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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Dr. 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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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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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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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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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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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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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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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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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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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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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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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.
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“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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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.”
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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.
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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.
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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.