/PWZbeq6MCKU

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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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  • Corroboration of a Major Role for Herpes Simplex Virus Type 1 in Alzheimer’s Disease www.frontiersin.org
    Alzheimer's Virus

    Strong evidence has emerged recently for the concept that herpes simplex virus type 1 (HSV1) is a major risk for Alzheimer’s disease (AD). This concept proposes that latent HSV1 in brain of carriers of the type 4 allele of the apolipoprotein E gene (APOE-ε4) is reactivated intermittently by events such as immunosuppression, peripheral infection, and inflammation, the consequent damage accumulating, and culminating eventually in the development of AD. Population data to investigate this epidemiologically, e.g., to find if subjects treated with antivirals might be protected from developing dementia—are available in Taiwan, from the National Health Insurance Research Database, in which 99.9% of the population has been enrolled. This is being extensively mined for information on microbial infections and disease. Three publications have now appeared describing data on the development of senile dementia (SD), and the treatment of those with marked overt signs of disease caused by varicella zoster virus (VZV), or by HSV. The striking results show that the risk of SD is much greater in those who are HSV-seropositive than in seronegative subjects, and that antiviral treatment causes a dramatic decrease in number of subjects who later develop SD. It should be stressed that these results apply only to those with severe cases of HSV1 or VZV infection, but when considered with the over 150 publications that strongly support an HSV1 role in AD, they greatly justify usage of antiherpes antivirals to treat AD. Three other studies are described which directly relate to HSV1 and AD: they deal respectively with lysosomal changes in HSV1-infected cell cultures, with evidence for a role of human herpes virus type 6 and 7 (HHV6 and HHV7) in AD, and viral effects on host gene expression, and with the antiviral characteristics of beta amyloid (Aβ). Three indirectly relevant studies deal respectively with schizophrenia, relating to antiviral treatment to target HSV1, with the likelihood that HSV1 is a cause of fibromyalgia (FM), and with FM being associated with later development of SD. Studies on the link between epilepsy, AD and herpes simplex encephalitis (HSE) are described also, as are the possible roles of APOE-ε4, HHV6 and HSV1 in epilepsy.

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  • Multiscale Analysis of Independent Alzheimer’s Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus www.cell.com
    Alzheimer's Virus Genome Neurodegeneration

    Summary Investigators have long suspected that pathogenic microbes might contribute to the onset and progression of Alzheimer’s disease (AD) although definitive evidence has not been presented. Whether such findings represent a causal contribution, or reflect opportunistic passengers of neurodegeneration, is also difficult to resolve. We constructed multiscale networks of the late-onset AD-associated virome, integrating genomic, transcriptomic, proteomic, and histopathological data across four brain regions from human post-mortem tissue. We observed increased human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) from subjects with AD compared with controls. These results were replicated in two additional, independent and geographically dispersed cohorts. We observed regulatory relationships linking viral abundance and modulators of APP metabolism, including induction of APBB2, APPBP2, BIN1, BACE1, CLU, PICALM, and PSEN1 by HHV-6A. This study elucidates networks linking molecular, clinical, and neuropathological features with viral activity and is consistent with viral activity constituting a general feature of AD.

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  • Alzheimer’s Disease-Associated β-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection www.sciencedirect.com
    Alzheimer's Immune System Virus Protein

    Summary

    Amyloid-β peptide (Aβ) fibrilization and deposition as β-amyloid are hallmarks of Alzheimer’s disease (AD) pathology. We recently reported Aβ is an innate immune protein that protects against fungal and bacterial infections. Fibrilization pathways mediate Aβ antimicrobial activities. Thus, infection can seed and dramatically accelerate β-amyloid deposition. Here, we show Aβ oligomers bind herpesvirus surface glycoproteins, accelerating β-amyloid deposition and leading to protective viral entrapment activity in 5XFAD mouse and 3D human neural cell culture infection models against neurotropic herpes simplex virus 1 (HSV1) and human herpesvirus 6A and B. Herpesviridae are linked to AD, but it has been unclear how viruses may induce β-amyloidosis in brain. These data support the notion that Aβ might play a protective role in CNS innate immunity, and suggest an AD etiological mechanism in which herpesviridae infection may directly promote Aβ amyloidosis.

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  • Transcriptional Effects of ApoE4: Relevance to Alzheimer’s Disease | SpringerLink link.springer.com
    Alzheimer's Protein

    The major genetic risk factor for sporadic Alzheimer’s disease (AD) is the lipid binding and transporting carrier protein apolipoprotein E, epsilon 4 allele (ApoE4). One of the unsolved mysteries of AD is how the presence of ApoE4 elicits this age-associated, currently incurable neurodegenerative disease. Recently, we showed that ApoE4 acts as a transcription factor and binds to the promoters of genes involved in a range of processes linked to aging and AD disease pathogenesis. These findings point to novel therapeutic strategies for AD and aging, resulting in an extension of human healthspan, the disease-free and functional period of life. Here, we review the effects and implications of the putative transcriptional role of ApoE4 and propose a model of Alzheimer’s disease that focuses on the transcriptional nature of ApoE4 and its downstream effects, with the aim that this knowledge will help to define the role ApoE4 plays as a risk factor for AD, aging, and other processes such as inflammation and cardiovascular disease.

    https://www.ncbi.nlm.nih.gov/pubmed/?cmd=historysearch&querykey=5

    Theendakara, V., Peters-Libeu, C.A., Bredesen, D.E. et al. Mol Neurobiol (2018) 55: 5243. https://doi.org/10.1007/s12035-017-0757-2

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  • More Evidence for Gut-Brain Link in Alzheimer's Disease www.medscape.com
    Nutrition Alzheimer's Gut Microbiome

    “Three key findings emerged: First, lower serum concentrations of primary bile acids synthesized in the liver from cholesterol were significantly associated with worse cognitive function, decreased hippocampal volume, and decreased brain glucose metabolism.

    Second, higher serum concentrations of secondary bile acids produced in the gut by bacteria were significantly associated with higher CSF phosphorylated tau and CSF total tau levels, as well as larger brain structural atrophy and decreased brain glucose metabolism.

    Third, higher serum concentrations of ratios of bacterially produced secondary bile acids to primary bile acids were significantly associated with lower CSF Aβ1-42 values, larger brain structural atrophy, and decreased brain glucose metabolism."

    https://www.medscape.com/viewarticle/899956

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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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  • Nutrient-induced Mitochondrial Activation (NiMA): A Novel Lysosome-to-Mitochondria Signaling Pathway Disrupted by Amyloid-β Oligomers papers.ssrn.com
    Nutrition Alzheimer's Metabolism Mitochondria Neuron Insulin Neurons Protein

    The mechanisms of mitochondrial dysfunction in Alzheimer’s Disease (AD) are incompletely understood. We show that activation of lysosomal mechanistic target of rapamycin complex 1 (mTORC1) by insulin or amino acids stimulates mitochondrial activity and regulates mitochondrial DNA synthesis in neurons. Amyloid-β oligomers, which are precursors of amyloid plaques in AD brain and stimulate mTORC1 protein kinase activity at the plasma membrane, but not at lysosomes, block this nutrient-induced mitochondrial activity (NiMA) by a mechanism dependent on tau, which forms neurofibrillary tangles in AD brain. NiMA was also disrupted in fibroblasts derived from a patient with tuberous sclerosis complex, a genetic disorder that causes dysregulation of lysosomal mTORC1. Thus, lysosomal mTORC1 couples nutrient availability to mitochondrial activity, and links mitochondrial dysfunction to AD by a mechanism dependent on soluble building blocks of plaques and tangles. https://ssrn.com/abstract=3188445

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  • Sulforaphane, which is high in broccoli sprouts, clears away brain amyloid plaques and tau tangles and ameliorated memory defects in mice. www.ncbi.nlm.nih.gov
    Alzheimer's Sulforaphane Protein NRF2

    Sulforaphane, which is high in broccoli sprouts, clears away brain amyloid plaques and tau tangles and ameliorated memory defects in mice engineered to get Alzheimer’s disease.

    The sulforaphane also increased heat shock proteins in the brain. Heat shock proteins play a role in disaggregating protein aggregates.

    The precursor to sulforaphane is found in cruciferous vegetables but is highest in broccoli sprouts which can contain up to 100 times more than mature broccoli.

    To learn more about the role sulforaphane plays in human health, check out my comprehensive video and the podcast I did with sulforaphane expert Dr. Jed Fahey.

    Sulforaphane video: https://www.foundmyfitness.com/episodes/sulforaphane

    Dr. Jed Fahey podcast: https://www.foundmyfitness.com/episodes/jed-w-fahey

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  • A small randomized controlled trial shows curcumin improves memory in older people. www.sciencedaily.com
    Alzheimer's Curcumin Protein Dairy

    A small randomized controlled trial shows that a bioavailable form of curcumin improves memory in older people with mild memory complaints.

    The curcumin group had a 28% improvement in their memory/attention abilities and fewer amyloid plaques and tau tangles in the brain via PET analysis while the placebo group showed no improvements.

    The curcumin was a bioavailable form of curcumin called Theracurmin. Those in the curcumin group took 90 mg of curcumin twice daily for 18 months.

    The mechanisms by which curcumin affect memory and plaque accumulation in humans are not known. However, animal studies have shown that curcumin prevents proteins from aggregating and amyloid plaque accumulation. Larger trials with the bioavailable form of curcumin need to be done before conclusions can be made particularly since clinical trials with non-bioavailable curcumin supplements have yielded mixed results.

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  • People that have their deep sleep cycle disrupted for one night experience a 10% increase in amyloid plaque levels. www.sciencedaily.com
    Alzheimer's Sleep Neurons Blue Light Time-Restricted Eating

    People that have their deep sleep cycle (slow-wave cycle) disrupted for one night experience a 10% increase in amyloid plaque levels compared to when their deep sleep cycle is uninterrupted.

    Amyloid beta plaques accumulate outside of neurons in the brain and disrupt synapses (the connections between two neurons that form memories) and is just one way that memory loss occurs in Alzheimer’s disease.

    This study showed that slow-wave sleep, which is the deep sleep that people need to wake up feeling rested, is important for preventing the accumulation of amyloid plaques. While a few nights of disrupted sleep is likely not a problem, it is the chronic disrupted slow-wave sleep (ie. sleep apnea) that may put a person at increased risk for Alzheimer’s disease.

    A few things that I have found improve my sleep are switching all blue lights off before sunset since blue light stops the production of melatonin. I have red lights that turn on before sunset and this has really helped my sleep pattern. Also, a bright light exposure first thing in the morning to start my circadian clock has really helped. Lastly, following a time-restricted eating pattern where I do not eat 4 hours before bed and a cold/quiet room also make a huge difference.

    My podcast with Dr. Satchin Panda discusses the importance of dark/light and food timing in sleep. Dr. Satchin Panda podcast: https://youtu.be/-R-eqJDQ2nU

    My podcast with Dan Pardi also discusses ways to optimize sleep. Dan Pardi podcast: video: https://youtu.be/VhMjrWlWhLU

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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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  • 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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  • Using sauna 4-7x per week lowered dementia risk by 66% & Alzheimer's risk by 65% after adjusting for diet/lifestyle. ageing.oxfordjournals.org
    Fulltext Alzheimer's Aging Heat Stress Dementia Blood Pressure Protein

    This study included over 2,000 middle-aged men that were followed for 20 years. The results were adjusted for many possible confounding factors including baseline age, alcohol consumption, BMI, physical exercise, socioeconomic status, systolic blood pressure, smoking status, type 2 diabetes, previous heart attack, resting heart rate and serum low-density lipoprotein cholesterol.

    One of the reasons I find this study so compelling even though it is associative data and does not establish causality is because the sauna activates heat shock proteins, which have been shown in countless animal studies to play a causal role in preventing Alzheimer’s disease and other neurodegenerative diseases.

    Anyone that follows me knows that I talk about saunas ALOT. I have a couple of videos where I discuss the effects of the sauna on longevity and in muscle mass and endurance. I discuss the role of heat shock proteins in both videos. I also have free reports with references covering all these topics that you can download on my website (foundmyfitness.com). Sauna longevity video: https://www.youtube.com/watch?v=eWKBsh7YTXQ Sauna muscle/endurance video: https://www.youtube.com/watch?v=aHOlM-wlNjM&t=1s

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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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  • Unraveling Alzheimer’s: Making Sense of the Relationship between Diabetes and Alzheimer’s Disease1 www.drperlmutter.com
    Alzheimer's Diabetes Insulin Resistance Insulin

    Abstract. Numerous studies have documented a strong association between diabetes and Alzheimer’s disease (AD). The nature of the relationship, however, has remained a puzzle, in part because of seemingly incongruent findings. For example, some studies have concluded that insulin deficiency is primarily at fault, suggesting that intranasal insulin or inhibiting the insulin-degrading enzyme (IDE) could be beneficial. Other research has concluded that hyperinsulinemia is to blame, which implies that intranasal insulin or the inhibition of IDE would exacerbate the disease. Such antithetical conclusions pose a serious obstacle to making progress on treatments. However, careful integration of multiple strands of research, with attention to the methods used in different studies, makes it possible to disentangle the research on AD. This integration suggests that there is an important relationship between insulin, IDE, and AD that yields multiple pathways to AD depending on the where deficiency or excess in the cycle occurs. I review evidence for each of these pathways here. The results suggest that avoiding excess insulin, and supporting robust IDE levels, could be important ways of preventing and lessening the impact of AD. I also describe what further tests need to be conducted to verify the arguments made in the paper, and their implications for treating AD

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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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  • Study finds women rated the most "neurotic" found to be pre-disposed to a 2-fold increased risk of Alzheimer's disease. www.cbsnews.com
    Alzheimer's Neurons

    A few things to know about this particular study:

    • It was done in women… this doesn’t necessarily mean the effect doesn’t exist in some form in men (they just don’t know).
    • Personality assessment was done using something called the Eysenck Personality Inventory, which is a commonly administered test to rate a person’s disposition, emotional stability and relative tendency toward introversion, associated with shyness or reserve, or extraversion, used to describe more outgoing people.
    • Stress was defined as anything stirring feelings of anxiety, irritability, tension, fear, nervousness or sleep disturbances.
    • Being extroverted or introverted on its own did not appear to heighten the risk of dementia, although the study found that women who were easily distressed and also tended to be introverted were at the highest risk for Alzheimer’s.
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