Memory
Episodes
In this clip, Dr. Rhonda Patrick explains how exercise boosts memory, cognition, and neurogenesis through serotonin and post-learning activity.
Dr. Rhonda Patrick explores taurine's longevity role, cocoa flavanols, training adaptations, and oral hyaluronic acid in a Q&A.
Dr. Axel Montagne discusses blood-brain barrier dysfunction in dementia and early-stage age-related cognitive decline.
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In this clip, Dr. Rhonda Patrick explains how exercise boosts memory, cognition, and neurogenesis through serotonin and post-learning activity.
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Rhonda Brain Diet Aging Hormones Omega-3 Fasting Memory Testosterone Dementia Development Skin CocoaDr. Rhonda Patrick explores taurine's longevity role, cocoa flavanols, training adaptations, and oral hyaluronic acid in a Q&A.
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Dr. Axel Montagne discusses blood-brain barrier dysfunction in dementia and early-stage age-related cognitive decline.
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In this clip, Tim Ferriss and Dr. Rhonda Patrick discuss vasopressin and its effects on pair bonding in both animals and humans.
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Resveratrol's science, effects in animals and humans, mechanisms, supplementation, and safety.
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Dr. Dale Bredesen describes the role that zinc status plays in the development of the toxic form of Alzheimer's disease.
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Learning events are "replayed" at rapid speed during deep sleep to reinforce learning | Matt Walker ClipDr. Matthew Walker describes how studies in rats and humans demonstrate that the brain "replays" events and experiences to facilitate learning.
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Dr. Matthew Walker describes how sound and smell cues played during learning and subsequent sleep can enhance memory formation and retrieval.
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Dr. Matthew Walker talks about the importance of identifying early-life windows of vulnerability to prevent or delay age-related cognitive decline.
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Dr. Matthew Walker describes how REM sleep facilitates creativity, new ideas, and wisdom.
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Dr. Matthew Walker describes the role that sleep plays in learning and new memory formation.
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Dr. Matthew Walker posits his theory that dreams are not forgotten; rather, they are merely inaccessible and may influence our wakeful state.
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Dr. Rhonda Patrick and Dr. Elissa Epel discuss how obesity affects genes in sperm DNA involved in metabolic health and cognitive function.
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Rhonda Nutrition Exercise Alzheimer's Aging Fasting Memory Genetics Mortality Sauna Time-Restricted Eating Cardiovascular Supplements Ketogenic DietDr. Rhonda Patrick answers audience questions on various health, nutrition, and science topics in this Q&A session.
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Dan Pardi: Ph.D. candidate studying sleep neurobiology at Stanford and University of Leiden, co-founder of Dan’s Plan online wellness company.
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Science on refined sugar: mortality, aging, brain function, memory, neuroinflammation, cancer, sex hormones, addiction & more.
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Heat Stress Exercise Brain Aging Performance Heart Disease Depression Memory Anxiety Cold Stress MortalityThis episode is a presentation Dr. Rhonda Patrick delivered at the Biohacker Summit in Helsinki, Finland in 2016.
Topic Pages
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Brain-derived neurotrophic factor (BDNF)
BDNF facilitates memory consolidation by enhancing hippocampal long-term potentiation through TrkB-mediated synaptic plasticity signaling.
News & Publications
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Ketogenic diet raises brain blood flow by 22% and increases brain-derived neurotrophic factor by 47%, highlighting its potential to support cognitive function even in people without cognitive impairment. pubmed.ncbi.nlm.nih.gov
Glucose has long been considered the brain’s primary fuel, but ketone bodies may offer critical support, especially during periods of low carbohydrate availability. A recent study found that a ketogenic diet boosted levels of brain-derived neurotrophic factor (BDNF)—a key protein that supports brain health—by 47%, highlighting the diet’s potential to support brain health even in people without cognitive impairment.
Researchers recruited 11 healthy but overweight adults to participate in a randomized, crossover study. Each participant followed two different diets: a ketogenic diet high in fat and low in carbohydrates, and a standard balanced diet. Each diet lasted three weeks and ended with brain imaging scans (using MRI and PET) and blood tests to measure brain blood flow and BDNF levels.
They found that the ketogenic diet markedly increased ketone levels in the blood compared to the standard diet. Brain blood flow rose by 22% after eating the ketogenic diet, and BDNF levels increased by 47%. Researchers also found a strong link between ketone levels in the blood and higher brain blood flow.
This was a small study, but the findings suggest that a ketogenic diet enhances brain blood flow and boosts vital brain-supporting proteins, even in people without memory loss. This opens up new possibilities for using ketogenic nutrition as a strategy to preserve cognitive function and support long-term brain health. Learn how to plan the optimal ketogenic diet in this clip featuring Dr. Dominic D'Agostino.
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Strawberry consumption boosts thinking speed and lowers systolic blood pressure by 3% in older adults. www.sciencedirect.com
Cognitive decline and cardiovascular disease often go hand in hand—and both become more common with age. Nutrition plays a key role in protecting brain and heart health, and certain fruits rich in antioxidants may offer targeted benefits. A recent study found that consuming fresh strawberries daily improved cognitive function and lowered systolic blood pressure by an average of 3% in older adults.
Researchers provided 35 healthy adults, ages 60 to 78, a strawberry powder or a placebo each day for eight weeks. Each person tried both options in random order, with a four-week break in between. The strawberry powder, made from freeze-dried fruit, delivered the same nutrients and antioxidants as two cups of fresh strawberries. The researchers measured the participants' cognitive function using standard tests and tracked markers of heart health, including blood pressure, waist size, blood lipids, and antioxidant levels.
The participants' thinking speed improved during the strawberry phase, while episodic memory improved modestly during the placebo phase. After eight weeks of strawberry consumption, systolic blood pressure dropped by an average of 3%, and waist size decreased slightly. Participants' blood antioxidant capacity increased with strawberries but decreased with the placebo. Triglycerides increased during the placebo period but remained stable with strawberries.
The findings from this small study suggest that regular strawberry intake supports brain and heart health in older adults. Strawberries are rich in polyphenols. Learn more about polyphenols in our overview article.
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Uphill walking, even at a slow pace, provides cognitive benefits by increasing brain lactate and stimulating BDNF production—a protein critical for memory and learning. www.sciencedirect.com
If you’re struggling to remember things, a robust workout might help. Scientists have discovered that exercise can increase levels of brain-derived neurotrophic factor (BDNF), a protein that supports learning and memory. A recent study in rats found that low-speed uphill exercise raises blood lactate levels, increasing lactate and BDNF in key brain regions involved in cognition.
Researchers divided rats into three groups: One remained inactive, another walked on a flat treadmill, and a third walked uphill at a 40% incline. The exercise sessions lasted either 30 or 90 minutes. To see if lactate from the blood contributed to brain changes, some rats also received a direct lactate injection.
Uphill exercise increased lactate levels in the animals' blood and brains, while flat treadmill walking did not. After 90 minutes, uphill exercise also raised BDNF levels in brain regions linked to memory and learning. The lactate injection showed that blood lactate passed into the brain, reinforcing that exercise-induced increases in blood lactate can influence brain chemistry.
These findings suggest that walking uphill—even slowly—provides cognitive benefits by raising brain lactate and stimulating BDNF production. This type of exercise could be a practical and safe way to support brain health, especially for older adults or those looking to enhance memory and learning. To learn more strategies to boost brain health, check out the Cognitive Enhancement Blueprint, a member-only perk.
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Cardiorespiratory fitness measures the body’s aerobic capacity—the ability to deliver oxygen to skeletal muscles—during sustained physical activity. A recent study found that better cardiorespiratory fitness boosts cognitive performance, even among people at greater risk for cognitive decline, such as older adults and APOE4 carriers.
Researchers collected information from more than 600 older adults regarding their age, sex, education, use of beta-blockers (drugs that lower heart rate), and APOE4 gene status (a genetic risk factor for Alzheimer’s). The participants underwent cardiorespiratory fitness testing on a treadmill. They also completed a comprehensive battery of neuropsychological tests to assess their cognitive function across multiple domains, including processing speed, executive function, working memory, episodic memory, and attention control.
Participants with higher cardiorespiratory fitness performed better on all cognitive assessment domains than those with poorer fitness—even among those at greater risk for cognitive decline, such as older adults and APOE4 carriers. Additionally, women, participants with fewer years of education, and those taking beta-blockers demonstrated greater cognitive performance in processing speed and executive function.
These findings suggest that better cardiorespiratory fitness in later life protects against cognitive decline.Although robust exercise is the best way to boost cardiorespiratory fitness, sauna use does, too. Learn more in our members-only report, Sauna Use: Implications for Aging and the Brain.
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Flaxseed oil is rich in alpha-linolenic acid (ALA), an omega-3 fatty acid. In the liver, ALA converts to docosahexaenoic acid (DHA), a crucial component of brain health. Evidence suggests that low DHA levels can impair cognitive function. However, a recent study in older adults found that supplemental flaxseed oil enhances cognitive function, particularly verbal fluency—the ability to retrieve and use words quickly.
The study involved 60 cognitively healthy older adults between the ages of 65 and 80. Half of the participants received 3.7 grams of flaxseed oil containing 2.2 grams of ALA daily for 12 weeks, and the other half received corn oil. Before and after the intervention, researchers assessed aspects of their cognitive function, including verbal fluency.
Verbal fluency relies on several cognitive skills, including recalling word meanings, finding the right words quickly, processing information efficiently, controlling impulses, holding and using information in the moment, switching between tasks or ideas, and adapting to new situations. It also involves multiple areas of the brain working together. Unfortunately, verbal fluency declines with age, impairing conversation and social interactions and serving as a predictor of Alzheimer’s disease.
The researchers found that participants who received the ALA-rich flaxseed oil supplement had higher verbal fluency than their peers who received the corn oil, suggesting that flaxseed oil is suitable for delivering crucial omega-3s to the brain. Learn more about the effects of omega-3s on brain health in this clip featuring Dr. Axel Montagne.
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Athletes exhibit 63% better working memory performance than sedentary people, underscoring the cognitive benefit of regular physical activity. www.tandfonline.com
Working memory, the brain’s system for temporarily storing and managing information, is crucial for recalling strategies and adapting to rapidly changing situations. A recent meta-analysis found that athletes outperform non-athletes by as much as 63% on working memory tasks.
Researchers analyzed 21 studies involving more than 1,400 participants across various sports, including basketball, football, and fencing. They assessed working memory through tasks like recalling sequences or matching stimuli after delays. The various studies compared athletes to non-athletes, including sedentary people, and examined factors like sports type and activity level.
The analysis revealed that athletes had a slight but consistent advantage in working memory compared to non-athletes, with a 30% improvement overall. When athletes were compared to sedentary people, their working memory performance was 63% better. However, the advantage dropped to just 15% when sedentary participants were excluded, suggesting a notable disadvantage for people with inactive lifestyles.
These findings suggest that sports expertise may enhance working memory, likely due to the cognitive demands of high-level performance. Moreover, sedentary lifestyles hinder working memory, underscoring the importance of regular physical activity for maintaining cognitive health. Physical activity also promotes longevity. Learn more about the longevity and brain-boosting effects of exercise in this episode featuring Dr. Rhonda Patrick.
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Eggs are a dietary paradox: high in cholesterol but rich in brain-boosting nutrients, including choline, lutein, and zeaxanthin. While some studies indicate that eggs maintain cognitive health, others report the converse. A recent study found that eating eggs may help women preserve semantic memory—crucial for language comprehension and factual recall—as they age.
Researchers analyzed data from 890 adults aged 55 and older. Participants reported their egg consumption using a food frequency questionnaire, and researchers measured their memory and thinking skills at two clinic visits about four years apart.
They found that women who ate five eggs weekly experienced less decline in verbal fluency, a measure of semantic memory, than those who ate fewer eggs. In men, researchers found no clear relationship between egg intake and changes in cognitive performance. Eating eggs did not appear to harm cognitive function in either sex.
These findings suggest that eggs play a small but beneficial role in preserving memory in women. They also align with other research demonstrating that people with moderate choline intake—roughly the amount in two eggs—are about half as likely to have low cognitive function than those with the lowest intake.
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A nasal spray delivering stem cell-derived extracellular vesicles reduces inflammation and improves brain function in a mouse model of Alzheimer's disease. isevjournals.onlinelibrary.wiley.com
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 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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Cannabis use is prevalent among teens, whose brains are undergoing massive developmental changes. Evidence suggests that THC (tetrahydrocannabinol), the primary psychoactive ingredient in cannabis, has profound effects on the brain, impairing neurodevelopment. A recent study in mice found that adolescent cannabis use influences gene expression and neural connections, potentially altering the brain’s structure.
Researchers exposed adolescent male mice to THC and then analyzed changes in gene expression and brain cell structure within the cerebral cortex—a brain region responsible for memory, thinking, learning, reasoning, problem-solving, emotions, consciousness, and sensory functions. They also scanned the brains of more than 450 adolescent human males to compare the cerebral cortex thickness of those who tried cannabis before age 16 to those who did not.
They found that adolescent mice exposed to THC exhibited less dendritic branching and fewer neural spines, indicating a loss of complexity in brain cells. Similarly, human teens who used cannabis had thinner cortex regions. Further analysis linked these structural changes to genes involved in brain development, including processes like learning and memory.
These findings suggest that early cannabis exposure interferes with the normal development of brain structure, especially in areas critical for learning and emotional regulation. This interference likely occurs through effects on specific genes and brain cells responsible for building neural connections during adolescence.
Teens aren’t the only ones at risk for the harmful developmental effects of THC exposure—the compound can pass into breast milk, influencing an infant’s neurodevelopment. Learn more in this clip featuring Dr. Rhonda Patrick.
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'Endurance training' for the brain improves cognitive function in older adults, offsetting the effects of fatigue. www.sciencedirect.com
Mental fatigue can severely impair cognitive and physical performance, especially in older adults, increasing their risk of falls, accidents, and other health concerns. A recent study found that combining cognitive and physical exercise training may help improve mental and physical function in older adults, particularly when tired.
Researchers randomly assigned 24 women aged 65 to 78 to one of three groups: brain+exercise training, exercise-only training, or no training (control). The brain+exercise and exercise-only groups completed three weekly sessions for eight weeks consisting of 20 minutes of resistance training (squats and bicep curls) and 25 minutes of endurance exercise (walking outside). The brain training consisted of various assessments that measure reaction time and cognitive inhibition—the brain’s ability to block distractions or irrelevant information—completed four times throughout the study.
The researchers found that the brain+exercise and exercise-only groups performed better than the control group on cognitive and physical tasks regardless of how tired they were. However, the brain+exercise group showed greater improvements, particularly when tired. On average, cognitive performance increased by 7.8% in the brain+exercise group compared to 4.5% in the exercise-only group. Similarly, physical performance improved by nearly 30% in the brain+exercise group compared to 22.4% in the exercise-only group.
The findings from this small study suggest that combining cognitive and physical training boosts mental and physical abilities in older adults, particularly when tired. This approach may help mitigate age-related declines and reduce the risk of falls and other health complications. Learn about the brain-protective effects of physical exercise in this episode featuring Dr. Rhonda Patrick.
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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
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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The brain’s hippocampus is vital for memory and learning but tends to shrink with age, contributing to cognitive decline. A recent study found that high-intensity interval training (HIIT) improves hippocampal-dependent cognitive abilities in older adults better than other forms of exercise.
Researchers randomly assigned 151 healthy adults aged 65 to 85 to one of three exercise regimens: low-intensity training, medium-intensity training, or HIIT. Over six months, participants attended 72 supervised sessions, underwent monthly cognitive testing, and provided blood samples. The researchers assessed the participants' brain volumes using magnetic resonance imaging (MRI) brain scans at various time points, with follow-ups continuing for five years.
They found that the HIIT group experienced marked improvements in hippocampal function. HIIT also reduced age-related brain volume loss, particularly in the hippocampus, and strengthened the connections between critical brain networks. The HIIT group’s cognitive improvements were associated with higher levels of brain-derived neurotrophic factor—a growth factor that supports brain function—and cortisol.
These findings suggest that HIIT protects against age-related cognitive decline and highlights its potential to preserve brain health in older adults. Learn more about the brain benefits of HIIT in this episode featuring Dr. Rhonda Patrick.
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Pregnancy transforms nearly every aspect of a woman’s body, but research indicates it also affects the brain. A recent study found that massive brain alterations occur during pregnancy, making it a critical neural adaptation period.
Researchers conducted an in-depth brain imaging analysis of a healthy 38-year-old woman who became pregnant for the first time. She underwent 26 brain scans, starting three weeks before conception and continuing for two years postpartum. They measured the woman’s hormone levels throughout the pregnancy and postpartum period.
They found widespread reductions in gray matter volume and cortical thickness, which became more pronounced as the pregnancy progressed. These changes were particularly evident in brain areas related to memory and emotional processing, including the hippocampus and parts of the cortex. In contrast, white matter integrity improved, suggesting enhanced communication between different brain regions as gestational weeks advanced.
These findings suggest that pregnancy is a dynamic period of brain remodeling, driven by rising hormone levels and possibly preparing the brain for motherhood. Learn how to optimize your health before, during, and after pregnancy in this Aliquot featuring Dr. Rhonda Patrick.
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A grandparent's fitness is linked to better memory in their grandchildren, an animal study suggests. www.jneurosci.org
Exercise can profoundly affect your brain, boosting memory and enhancing cognitive performance. But imagine if your daily exercise routine could boost your grandchildren’s brainpower. A recent study in mice found that cognitive benefits from physical activity can be passed down to future generations, even if they don’t exercise.
Researchers compared the cognitive performance of male mice whose grandfathers exercised regularly with those whose grandfathers were sedentary. They also analyzed genetic markers related to brain function in both groups.
Mice with active grandfathers had better memory recall, particularly in tasks requiring spatial (recalling locations) and non-spatial (recalling facts and events) memory. Although their cognitive abilities improved, these mice didn’t experience the new brain cell growth observed in the exercising grandfathers. Additionally, the researchers identified 35 microRNA molecules related to brain function, with two associated with poorer cognitive performance.
microRNAs are small molecules that regulate gene activity by determining which proteins are produced in cells. They play a key role in many biological functions, including development, disease progression, and how cells respond to changes in their environment.
These findings suggest that the cognitive benefits of exercise can be passed down to future generations. Check out the Cognitive Enhancement Blueprint—a members' only perk—to learn more about the effects of exercise on brain health and function.
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Ketones may protect against cognitive decline by mitigating insulin resistance-induced neuronal damage. www.futurity.org
Insulin regulates many processes involved in memory and cognitive function. However, age-related insulin resistance in the brain disrupts neuronal synaptic activity and contributes to cognitive decline. A recent study found that ketones may protect the brain from age-related insulin resistance in the brain.
Researchers induced acute insulin resistance in mouse hippocampal tissue and determined its effects on neuronal function. Then, they administered beta-hydroxybutyrate, a type of ketone, to the tissues and evaluated the outcomes.
They found that insulin resistance adversely affected aspects of neuronal communication, including synaptic activity, axonal conduction, network synchronization, synaptic plasticity, and action potential properties. However, ketones restored these functions.
These findings suggest that ketones rescue the brain from the deleterious effects of acute insulin resistance. The high blood glucose levels associated with insulin resistance induce glucotoxicity, which causes structural damage and functional impairments of neuronal cells. Learn more about the effects of insulin resistance in the brain in this clip featuring Dr. Dale Bredesen.
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More than half of teens have high blood pressure, impairing memory and cognitive performance. physoc.onlinelibrary.wiley.com
Hypertension – high blood pressure – affects more than 1.3 million adults worldwide. However, hypertension is becoming increasingly common in teens, too, raising concerns about the condition’s effects. A recent study found that teens with high blood pressure and arterial stiffness exhibit poor cognitive function.
The study involved 116 male and female teens (average age, 16 years). Researchers measured their physical activity and sedentary time with a combined accelerometer and heart rate monitor. They assessed their cognitive function through psychomotor function, attention, working memory, and learning tests. They measured the participants' blood pressure and evaluated aspects of their arterial health, including pulse wave velocity—a measure of arterial stiffness.
They found that more than half (50.4%) of the teens were pre-hypertensive or had stage 1 or 2 hypertension. Teens with higher systolic blood pressure exhibited poorer overall cognition and slower reaction times than those who were normotensive. Those with increased pulse wave velocity exhibited diminished accuracy in working memory tasks.
These findings suggest that high blood pressure and arterial stiffness contribute to poor cognitive function in teens. Preventing high blood pressure during this critical developmental period could support better cognitive outcomes, highlighting the importance of cardiovascular health in youth.
The average teen spends several hours each day in screen time, contributing to increased sedentary behavior and higher blood pressure. Learn more about the harmful effects of excessive screen time in teens and children in this short video featuring Dr. Rhonda Patrick.
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Chronic inflammation in early adulthood can impair cognitive performance by midlife, with 39% of young adults showing high inflammation levels. pubmed.ncbi.nlm.nih.gov
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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Urolithin A, a compound derived from pomegranates and walnuts, boosts mitophagy and enhances cognitive function in aged mice. neurosciencenews.com
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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Exercise preserves cognitive function in mice by inhibiting neuroinflammation. www.sciencedirect.com
Cognitive function typically declines with aging, but evidence suggests physical activity can help mitigate some of these declines. A recent study in mice found that exercise improves memory and spatial learning by inhibiting neuroinflammation, primarily via the actions of irisin, a myokine, and brain-derived neurotrophic factor (BDNF), a growth factor and signaling protein.
Researchers conducted a two-part study to investigate the effects of regular, low-intensity exercise on cognitive function in mouse models of inflammation-driven memory impairment and microglia (brain immune cell) degeneration.
First, they assessed the animals' neuroprotective and antioxidant marker levels and subjected them to various memory and behavioral tests. They found that exercise reduced memory problems and cognitive losses by increasing the expression of irisin. In turn, irisin activated BDNF and nuclear factor erythroid 2-related factor 2 (Nrf2), reducing inflammation and blocking the activity of BACE-1, an enzyme critical for amyloid-beta production.
Then, they studied the effects of irisin on microglia. They found irisin blocked the NF-κB/MAPK/IRF3 pro-inflammatory signaling pathway. It also lowered pro-inflammatory markers while increasing the expression of Nrf2.
Nrf2 is a cellular protein that activates the transcription of more than 200 cytoprotective proteins that protect against oxidative stress due to injury, inflammation, and normal aging processes. It is an element of the Keap1-Nrf2-ARE biological pathway, a mediator of protective responses to oxidative and electrophilic stressors. Hormetic stressors like exercise, heat exposure, and dietary components trigger Nrf2 activity. Sulforaphane, a compound derived from broccoli, is the most potent naturally occurring hormetic inducer of Nrf2 activity. Learn more about Nrf2 in this clip featuring Dr. Jed Fahey.
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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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A single session of high-intensity resistance training boosts memory and brain connectivity – particularly in the hippocampus – an indicator of enhanced cognitive health. onlinelibrary.wiley.com
High-intensity resistance training, also known as functional training, requires the body to exert considerable effort against weights or resistance. Evidence suggests this type of training confers myriad physical and mental health benefits, including improved metabolic function and mood, particularly in older adults. A recent study found that engaging in a single session of high-intensity resistance training enhanced memory capabilities.
The study involved 60 young, healthy adults who took memory tests and underwent resting-state functional magnetic resonance imaging of their brains. Then, half of the participants engaged in a single high-intensity resistance training session, while the other half did not. The training involved three resistant exercise sets at 75 to 80 percent of the participants' one-rep max, with one minute of rest between sets and a total duration of under seven minutes. Two days later, both groups repeated the memory tests and brain imaging scans.
Those who participated in the resistance exercise session exhibited marked improvements in memory recall compared to the non-exercising group. These memory improvements correlated with greater connectivity in the left posterior region of the hippocampus, an area involved in memory.
The findings from this small study suggest that just one session of high-intensity resistance training has considerable influence on memory, highlighting its potential to promote cognitive health and neural plasticity. Learn more about high-intensity resistance training in this clip featuring Dr. Martin Gibala.
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Yoga improves memory and boosts cognition in older women at risk for Alzheimer's, demonstrating increased hippocampal connectivity and expression of anti-aging markers. www.sciencedaily.com
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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Aging undermines the brain's capacity for maintaining working memory, with subtle declines in neuron activity and connectivity in the prefrontal cortex. www.sciencedaily.com
As the brain ages, cognitive functions decline, with working memory – a form of short-term memory necessary for reasoning, decision-making, and behavior – among the earliest affected. The brain’s prefrontal cortex is crucial in working memory, showing sustained activity during memory-guided behavior. A recent study in mice found that aging reduces the prefrontal cortex’s ability to maintain working memory, with older mice showing less effective communication between memory-coding neurons.
Using imaging techniques to see how neurons behave during memory tasks involving touch and sound, researchers tracked brain activity in mice of varying ages. They also used light-based interventions to temporarily disrupt brain activity, observing how this affected the animals' ability to perform the tasks.
They discovered that with aging, the prefrontal cortex had fewer neurons responsible for managing actions, and the signals from these neurons weakened. Furthermore, whereas young mice used both broad and specific memory strategies, older mice mainly relied on specific strategies, indicating a subtle decline in the brain’s memory circuits over time.
The researchers also observed a drop in the resting brain connections among neurons managing actions, beginning around middle age. This drop in connections became even more pronounced when the mice were doing tasks, suggesting that the brain’s ability to retain thoughts might weaken with age. Additionally, the brains of middle-aged mice were more easily disrupted by light-based interventions, hinting at a greater risk to their thought-retention processes as they age.
The findings in this mouse study suggest that aging leads to a marked decrease in brain connectivity and neuron activity in the prefrontal cortex, affecting memory retention and making it more susceptible to disruptions. The blood-brain barrier is a critical player in brain connectivity, and its impairment during aging contributes to cognitive dysfunction. Learn more in this episode featuring Dr. Axel Montagne.
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Pericytes are pivotal in the formation and storage of long-term memories. www.sciencedaily.com
Tiny contractile cells surrounding the brain’s capillaries called pericytes regulate vascular blood flow and maintain blood-brain barrier integrity. Pericytes detach from the blood vessels in aging, driving the pathophysiology of neurological dysfunction, vascular dementia, and stroke. A recent study in rodents shows that pericytes also play roles in long-term memory formation.
Researchers measured the amount of insulin-like growth factor 2 (IGF2) produced by various cells in the hippocampus of rodents. IGF2, a peptide hormone produced in multiple tissues, regulates growth during fetal development and participates in the cell cycle throughout the lifespan. After determining that pericytes contributed the greatest amount of hippocampal IGF2, they assessed learning’s influence on IGF2.
They found that learning increased pericyte IGF2 production in the hippocampus, especially in the dentate gyrus, a highly vascularized area responsible for episodic memory – long-term memory that involves conscious recollection of previous experiences and their associated contexts, such as sounds and smells. Animals lacking the ability to produce IGF2 in their pericytes exhibited poor learning and memory.
The detachment and loss of pericytes play a crucial role in the progression of cerebral small vessel disease and neurodegenerative disorders that involve blood-brain barrier dysfunction. These specialized endothelial cells envelop a significant portion, up to 80 percent, of the brain capillary surface area in the cortex and hippocampus of the human brain. They also enwrap the tiniest vessels constituting the blood-brain barrier.
Exercise mitigates the proinflammatory state that drives pericyte loss in aging, possibly providing a mechanism for exercise’s memory-enhancing effects. Learn more about links between exercise, pericytes, and brain health in this episode featuring Dr. Axel Montagne.
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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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Platelet-derived 'exerkines' produced during exercise promote neurogenesis, boosting brain health and cognition. www.sciencedaily.com
The benefits of physical activity on the brain’s aging process are widely known. Evidence suggests that exerkines, a class of molecules released into the bloodstream in response to exercise, drive many of these benefits. Findings from a recent study in mice found that PF4, an exerkine derived from platelets, promotes the production of hippocampal precursor cells in the brains of older mice.
Researchers injected PF4 into mice and assessed its effects on hippocampal neurogenesis (the growth of new brain cells). Then they investigated the effects of exercise on blood platelets.
They found that systemic elevation of PF4 levels mitigated age-related declines in brain regeneration and cognitive function, an effect that was dependent upon hippocampal neurogenesis. They also found that exercise triggered platelet activation, which in turn increased the production of hippocampal precursor cells in the brains of older mice.
These findings underscore the crucial role of platelets in mediating the rejuvenating effects of exercise on the aging brain. It also sheds light on the potential mechanisms that link physical activity with improved brain health in aging, with possible implications for people who are unable to exercise due to advanced age, mobility issues, or various health conditions.
Interestingly, heat stress also promotes PF4. In a study involving endurance cyclists exercising in hot conditions, PF4 increased by as much as 150 percent. Sauna use has similar effects on PF4. Learn about other effects of heat stress from sauna use in our overview article.
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Impairment of associative learning caused by obesity and insulin insensitivity offset by anti-obesity drug liraglutide in recent study www.sciencedaily.com
Associative learning is a psychological process that occurs when two initially unrelated elements, such as objects, sights, sounds, ideas, or behaviors, become linked in the brain. Classic examples include associating pain with touching a hot stove or connecting foodborne illness with eating a particular food. People with obesity and poor insulin sensitivity have impaired associative learning. However, a recent study shows that liraglutide, a drug used to treat type 2 diabetes and obesity, restores associative learning capability in people with obesity.
The study involved 54 adults, half with normal body weight (high insulin sensitivity) and half with obesity (reduced insulin sensitivity). Researchers gave participants either liraglutide or a placebo in the evening and tested their learning abilities the next morning.
They found that people with obesity and reduced insulin sensitivity encountered difficulties when attempting to establish connections between sensory signals, and their brain activity related to learning was weaker than in normal-weight individuals. However, just one dose of liraglutide reversed these issues in people with obesity and reduced insulin sensitivity, exhibiting brain activity comparable to that of normal-weight participants, indicating that the drug improved their learning abilities.
Liraglutide is a glucagon-like peptide 1 receptor agonist (GLP-1RA), a type of drug used to treat type 2 diabetes, overweight, and obesity. GLP-1RA medications work in the pancreas to lower blood glucose levels by promoting the production and release of insulin. They also support beta cells synthesis, growth, and survival while reducing their apoptosis rate.
These findings suggest that liraglutide, an anti-obesity drug, affects brain activity in people with obesity and reduced insulin sensitivity. This study was small, however, so validating the results requires more research.
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Melatonin improves memory formation in mice, study finds. neurosciencenews.com
Melatonin, often called the “sleepiness hormone,” regulates the sleep-wake cycle in mammals, modulates the expression of more than 500 genes, and exerts potent antioxidative and anti-inflammatory properties. A new study in mice suggests that melatonin also influences memory formation. Mice performed better on memory tests after receiving melatonin.
Researchers gave male mice melatonin, ramelteon (a drug that activates melatonin receptors), and AMK (a melatonin metabolite) to assess their effects on memory formation while completing a task involving recognizing new objects. Then, they examined the compounds' effects on the phosphorylation (the addition of phosphate groups to proteins) of five key proteins associated with memory formation. To avoid potential variations in melatonin due to female reproductive cycles, the researchers did not investigate the compounds' effects on female mice.
They found that when the mice received the three compounds immediately after learning, they formed long-lasting memories. However, the compounds exerted variable effects on the memory-related proteins depending on their location in the brain.
These findings suggest that melatonin improves memory by influencing the phosphorylation of memory-related proteins, whether through receptors or other pathways in the brain. They also bring attention to the many ways in which melatonin, memory, and sleep are intricately linked. For example, sleep deprivation markedly impairs memory formation. Learn more in this clip featuring sleep expert Dr. Matthew Walker.
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Enhancing brain health in older adults: Olfactory stimulation via aromatherapy shows promise in cognitive function preservation. neurosciencenews.com
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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Daily multivitamin supplementation boosts memory in older adults, particularly those with cardiovascular disease. neurosciencenews.com
Short-term memory – such as remembering a list of items or numbers shortly after hearing them – is particularly vulnerable as we age. But a new study shows that multivitamin/multimineral supplementation bolsters short-term memory in older adults, especially those with cardiovascular disease.
The study involved more than 3,500 older adults (average age, 71 years) enrolled in the COSMOS trial. About half of the participants took a daily multivitamin/multimineral supplement for three years, and the other half took a placebo. All participants completed a battery of cognitive tests at the one-, two-, and three-year points.
The tests revealed that those who took the supplement performed better on short-term memory tests than those who took the placebo, an effect that endured over the entire three-year study. Participants with cardiovascular disease scored lower on memory tests initially, but after taking the multivitamin/multimineral supplements for a year, their memory scores improved, reaching a level comparable to those without cardiovascular disease.
These findings suggest that multivitamin/multimineral supplementation benefits short-term memory in older adults. The study’s authors proposed that the cognitive effects of multivitamin/multimineral intervention may occur by activating vitamin and mineral receptors in the hippocampus, given its prominent role in recall memory. Learn how vitamins and minerals influence other aspects of aging in this episode featuring Dr. Bruce Ames.
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Omega-3 supplementation in mice reverses aging effects on brain's lipid rafts, enhancing cognitive function. onlinelibrary.wiley.com
Lipid rafts – cholesterol-filled “bubbles” found in neuronal cell membranes – play a crucial role in synaptic plasticity and memory formation. However, lipid rafts undergo extensive changes during aging, ultimately contributing to cognitive decline. A new study in mice shows that omega-3 fatty acids preserve lipid raft integrity and bolster cognitive function.
Researchers fed young and old female mice a regular diet or a diet supplemented with omega-3 fatty acids. Then they examined the animals' brains to determine the omega-3s' effects on the structure and properties of the lipid rafts.
They found that older mice fed a regular diet exhibited changes consistent with lipid raft aging, including reduced omega-3 fatty acid concentrations, increased membrane lipid saturation, and altered lipid composition. However, omega-3 supplementation reversed these changes to the point where they resembled the lipid rafts typically seen in younger mice. In addition, omega-3 supplementation influenced the distribution and accumulation of glutamate receptors and ion channels involved in synaptic plasticity, potentially influencing memory formation.
These findings suggest that omega-3 fatty acids counteract age-related changes in the brain, specifically in lipid rafts, and preserve cognitive function and memory in aging. Learn more about omega-3s' roles in preserving cognitive function in this clip featuring Dr. Axel Montagne.
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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
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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Improved memory and emotional recognition linked to nasal breathing. www.jneurosci.org
Breathing is an essential and regular process that provides the body with oxygen and removes carbon dioxide. But new research indicates that breathing influences brain function. People who breathed through their noses performed better on memory and emotional expression interpretation tests than when they breathed through their mouths.
Researchers investigated the relationship between breathing, the brain, and thinking. First, they conducted intracranial electroencephalograms (EEGs) to assess the effects of nasal versus oral breathing in eight people. Then they administered various tests to 107 healthy young people to determine the effects of nasal versus oral breathing on memory and the ability to interpret emotional expressions.
The intracranial EEGs revealed that when the participants breathed through their noses, their brainwaves in areas related to smell and emotions synchronized with their breathing patterns. However, breathing through their mouths diminished these effects. Similarly, when participants breathed through their noses, they performed better on memory tests. Interestingly, breathwork also influenced their ability to interpret emotional expressions. For example, their ability to interpret fear was faster during inhalation versus exhalation.
These findings suggest that breathing, especially nasal breathing, has more complex effects on the body than previously understood. They also highlight a novel means to improve cognitive function. Learn about other effects of breathing techniques in this clip featuring Wim Hof.
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Consuming 500 milligrams of cocoa flavanols daily improves hippocampal memory function in older adults, study finds. www.pnas.org
Dietary components play critical roles in cognitive function as we age. A new study shows that flavanols – bioactive compounds found in tea, apples, berries, grapes, cocoa, and other fruits and vegetables – improve memory. People who took a flavanol-rich cocoa supplement performed better on memory tests than those who didn’t.
Researchers conducted a three-year study involving more than 3,500 older adults. Half of the participants received a cocoa extract containing 500 milligrams of flavanols daily, while the other half received a placebo. The researchers gave the participants memory tests before and after the intervention, and they assessed the participants' overall diet quality using the Healthy Eating Index.
They found that people with higher flavanol intake and better overall diet quality at the beginning of the study had better memory performance, particularly in tasks involving the hippocampus – the area of the brain responsible for memory consolidation. However, after one year of intervention, the researchers found that memory improved among those with lower diet quality or low flavanol intake.
These findings suggest that low dietary flavanol intake contributes to age-related cognitive decline, specifically hippocampal-dependent memory, but flavanol supplementation counteracts these effects. They also underscore the importance of including flavanol-rich foods in the diet throughout the lifespan for optimal cognitive performance.
Evidence suggests flavanols promote angiogenesis (the formation of new blood vessels), which is crucial for adequate blood flow to the brain. Learn how blood flow to the brain influences cognitive function in this episode featuring Dr. Axel Montagne.
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A new study finds that exercise maintains critical connections in the brains of older adults while boosting fitness. Older adults who walked regularly performed better on tests of cognitive function and memory and had better cardiorespiratory fitness.
The study involved 33 older adults (average age, 78 years). Participants walked on a treadmill for 30 minutes a day, four times a week, for 12 weeks and underwent tests before and after the intervention to assess their physical and cognitive performance. In addition, researchers performed functional MRIs to examine the neural connections in their brains.
They found that participants' cardiorespiratory fitness improved by more than 10 percent. They also demonstrated improvements in cognitive performance, particularly in verbal fluency, verbal learning, and memory. The MRIs revealed that participants experienced increased connectivity between the default mode network and regions of the brain involved in memory.
The default mode network is a collection of interconnected neural structures involved in attention and focus. Disturbances in default mode network connectivity are associated with poor working memory, reduced performance, and work-related productivity losses.
Although this was a small study, it supports a growing body of evidence suggesting exercise is a potent strategy for staving off cognitive decline in aging. One contributor to cognitive decline is the loss of blood-brain barrier integrity. Learn how vigorous exercise helps maintain blood-brain barrier integrity as we age in this episode featuring Dr. Axel Montagne.
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Harmful effects of concussion are still present six months post-injury. medicalxpress.com
Press release:
The harmful effects of concussion on the brain can linger long after the initial injury, a new study shows. Nearly half of all people who experienced even a mild concussion exhibited altered brain connectivity and impaired emotional and cognitive function six months post-injury.
Researchers compared brain scans of 108 people who had experienced a mild concussion to those of 76 healthy people. They also assessed those who had had a concussion for persistent symptoms.
They found that 47 percent of the people with mild concussion were not fully recovered six months post-injury, demonstrated by hyperconnectivity in the thalamus – a region of the brain that relays sensory impulses from receptors in various parts of the body to the cerebral cortex. This hyperconnectivity was associated with impaired emotional and cognitive function.
A concussion is a disruption in normal brain function caused by an external mechanical force. Even mild concussions have been shown to elicit acute and chronic damage to the brain. Symptoms of concussion include depression, cognitive impairment, headaches, and fatigue, many of which are still present as late as six months post-injury. People who experience three or more concussions tend to exhibit cognitive deficits that worsen with each subsequent concussion.
These findings indicate that even mild concussions can have long-term deleterious effects on the brain. Evidence suggests that sulforaphane, a bioactive compound derived from broccoli, promotes recovery from concussion. Learn more in this clip featuring Dr. Rhonda Patrick.
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Fermented dairy product consumption improves memory. www.nutraingredients-usa.com
A new small study shows that drinking a fermented dairy beverage improves memory in healthy adults. People who consumed kefir exhibited improvements in relational memory – the capacity to remember associations between objects, places, people, or events, such as associating a name with a face.
The study involved 26 healthy young adults. About half of the participants consumed an 8-ounce serving of kefir (a yogurt-like probiotic drink) daily for four weeks, while the other half consumed an 8-ounce serving of low-fat, lactose-free milk. After a two-week washout period, the two groups switched beverages for an additional four weeks. Researchers assessed the participants' relational memory, mood, and microbiota composition before and after each intervention.
They found that participants who consumed the kefir showed improvements in their relational memory. In addition, the number of Lactobacillus bacteria in their guts increased by 235 percent. However, the researchers did not identify any associations between microbiota changes and memory performance or mood, a finding that may have been related to the small study size, according to the study’s authors.
Lactobacillus bacteria are among the most abundant bacterial species in the human gut. They are commonly referred to as “good bacteria” due to their beneficial effects on human health, particularly that of the gut. Learn about Lactobacillus reuteri, a type of Lactobacillus that strengthens the gut barrier, reducing leakiness and potentially influencing brain health.
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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
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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Estrogen fluctuations may trigger atypical hippocampal working memory function in women with a BDNF genotype present in one in four women. (2017) www.sciencedaily.com
From the article:
The findings may help to explain individual differences in menstrual cycle and reproductive-related mental disorders linked to fluctuations in the hormone. They may also shed light on mechanisms underlying sex-related differences in onset, severity, and course of mood and anxiety disorders and schizophrenia, which are often marked by working memory deficits. The gene-by-hormone interaction’s effect on circuit function was found only with one of two versions of the gene that codes for BDNF [Val66Met genotype] (brain-derived neurotrophic factor), a chemical messenger operating in the circuit. This version occurs in about a fourth of white women.
The researchers experimentally manipulated estrogen levels over several months in healthy women with both versions of the gene while monitoring their brain activity as they performed a working memory task. When exposed to estrogen, an area in the brain’s memory hub that is typically suppressed during such tasks instead activated in those with the uniquely human gene variant. Both PET (positron emission tomography) and fMRI (functional magnetic resonance imaging) scans showed the same atypical activation. Such gene-hormone interactions may confer risk for mental illnesses, say the researchers.
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Estrogen therapy was less memory-enhancing in mice raised in a stimulating environment than in mice raised in non-stimulating environments. (2004) www.sciencedaily.com
From the article:
“We saw no beneficial effect of estrogen in the animals in cognitively and physically stimulating environments (also known as enriched environments),” said Karyn Frick, assistant professor of psychology and principal investigator on the study. “This fits in nicely with human data and might help to explain why studies of hormone replacement therapy (HRT) do not show beneficial effects for all women. Most studies of HRT use very well-educated women. These results might spur researchers to include a broader population with a greater variation in education and socioeconomic status.”
[…]
“Animals [that had their ovaries removed to simulate menopause] raised in standard conditions showed significant spatial and object memory improvement when treated with a high dose of estrogen, whereas memory in animals in the enriched environment were unaffected or impaired by estrogen treatment,” Frick said. “Among mice not treated with estrogen, enrichment treatment alone significantly improved spatial memory. The behavioral changes were also associated with alterations in a part of the brain critical for memory. These data suggest that estrogen benefits mice raised in un-stimulating environments more than those raised in cognitively and physically stimulating environments.”
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Improved hippocampal estrogen reception sharpened spatial learning in estrogen receptor-α knockout mice with low estrogen levels. (2008) www.sciencedaily.com
From the article:
Changes in the estrogen receptor have been associated with age-related memory deficits and an increased incidence of Alzheimer’s disease among women In addition, previous studies have shown estrogen replacement may improve cognition in postmenopausal women and younger women with low estrogen levels. Estrogen also appears to protect against Alzheimer’s disease and dementia.
[…]
The mice had unusually low levels of estrogen because their ovaries were removed at an early age. However, scientists were still able to rescue learning ability by delivering the correct gene to produce estrogen receptor-alpha directly to the hippocampus.
Mice that lacked the estrogen receptor showed poor ability to locate a platform hidden in a small swimming tank over a training period of several days. After receiving the gene, the mice learned to locate the platform in two days of training.
[…]
Recordings made from the brain tissue of treated mice showed signals were strongly communicated across the gaps, or synapses, between hippocampal cells, similar to what would happen with estrogen replacement.
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In young female athletes with exercise-induced amenorrhea, estrogen replacement may improve their verbal memory and cognitive flexibility. (2016) www.sciencedaily.com
From the article:
Study participants were randomly assigned to one of three treatment groups for six months: (1) oral estradiol and progesterone at a dose similar to that in many birth control pills (16 participants); (2) transdermal estradiol, better known as the estrogen patch, at a physiological replacement dose with cyclic progesterone (13 athletes); or (3) no estrogen (19 subjects). Participants who received estrogen therapy also received progesterone because giving estrogen alone can increase the long-term risk of uterine cancer, Baskaran noted.
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Compared with those who received no hormone treatment, athletes in the two estrogen treatment groups taken together had significantly better verbal memory and cognitive flexibility scores at the end of six months than their pre-treatment scores, the investigators reported. The estrogen recipients had greater improvement in both immediate recall of words and in their ability to flexibly switch back and forth between tasks, even when the researchers controlled for patient age and pre-treatment test scores.
When the researchers evaluated the estrogen treated groups separately versus no treatment, they found significantly greater improvement in certain cognitive tests only in the group that received transdermal estrogen.
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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
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.
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.
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.
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
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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Estradiol may heighten the sensitivity of sound-processing neurons and activate genes that instruct the brain to lay down memories of sounds. (2009) www.sciencedaily.com
From the article:
Previous studies have hinted at a connection between estrogen and hearing in women who have low estrogen, such as often occurs after menopause, says Pinaud. No one understood, however, that estrogen was playing such a direct role in determining auditory functions in the brain, he says. “Now it is clear that estrogen is a key molecule carrying brain signals, and that the right balance of hormone levels in men and women is important for reasons beyond its role as a sex hormone,” says Pinaud.
Pinaud, along with Liisa Tremere, a research assistant professor of brain and cognitive sciences, and Jin Jeong, a postdoctoral fellow in Pinaud’s laboratory, demonstrated that increasing estrogen levels in brain regions that process auditory information caused heightened sensitivity of sound-processing neurons, which encoded more complex and subtle features of the sound stimulus. Perhaps more surprising, says Pinaud, is that by blocking either the actions of estrogen directly, or preventing brain cells from producing estrogen within auditory centers, the signaling that is necessary for the brain to process sounds essentially shuts down. Pinaud’s team also shows that estrogen is required to activate genes that instruct the brain to lay down memories of those sounds.
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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
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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High estradiol levels may interfere with latent inhibition, resulting in impaired attention and learning, rat study suggests. (2010) www.sciencedaily.com
From the article:
Human females have high estrogen levels while they are ovulating. These high levels have also been shown to interfere with women’s ability to pay attention.
[…]
Latent inhibition is observed in many species and is believed to be the important part of learning, which enables individuals to interact successfully in their environment. It is a test of new memory formation.
In the Brake protocol, rats received a pre-exposure phase during which they were repeatedly exposed to a tone, with no consequence. Once they became used to this tone and ignored it, the test dynamics changed and another stimulus was linked to the tone. Rats with low levels of estrogen quickly learned that the tone was associated with the new stimulus whereas those with higher levels of estrogen took longer to form this memory.
“We only observed this effect in adult female rats,” says Brake. “This and our other findings indicate that estrogen directly effects the brain, perhaps by interfering with brain signaling molecules. Our study helps clear up the controversy about the effects of estrogen, the next step is to look at how this occurs.”
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From the article:
Using a variety of techniques to look directly at the tissue, the team saw that in APOE4 brains, aberrant amounts of cholesterol accumulated within cell bodies, especially of oligodendrocytes, but was relatively lacking around neural axons.
To understand why, the team used patient-derived induced pluripotent stem cells to create lab cell cultures of oligodendrocytes engineered to differ only by whether they had APOE4 or APOE3. Again APOE4 cells showed major lipid disruptions. In particular, the afflicted oligodendrocytes hoarded extra cholesterol within their bodies, showed signs that the extra internal fats were stressing organelles called the endoplasmic reticulum that have a role in cholesterol transport, and indeed transported less cholesterol out to their membranes. Later, when they were co-cultured with neurons, the APOE4 oligodendrocytes failed to myelinate the neurons as well as APO3 cells did, regardless of whether the neurons carried APOE4 or APOE3.
The team also observed that in postmortem brains there was less myelination in APOE4 carriers than APOE3 carriers.
[…]
Eager to find a potential intervention, the team focused on drugs that affect cholesterol, including statins (which suppress synthesis) and cyclodextrin, which aids cholesterol transport. The statins didn’t help, but applying cyclodextrin to APOE4 oligodendrocyte cultured in a dish reduced accumulation of cholesterol within the cells and improved myelination in co-cultures with neurons. Moreover, it also had these effects in APOE4 mice.
Finally, the team treated some APOE4 mice with cyclodextrin, left others untreated, and subjected them all to two different memory tests. The cyclodextrin-treated mice performed both tests significantly better, suggesting an association between improved myelination and improved cognition.
Tsai said a clear picture is emerging in which intervening to correct specific lipid dysregulations by cell type could potentially help counteract APOE4’s contributions to Alzheimer’s pathology.
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Estrogen may protect against fear overexpression during the recall of fear and extinction memories. (2021) www.sciencedaily.com
From the article:
Participants underwent a fear-conditioning paradigm in which two of four photographs of neutral male faces were paired with a loud burst of white noise. Following the conditioning, the subjects underwent fear extinction, in which two photographs – only one of which had been paired with the noise – were again presented, but this time with no noise stimulus. The next day, subjects were shown all four photographs again, including the two that had been presented in the extinction phase and thus ready for extinction recall, and two of them without previous extinction – thus subject to fear recall. During all presentations, the researchers measured skin conductance responses (SCR), a peripheral readout of fear expression, and brain oscillations measured by electroencephalography.
Mr. Bierwirth said: “We found stronger peripheral fear expression (via SCR) during fear recall and extinction recall under low-E2 conditions, that is, in men and in OC women, compared to mid-cycle women with higher E2 [estradiol] levels. Most importantly, we also observed enhanced theta oscillations in the medial prefrontal cortex and especially in the dorsal anterior cingulate cortex (dACC), in men and OC women compared to MC women.”
Importantly, the authors also point out that subjects were examined during their natural E2 status. They were not randomized to experimentally manipulated estrogen levels and so causal inferences about estrogen cannot be drawn.
Fear recall-related dACC theta oscillations were attenuated in women with higher E2 levels, which, importantly, supports previous findings suggesting a protective role for E2 against fear overexpression during the recall of fear and extinction memories. The data demonstrate that peripheral and brain oscillatory correlates of fear memory recall do not differ between the sexes per se but vary with E2 status, even among women.
From the publication:
Rodent studies show that theta oscillations (4–8 Hz) in the prelimbic cortex (homolog of the primate dACC) were augmented during fear recall and reduced to baseline levels during extinction recall.
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Neuron-derived estrogen may regulate synaptic plasticity and memory, mouse study suggests. (2019) www.sciencedaily.com
From the article:
Brann and his colleagues found that mice whose neurons don’t make estrogen have impaired spatial reference memory – like a baseball player not knowing where home plate is and what it means to get there – as well as recognition memory and contextual fear memory – so they have trouble remembering what’s hazardous – they report in the Journal of Neuroscience.
Restoring estrogen levels to the brain area rescues these impaired functions, Brann and his colleagues report.
It was known that aromatase, the enzyme that converts testosterone to estrogen, was made in the brain’s hippocampus and cerebral cortex in a variety of species that includes humans, Brann says, and that they all can have memory deficits when aromatase is blocked. Patients who take an aromatase inhibitor for estrogen-dependent breast cancer also have reported memory problems.
[…]
Knocking out aromatase also decreased expression of CREB, a major transcription factor known to play a key role in learning and memory, the scientists write, as well as neuron-nourishing brain derived neurotrophic factor, or BDNF.
[…]
The scientists say these findings implicate neuron-derived estrogen as a novel neuromodulator, basically a critical messenger one neuron relies on to communicate with others, which is essential to key functions like cognition.
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Testosterone deprivation therapy in men may be associated with a loss of memory consolidation. (2004) www.sciencedaily.com
From the article:
“A colleague looked at (the study results) and said, ‘Wow, that looks exactly like what happens with a lesion in the hippocampus,’” Janowsky said. “When others have done studies like this on people who have hippocampal damage from early Alzheimer’s disease or lesions due to strokes, this is the pattern.”
The study examined 30 individuals - 14 men undergoing androgen deprivation treatment for prostate cancer and 16 healthy, age-matched men - from the Portland area. Participants were shown lists of words and, to encode them, were asked to identify whether the words were in capital or lowercase letters, which requires shallow or “perceptual” processing, or whether they represented objects that occurred in nature or were artificially made, which requires deep or “semantic” processing.
Participants were then shown another list containing words they’d just seen as well as new words and were asked whether they’d seen each word before. This test was performed at three time intervals: immediately, after two minutes and after 12 minutes.
Testosterone-deprived men can “immediately get the information in, but then the hippocampus can’t consolidate it and send it off for storage,” Janowsky said. “When you look at their memory, they’re perfectly normal when they’re immediately asked to recall something, but they can’t hold or save the information as well in order to recall it over a retention interval, over a period of time. They’re faster at forgetting.”
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In men with Alzheimer's disease, free testosterone levels were about half those of healthy men. (2004) www.sciencedaily.com
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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Higher testosterone levels may be associated with better cognitive function in older men. (2002) www.sciencedaily.com
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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Memory loss often occurs with aging and may be the result of health disorders, emotional problems, mild cognitive impairment, or another type of dementia. Findings from a new study suggest that transcranial alternating current stimulation improves memory in older adults.
Transcranial alternating current stimulation is a non-invasive therapy that passes a mild electrical current to the brain via electrodes attached to the scalp, altering brain rhythms and improving functionality. It is currently under study as a treatment for depression, anxiety, and cognitive, speech, or motor symptoms related to various movement disorders, such as Parkinson’s disease.
The study involved 150 healthy older adults (aged 65 years and older). The researchers applied transcranial alternating current stimulation to the participants' brains at varying frequencies once a day for four days. As a placebo treatment, participants received a much shorter duration treatment. Participants took memory tests before and after their respective treatments.
Participants that received the transcranial alternating current stimulation showed improvements in both working and long-term memory as early as two days after initiating treatment. These improvements were still present at follow-up testing one month later. Participants with poorer cognitive function at the beginning of the treatment showed greater, longer-lasting memory improvements.
These findings suggest that transcranial alternating current stimulation improves memory in older adults and may be suitable as a non-invasive therapy for memory loss.
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Blockade of IL-6 receptor improved cognition in patients with schizophrenia. (2016) www.sciencedaily.com
From the article:
After just two intravenous doses in eight weeks of tocilizumab, an immune-suppressing drug regularly prescribed for rheumatoid and juvenile arthritis, study participants had significantly improved cognitive ability, said Dr. Brian J. Miller, a psychiatrist at the Medical College of Georgia at Augusta University.
[…]
Anywhere from 25 to 50 percent of patients may have inflammation in the brain contributing to that dysfunction. Problems range from having trouble remembering important numbers to impairment of executive function that enables them to analyze, organize, and generally manage their lives.
Tocilizumab targets the receptor for IL-6, a protein which helps regulate inflammation that is often elevated in patients with schizophrenia. Higher IL-6 levels also have been correlated with a smaller hippocampus, a center for learning and memory in the brain, as well as experiencing more psychiatric symptoms.
The five study patients did not experience improvement in overall levels of psychiatric symptoms, such as hallucinations and delusions, more classic symptoms of schizophrenia, which were already well-controlled with antipsychotics, Miller said.
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Maternal IL-6 during pregnancy can be estimated from newborn brain connectivity and negatively correlates with offspring working memory. (2018) www.sciencedaily.com
From the article:
[…] collected blood samples from 84 expectant mothers at each pregnancy trimester. The samples were measured for levels of the cytokine interleukin-6, or IL-6, an inflammatory marker known to play a role in fetal brain development.
Four weeks following birth, brain connectivity patterns of the offspring were assessed using functional magnetic resonance imaging, or fMRI, scans. At age 2, the children were also tested for working memory performance, a key skill that supports academic achievement and is frequently compromised in mental health disorders.
The data from mother and child show that differences in the levels of inflammatory markers are directly associated with differences in newborn brain communication, and later to working memory scores at age 2. Higher levels of the marker during pregnancy tended to result in less working memory capacity in the child.
“Importantly, this doesn’t mean that every exposure to inflammation will result in a negative impact to the child; however, these findings provide new avenues for research, and can help health care providers think about how, and when, inflammation might impact a child’s long-term learning development and mental health,” said Alice Graham, Ph.D., postdoctoral fellow in behavioral neuroscience in the OHSU School of Medicine.
A notable aspect of the study, according to Graham, is the development of a model that can accurately estimate information about maternal inflammation during pregnancy based only on newborn brain functioning.
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Interleukin-6 (IL-6) mediates delirium-like phenotypes in a mouse model of urinary tract infection. (2021) www.sciencedaily.com
From the article:
In a Y-shaped maze with three arms to explore, uninfected mice tended to explore all three arms, while mice with UTIs [urinary tract infection] kept returning to the same one, suggesting a lapse in short-term memory, another feature of delirium.
The investigators also observed structural changes in the brains of mice with UTIs.
In a previous study led by Lahiri, published in February in the American Journal of Respiratory Cell and Molecular Biology, investigators found a connection between ventilator-induced lung injury and delirium. Lahiri and colleagues theorized that in both cases this was because of the reaction of IL-6, which helps regulate immune response, to the lung injury or the UTI.
“Occasionally, when the response of IL-6 is excessive, our research indicates that there can be brain injury,” Lahiri said. “IL-6 induces changes within the neurons that our studies connected with delirium-like behavior. This is the first time this type of structural and functional change has been demonstrated. We’ve now shown two distinct models of this connection, one non-infectious and one infectious.”
In the current study, when investigators treated some of the infected mice with antibodies that blocked the effects of IL-6, the delirium-like behavior of those animals resolved. “Treatment with anti-IL-6 antibody in the UTI group normalized all the brain changes, both structural and functional,” Lahiri said. “A wealth of studies have shown a link between IL-6 and delirium, but only this study and our previous study have shown that IL-6 may play a direct pathological role in delirium.”
If symptoms are treated early, he added, full recovery is possible, and the next step is to design clinical trials with anti-IL-6 antibodies as a treatment for patients with UTI-induced delirium.
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Intranasally administered interleukin-6 (IL-6) helps the brain retain emotional and procedural memories during REM sleep. (2009) www.sciencedaily.com
From the article:
“Here, we provide the first evidence that the immunoregulatory signal interleukin-6 plays a beneficial role in sleep-dependent formation of long-term memory in humans.”
To make this discovery, Marshall and colleagues had 17 healthy young men spend two nights in the laboratory. On each night after reading either an emotional or neutral short story, they sprayed a fluid into their nostrils which contained either interleukin-6 or a placebo fluid. The subsequent sleep and brain electric activity was monitored throughout the night. The next morning subjects wrote down as many words as they could remember from each of the two stories. Those who received the dose of IL-6 could remember more words.
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Exercise protected mice from toxin-induced hippocampal damage by stimulating the production of interleukin-6 in the brain. (2011) www.sciencedaily.com
From the article:
Previous research has already demonstrated that exercise after brain injury can help the repair mechanisms. This new study shows that exercise before the onset of damage modifies the brain environment in such a way that the neurons are protected from severe insults. The study used an experimental model of brain damage, in which mice are exposed to a chemical that destroys the hippocampus, an area of the brain which controls learning and memory. Mice that were exercised regularly prior to exposure produced an immune messenger called interleukin-6 in the brain, which dampens the harmful inflammatory response to this damage, and prevents the loss of function that is usually observed.
Pharmacological therapies to downregulate inflammation and address cognitive decline in older adults, and those with Alzheimer’s disease, have been less successful. This research helps understand how exercise could be used to affect the path of many human conditions, such as neurodevelopmental disorders and neurodegenerative diseases. In addition, as a chemical model of neuronal damage was used, it also raises the possibility that exercise could offer protection against the potentially harmful effects of environmental toxins.
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Evidence in mice suggests that TNF-alpha release in response to viral infection causes learning problems. (2017) www.sciencedaily.com
From the article:
Evidence in mice suggests that the entry of a virus anywhere in the bloodstream turns on “first responder” immune cells called CX3CR1highLY6Clow monocytes, which then release the inflammatory signaling protein TNF-α. According to the authors of the study, TNF-α then travels to the brain where it blocks the formation of nerve cell connections needed to turn sensory information into memories.
[…]
Researchers also measured the levels of pro-inflammatory signaling proteins (cytokines) in mice at several time points after the injection of poly(I:C), and found a larger, longer-lasting increase in levels of TNF-α than in other cytokines. Given their findings, the team guessed that the impact of systemic immune response on brain cell connections was executed through TNF-α signaling. Indeed, mice engineered to lack TNF-α signals in white blood cells saw neither a drop in dendritic spine formation nor in motor learning ability when exposed to the viral mimetic.
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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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How cranberries could improve memory and ward off dementia www.sciencedaily.com
Eating polyphenol-rich cranberries improves memory and neural functioning in older adults.
As many as 55 million people worldwide have dementia, a figure expected to triple in the next three decades. Evidence suggests that dietary patterns and components may reduce the risk of developing dementia. Findings from a recent study suggest that eating cranberries improves memory and neural functioning in older adults.
Cranberries, like many other red, purple, or blue fruits, are rich in bioactive compounds called polyphenols, including anthocyanins, proanthocyanidins, flavonols, and others. Robust evidence indicates that these compounds exert antioxidant, anti-inflammatory, and/or neuroprotective effects in humans.
The investigators conducted a randomized, placebo-controlled trial involving 60 healthy adults between the ages of 50 and 80 years. Half of the participants consumed 4.5 grams of freeze-dried cranberry powder (to be mixed in liquid) every day for 12 weeks. The daily portion of supplemental cranberry powder was roughly equivalent to eating about one-half cup of fresh cranberries and provided 59 milligrams of anthocyanins, 281 milligrams of proanthocyanidins, and 20 milligrams of flavonols. The other half of the participants consumed a similar-looking non-nutritive powder for the duration of the study. Before, during, and after the intervention, participants underwent cognitive testing and provided blood samples for biochemical assessment. A subset of participants underwent magnetic resonance imaging (MRI) studies.
At the end of the intervention, participants who received the cranberry powder exhibited improvements in visual episodic memory. In addition, their low-density lipoprotein cholesterol (which contributes to atherosclerosis and impaired brain function) decreased. The MRIs revealed that the supplemented group had increased blood flow to areas of the brain involved in memory formation and consolidation.
These findings suggest that polyphenol-rich cranberries improve memory and aspects of neural functioning in older adults. It is noteworthy, however, that many commercial cranberry products contain copious amounts of added sugar to counter the berries' tartness. Because sugar can have harmful effects on brain and metabolic health, consuming unsweetened cranberries (or other berries) will likely have the greatest benefits on cognition.
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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
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
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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Intense cycling exercise at 80% maximum heart rate improves memory via endocannabinoid action on the hippocampus www.sciencedaily.com
Exercise activates the endocannabinoid system to promote learning and memory formation.
Scientists have identified robust links between physical exercise and brain health. Some of the mechanisms that drive the beneficial effects of exercise on the brain include increases in brain volume and connectivity, improved blood flow, enhanced synaptic plasticity, and increased neurogenesis – the formation of new neurons. Findings from a 2020 study suggest that moderate- to vigorous-intensity exercise improves motor sequence memory via endocannabinoid action on the hippocampus.
Motor sequence memory involves learning predefined sequences of interrelated motor actions, such as playing the piano or dancing. The hippocampus interacts with various neural networks to support the formation of motor sequency memory.
Endocannabinoids are small lipid molecules produced in the body that bind to cannabinoid receptors in the central and peripheral nervous systems. Endocannabinoids regulate many physiological processes, including movement control, pain processing, brain development, and learning and memory. The two major endocannabinoids in the body are anandamide and 2-arachindonyl glycerol.
The study involved 15 healthy adults (average age, 23 years) who had at least fair respiratory fitness, as measured via VO2 max. Participants completed a serial reaction time task (a widely used measure of learning and memory) before and after three conditions: moderate-intensity exercise, vigorous-intensity exercise, and rest. Prior to performing the task, participants consumed a standardized carbohydrate-rich breakfast. During the task, the investigators measured the participants' behavior, brain activity, and circulating anandamide (endocannabinoid) levels.
They found that vigorous-intensity exercise markedly improved motor sequence memory compared to rest. Moderate-intensity exercise also improved motor sequence memory, but to a lesser degree. The improvements coincided with increased levels of the endocannabinoid anandamide and enhanced hippocampal activity.
These findings suggest that vigorous-intensity exercise promotes motor sequence memory and learning and underscore the benefits of exercise on cognitive function. Learn about the beneficial effects of aerobic exercise in our overview article.
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Omega-3 prevents memory and learning impairment caused by high-fructose diets in mice www.sciencedaily.com
From the article:
Gomez-Pinilla and study co-author Rahul Agrawal, a UCLA visiting postdoctoral fellow from India, studied two groups of rats that each consumed a fructose solution as drinking water for six weeks. The second group also received omega-3 fatty acids in the form of flaxseed oil and docosahexaenoic acid (DHA), which protects against damage to the synapses – the chemical connections between brain cells that enable memory and learning.
[…]
The animals were fed standard rat chow and trained on a maze twice daily for five days before starting the experimental diet. The UCLA team tested how well the rats were able to navigate the maze, which contained numerous holes but only one exit. The scientists placed visual landmarks in the maze to help the rats learn and remember the way.
Six weeks later, the researchers tested the rats' ability to recall the route and escape the maze. What they saw surprised them.
“The second group of rats navigated the maze much faster than the rats that did not receive omega-3 fatty acids,” Gomez-Pinilla said. “The DHA-deprived animals were slower, and their brains showed a decline in synaptic activity. Their brain cells had trouble signaling each other, disrupting the rats' ability to think clearly and recall the route they’d learned six weeks earlier.”
The DHA-deprived rats also developed signs of resistance to insulin, a hormone that controls blood sugar and regulates synaptic function in the brain.
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Mid-life long duration antibiotic use of >= two months linked to poorer scores in cognition, learning, working memory, and attention in later life www.sciencealert.com
Antibiotic use in midlife increases a person’s risk for neuropsychiatric diseases.
Antibiotics are prescribed for a wide range of infectious diseases. In 2015, healthcare providers in the United States wrote nearly 270 million antibiotic prescriptions – more than 800 antibiotic prescriptions for every 1,000 people. Health experts estimate that 30 percent of these prescriptions were likely unnecessary. Findings from a new study suggest that antibiotic use in midlife increases a person’s risk for neuropsychiatric diseases.
The study included approximately 15,000 midlife participants (average age, 55 years) enrolled in the Nurses’ Health Study II, an ongoing prospective cohort study of female nurses. The participants completed questionnaires regarding their general health, diet, lifestyle, and medication use during the previous four years, including antibiotic use and the reason for which the antibiotic was prescribed. The investigators categorized the participants' cumulative antibiotic use as none, one to 14 days, 15 days to two months, and two months or more. Participants also completed a battery of neuropsychological tests.
The investigators found that participants who took antibiotics for at least two months over the previous four years were more likely to perform worse on neuropsychological tests than participants who did not take antibiotics. The influence of antibiotic use on neuropsychological test scores was roughly equivalent to three to four years of aging. These findings held true even after considering other factors that could influence cognitive function, including age and coexisting illnesses.
These findings suggest that longer exposure to antibiotics in midlife negatively influences cognitive health, underscoring the importance of moderating antibiotic use in older adults. They also support findings from animal studies that suggest antibiotic use early in life alters neuropeptide signaling pathways that influence behavioral development. Learn more about the effects of antibiotic use in early life in this clip featuring Dr. Eran Elinav.
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Consumption of a fermented dairy beverage improves hippocampal-dependent relational memory in a randomized, controlled cross-over trial www.tandfonline.com
Drinking kefir, a probiotic dairy beverage, improves memory.
The community of microbes that comprise the gut microbiota act a bit like a sensory organ in the body, communicating information about the outside world to the brain and forming a gut-brain axis. Antibiotic and other medication use and changes in the diet can modulate the gut microbiota community in ways that reduce or increase the risk of neuropsychiatric illnesses such as depression. Findings of a recent report show that consuming a fermented dairy beverage may improve memory via changes in the gut-brain axis.
The hypothalamic-pituitary-adrenal axis (i.e., gut-brain axis) is formed by neural and endocrine connections between the hypothalamis, a brain region that controls body temperature, hunger, and sleep; the pituitary gland, a endocrine organ in the brain that produces hormones; and the adrenal gland, which is located above the kidneys and produces hormones that regulate stress such as adrenaline and cortisol. This axis of stress control communicates directly with the hippocampus, the memory center of the brain, which helps the brain retain memories of stressful situations, but also contributes to the development of depression. Previous research shows that probiotics can reduced depression severity; however, additional research is necessary to understand the mechanisms of this relationship.
The authors recruited 18 healthy adults and randomly assigned them to consume eight ounces of either kefir (i.e., a fermented dairy beverage with 12 strains of active bacteria) or low-fat lactose-free milk daily for four weeks. Participants completed questionnaires about their health, performed cognitive testing with electroencephalogram (EGG) measurement, and provided a fecal sample for the sequencing of the gut microbiome. After a washout period of about three weeks, participants switched to the opposite treatment and repeated the experiment.
The authors found that Lactobascillus bacteria more than doubled following kefir consumption suggesting significant change in the gut microbial community. Participants consuming kefir performed better on two measures of memory called misplacement and object-location binding. The researchers did not observe changes in depression scores in either group.
It’s important to note that more than 50 percent of participants in the study had a post-graduate degree, which could skew these results. Future studies in larger and more diverse populations are needed to better understand the effects of probiotics on the brain.
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Exercise induces epigenetic changes in mice that enhance learning and brain function in their offspring www.sciencedaily.com
From the article:
In mice, the scientists showed that learning ability was passed onto the next generation by epigenetic inheritance. When Fischer and co-workers exposed mice to a stimulating environment in which they had plenty of exercise, their offspring also benefited: compared to the mice of a control group, they achieved better results in tests that evaluate learning ability. These rodents were also found to have improved synaptic plasticity in the hippocampus, a region of the brain important for learning
Both mental and physical activity of the parents matter:
The researchers also found that miRNA212 and miRNA132 accumulated in the brains and sperm of mice after physical and mental activity. It was previously known that these molecules stimulate the formation of synapses in the brain, thus improving learning ability. Through the sperm, they are transmitted to the next generation. “Presumably, they modify brain development in a very subtle manner improving the connection of neurons. This results in a cognitive advantage for the offspring,” says Fischer.
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Six months of daily aerobic exercise directly impacts tests of executive function, mental flexibility, self-correction, and verbal fluency www.sciencedaily.com
From the article:
Participants were enrolled in a supervised aerobic exercise program held three days a week. As they progressed through the program, they increased their workout from an average of 20 minutes a day to an average of at least 40 minutes. In addition, people were asked to work out on their own once a week.
Researchers found that after six months of exercise, participants improved by 5.7% on tests of executive function, which includes mental flexibility and self-correction. Verbal fluency, which tests how quickly you can retrieve information, increased by 2.4%.
[…]
Before and after six months of aerobic activity, the participants' average peak blood flow to the brain was measured using ultrasound. Blood flow rose from an average of 51.3 centimeters per second (cm/sec) to an average of 52.7 cm/sec, a 2.8% increase. The increase in blood flow with exercise was associated with a number of modest but significant improvements in aspects of thinking that usually decline as we age, Poulin said.
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Memory reactivation during sleep enhances ability to recall faces and names. www.sciencedaily.com
Remembering a person’s face – and the name that goes with it – are fundamental aspects of social and professional relationships. Scientists think that, like many other aspects of memory, sleep plays an important role in the ability to recall faces and names. Findings from a new study suggest that targeted memory reactivation helps people recall faces and names.
Targeted memory reactivation is an experimental tool that relies on context-dependent memory, a type of memory that occurs when contextual cues facilitate memory recall. It is based on the premise that during memory storage, contextual information, such as sounds, smells, or tastes, are also stored. Retrieval of the memories is enhanced when exposed to the context. Although smells are among the strongest cues for inducing and retrieving memories, sounds can also provide strong stimuli for learning.
In the present study, 80 college-age students taking either a Latin-American history class or a Japanese history class heard their classmates' names while viewing pictures of the classmates' faces and listening to either Latin-American or Japanese music, respectively. Later, during a period of sleep, the students listened to softly played recordings of some of the names and the associated music. The investigators measured the participant’s sleep quality using electroencephalography and assessed the students' recall of their classmates' names while viewing their pictures.
They found that the students' ability to place a name with a face was enhanced if they heard the name and the associated music during a period of sleep. However, students who experienced poor quality sleep performed worse on recall tests than those with good quality sleep.
These findings suggest that targeted memory reactivation enhances memory consolidation, especially in the setting of deep, good quality sleep. Learn more about targeted memory reactivation in this clip featuring sleep expert Dr. Matthew Walker.
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COVID-19 illness is linked with impaired cognitive function even months after recovery. www.sciencedaily.com
Researchers and clinicians are growing increasingly concerned about the possibility of COVID-19 having a persistent impact on health that extends far beyond recovery from acute illness. In particular, anecdotal reports of former patients experiencing depression, “brain fog,” and difficulty finding the right words in conversation even months later appear to point to a potential long-term impact on cognition. A recent large-scale study offers evidence that COVID-19 promotes long-term cognitive deficits, even among those who experience the mildest form of the disease.
The study recruited a representative cohort of 81,337 UK participants (average age, 46 years) to take part in a citizen science project known as the Great British Intelligence Test, a widely promoted free opportunity for people to identify their cognitive strengths. Participants performed a series of clinically validated online tasks assessing their emotional processing abilities, as well as cognitive skills such as attention, problem solving, and working memory. Scores from this latter group of tests were pooled to extract a composite score of global cognitive ability for each participant.
After completing the cognitive tasks, participants were asked to provide some details about their experiences with COVID-19 – information that the researchers went on to use to build a predictive model of their global cognitive and emotional processing abilities.
Their analysis revealed that clinically confirmed cases of COVID-19 infection were associated with significant cognitive deficits even nine months following infection (the longest period recorded in the study). This was particularly evident in complex tasks that required participants to reason, plan ahead, and solve problems using analogies, although the researchers also observed a general slowing of reaction times across all tasks.
The scale of this cognitive impairment depended on the severity of respiratory symptoms. People who had severe cases of COVID-19 that required hospitalization and ventilation exhibited the greatest cognitive decline, surpassing the average decline observed in former stroke victims, as well as the mean cognitive difference between groups that differed by 10 years of age.
Perhaps most surprisingly, the researchers found a significant degree of cognitive decline even in mild cases of COVID-19 who remained at home for the duration of their illness. These individuals performed below what would have been expected if they had not contracted the infection, roughly equivalent to 3.5 IQ points in a classic intelligence test.
This study offers evidence that COVID-19 infection might have long-term health implications far beyond respiratory symptoms and that recovery may be associated with tangible impairments in certain aspects of higher cognitive function. It remains to be explored whether these deficits remain in the longer term.
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Intermittent fasting improves long term memory retention in mice. www.sciencedaily.com
Intermittent fasting is a broad term that describes periods of fasting between meals, lasting several hours to days. Intermittent fasting increases ketone production because it uses stored fat as an energy source. It also activates genetic pathways associated with enhanced healthspan and longevity. Caloric restriction, which typically involves a 10 to 40 percent reduction in total caloric intake, activates similar pathways. Findings from a new study suggest that intermittent fasting is more effective than caloric restriction in activating klotho, a longevity gene, to improve long-term memory retention in mice.
The klotho gene provides the instructions for making the klotho protein in mammals, including mice and humans. Klotho is produced primarily in the kidneys, but some is produced in the brain, where it appears to play a role in cognition and in neurogenesis, the process of forming new neurons. Neurogenesis is the basis for memory, but it declines with age, leading to cognitive decline.
The authors of the study assigned mice to one of three feeding regimens: intermittent feeding every other day (approximately 10 percent fewer calories over a one-week period); 10 percent calorie restriction; or eating freely. After the mice had followed their respective feeding regimens for three months, the authors of the study subjected them to behavioral studies (to assess spatial learning and memory, conducted at 24 hours and ten days post regimen) or gene expression studies.
The memory assessment conducted at 10 days post regimen revealed that the mice in the intermittent feeding group performed 25 percent better than those in the caloric restriction group and 30 percent better than those that ate freely. The mice in the intermittent feeding group also exhibited more signs of hippocampal neurogenesis and upregulation of the klotho gene. Further analysis revealed that adult hippocampal neurogenesis is dependent upon klotho activity.
These findings demonstrate that the longevity gene klotho is necessary for neurogenesis and that intermittent feeding may be beneficial in promoting memory retention in humans. A ketogenic diet also improves memory in mice. Learn more in this episode featuring aging expert Dr. Eric Verdin.
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Excess sugar intake in early life impairs memory in adulthood via changes in the gut microbiota. www.sciencedaily.com
A healthy gut microbiota is important for cognitive function at any age, but especially during development. Poor dietary quality in early life (i.e., consuming excess sugar) negatively impacts the composition of the gut microbiota and impairs cognitive functioning; however, the mechanisms that drive these changes are unclear. Authors of a new report detail the functional relationship between detrimental gut microbes and hippocampal memory in rats exposed to excess sugar during adolescence.
Germ-free mice, which are born and raised in a sterile environment, demonstrate impaired brain development compared to mice with a normal gut microbiota. This suggests that microbiota composition in early life may impact cognitive function in adulthood. Dietary strategies that minimize sugar intake may improve microbiota quality and maximize developmental potential in children and adolescents.
The investigators conducted a two-part experiment in rats. In the first experiment, they fed sugar-sweetened water or plain water to juvenile rats for 11 weeks. They sequenced bacterial DNA from the rats' fecal samples to measure changes in the gut microbiota. In the second experiment, the researchers treated juvenile rats with antibiotics or a placebo for seven days. Then they treated one half of the antibiotic group with a bacterial culture of Parabacteroides distasonis and Parabacteroides johnsonii, while the other half received a placebo. In both experiments, rats completed a series of tests to measure memory function in adulthood. Finally, the researchers measured gene expression in the hippocampus, one the major memory centers of the brain.
Adult sugar-fed rats exhibited impaired performance on memory tasks associated with the hippocampus, but not other memory centers. The authors discovered that sugar consumption led to an increase in Parabacteroides bacteria in the gut that correlated with impaired hippocampal function. When antibiotic-treated rats were given Parabacteroides distasonis and Parabacteroides johnsonii as a supplement in adolescence, they exhibited similar deficits in memory performance in adulthood as sugar-fed rats. Sugar consumption altered the expression of genes associated with neurotransmitter signaling, while Parabacteroides treatment altered genes associated with metabolic function, neurodegenerative disease, and dopamine signaling.
The authors of this comprehensive report concluded that early-life dietary factors like sugar consumption impact brain development and may impair memory via changes in the gut microbiota.
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Lithium blocks some of the sleep disturbances, memory loss, and learning problems tied to fetal alcohol syndrome in mouse study www.sciencedaily.com
From the article:
The new study found that giving the drug to newborn mice 15 minutes after “binge” alcohol consumption eliminated the hyperactivity and sleep deficits seen when rodents exposed to alcohol became adults. Moreover, the researchers report, lithium chloride-treated mice were much less likely to show the 25 percent drop in memory and cognitive test scores seen in untreated mice given the same amount of alcohol.
“Our study showed that lithium chloride prevented many of the damaging neurological effects of alcohol abuse on the still-developing brain, especially the impact on the parts of the brain controlling sleep,” says co-senior study investigator Donald Wilson, PhD.
Promoting BDNF as one pathway to brain cell survival:
“Lithium chloride is known to block many pathways that lead to brain cell death, while promoting others that lead to survival, like brain-derived neurotrophic factor, or BDNF,” says Saito, a research assistant professor at NYU Langone. Further experiments are needed, she says, to determine if chemicals that stimulate BDNF production also blunt the effects of alcohol abuse in newborn mammals.
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The combination of tobacco and alcohol may exacerbate deleterious effects in memory region: increased oxidative stress in hippocampus, less BDNF www.sciencedaily.com
From the article:
The researchers treated rats with alcohol, tobacco smoke or both twice a day for 28 days and then compared their brains with control animals that didn’t receive either substance. They found that the combined alcohol and smoking treatment increased the level of reactive oxygen species in the hippocampus compared with control animals or rats given tobacco smoke alone. In all of the brain areas studied, combined alcohol and smoking increased the levels of specific pro-inflammatory cytokines more than either treatment alone.
Reduced levels of BDNF, another harbinger of bad news:
And in the striatum and frontal cortex, rats with both treatments showed lower levels of brain-derived neurotrophic factor, a growth factor that helps existing neurons survive and stimulates the growth of new ones. These results suggest that alcoholics who smoke could be at additional risk for neural damage, the researchers say.
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BDNF variant may mediate degree of brain benefits from exercise. www.sciencedaily.com
Exercise improves cognitive function and reduces the risk neurodegenerative diseases such as Alzheimer’s disease. Some of these benefits are mediated by brain-derived neurotrophic factor (BDNF). Findings from a 2012 study showed that regular exercise improved cognitive function and increased BDNF levels, but a genetic variant in BDNF influenced the degree of these effects.
BDNF is a protein that acts on neurons in the central and peripheral nervous systems. A single-nucleotide polymorphism (SNP) in the gene that encodes BDNF causes a substitution of the amino acid valine (Val) by methionine (Met) in the BDNF protein. This genetic variant, known as Val66Met, alters exercise-driven release of BDNF and affects learning, memory, and emotion.
The intervention study involved 75 sedentary, healthy, young adults between the ages of 18 and 35 years. The participants took memory tests and mental health surveys before and after engaging in their randomly assigned respective activities: no exercise; four weeks of exercise with exercise and a test on the last day; four weeks of exercise, without exercise on the final test day; or a single bout of exercise on the last test day.
The participants who engaged in exercise showed improvements in memory and experienced lower levels of perceived stress, but only if they exercised for four weeks including the final day of testing. Participants who engaged in a single bout of exercise showed no changes in memory performance and demonstrated higher perceived stress levels. The authors of the study noted improvements in the participants' memory only if they did not carry the Val66Met variant, suggesting that the associated reduction in BDNF release attenuated some of the cognitive benefits of exercise. They also noted that the improvements in cognitive function were not correlated to improvements in mental health.
These findings suggest that the variable effects of exercise on brain function are related to a genetic variant that influences the production of BDNF.
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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
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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Six weeks of 20-minute high-intensity interval training significantly improves "high-interference" memory, large fitness gains associated w/ more BDNF www.sciencedaily.com
From the article:
Scientists have found that six weeks of intense exercise – short bouts of interval training over the course of 20 minutes – showed significant improvements in what is known as high-interference memory, which, for example, allows us to distinguish our car from another of the same make and model.
[…]
They also found that participants who experienced greater fitness gains also experienced greater increases in brain-derived neurotrophic factor (BDNF), a protein that supports the growth, function and survival of brain cells.
“Improvements in this type of memory from exercise might help to explain the previously established link between aerobic exercise and better academic performance,” says Jennifer Heisz, an assistant professor in the Department of Kinesiology at McMaster and lead author of the study.
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From the article:
“Up to now the only known approach to inducing brown fat has been through exposure to chronic cold. Our research reveals a novel way of doing this without cold exposure. We show that animals living in an enriched environment become lean and resistant to diet-induced obesity, even in the presence of unlimited food.”
[…]
The current study used a similarly designed environment, with 15-20 mice housed in large containers equipped with running wheels, tunnels, huts, wood toys, a maze, and nesting material, in addition to unlimited food and water.
Key findings include the following:
• Enriched animals showed a significant reduction in abdominal white fat mass (49 percent less than controls).
• Exercise (running in a wheel) alone did not account for the changes in body composition and metabolism of enriched animals.
• Fed a high fat diet (45 percent fat), enriched animals gained 29 percent less weight than control mice and remained lean, with no change in food intake. Enriched animals also had a higher body temperature, suggesting that greater energy output, not suppressed appetite, led to the resistance to obesity.
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Increased visceral fat impairs cognition through chronic microglial activation mediated by IL-1 beta release [animal research] www.sciencedaily.com
Scientists find that visceral fat, a type of adipose tissue that produces high levels of inflammatory signals known as adipokines, impair learning and memory in mice by setting off an inflammatory cascade mediated by the release of IL-1 beta, which crosses the blood-brain barrier leading to chronic activation of microglia.
From the article:
“We have identified a specific signal that is generated in visceral fat, released into the blood that gets through the blood brain barrier and into the brain where it activates microglia and impairs cognition.”
Visceral fat as the ring leader:
They looked further and found that just transplanting the visceral fat caused essentially the same impact as obesity resulting from a high-fat diet, including significantly increasing brain levels of interleukin-1 beta and activating microglia. Mice missing interleukin-1 beta’s receptor on the microglia also were protected from these brain ravages.
[…]
To measure cognitive ability, the scientists looked at mice’s ability to navigate a water maze after 12 weeks on a high- or low-fat diet. They found it took the normal, or wild type, mice consuming the higher fat diet as well as the visceral transplant recipients with NLRP3 intact longer to negotiate the water maze. In fact, while they could reach a platform they could see, they had trouble finding one beneath the water’s surface that they had been taught to find. Mice with the interleukin-1 receptor knocked out, could find it just fine, Stranahan says.
The high-fat diet, transplant mice also had weaker connections, or synapses, between neurons involved in learning and memory. Mice on a high-fat diet but missing NLRP3 were spared these changes, like mice on a low-fat diet.
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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
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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Vitamin C status important for fetal hippocampal development: deficiency leads to a 10-15 percent reduction www.sciencedaily.com
According to animal research, even mild vitamin C deficiency may impact fetal hippocampal development, a part of the brain crucial for learning and memory.
From the article:
“Even marginal vitamin C deficiency in the mother stunts the fetal hippocampus, the important memory centre, by 10-15 per cent, preventing the brain from optimal development,” says Professor Jens Lykkesfeldt.
[…]
“People with low economic status who eat poorly – and perhaps also smoke – often suffer from vitamin C deficiency. Comparatively speaking, their children risk being born with a poorly developed memory potential. These children may encounter learning problems, and seen in a societal context, history repeats itself because these children find it more difficult to escape the environment into which they are born,” says Jens Lykkesfeldt.
From an earlier study’s press release:
Guinea pigs subjected to moderate vitamin C deficiency have 30 per cent less hippocampal neurones and markedly worse spatial memory than guinea pigs given a normal diet. […] The highest concentration of vitamin C is found in the neurons of the brain and in case of a low intake of vitamin C, the remaining vitamin is retained in the brain to secure this organ.
Vitamin C deficiency is widespread and may impact early development:
In some areas in the world, vitamin C deficiency is very common – population studies in Brazil and Mexico have shown that 30 to 40 per cent of the pregnant women have too low levels of vitamin C, and the low level is also found in their foetuses and new-born babies.
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Mild hearing loss – when hearing is still considered normal – is linked to cognitive decline. www.sciencedaily.com
Approximately two-thirds of all adults over the age of 70 have some degree of hearing loss. Few people seek out treatment, however. A recent study found that even mild hearing loss – when hearing is still considered normal by most people – is linked to cognitive decline.
The participants in the cross-sectional study, which included more than 6,000 men and women who were 50 years or older (average age, 59 years) and living in the United States, were part of the Hispanic Community Health Study and the National Health and Nutrition Examination Study (NHANES). Each of the participants completed a series of tests to gauge neurocognitive function. They also underwent audiometry tests to assess their hearing.
The association between cognitive decline and hearing loss first appears with mild hearing loss and progresses in a dose-dependent manner as hearing worsens. The authors of the study used statistical models to identify associations between hearing loss and cognitive decline. They found that for every 10 dB decrease in hearing, cognitive function decreased as well, especially among those who were in the earliest stage of hearing loss.
Interestingly, a related study found that the risk of developing mild hearing loss was nearly 30 percent lower among people who adhered to healthy dietary patterns such as the DASH diet or the Mediterranean diet, suggesting that diet may play a role in preventing mild hearing loss.
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12 weeks of high-intensity interval training improves memory by 30% in older adults between the ages of 60 and 88. www.sciencedaily.com
Cognitive decline and associated memory loss are common features of aging, affecting approximately 16 million people living in the United States. A recent study found that high-intensity interval training improves memory in older adults.
The study involved 64 sedentary older adults between the ages of 60 and 88 years who were randomized to participate in 12 weeks of high-intensity interval training, moderate continuous training, or stretching (which served as the control group). Each of the participants' memory and executive functions were assessed before the training began.
The participants in the high-intensity group performed four intervals of high-intensity exercise on a treadmill for four minutes, followed by a period of recovery. The participants in the moderate continuous group performed a single set of moderate-intensity aerobic exercise for approximately 50 minutes.
At the end of the study period, participants who engaged in high-intensity exercise performed better on memory tests than those who engaged in moderate continuous training or stretching only. The participants who saw the greatest fitness gains also saw the greatest memory improvements. Both high-intensity interval and moderate continuous exercise improved executive function in the participants.
These findings suggest that aerobic exercise, especially if it includes high-intensity interval training, has the potential to enhance memory in older adults.
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THC given to old mice improved performance on memory tests. www.scientificamerican.com
THC (found in cannabis) that was given to old mice improved performance on learning and memory tests, improved connections between neurons, and resulted in gene activation profiles in the hippocampus that resembled young mice.
The mice that were 12 months old (mature mice) and 18 months old (old mice) both performed better after given THC and this on was dependant on activation of glutamatergic CB1 receptors and histone acetylation that was induced by THC.
In contrast, young mice given THC performed worse on memory tests. The mice termed “young” in this study were 2 months old. They performed worse on memory tests after given THC. Typically a mouse is termed “adult” if it is 3 months old. It seems possible that some brain development may still occur at 2 months of age but I’m not sure.
It is unclear whether THC will improve memory in older adults but this preclinical study provides strong evidence along with a mechanism that it might.
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Prenatal exposure to organophosphate pesticides has been associated with reduced IQs, mental and motor delays among preschoolers, memory and attention journals.plos.org
Prenatal exposure to organophosphate pesticides has been associated with reduced IQs, mental and motor delays among preschoolers, memory and attention deficits, and autism (review of 27 studies).
A higher likelihood of an autism diagnosis was observed for children born to women residing within (versus beyond) 1.5 km of organophosphate pesticide applications on agricultural fields. Another recent study showed that higher organophosphate pesticide metabolite concentrations in maternal urine during pregnancy were associated with autism traits identified in adolescence. Risks for impaired neurodevelopment were greater among children of farmworkers, who experience higher exposures, and children with genetic susceptibility factors that reduce capacity to detoxify organophosphate pesticides.
Still, these are associations and it is difficult to establish causality. Animal studies have shown effects on cognition, motor activity, and social behaviors when dosed in early life with concentrations of organophosphates.
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Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement. - PubMed - NCBI www.ncbi.nlm.nih.gov
Adamsky, A., et al. (2018). Astrocytic Activation Generates De Novo Neuronal Potentiation and Memory Enhancement. Cell 174, 59–71.
Astrocytes respond to neuronal activity and were shown to be necessary for plasticity and memory. To test whether astrocytic activity is also sufficient to generate synaptic potentiation and enhance memory, we expressed the Gq-coupled receptor hM3Dq in CA1 astrocytes, allowing their activation by a designer drug. We discovered that astrocytic activation is not only necessary for synaptic plasticity, but also sufficient to induce NMDA-dependent de novo long-term potentiation in the hippocampus that persisted after astrocytic activation ceased. In vivo, astrocytic activation enhanced memory allocation; i.e., it increased neuronal activity in a task-specific way only when coupled with learning, but not in home-caged mice. Furthermore, astrocytic activation using either a chemogenetic or an optogenetic tool during acquisition resulted in memory recall enhancement on the following day. Conversely, directly increasing neuronal activity resulted in dramatic memory impairment. Our findings that astrocytes induce plasticity and enhance memory may have important clinical implications for cognitive augmentation treatments.
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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
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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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.comExercise 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.