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Is Nicotine a Safe Cognitive Enhancer?

Posted on April 1st 2025 (about 2 months)

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

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

Posted on September 23rd 2024 (8 months)

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

alcohol

The Truth About Alcohol: Risks, Benefits, and Everything In-Between | Dr. Rhonda Patrick

Posted on June 27th 2024 (11 months)

In this episode, we’re taking a deep dive into alcohol. We’ll explore the science, misconceptions, controversies, and health effects of this widely used drug.

Topic Pages

  • Aerobic exercise

    Aerobic exercise, physical activity that increases breathing and heart rate, promotes cardiovascular, brain, and whole-body health.

  • Alcohol

    Alcohol is one of the most widely used and abused drugs and is associated with several health conditions.

  • Berberine

    Berberine is a plant-based compound with pharmacological actions that share many features with metformin.

  • Blood-brain barrier

    The blood-brain barrier allows the passage of nutrients and cell signals from the bloodstream to the brain while excluding harmful substances.

  • Brain-derived neurotrophic factor (BDNF)

    BDNF is a growth factor known for its influence on neuronal health and for its role in mediating the beneficial cognitive effects associated with exercise.

  • Breast milk and breastfeeding

    Breast milk is a complex, dynamic fluid containing nutritional and non-nutritional components that support infant development. Breastfeeding benefits both infants and mothers.

  • Choline

    Choline is an essential nutrient critical for various bodily functions, including brain development, liver health, and muscle function.

  • Cold exposure

    Cold exposure may be a hormetic stressor that reduces inflammation, activates antioxidant enzymes, and boosts the immune system to protect against age-related diseases.

  • Creatine

    Creatine is a naturally occurring compound best known for its widespread use as a dietary supplement to enhance physical performance.

  • Depression

    Depression – a neuropsychiatric disorder affecting 322 million people worldwide – is characterized by negative mood and metabolic, hormonal, and immune disturbances.

  • Exercise Intensity

    Vigorous exercise exerts several benefits on cardiovascular health, metabolic health, and longevity.

  • Microplastics

    Microplastics are tiny plastic particles, less than 5 millimeters in size, that pose immense environmental and health risks due to their widespread presence.

  • Multivitamins

    Multivitamin and multimineral supplements are used by nearly one-third of adults to improve health and mitigate disease risk.

  • Omega-3 fatty acids

    Omega-3 fatty acids play critical roles in human health and may be beneficial in ameliorating symptoms associated with chronic health conditions and in combating aging-related diseases.

  • Polyphenol-rich diets and neurodegeneration (glycemic control)
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    Polphenol-rich diets promote better glucose regulation can help slow brain aging, preserve hippocampal function, and reduce cognitive decline over time.

  • Polyphenols

    Polyphenols are bioactive plant compounds with a wide range of health benefits.

  • Red light therapy (photobiomodulation)

    Photobiomodulation is a non-invasive, light-based therapeutic technique that stimulates biological processes within cells and tissues, with potential applications in medicine, dentistry, cosmetic procedures, and scientific research.

  • Salmon roe

    Salmon roe, the internal egg mass found in female salmon, is rich in protein, vitamins, and the omega-3 fatty acids EPA and DHA.

  • Sirtuins

    Sirtuins play a key role in healthspan and longevity by regulating a variety of metabolic processes implicated in aging.

  • Small vessel disease

    Small vessel disease is a generic term that describes dysfunction of blood vessels that occurs with aging and contributes to cognitive decline, cardiovascular disease, frailty, and stroke.

  • Sulforaphane

    Sulforaphane is a bioactive compound that exerts potent antioxidant and anti-inflammatory properties and may be beneficial against a wide range of chronic and acute diseases.

  • Ultra-processed Foods (UPFs)

    UPFs are formulations of mostly cheap industrial sources of dietary energy (calories) and nutrients plus additives that have negative effects on human health.

News & Publications

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

    Study link:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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  • Mouse study suggests that interleukin-6-releasing immune cells outside the brain influence the propensity to develop depression. (2013) www.sciencedaily.com
    Brain Inflammation Depression IL-6

    Psychosocial stress promotes the release of IL-6, potentially driving the development of depression.

    Psychosocial stress, such as that experienced with divorce, discrimination, trauma, or the death of a child, can have profound effects on the human body. For example, evidence indicates that stress alters the immune system, driving inflammatory processes and impairing antiviral responses. Findings from a 2013 study suggest that psychosocial stress promotes the release of interleukin 6 (IL-6), potentially driving the development of depression.

    IL-6 is a pro-inflammatory cytokine that plays an important role as a mediator of fever and the body’s immune response. It is produced by almost all immune cells and is induced in the context of infection, autoimmunity, or cancer. Many physiological processes are influenced by IL-6, including glucose metabolism, blood cell production, neuroendocrine regulation, and fatigue, among others. IL-6 levels are often elevated in people who have depression.

    The investigators conducted their study using mice that had undergone radiation to destroy their bone marrow, compromising their immune function. Then they transplanted bone marrow from mice that exhibited either high or low levels of IL-6 levels in response to stress into the immune-compromised animals. Then they exposed the animals to a social stressor.

    They found that mice that received transplants from those that exhibited high IL-6 levels in response to stress demonstrated more depression-like behaviors than the mice that received transplants from those that exhibited low IL-6 levels. These findings suggest that IL-6 promotes a pro-inflammatory state that promotes depression-like symptoms in response to psychosocial stress. Identifying therapeutic strategies that inhibit IL-6 may benefit people who are vulnerable to the effects of psychosocial stress.

    Interestingly, hyperthermia, such as that experienced with sauna use or hot baths, has been shown to reduce IL-6 levels. Learn more about the beneficial effects of sauna use in our overview article.

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  • Microglial interleukin-6 signaling and prostaglandin synthesis may regulate depressive symptoms in neurological disorders. (2021) www.sciencedaily.com
    Brain Inflammation Depression Mental Health IL-6

    Microglia and IL-6 drive the negative mood often associated with inflammation.

    People who have certain neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, or stroke, often exhibit low mood. Evidence suggests that inflammation plays a role in the pathogenesis of these neurological disorders and likely influences mood, as well. Findings from a 2021 study suggest that microglia activation drives the low mood often associated with neurological disorders.

    Microglia are the brain’s resident immune cells. They serve an essential role in maintaining brain microenvironment homeostasis. Acute activation of microglia modulates inflammation and neurotoxicity, but chronic activation promotes brain inflammation and damage. Evidence suggests that microglia activation influences mood.

    The investigators used chemogenetics, a research technique that uses drugs or other chemicals to modulate neural activity, to stimulate microglia activation in the brains of mice. They noted that levels of interleukin-6 (IL-6, a pro-inflammatory cytokine) and prostaglandins (hormone-like molecules that are involved in inflammation) increased in the animals' brains. In addition, the animals exhibited a low mood. Blocking microglia activity restored the animals' positive mood, however.

    These findings suggest that microglia drive the low mood often associated with inflammation and that IL-6 is a prominent player in this process. Learn more about the role of inflammation and mood in this episode featuring Dr. Charles Raison.

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  • Blocking soluble TNF signaling attenuates loss of dopaminergic neurons in models of Parkinson’s disease. (2006) www.sciencedaily.com
    Brain Parkinson's Neurons TNF-Alpha

    Blocking the action of TNF-alpha may slow the progression of Parkinson’s disease.

    Parkinson’s disease is a progressive neurodegenerative disorder that affects the central nervous system. It is caused by the destruction of nerve cells in the part of the brain called the substantia nigra. Approximately 1 percent of all adults over the age of 60 years lives with Parkinson’s disease. Findings from a 2006 study suggest that blocking the action of tumor necrosis factor-alpha slows the progression of Parkinson’s disease.

    Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine that is produced by a wide range of cells, including macrophages, lymphocytes, glial cells, and others. TNF-alpha signaling inhibits tumorigenesis, prevents viral replication, and induces fever and apoptosis. Dysregulation of the TNF-alpha signaling pathway has been implicated in a variety of disorders, including cancer, autoimmune diseases, Alzheimer’s disease, and depression.

    The investigators injected the brains of mice with either lipopolysaccharide (LPS, an endotoxin that promotes acute inflammation) or 6-hydroxydopamine (a neurotoxin) and assessed the animals' brains for evidence of substantia nigra cell death. They injected a compound called XENP345 (a TNF-alpha inhibitor) into the brains of some of the mice. They also applied LPS and 6-hydroxydopamine to cultured neuronal cells and assessed the effects of XENP345 on cell death.

    They found that both LPS and 6-hydroxydopamine caused marked cell death in the substantia nigra region of the animals' brains. They also found that inhibiting TNF-alpha via XENP345 in the brains and in cultured cells reduced cell death by roughly half.

    These findings suggest that inhibiting the activity of the pro-inflammatory cytokine TNF-alpha reduces cell death in an animal model of Parkinson’s disease. Robust evidence indicates that exercise, which also reduces inflammation, slows the progression of Parkinson’s disease. Learn more about the effects of exercise on Parkinson’s disease in this episode featuring Dr. Giselle Petzinger.

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  • TNF-alpha production within the brain may partially explain the behavioral changes in mice with cholestatic liver damage. (2006) www.sciencedaily.com
    Brain Inflammation Behavior TNF-Alpha

    TNF-alpha in the brain drives sickness behaviors associated with liver disease.

    Many liver disorders cause behavioral symptoms, often referred to as sickness behaviors, such as fatigue, loss of appetite, and “brain fog.” Evidence suggests that these symptoms arise from alterations in the central nervous system, but scientists don’t fully understand what drives them. Findings from a 2006 study suggest that sickness behaviors in the setting of cholestasis, a common liver disorder, are caused by the presence of tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, in the brain.

    Cholestasis is characterized by impaired bile flow and subsequent retention of bile acids, bilirubin, and other substances, including lipopolysaccharide, an endotoxin, in the liver and blood. It is a common disorder of pregnancy but can affect all demographics, including children. Most people with cholestasis report experiencing sickness behaviors, especially fatigue, which occurs in roughly 86 percent of people with the disorder.

    TNF-alpha is produced by many types of immune cells. It exists in soluble and transmembrane forms, both of which mediate a variety of opposing physiological and pathological functions, depending on which of its receptors it binds to. For example, binding to TNF receptor 1 promotes apoptosis (programmed cell death) and inflammation; binding to TNF receptor 2 promotes cell survival, resolution of inflammation, immunity, and cellular repair. Elevated TNF-alpha is associated with chronic pain syndromes and anxious behaviors.

    The investigators tied off the bile ducts of healthy mice to induce cholestasis. Then they isolated endothelial cells from the blood vessels in the animals' brains to see if the cells were activated and if the cells interacted with immune cells. They also measured TNF-alpha production by monocytes (white blood cells).

    They found that endothelial cells were activated in the setting of cholestasis, and these activated cells readily interacted with immune cells that had been recruited to the brain. In turn, the immune cells increased their production of TNF-alpha. In light of the known effects of TNF-alpha on sickness behaviors, these findings suggest that TNF-alpha production in the brain mediates sickness behaviors in mice with liver disease.

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  • In a mendelian randomization study, genetically predicted levels of interleukin 6 (IL-6) were associated with neuropsychiatric disorders. www.sciencedaily.com
    Brain Inflammation Mental Health Genetics IL-6

    IL-6 may drive inflammation in neuropsychiatric disorders.

    Neuropsychiatric disorders are the leading cause of disability among people living in the United States, accounting for nearly 20 percent of all years of life lost to disability and premature death. Evidence suggests that brain inflammation is a key player in neuropsychiatric disorders, the effects of which may be bidirectional. A recent study identified potential links between inflammation and structural alterations in regions of the brain implicated in neuropsychiatric disorders.

    The brains of people with neuropsychiatric disorders exhibit a range of abnormal structural alterations, but researchers don’t fully understand what drives these abnormalities. One possible player is interleukin-6 (IL-6), a cytokine that can cross the blood-brain barrier, increasing the barrier’s permeability and promoting brain inflammation. In turn, this inflammation can impair synaptic pruning, a natural process that occurs in the brain between early childhood and adulthood and eliminates extra synapses. Inappropriate synaptic pruning is associated with some neuropsychiatric disorders, including schizophrenia and autism.

    The investigators searched for evidence of potential causality in the association between inflammatory cytokines and altered brain structure using Mendelian randomization, a research method that provides evidence of links between modifiable risk factors and disease based on genetic variants within a population. Using data from more than 20,000 adults enrolled in the UK Biobank study, the researchers looked for associations between genetic variants that influence levels of interleukin-6 (IL-6, a pro-inflammatory cytokine), as well as other inflammatory factors. and changes in gray matter volume in specific areas of the brain. They also examined postmortem brain tissue to assess gene expression in the brain areas of interest.

    They found that genes that influence the production of pro-inflammatory molecules, especially IL-6, are strongly linked with brain structure in the temporal and frontal regions of the brain, areas of the brain commonly implicated in neuropsychiatric disorders. The postmortem analyses revealed that the overproduction of these pro-inflammatory genes is associated with disorders such as epilepsy, cognitive disorder, schizophrenia, psychotic disorder, and autism spectrum disorder.

    These findings suggest that pro-inflammatory pathways, especially those associated with IL-6, are essential for normal brain structural development and IL-6 elevation may drive structural alterations implicated in neuropsychiatric disorders. Evidence suggests that heat stress reduces symptoms associated with depression, a type of neuropsychiatric disorder. Learn about a clinical trial that is investigating the benefits of heat stress in this episode featuring Dr. Ashley Mason.

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  • Low levels of interleukin-6 (IL-6) in the prefrontal cortex enhanced reversal learning in rats. (2014) www.sciencedaily.com
    Brain IL-6

    Cytokine signaling in the brain promotes cognitive flexibility.

    Cytokines are small signaling proteins that play essential roles in the body’s inflammatory process. They are produced primarily by immune cells, but they are also produced at basal levels in the brain, where they participate in memory and learning. Findings from a 2014 study suggest that cytokine signaling in the brain is necessary for reversal learning.

    Reversal learning is a form of cognitive flexibility. It allows an organism to determine that a reward for a particular activity has changed and then adjust its behavior accordingly. Reversal learning enables an organism to disengage from ongoing behavior, a quality that is related to impulsive or compulsive actions. Evidence suggests that reversal learning is impaired in neuropsychiatric disorders such as depression, schizophrenia, and obsessive-compulsive disorder.

    The researchers conducted a three-part experiment. First, they blocked the production of interleukin-6 (IL-6), a type of cytokine, in the brains of rats. They subjected one-half of the rats to cold stress (which has been shown to impair reversal learning), and the other half was left in a non-stressful environment. Then they tested both the stressed and non-stressed animals' reversal learning capacities. Surprisingly, they found that blocking IL-6 impaired reversal learning in both groups of animals, suggesting that basal IL-6 activity in the brain (in the absence of stress or inflammation) may aid learning.

    In their second experiment, the researchers determined that IL-6 is produced in the orbitofrontal cortex, a region of the brain responsible for decision-making and learning. They also determined that the mechanism by which IL-6 facilitates reversal learning was a signaling pathway called JAK/STAT, which is involved in multiple physiological processes.

    Finally, they restored IL-6 levels in the orbitofrontal cortex region of the animals' brains. They subjected them to cold stress again and re-tested their reversal learning capacities. They found that restoring IL-6 to the animals' brains attenuated the stress-induced reversal learning losses.

    These findings suggest that a basal level of the cytokine IL-6 is essential for reversal learning in rats. The researchers posited that although IL-6 is typically a pro-inflammatory cytokine, it may exert differential effects under different conditions. For example, it may promote learning deficits under inflammatory conditions, but facilitate learning under basal (non-stressed, non-inflammatory) conditions.

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  • Children who lack sleep may experience detrimental impact on brain and cognitive development that persists over time www.eurekalert.org
    Brain Sleep

    Children who don’t get enough sleep have altered brain structure and impaired brain function.

    Sleep is essential for normal brain development in children. The American Academy of Pediatrics recommends that children between the ages of six and 12 years sleep nine to 12 hours every night for optimal health, but many children do not meet these recommendations. Findings from a recent study suggest that children who don’t get enough sleep have altered brain structure and impaired brain function.

    The investigators analyzed structural magnetic resonance imaging data and medical records for more than 8,300 children between the ages of nine and ten years who were enrolled in the Adolescent Brain Cognitive Development (ABCD) Study. They also assessed the children’s cognitive performance and mental health status. The parents of the children in the study provided information about their child’s nightly sleep duration. Assessments were repeated when the children reached the ages of 11 to 12 years.

    The study revealed that brain volumes in areas responsible for attention, memory, and inhibition were lower in sleep-deprived children than in those who received adequate sleep. In addition, children who had shorter sleep duration were more likely to experience depression and anxiety and exhibit impulsive behavior and poor cognitive performance. The association between poor sleep and depression persisted at the two-year follow-up.

    These findings underscore the importance of adequate sleep for proper brain function, especially in the developing brain. Learn more about the importance of sleep in this episode featuring Dr. Matthew Walker.

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  • Periodontal Condition Is Correlated with Deep and Subcortical White Matter Hyperintensity Lesions in Japanese Adults www.mdpi.com
    Brain Aging Inflammation Small Vessel Disease

    Gum disease may increase the risk of white matter hyperintensities, a type of brain lesion.

    White matter hyperintensities are brain lesions that appear as intense white spots on magnetic resonance imaging (MRI) scans. They are often indicators of cerebral small blood vessel disease and are considered a risk factor for dementia. High blood pressure is the primary contributor to white matter hyperintensity formation, but other factors likely play roles, as well. Findings from a 2020 study suggest that periodontitis is associated with white matter hyperintensities.

    Periodontitis is a chronic inflammatory condition of the gums, characterized by red, tender, swollen, or bleeding gums. It is typically caused by poor oral hygiene and is more common with age, manifesting in more than two-thirds of adults over the age of 65 years. Periodontitis is diagnosed using a periodontal probe, which is used to assess the depth of pockets in the gum. In a healthy mouth, a pocket can be anywhere from 1 to 3 millimeters deep. Deeper pockets are indicators of gum inflammation and disease.

    The study involved more than 400 adults (average age, 54 years) who underwent a routine dental exam that included pocket depth probing. The investigators performed MRI scans on the participants to identify the presence of white matter hyperintensities, which were classified according to their size, number, and severity. They gathered information about the participants' general health and lifestyles and measured their C-reactive protein (CRP, a biomarker of inflammation). They found that nearly half of the participants had white matter hyperintensities. Those who did were nearly three times more likely to be at least 65 years old, more than twice as likely to have elevated systolic blood pressure, and nearly twice as likely to have deeper pocket depth (6 millimeters or more). Having white matter hyperintensities was not associated with the participants' CRP levels.

    These findings suggest that older age, elevated blood pressure, and periodontitis are associated with an increased risk of developing white matter hyperintensities, but inflammation is not a driver of this association. Evidence indicates that white matter hyperintensities are predictive of the amount and degree of leakage of the blood-brain barrier leakage. Learn more in our overview article.

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  • Lost memory in menopause explained: Estrogen provides a protective role in mitigating effects of visceral fat on brain structural networks and memory jamanetwork.com
    Brain Alzheimer's Obesity Memory Estrogen Visceral Fat

    Estrogen mitigates the association between visceral fat on cognitive decline.

    Estradiol, a form of estrogen, is the primary female sex hormone. It participates in menstrual cycle regulation and drives the development of female secondary sex characteristics, such as breasts, a wider pelvis, and gynoid fat – fat that forms around the hips, thighs, and breasts. Evidence suggests that estradiol exerts both cardioprotective and neuroprotective effects. Findings from a 2020 study demonstrate that estradiol mitigates the association between visceral fat on cognitive decline.

    Cognitive decline is characterized by altered brain structural networks and accelerated degeneration with aging. Scientists don’t fully understand the biological mechanisms that drive cognitive decline, but evidence indicates that visceral fat – a type of fat that accumulates in the abdominal cavity – may play a role. Visceral fat is metabolically active and is associated with increased markers of inflammation and oxidative stress, and decreased levels of anti-inflammatory proteins, such as adiponectin

    The cross-sectional study involved 974 cognitively healthy females and males (average age, ~50 years). Using magnetic resonance imaging, the investigators measured the participants' gray matter volume, cerebral cortex area, intracranial blood vessels, and visceral fat. They also measured estradiol concentrations in a subset (390) of the females. All the participants completed neuropsychological testing to assess memory performance.

    The investigators found that visceral fat exacerbated the harmful effects of aging on the brain’s structural networks in both females and males. However, estradiol mitigated some of these effects in the females, but not the males. Females between the ages of 35 and 55 years (the period surrounding menopause) who had lower estradiol concentrations were more likely to exhibit greater structural network impairments and worse memory performance.

    These findings suggest that estradiol mitigates some of the harmful effects of visceral fat on the brain’s structural networks and cognitive health. Interestingly, the fasting-mimicking diet preferentially depletes visceral fat. Learn more in this clip featuring Dr. Valter Longo.

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  • Nerve Stimulation Promotes Resolution of Inflammation. neurosciencenews.com
    Brain Inflammation

    Vagus nerve stimulation promotes the resolution of inflammation.

    Inflammation is a necessary component of the body’s immune response. But unresolved inflammation is harmful to the body and can promote a wide range of chronic diseases. Findings from a recent study suggest that stimulation of the vagus nerve promotes the resolution of inflammation.

    The vagus nerve is the tenth cranial nerve. Its name, “vagus,” comes from the Latin term for “wandering” – a characteristic of the nerve, which arises in the brain and extends to organs in the neck, chest, and abdomen. The vagus nerve is the primary component of the parasympathetic nervous system, which regulates many crucial biological processes, including mood control, digestion, heart rate, and immune response. Evidence from animal studies suggests that stimulating the vagal nerve reduces the release of proinflammatory cytokines that drive acute inflammation.

    Using a mild electrical current, the investigators stimulated the vagus nerve of mice. Then, after inducing an inflammatory response in the animals' abdomens, they measured neutrophils (immune cells) and anti-inflammatory markers in fluid taken from the abdominal region.

    They found that mice that received the vagus nerve stimulation had higher levels of specialized pro-resolving mediators, or SPMs, in their abdominal fluid. SPMs are byproducts of omega-3 fatty acid metabolism that play critical roles in resolving inflammation. The stimulated mice also had fewer neutrophils in their abdominal fluid, an indication that neutrophil infiltration had ceased, a key process in the resolution of inflammation.

    These findings suggest that vagus nerve stimulation promotes the resolution of inflammation via the promotion of SPM biosynthesis. Learn more about SPMs and omega-3 metabolism in this episode featuring Dr. Bill Harris.

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  • Researchers discover fundamental roles of glucosamine in brain www.sciencedaily.com
    Brain

    Glucosamine plays important roles in brain function.

    Glucosamine is a type of sugar found in the muscles, cartilage, and other soft tissues of the body. It is commonly marketed as a dietary supplement used for joint pain and stiffness. Evidence from a 2021 study suggests that glucosamine is prevalent in brain glycogen, where it plays important roles in glycosylation.

    Glycogen is a multi-branched polysaccharide that serves as the stored form of glucose in the human body. Most of the body’s glycogen stores are found in the muscles and liver, but some glycogen is found in the brain, primarily in the astrocytes, a type of cell involved in neurogenesis and blood-brain barrier maintenance. In diseases in which glycogen storage is impaired, glycogen-like cellular aggregates called polyglucosan bodies can form in the brain, altering brain function and driving dementia.

    Glycosylation is a biochemical process in which glucose is added to an amino acid. It plays important roles in determining the structure, function, and stability of proteins. Glycosylation influences neurological function, and disturbed glycosylation is implicated in the pathogenesis of many neurological disorders, including cognitive decline.

    The investigators conducted a multi-part study. First, they determined the overall composition of the sugars in the glycogen of liver, muscle, and brain tissue of mice using gas chromatography and mass spectrometry. They found that liver glycogen contained just 0.1 percent glucosamine, and muscle glycogen contained approximately 1 percent of the sugar. However, brain glycogen contained 25 percent glucosamine.

    Then, using a special form of mass spectrometry (called “MALDI TW IMS”), they quantified and tracked the movement of the glucosamine in the brains of healthy mice and mice that had glycogen storage diseases. They found that the mice with the glycogen storage diseases had impaired glucosamine movement, abundant polyglucosan bodies, and evidence of impaired cell metabolism and glycosylation.

    These findings suggest that glucosamine in brain glycogen is essential for brain health. They also may help identify strategies for treating glycosylation disorders, which cause severe neurological symptoms, including dementia.

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  • Keep exercising: New study finds it's good for your brain's gray matter www.sciencedaily.com
    Exercise Brain

    Cardiorespiratory fitness helps prevent age-related brain volume losses.

    The brain loses about 5 percent of its volume every decade after the age of 40 years, likely due to the death of neurons in the gray matter. These losses contribute to age-related cognitive decline and loss of neuroplasticity, the brain’s ability to change and adapt to new exposures. Findings from a 2020 study suggest that having greater cardiorespiratory fitness helps prevent age-related brain volume losses.

    Cardiorespiratory fitness is a measure of the body’s aerobic capacity – the ability to deliver oxygen to skeletal muscles – during sustained physical activity. Poor cardiorespiratory fitness, along with dyslipidemia, family history, hypertension, age, cigarette smoking, diabetes mellitus, obesity, and physical inactivity, increases a person’s risk for cardiovascular disease and death. The most accurate way to assess cardiorespiratory fitness involves measuring maximal oxygen uptake, often referred to as VO2 max, during a graded exercise test in a laboratory, clinical, or research setting.

    The study involved more than 2,000 healthy adults (average age, 52 years) who were enrolled in a larger, ongoing study. The investigators measured the participants' cardiorespiratory fitness, assessed via VO2 max while riding on an exercise bike. They collected the participants' demographic data, and they measured their brain volumes via magnetic resonance imaging scans.

    They found that participants with greater cardiorespiratory fitness tended to have greater gray matter and total brain volumes. They also had more clusters of gray and white matter tissue in brain areas responsible for cognitive function rather than movement. These findings held true even when taking the participants' ages, education levels, smoking status, blood pressure, and body weights into consideration.

    These findings suggest that having greater cardiorespiratory fitness ameliorates some of the brain volume losses associated with aging and underscore the importance of exercising throughout the lifespan. Learn more about the health benefits of exercise in our overview article.

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  • High and low exercise intensity found to influence brain function differently www.sciencedaily.com
    Exercise Brain

    Aerobic exercise influences many aspects of human health, including brain health. For example, exercise promotes the release of brain-derived neurotrophic factor, better known as BDNF, a cell-signaling protein that influences the formation, growth, survival, and development of neurons. Findings from a 2020 study suggest that exercise intensity determines which parts of the brain are affected during a workout.

    Exercise intensity is defined as how hard the body works during exercise. During low-intensity aerobic exercise, a person’s heart rate is typically maintained at a steady pace of about 50 percent of its maximum ability, and workouts last for at least 30 minutes. During high-intensity aerobic exercise, a person’s heart rate is typically 75 percent of its maximum ability or higher. For example, high-intensity interval training, often referred to as HIIT, is a popular form of high-intensity exercise involving short bursts of intense aerobic exercise interspersed with periods of rest or lower-intensity exercise. During a typical HIIT session, exercisers typically achieve 80 to 100 percent of their VO2max (a measure of respiratory function) or maximum heart rate. Most HIIT workouts are brief, lasting just 15 to 30 minutes.

    The study involved 25 healthy male athletes who engaged in both low-intensity and high-intensity aerobic exercise sessions on a treadmill. The sessions lasted for approximately 30 minutes and were separated by at least two days. The participants underwent a battery of tests to determine their mental state, cognitive performance, and attention. Before and after the exercise sessions, they underwent resting-state functional magnetic resonance imaging (rs-fMRI), a technique that characterizes the functional connectivity of neuronal networks when the brain is at rest.

    The investigators found that the participants' moods improved after both exercise intensities. However, the rs-fMRIs revealed that the different intensities affected different parts of their brains. The low-intensity exercise turned on the activity of brain networks involved in cognitive function and attention processing. On the other hand, the high-intensity exercise turned on networks involved in mood and emotions and turned off networks involved in motor function.

    These findings suggest that differing exercise intensities affect different parts of the brain during exercise and underscore the importance of varying workout programs. Learn more about the effects of aerobic exercise on health in our overview article.

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  • Heightened dream recall ability linked to increased creativity and functional brain connectivity www.psypost.org
    Brain Sleep

    People who frequently recall their dreams tend to be more creative.

    Dreams are a state of consciousness that occurs during sleep. Typically characterized by sensory, cognitive, and emotional experiences, dreams share many similarities with hallucinations. Scientists formerly believed that dreams only occurred during the rapid eye movement, or REM, stage of sleep, but recent research indicates that they can occur at any time during sleep. Findings from a recent study suggest that people who frequently recall their dreams tend to be more creative and exhibit increased functional connectivity in the brain’s default mode network.

    The default mode network is a collection of interconnected neural structures that demonstrate low activity when a person is engaged in a particular task but high activity when not. It also demonstrates activity when a person tries to remember past events or imagine future events. Although some evidence suggests that the default mode network is involved in self-focused, ruminative thought, other evidence suggests it is involved in creativity and spontaneous thought processes.

    The study involved 55 healthy adults (19 to 29 years old) who had normal sleep patterns. Roughly half of the participants reported that they frequently recalled their dreams, recalling about six dreams per week, and the other half reported that they rarely recalled their dreams, recalling fewer than one dream per week. All participants underwent functional magnetic resonance imaging (fMRI) scans while sleeping. Before their scans, they answered questions about their personality, anxiety levels, cognitive ability, and sleep quality. They also completed a battery of tests to gauge memory and creativity.

    They found that both groups of participants had similar personalities, anxiety levels, sleep quality, and cognitive abilities. But participants who frequently recalled their dreams performed better on creativity tests than those who rarely recalled their dreams, suggesting they had greater creative skills. The fMRIs revealed that frequent recallers also exhibited enhanced functional connectivity within the default mode network of their brains than infrequent recallers.

    These findings suggest that high recall of dreams is associated with greater creativity and functional connectivity in the default mode network of the brain, and this connectivity promotes creative thinking during both wakefulness and sleep. Learn more about the roles of dreams in creativity in this clip featuring Dr. Matthew Walker.

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  • Peripheral amyloid-beta produced in the liver in type 2 diabetes may be a crucial link to Alzheimer’s disease www.sciencedaily.com
    Brain Alzheimer's Diabetes Neurodegeneration

    Amyloid-beta produced in peripheral tissues provides a link between diabetes and Alzheimer’s disease risk.

    Type 2 diabetes, a metabolic disorder characterized by glucose intolerance and insulin resistance, poses a significant public health concern, affecting roughly 470 million people worldwide. Having type 2 diabetes greatly increases a person’s risk of developing Alzheimer’s disease, but scientists don’t fully understand the mechanisms that drive the increased risk. Findings from a recent study suggest that amyloid-beta produced in tissues outside the brain provides the link between type 2 diabetes and Alzheimer’s disease.

    Amyloid-beta, a toxic peptide produced in the brain, clumps together and forms plaques with age. Its accumulation is a pathological hallmark of Alzheimer’s disease. However, amyloid-beta is produced in peripheral tissues, as well, including those that are sensitive to glucose or insulin, such as the pancreas, adipose tissues, skeletal muscles, and liver. Scientists don’t fully understand the roles peripheral amyloid-beta plays in human health.

    The investigators conducted a three-part experiment in mice, live mouse tissues, and cell cultures. First, they injected mice with glucose after they had fasted for 16 hours to examine the effects of glucose and insulin on blood amyloid-beta levels. They found that the mice experienced a transient increase in blood levels of glucose, insulin, and amyloid-beta. Then they injected amyloid-beta and glucose into mice that can’t produce the protein and found that amyloid-beta suppressed the animals’ insulin response.

    Next, they applied glucose and insulin to live tissues from the pancreas, adipose tissue, skeletal muscle, liver, and kidneys of mice. They found that glucose stimulated the release of amyloid-beta from the pancreas, whereas insulin stimulated its release from adipose tissue, skeletal muscle, and liver tissue. However, when the scientists added glucose along with amyloid-beta to the pancreatic tissue, insulin release was suppressed.

    Finally, they used antibodies that target the amyloid-beta protein to determine where the protein was produced. They found that amyloid-beta was produced and stored in the beta cells of the pancreas and released into circulation when stimulated with glucose.

    These findings suggest that amyloid-beta protein produced in peripheral tissues modulates insulin secretion. They may further provide a mechanism linking type 2 diabetes to Alzheimer’s disease. The investigators posited that high blood glucose and insulin levels that occur in the setting of diabetes increase peripheral amyloid-beta production, altering the balance between brain and peripheral amyloid-beta levels and suppressing the protein’s efflux from the brain. Furthermore, high insulin levels in the brain may impair normal degradation of brain amyloid-beta, increasing the protein’s levels in the brain and driving its accumulation. Learn more about the role of amyloid-beta in Alzheimer’s disease in this clip featuring Dr. Dale Bredesen.

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  • Leaky blood-brain barrier caused by cerebral small vessel disease increases the prevalence of white-matter hyperintensities and brain damage www.sciencedaily.com
    Brain Aging Dementia Blood-Brain Barrier Small Vessel Disease

    Poor blood-brain barrier integrity drives white matter losses.

    White matter hyperintensities are areas in the brain that appear as intense white spots on magnetic resonance imaging (MRI) scans. They are often indicators of cerebral small blood vessel disease and are considered a risk factor for dementia. A 2021 study found that breaches in blood-brain barrier integrity are associated with brain tissue losses and precede the appearance of white matter hyperintensities.

    The blood-brain barrier, a specialized system of endothelial cells that shields the brain from toxins present in the blood, supplies the brain’s tissues with vital nutrients and substances necessary for neuronal and metabolic function. The structural integrity of the blood-brain barrier is therefore critical for homeostatic maintenance of the brain microenvironment.

    The study involved 43 patients (average age 58 years) who had been diagnosed with cerebral small vessel disease, as evidenced by having experienced a stroke or demonstrating mild cognitive impairment. At the beginning of the study and two years later, participants underwent a variety of MRI techniques that quantified their overall blood-brain barrier permeability as well as the areas surrounding white matter hyperintensities.

    The MRIs revealed that participants who had the greatest amount of leaky brain tissue at the beginning of the study exhibited greater white matter tissue losses two years later. These tissue losses translated to greater permeability, a phenomenon particularly evident in the areas surrounding the brain lesions associated with white matter hyperintensities.

    These findings suggest that losses in blood-brain barrier integrity damage brain tissue, driving increased permeability and white matter losses. In turn, these changes potentiate the disease processes associated with cerebral small vessel disease. Learn more about the blood-brain barrier in our overview article.

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  • Intense cycling exercise at 80% maximum heart rate improves memory via endocannabinoid action on the hippocampus www.sciencedaily.com
    Exercise Brain Performance Memory Cannabinoid Aerobic

    Exercise activates the endocannabinoid system to promote learning and memory formation.

    Scientists have identified robust links between physical exercise and brain health. Some of the mechanisms that drive the beneficial effects of exercise on the brain include increases in brain volume and connectivity, improved blood flow, enhanced synaptic plasticity, and increased neurogenesis – the formation of new neurons. Findings from a 2020 study suggest that moderate- to vigorous-intensity exercise improves motor sequence memory via endocannabinoid action on the hippocampus.

    Motor sequence memory involves learning predefined sequences of interrelated motor actions, such as playing the piano or dancing. The hippocampus interacts with various neural networks to support the formation of motor sequency memory.

    Endocannabinoids are small lipid molecules produced in the body that bind to cannabinoid receptors in the central and peripheral nervous systems. Endocannabinoids regulate many physiological processes, including movement control, pain processing, brain development, and learning and memory. The two major endocannabinoids in the body are anandamide and 2-arachindonyl glycerol.

    The study involved 15 healthy adults (average age, 23 years) who had at least fair respiratory fitness, as measured via VO2 max. Participants completed a serial reaction time task (a widely used measure of learning and memory) before and after three conditions: moderate-intensity exercise, vigorous-intensity exercise, and rest. Prior to performing the task, participants consumed a standardized carbohydrate-rich breakfast. During the task, the investigators measured the participants' behavior, brain activity, and circulating anandamide (endocannabinoid) levels.

    They found that vigorous-intensity exercise markedly improved motor sequence memory compared to rest. Moderate-intensity exercise also improved motor sequence memory, but to a lesser degree. The improvements coincided with increased levels of the endocannabinoid anandamide and enhanced hippocampal activity.

    These findings suggest that vigorous-intensity exercise promotes motor sequence memory and learning and underscore the benefits of exercise on cognitive function. Learn about the beneficial effects of aerobic exercise in our overview article.

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  • Inhibiting the Mfsd2a transporter that brings omega-3 DHA into the brain promotes leakage of brain barrier www.sciencedaily.com
    Brain Cancer Aging Omega-3 Blood-Brain Barrier

    Impaired transport of DHA disrupts the blood-brain barrier.

    Lipid rafts – cholesterol-filled “bubbles” found in the cell membrane – serve as staging areas for many cellular activities. One type of lipid raft, called caveolae, facilitates the transport of substances across the membrane of endothelial cells. Findings from a 2017 study demonstrate that suppression of caveolae-mediated transport in brain endothelial cells protects the integrity of the blood-brain barrier.

    The blood-brain barrier is a highly selective semi-permeable barrier made up of endothelial cells connected via tight junctions. This barrier separates the circulating blood from the brain’s extracellular fluid and prevents the entry of substances that may be neurotoxic. Disruption of the blood-brain barrier has been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, among others.

    The investigators' previous research showed that a critical player in blood-brain barrier function is Mfsd2a, a transmembrane protein found exclusively on the endothelial cells that line blood vessels on the barrier. Mfsd2a participates in lipid transport and is the sole means by which lysophospholipid DHA, the brain’s preferred form of DHA (a type of omega-3 fatty acid) is delivered to the brain.

    Using mice that carried a mutation that blocked Mfsd2a’s capacity to transport DHA, the investigators assessed blood-brain barrier function as well as caveolae formation and activity in the animals' brains. Then they compared the lipid composition of brain endothelial cells to lung epithelial cells, which lack Mfsd2a.

    They found that mice that lacked Mfsd2a function had leakier blood-brain barriers and greater caveolae formation and activity than normal mice. They also found that brain endothelial cells had higher lipid concentrations than lung epithelial cells. The most abundant lipid in the brain endothelial cells was DHA, which was found in concentrations that were two to five times higher.

    These findings suggest that Mfsd2a-mediated transport of lipids, particularly DHA, impairs caveolae activity, thereby preserving blood-brain integrity. Learn more about links between Mfsd2a, DHA, and brain health in this open-access peer-reviewed article by Dr. Rhonda Patrick..

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  • Oleic acid produced by cells in the brain (and found in olive oil) may be a key cell proliferation and neurogenesis signal www.sciencedaily.com
    Brain Neurogenesis

    Oleic acid produced in the brain promotes neurogenesis – the generation of new neurons.

    Oleic acid is a monounsaturated fatty acid produced in plants and is the primary fatty acid found in olive oil. Interestingly, oleic acid is also produced in the human brain. Findings from a recent study suggest that brain-derived oleic acid activates neural stem cells in the hippocampus, promoting neurogenesis – the generation of new neurons.

    The hippocampus is a small organ located within the brain’s medial temporal lobe. It is an important part of the limbic system (the region that regulates emotions) and plays critical roles in memory, learning, and spatial navigation. The neurons in the hippocampus are particularly vulnerable to amyloid-beta plaque accumulation, tau tangle formation, and subsequent atrophy – early indicators of Alzheimer’s disease.

    The investigators used spectroscopy, a research tool that uses light scatter to measure concentration, to look for the presence of monounsaturated fatty acids in neural progenitor cells. These cells differ from stem cells in that they can undergo only a limited number of replication cycles. They found that the progenitor cells contained several monounsaturated fatty acids, the most abundant of which was oleic acid. Treating the cells with a chemical that blocked the activity of enzymes involved in oleic acid production dramatically reduced the cells' survival.

    Next, they used spectroscopy to look for the presence of monounsaturated fatty acids in the brains of mice. They found an abundance of the fatty acids, especially oleic acid, in the dentate gyrus, the region of the hippocampus where neurogenesis occurs. Then, using homology modeling (a type of computer-based study technique) they observed that oleic acid bound to TLX, a protein in neural stem cells that regulates neurogenesis, switching on the protein’s activity and driving the production of new neurons.

    These findings suggest that oleic acid produced in the brain activates neurogenesis. Therapeutic modulation of TLX may be a means to counteract the effects of impaired neurogenesis in age-related cognitive decline, depression, Alzheimer’s disease, and other conditions. Brain-derived neurotropic factor, or BDNF, also promotes neurogenesis. Learn more about BDNF and the lifestyle behaviors that promote its production in our overview article.

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  • Mid-life long duration antibiotic use of >= two months linked to poorer scores in cognition, learning, working memory, and attention in later life www.sciencealert.com
    Brain Aging Microbiome Performance Memory Antibiotics Dementia

    Antibiotic use in midlife increases a person’s risk for neuropsychiatric diseases.

    Antibiotics are prescribed for a wide range of infectious diseases. In 2015, healthcare providers in the United States wrote nearly 270 million antibiotic prescriptions – more than 800 antibiotic prescriptions for every 1,000 people. Health experts estimate that 30 percent of these prescriptions were likely unnecessary. Findings from a new study suggest that antibiotic use in midlife increases a person’s risk for neuropsychiatric diseases.

    The study included approximately 15,000 midlife participants (average age, 55 years) enrolled in the Nurses’ Health Study II, an ongoing prospective cohort study of female nurses. The participants completed questionnaires regarding their general health, diet, lifestyle, and medication use during the previous four years, including antibiotic use and the reason for which the antibiotic was prescribed. The investigators categorized the participants' cumulative antibiotic use as none, one to 14 days, 15 days to two months, and two months or more. Participants also completed a battery of neuropsychological tests.

    The investigators found that participants who took antibiotics for at least two months over the previous four years were more likely to perform worse on neuropsychological tests than participants who did not take antibiotics. The influence of antibiotic use on neuropsychological test scores was roughly equivalent to three to four years of aging. These findings held true even after considering other factors that could influence cognitive function, including age and coexisting illnesses.

    These findings suggest that longer exposure to antibiotics in midlife negatively influences cognitive health, underscoring the importance of moderating antibiotic use in older adults. They also support findings from animal studies that suggest antibiotic use early in life alters neuropeptide signaling pathways that influence behavioral development. Learn more about the effects of antibiotic use in early life in this clip featuring Dr. Eran Elinav.

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  • Medium chain triglycerides (MCTs) improved cognition in patients with Alzheimer's disease. www.ncbi.nlm.nih.gov
    Brain Alzheimer's Neurodegeneration

    Medium-chain triglycerides improve cognitive function in Alzheimer’s disease.

    The brain relies heavily on glucose as its primary fuel, burning as much as 130 grams of glucose per day. However, glucose metabolism in the brain is impaired in Alzheimer’s disease, contributing to many of the disease’s symptoms. Findings from a recent study demonstrate that ketones derived from medium chain triglyceride metabolism may provide an alternative fuel source for the brain in the setting of Alzheimer’s disease.

    Ketones are molecules produced by the liver during the breakdown of fatty acids. Ketone production occurs during periods of low food intake (such as during fasting), carbohydrate-restrictive diets, starvation, or prolonged intense exercise. Humans produce three types of ketones: acetoacetate, beta-hydroxybutyrate, and acetone. Ketones are readily used as energy by a diverse array of cell types, including neurons, and some evidence suggests that ketones improve cognitive function.

    Medium-chain triglycerides (MCTs) are a class of saturated fats. They are composed of medium-length fatty acid chains (six to 12 carbons long) bound by a glycerol backbone. Medium-chain triglycerides occur naturally in coconut oil, palm oil, and butter, but they can also be synthesized in a laboratory or food processing setting and provided as dietary supplements.

    The randomized, placebo-controlled trial involved 20 adults between the ages of 53 and 84 years who had been diagnosed with Alzheimer’s disease. The investigators used a crossover design, which allows all participants to receive the same treatment, at different times. In this trial, half of the participants received an average of two tablespoons of MCTs daily for three months, while the other half received a comparable amount of olive oil for the same duration. Then the participants switched to the opposite treatment. Participants underwent cognitive testing before, during, and after the intervention. After completing both forms of the intervention, all the participants received MCTs for six months. The investigators collected the participants' demographic and health data, which included measures of blood lipids, fasting insulin, body mass index, and body fat composition.

    They found that 80 percent of the participants demonstrated improved or stable cognitive function while taking the MCTs. The greatest improvements were seen among participants who received MCTs last (providing them nine months of uninterrupted treatment) and among those who were older than 73 years.

    These findings suggest that long-term MCT intake stabilizes cognitive function in adults with Alzheimer’s disease, especially in mild to moderate disease. This was a small study, however, so larger studies are needed to confirm these findings.

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  • Milk May Exacerbate Multiple Sclerosis Symptoms www.sciencedaily.com
    Brain Multiple Sclerosis Autoimmunity

    Antibodies that destroy myelin in multiple sclerosis may cross-react with casein, a milk protein.

    Multiple sclerosis (MS) is a neurodegenerative and autoimmune disease caused when the immune system attacks myelin proteins on nerves, mistaking them for proteins produced by pathogens. The cause of this immune confusion is complex but may involve exposure to proteins found in cow’s milk, which anecdotally worsen MS symptoms for some patients. New research supports this anecdotal evidence, finding that MS autoantibodies cross-react with casein, the principal protein in cow’s milk.

    In order to create antibodies that react to new pathogens, B cells (a type of immune cells) use somatic hypermutation, a process during which they intentionally mutate regions of their DNA involved in antibody production. These rapid mutations are needed to increase antibody repertoire, the collection of an individual’s B cell receptor and antibody sequences; however, somatic hypermutation can result in the creation of autoantibodies, which bind to self-proteins produced by the body. While autoimmune B cells are usually destroyed shortly after creation, lingering autoimmune cells can proliferate and lead to diseases such as type 1 diabetes, rheumatoid arthritis, and MS. One reason autoantibodies persist is cross-reactivity with other proteins, such as those produced by pathogens or absorbed from the diet, especially in cases where gut leakiness increases the introduction of new proteins to the blood.

    The investigators gave one group of mice an injection of casein with adjuvants, which are compounds added to vaccines to increase the body’s antibody response. To compare casein to other milk proteins, they also immunized one group of mice with alpha-lactalbumin and another with beta-lactoglobulin, both whey proteins, for a total of three mouse groups. Changes in behavior and nerve degeneration were observed at 13, 20, or 40 days after immunization. The researchers also collected blood samples from 39 patients with MS and 23 patients with other neurological diseases in order to test for cross-reactivity of autoantibodies with casein.

    Mice immunized with casein exhibited a range of MS symptoms such as weakness and disorientation, while mice immunized with whey proteins did not. Immunization with casein led to a progressive increase in casein-reactive antibodies and deterioration of myelin in nerves of the lower spinal cord. The researchers found that casein-immunized mice produced autoantibodies that cross-react with myelin-associated glycoprotein (MAG), a protein produced by nerve cells called oligodendrocytes, which have a similar structure to casein. Finally, they found that 42 percent of participants with MS had casein-reactive antibodies compared to only 28 percent of participants with other neurological disorders.

    While it is not clear from these results what role dairy consumption plays in the development of MS, the authors suggest that some patients with MS may benefit from restricting dairy in their diet.

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  • Consumption of a fermented dairy beverage improves hippocampal-dependent relational memory in a randomized, controlled cross-over trial www.tandfonline.com
    Brain Memory Dairy

    Drinking kefir, a probiotic dairy beverage, improves memory.

    The community of microbes that comprise the gut microbiota act a bit like a sensory organ in the body, communicating information about the outside world to the brain and forming a gut-brain axis. Antibiotic and other medication use and changes in the diet can modulate the gut microbiota community in ways that reduce or increase the risk of neuropsychiatric illnesses such as depression. Findings of a recent report show that consuming a fermented dairy beverage may improve memory via changes in the gut-brain axis.

    The hypothalamic-pituitary-adrenal axis (i.e., gut-brain axis) is formed by neural and endocrine connections between the hypothalamis, a brain region that controls body temperature, hunger, and sleep; the pituitary gland, a endocrine organ in the brain that produces hormones; and the adrenal gland, which is located above the kidneys and produces hormones that regulate stress such as adrenaline and cortisol. This axis of stress control communicates directly with the hippocampus, the memory center of the brain, which helps the brain retain memories of stressful situations, but also contributes to the development of depression. Previous research shows that probiotics can reduced depression severity; however, additional research is necessary to understand the mechanisms of this relationship.

    The authors recruited 18 healthy adults and randomly assigned them to consume eight ounces of either kefir (i.e., a fermented dairy beverage with 12 strains of active bacteria) or low-fat lactose-free milk daily for four weeks. Participants completed questionnaires about their health, performed cognitive testing with electroencephalogram (EGG) measurement, and provided a fecal sample for the sequencing of the gut microbiome. After a washout period of about three weeks, participants switched to the opposite treatment and repeated the experiment.

    The authors found that Lactobascillus bacteria more than doubled following kefir consumption suggesting significant change in the gut microbial community. Participants consuming kefir performed better on two measures of memory called misplacement and object-location binding. The researchers did not observe changes in depression scores in either group.

    It’s important to note that more than 50 percent of participants in the study had a post-graduate degree, which could skew these results. Future studies in larger and more diverse populations are needed to better understand the effects of probiotics on the brain.

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  • Maintaining a lower systolic blood pressure (less than 120 mm Hg) may reduce the amount of white matter lesions, reducing risk of dementia www.sciencedaily.com
    Brain Aging Dementia Blood Pressure

    Maintaining a systolic blood pressure of 120 or less may protect against dementia and cognitive decline. Nearly two-thirds of adults living in the United States have hypertension (high blood pressure), defined as having a systolic pressure of 130 or higher or a diastolic pressure of 80 or higher. Hypertension damages small blood vessels in the eyes, kidneys, and other tissues, increasing the risk for disease and dysfunction. A 2019 study found that intensive blood pressure control in patients with hypertension reduces the risk of developing small blood vessel damage-related white matter lesions in the brain.

    Intensive blood pressure control is an aggressive treatment protocol for hypertension that seeks to achieve a target systolic blood pressure goal of 120 or less. This differs from standard treatment protocols, which stipulate that within three months of starting medication therapy to reduce high blood pressure, a patient’s target pressures (systolic and diastolic) should be less than 140/90. After three months, the target pressures should be less than 130/80.

    White matter lesions are areas in the brain that appear as intense white spots on magnetic resonance imaging (MRI) scans. They are often indicators of small blood vessel disease and are considered a risk factor for dementia.

    The study involved 670 adults (average age, 67 years) who had hypertension. Roughly half of the participants underwent intensive blood pressure control treatment, while the other half underwent standard treatment. The investigators performed MRI scans of all participants at the beginning of the intervention and again about four years later.

    They found that participants who underwent intensive blood pressure control had fewer white matter lesions in their brains compared to those who underwent the standard treatment. Interestingly, those who underwent intensive treatment exhibited greater brain volume losses than those who underwent standard treatment, but this difference was not statistically significant.

    These findings suggest that intensive blood pressure control reduces white matter lesions in the brains of people with hypertension and support findings from a related study that demonstrated that intensive blood pressure control may reduce the risk of adverse cognitive outcomes.

    Hypertension is highly preventable with lifestyle modifications that involve diet and exercise. For example, dietary components, such as potassium and magnesiumquercetin and vitamin D lower blood pressure. Aerobic exercise also lowers blood pressure. Learn about other beneficial effects of aerobic exercise in our overview article.

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  • Red wine mitigates the negative neurological effects of high LDL cholesterol even without reducing its levels directly. www.tandfonline.com
    Brain Cholesterol Inflammation Alcohol

    Since the 1980’s, clinicians and researchers have been puzzled by the “French paradox”: the observation that residents of France have a surprisingly low incidence of cardiovascular disease given their high rates of smoking, intakes of saturated fat, and hypercholesterolemia (i.e. abnormally high serum levels of harmful low-density lipoprotein (LDL) cholesterol). A recent study now offers evidence that the negative health impacts of these common risk factors might be effectively mitigated by the French habit of regular red wine consumption.

    The authors of this study examined mice that had been genetically modified to lack LDL receptors – proteins crucial for removing LDLs from the bloodstream and initiating their degradation. This genetic modification, known as a “knock-out”, meant that the mice experienced a virtually life-long state of hypercholesterolemia, which served as the biological backdrop for an experiment on the potential health effects of wine consumption.

    At the age of three months (early mouse adulthood), animals were randomly assigned to receive 60 days of unlimited access to either plain tap water or red wine diluted to yield a 6% ethanol solution. This concentration ensured that the animals consumed the human equivalent of a 5-ounce glass of wine on a daily basis.

    When the researchers tested the mice on a variety of cognitive tasks, they discovered that the water-only group displayed learning and memory impairments characteristic of their poor lipid profiles. Their performance was particularly poor on a short-term memory test, where the animals turned out to be unable to recognize objects they had seen only an hour prior. Long-term memory retention was also compromised. In a test that required the animals to remember the location of an escape platform hidden in a tub of opaque water, the mice swam in the right direction only 20 percent of the time.

    Interestingly, wine-consuming mice were not impaired to the same degree. And while their plasma lipid profiles were no better compared to their water-drinking peers, they had substantially lower levels of several biomarkers of neuroinflammation, such as GFAP and lectin. The findings indicate that red wine compounds might help protect against the negative health outcomes of hypercholesterolemia by interfering with the associated inflammatory processes.

    Link to full study.

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  • Could the cure to alcoholism be a liver hormone modulated by aerobic exercise? FGF21 changes behavior of monkeys, reducing alcohol consumption by 50% newatlas.com
    Exercise Brain Behavior Addiction Aerobic FGF21

    From linked article:

    The researchers gave the monkeys a two-bottle choice between water and ethanol, and administered one group an analog of FGF21 to see what effect it had. Sure enough, the test monkeys drank 50 percent less alcohol than the control group. Similar tests in mice also saw a 50-percent reduction in alcohol consumption after being given either human FGF21 or an analog. Interestingly though, the mice and monkeys still chose the ethanol just as often as before, but they drank far less each time.

    Fibroblast growth factor 21 happens to be modulated by aerobic exercise:

    In a new study published in the scientific Journal of Clinical Investigation – Insight, the researchers show that cardio training on an exercise bike causes three times as large an increase in the production of the hormone FGF21 than strength training with weights. FGF21 has a lot of positive effects on metabolism.

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  • Rebalancing gut microbiome with butyrate lengthens survival in mouse model of ALS by repairing intestinal permeability www.sciencedaily.com
    Brain Aging Microbiome Neurodegeneration Butyrate Intestinal Permeability

    From the article:

    In a mouse model of ALS, the compound butyrate helped correct a gut microbiome imbalance and reduced gut leakiness – both symptoms of ALS. The treated mice lived also longer compared to mice that weren’t given butyrate.

    […]

    When the researchers fed the ALS-prone mice butyrate in their water, starting when the mice were 35 to 42 days old, the mice showed a restored gut microbiome profile and improved gut integrity. Butyrate-treated mice also showed improved neuromuscular function and delayed onset of ALS symptoms. Treated mice showed symptoms at 150 days old compared to control mice at about 110 days. Treated mice also lived an average 38 days longer than mice not given butyrate.

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  • The brain can remember and resurrect immune responses to previous infections. www.scientificamerican.com
    Brain Immune System

    The brain’s inner workings have traditionally been viewed as separate from “unconscious” physiological functions like immunity. Yet, recent research has uncovered a surprising degree of reciprocal brain-immune system interaction. For example, biomarkers of peripheral immunity influence brain aging and cognition, and dopamine-rich reward circuits in the brain influence systemic antibacterial activity in immune cells. A recent study now reveals that specific brain cells store memories of the body’s past experiences with infections, potentially reawakening previous immune responses.

    The researchers first measured brain activity in a group of mice that had inflammatory bowel disease. Their measurements revealed that the bowel inflammation and its associated immune response generated a broad pattern of activity across several regions of the brain, especially the insular cortex, a region considered crucial for receiving and processing information about internal bodily states and immune system activities.

    Then, to test whether the pattern of neuronal activity in the insular cortex represented a true memory of bowel inflammation, they examined how the mice reacted when the insular neurons were reactivated four weeks after the animals' recovery from illness. The result was a near-perfect revival of the original immune response to bowel inflammation, including a surge of white blood cells to the colon, heightened activation of a range of T-cells specialized for sensing and attacking pathogens, and a spike in pro-inflammatory molecules such as interleukins and tumor necrosis factor-alpha.

    The brain-induced immune event exhibited two features that indicated it was a form of recollection. First, it was exclusively located in the colon, suggesting a relatively precise “memory” of bowel inflammation rather than a generic signal for immune defense. Second, a repeated experience with simulated bowel disease caused the insular cortex to generate a new and largely non-overlapping pattern of immune-triggering activity. This indicates that the insular cortex is capable of “remembering” distinct episodes of the body’s encounters with disease.

    This study provides some of the first causal evidence that brain cells can form memories of past immune reactions – a property that may have evolved to help bodily tissues become faster and more precise in how they tackle future infections. While the mechanisms of these neuro-immune interactions are not fully understood, the interactions offer the potential for targeted insular brain stimulation to treat severe autoimmune and inflammatory health conditions.

    Link to full publication.

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  • Maternal body weight influences risk of ADHD and obesity in offspring. apple.news
    Brain Obesity Pregnancy ADHD Genetics

    A woman’s body weight before and during pregnancy can have profound health effects on both mother and child. Women with obesity are at greater risk for developing pregnancy complications that can impair infant neurodevelopment, such as gestational diabetes, preeclampsia, preterm birth, and birth trauma. Findings from a new study suggest that maternal obesity contributes to attention deficit hyperactivity disorder (ADHD) and obesity in offspring.

    ADHD is a neuro-behavioral condition characterized by inattention and/or hyperactive or impulsive behavior that interferes with functioning, learning, or development. Obesity is characterized as having excessive body fat – typically defined as having greater than 25 percent body fat for males and greater than 33 percent body fat for females.

    The study included nearly 3,000 Finnish women and their offspring (~9,400 children). The authors of the study collected information about the children’s behavior and attention span from mothers and teachers. They gathered anthropometric data to determine the mothers' and children’s body mass index (BMI), a proxy for body fatness. They used Mendelian randomization and polygenic risk scores to assess risk for ADHD and/or obesity. Mendelian randomization is a research method that provides evidence of links between modifiable risk factors and disease based on genetic variants within a population. A polygenic risk score estimates a person’s genetic propensity for developing a trait or disease.

    They found that children whose mothers had a high BMI were more likely to develop ADHD, independent of genetic makeup. The Mendelian randomization analysis identified a bidirectional link between developing ADHD and obesity-related traits, suggesting that certain genetic variations may predispose children to both ADHD and obesity concurrently. The polygenic risk score revealed evidence for genetic overlap between having ADHD and greater BMI.

    These finding suggest that both genetic and prenatal environmental factors influence the likelihood that a woman’s child will develop ADHD and obesity. They also underscore the importance of maintaining a healthy maternal body weight before and during pregnancy.

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  • Maternal diabetes causes birth defects by increasing cellular aging. apple.news
    Brain Aging Diabetes Pregnancy

    Neural tube defects (e.g., spina bifida, hydranencephaly) are a group of birth defects caused by incomplete development of the outer layers of the brain or spinal cord. Prenatal folate supplementation prevents an estimated 70 percent of neural tube defects, but additional therapies are needed. A recent report describes the relationship between maternal diabetes and abnormal cell aging in the fetal nervous system in mice.

    Previous research has demonstrated a relationship between maternal diabetes and the incidence of neural tube defects in mice; however, the mechanisms that drive this relationship are unknown. High blood glucose levels cause oxidative damage and promote cellular senescence, a state in which cells are not metabolically active and do not reproduce. Aging cells accumulate damage over time and become senescent. In adults, an excess of senescent cells can promote inflammation and disease. In the developing fetus, senescence is vital for tissue remodeling and the building of limbs and organs. However, inappropriate senescence may lead to abnormal development.

    The investigators used multiple mouse models in their study. In a first experiment, they used a strain of mice that develop diabetes and compared them to wild-type mice that are not predisposed to any disease. They injected pregnant females from both groups with either rapamycin, a compound that slows cellular aging by inhibiting the enzyme mTOR, or a placebo. In a second experiment, they used diabetic and non-diabetic strains of knockout mice, whose genomes do not contain the gene FoxO3a, a regulator of aging that may slow cellular senescence.

    Maternal diabetes increased the abundance of biomarkers of cellular senescence and DNA damage in the lining of the brain in offspring. Pregnant diabetic mice that were exposed to rapamycin had offspring with lower levels of senescence biomarkers and fewer neural tube defects compared to placebo. Offspring from FoxO3a knockout mice experienced the same decrease in senescence biomarkers and neural tube defect rates as rapamycin-treated mice.

    These results elucidate the mechanisms by which maternal diabetes can cause birth defects through metabolic changes that accelerate aging. Learn more about the role of cellular senescence in aging in this episode featuring Dr. Judith Campisi.

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  • Whole-body hyperthermia activates muscle hormone irisin and increases neuroprotective factors. www.sciencedirect.com
    Exercise Brain Muscle Sauna BDNF Neurodegeneration

    Exposure to high heat while sauna bathing causes mild hyperthermia – an increase in the body’s core temperature – that induces a thermoregulatory response to restore homeostasis and condition the body for future heat stressors. These adaptations to high temperatures involve increased production of brain derived neurotrophic factor (BDNF), a promoter of neuroplasticity, and irisin, a biomarker of exercise. Findings of a new report demonstrate that whole-body hyperthermia increases BDNF and irisin in healthy young adults.

    Whole-body hyperthermia is a therapeutic strategy used to treat various diseases, including cancer and depression. Previous research has shown that use of a hyperthermia chamber increases BDNF to a greater extent than light intensity exercise. Some research has suggested that BDNF production is stimulated by irisin, a hormone secreted from muscle in response to exercise. Irisin may mediate some of the beneficial effects of exercise and sauna use in humans, but additional research is needed.

    The authors recruited 20 male participants (average age, 22 years) and assessed their baseline heat tolerance using a hyperthermia protocol. Participants reclined in a hyperthermia chamber while the researchers increased the temperature of the chamber by 50 degrees F every ten minutes until the participant reached their personal heat threshold. Next, participants completed ten hyperthermia sessions tailored to their baseline conditioning, during which the hyperthermia chamber was set to a temperature of 150 to 175 degrees F. Following a three-week wash-out period, they completed ten sham treatments over two weeks, during which the hyperthermia chamber was set to a temperature of 75 to 77 degrees F.

    Participants had an average core body temperature of 102 degrees F at the end of each whole-body hyperthermia treatment. Following ten whole-body hyperthermia treatments, participants had a significant increase in circulating irisin levels (6.3 micrograms per milliliter) compared to their baseline levels (5.0 micrograms per milliliter) and compared to their irisin levels following the sham treatment (5.4 micrograms per milliliter). Whole-body hyperthermia treatment also significantly increased BDNF levels (28.3 picograms per liter) compared to baseline (25.9 picograms per liter).

    In healthy young adults, ten whole-body hyperthermia significantly increased irisin and BDNF levels. The authors noted that future studies should explore the effects of whole-body hyperthermia on adipose tissue, which also produces irisin.

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  • Folate reduces risk for Alzheimer’s disease. www.frontiersin.org
    Brain Alzheimer's Micronutrients Folate Neurodegeneration

    Alzheimer’s disease, the most common type of neurodegenerative disease in older adults, causes a progressive deterioration of cognitive function. Recent research indicates that folate (vitamin B9) deficiency may play a role in Alzheimer’s pathology along with other micronutrients, such as vitamin A. A recent systematic review and meta-analysis reports that folate deficiency increases the risk for Alzheimer’s disease.

    Folate is an essential nutrient used by the body to create new DNA and RNA and to metabolize amino acids, all of which are necessary for cell division. Good sources of folate include legumes, such as peanuts and chickpeas, and green vegetables such as spinach and asparagus. Previous research has shown that folate supplementation improves cognitive function in older adults through mechanisms that are not well-understood, but likely involve reduced inflammation. Because dose, population characteristics, and testing methods often vary among clinical trials, coming to a consensus about the efficacy of an investigational treatment presents challenges; however, review articles can be a valuable way to combine and report existing data in a new and helpful way. This study is a systematic review and meta-analysis, meaning that the authors searched existing literature for studies related to folate and Alzherimer’s disease, collected studies based on a set of criteria meant to select for high-quality design, and then combined the data and reanalyzed it.

    The authors selected 59 studies that met their criteria for high-quality design. In a sample of more than 2,000 participants from a collection of case-control studies, participants with folate deficiency (less than 13.5 nanomoles per liter) were more than twice as likely to develop Alzheimer’s disease compared to participants with normal folate status (greater than 13.5 nanomoles per liter). Likewise, data from a collection of five cohort studies revealed that participants with folate deficiency were 88 percent more likely to develop Alzheimer’s disease compared to individuals with sufficient folate status. Finally, in a sample of 11 cohort studies, participants who consumed less than the recommended dietary allowance (400 micrograms) were 70 percent more likely to develop Alzheimer’s disease than those who consumed 400 micrograms of folate per day or more.

    This review of the evidence supports a relationship between folate intake and serum folate concentration in reducing risk for developing Alzheimer’s disease. Future studies should utilize an interventional design to investigate the mechanisms of folate in Alzheimer’s pathology.

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  • Stimulant medications increase willingness to expend effort, not ability. www.sciencedaily.com
    Brain ADHD Dopamine

    Executive function refers to a set of cognitive abilities that facilitate control over voluntary behaviors, including attention control, working memory, and cognitive flexibility. While executive functions are critical for complex tasks such as planning, they are also mentally taxing. Without sufficient motivation, people with poor executive function may struggle to meet goals. Researchers report their findings that dopamine signaling is responsible for the effects of Ritalin and other stimulant medications on motivation and executive function.

    Dopamine is one of the most abundant neurotransmitters in the brain and is involved in reward-motivated behavior, learning, and memory. Activities that provide a reward (e.g., food, money) increase dopamine levels, causing a sensation of pleasure that enhances learning by deeply encoding memories related to rewarding activities. Motivation to complete a task is based, in part, on whether a task is judged to provide sufficient pleasure relative to the cost of its required effort. Capacity to synthesize dopamine varies from person to person; however, lower dopamine levels in key brain areas are associated with attention deficit hyperactivity disorder (ADHD), substance use disorders, and Parkinson’s disease. Drugs such as methylphenidate (i.e., Ritalin), a medication used to treat ADHD, and sulpiride, a medication used to treat schizophrenia and depression, interact with dopamine receptors in the brain and can increase motivation.

    The authors recruited 50 healthy adults (ages, 18 to 43 years). Participants completed a test called a cognitive effort-discounting paradigm. In this test, participants are asked how much money they would want to receive in exchange for completing tasks of varying difficulty. The authors measured the estimated effort cost as the amount of money necessary to make participants willing to perform a cognitively difficult working memory task. Participants completed effort-discounting tasks under the influence of 20 milligrams of methylphenidate, 400 milligrams of sulpiride, or a placebo on three separate testing days. The researchers used a positron emission tomography (PET) scan to measure dopamine synthesis capacity in the caudate nucleus, a brain region responsible for reward-based learning. Finally, the researchers used a statistical model based on the effort-discounting task to further explore the effects of methylphenidate and sulpiride on motivation.

    While on the placebo treatment, participants’ willingness to expend cognitive effort increased as their baseline dopamine synthesis capacity increased. Notably, while performance on the working memory task decreased with difficulty, there was no relationship between task performance and dopamine levels. Both methylphenidate and sulpiride increased willingness to expend cognitive effort, but only in participants with low baseline dopamine synthesis capacity. Using their computer model, the investigators found that methylphenidate increased feelings of reward while sulpiride decreased effort cost. Further, they found that the cost-benefit analysis involved in the decision to expend effort occurs early in the decision-making process and can be measured by patterns in gaze (focusing on a reward or cost of a task) during cognitive testing. While higher baseline dopamine synthesis capacity and drug administration did not affect gaze patterns directy, higher dopamine levels strengthened the impact of gaze and attention to the benefits versus the costs of a decision.

    These findings indicate that Ritalin and other attention-enhancing drugs work by increasing willingness to attempt cognitively-difficult tasks, not the ability.

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  • Fecal microbiota transplantation from young mice reverses aging effects. www.sciencedaily.com
    Brain Aging Microbiome Immune System Microbes

    Declines in brain function are common with age owing to metabolic and immune alterations that include changes to the gut microbiota, the community of microorganisms that inhabit the intestines. While a diverse microbial community with many species of beneficial bacteria is associated with improved nutrition and reduced inflammation, older adults (especially residents of long-term care facilities) have perturbations in microbiota composition that increase the risk for cognitive decline and frailty. Findings of a report released this month show that fecal microbiota transplantation from young to aged mice reverses age-associated cognitive impairment.

    Fecal microbiota transplantation is a therapy in which microbes are isolated from the stool of a donor, processed, filtered, and administered to a recipient by nasogastric tube or enema. Previous research demonstrates the efficacy of fecal microbiota transplantation in treating infection with Clostridium difficile, a hospital-acquired infection that is difficult to treat with antibiotics, and a growing list of other diseases such as inflammatory bowel disease, metabolic syndrome, neurodevelopmental disorders (e.g., autism), and autoimmune diseases. Fecal microbiota transplantation improves health partially by increasing microbiota alpha diversity, meaning the number of species in an individual’s microbiota, also called “richess.” A microbiota with high richness is more likely to contain key beneficial species, such as those that produce neuroprotective short chain fatty acids.

    Given the wide range of diseases associated with gastrointestinal microbiota composition, its effects on aging are an area of intense interest. Prior investigations have demonstrated that transfer of the fecal microbiota from aged mice to young mice alters immunity, neurogenesis, and cognition; however, the consequence of fecal transplantation from young mice to aged mice is unknown.

    The investigators performed their experiment using young and aged male mice. They assigned aged mice to receive a fecal microbiota transplant from either a young mouse (the experimental group) or aged mouse (the control group). For further comparison, the researchers also assigned a group of young mice to receive a fecal microbiota transplant from another young mouse. Mice received the fecal microbiota transplant treatments once per day for three days, then twice weekly for four weeks. The mice completed a battery of tests to assess cognitive function. The researchers collected fecal samples in order to sequence the DNA of the microbiota and blood samples in order to measure hormones, cytokines, and other immune markers before and after the four weeks of treatment. Finally, they analyzed changes to gene expression and metabolism in the hippocampus, the brain region most-associated with age-related cognitive decline.

    At baseline, young and aged mice had distinctly different microbiota composition. Following four weeks of microbiota transplantation, young mice, aged mice receiving a young transplant, and aged mice receiving an aged transplant all had similar microbiota composition. Aged mice tended to have more over-reactive T cells, dendritic cells, and macrophages, especially in the lymph nodes that line the intestines. Aged mice also showed enlargement of microglia (the predominant immune cells in the brain), a common feature of neurodegenerative diseases. Microbiota transplantation from young mice reversed these age-related effects on brain and peripheral immunity. Amino acid metabolism in the hippocampus, which is necessary for neurotransmission and cognition, was impaired in aged mice, but restored following microbiota transplantation from young mice. Finally, the improved hippocampal metabolism in aged mice that received a young microbiota transplant translated to increased learning and long-term memory and reduced anxiety-related behaviors compared to aged mice receiving an aged microbiota transplant.

    These results reveal the potential benefits of fecal microbiota transplantation from young donors as a therapy to promote healthy aging.

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  • Psilocybin, the active ingredient of "magic mushrooms," triggers rapid and lasting growth of new connections in the brain.
    Brain Mushroom Psychedelic LSD

    Psilocybin is a bioactive psychedelic compound present in certain varieties of mushrooms, commonly referred to as “magic” mushrooms. With clinical trials finding psilocybin treatment to be effective at reducing symptoms of treatment-resistant depression and obsessive compulsive disorder, increasingly more attention is being drawn to the potential mental health benefits of the compound. Findings from a recent study indicate that a single dose of psilocybin triggers a tangible and lasting proliferation of new neuronal connections in the mouse brain, improving brain plasticity.

    In the first phase of their study, the researchers set out to identify a dose of psilocybin that was sufficient to trigger behavioral indicators of mice having a psychedelic-like experience. This involved injecting 82 mice with five doses of psilocybin or a saline solution (of 0, 0.25, 0.5, 1, and 2 milligrams per kilogram of bodyweight) and pinpointing the minimal dose of the drug that reliably caused the animals to twitch their heads. Then, after providing the animals a “psychedelic” dose of one milligram per kilogram of bodyweight, the researchers examined whether psilocybin had an influence on the neurons of the rodents’ frontal cortex – an area of the mammalian brain heavily involved in higher-level cognition, imagination, and decision-making. Their focus fell primarily on the neurons’ dendritic spines: tiny mushroom-like protrusions of membrane that act as neuronal connections by receiving signals and passing them on as electrical impulses.

    To track these miniscule anatomical structures using a microscope, the researchers used genetically modified mice whose frontal cortex neurons (spines included) produced a glowing green fluorescent protein known as GFP. All mice began with receiving two microscopy sessions during which the researchers quantified baseline densities of dendritic spines in a tiny section of their frontal cortex. The animals were then randomly allocated to receive either a single dose of psilocybin or a control saline injection, after which the researchers quantified their spine densities on five more occasions (days 1, 3, 5, 7, and 34), blinded to whether the mice had received the active compound or saline.

    Tracking spine densities this way revealed that a single dose of psilocybin reliably induced a significant increase in the formation of new spines, which peaked at a 12 percent increase one week after exposure. A proportion of these new connections persisted 34 days after drug exposure. Interestingly, the effect was more pronounced in female animals, although whether this has any therapeutic implications remains to be seen.

    This study provides anatomical evidence that psilocybin is capable of stimulating new and lasting connections in the brain – an occurrence that may contribute to the drug’s ability to change mental state both in the short and longer terms. As recent studies report that psychedelic compounds promote mTOR signaling and protein synthesis to stimulate and support the production of new cellular machinery (e.g., dendritic spines), scientists are on the cusp of understanding the biological mechanisms and therapeutic potential of these compounds.

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  • Lutein and zeaxanthin supplementation improves visual processing in younger healthy adults. journals.plos.org
    Brain Eyes Carotenoids

    Cognitive function, including complex executive functions like working memory and basic functions like sensory processing, progressively declines with age. While executive function loss is highly variable and easily measurable in older adult populations, younger adults usually perform at a level consistent with their peers, which makes studying cognitive decline in younger adults difficult. In a 2014 report, researchers measured visual processing ability in young adults before and after supplementation with lutein and zeaxanthin.

    Visual processing refers to the brain’s ability to utilize and interpret visual information. Because visual processing utilizes similar brain architecture as more complex tasks such as working memory, it is a useful measure in assessing brain health and cognitive decline.

    Lutein and zeaxanthin are carotenoid pigments found in foods that accumulate in the retina and throughout the brain and perform light-absorbing, antioxidant, and anti-inflammatory functions. Animal research has demonstrated that the density of these pigments in the eye is a good indicator of their density in the brain, providing researchers a non-invasive means to measure the relationship between pigmentation and cognitive function. Higher pigment density in the eye[has been associated with better cognitive performance and visual processing speed in older adults with or without cognitive decline.

    Researchers measured the baseline visual processing speed and retinal concentration of lutein and zeaxanthin in healthy young adults (average age, 22 years). They assigned participants to consume either placebo, zeaxanthin only (20 milligrams), or a combination of zeaxanthin (26 milligrams), lutein (8 milligrams), and mixed omega-3 fatty acids (190 milligrams) per day for four months. They measured retina pigmentation and visual processing speed again following the intervention.

    The authors reported a moderate, yet statistically significant, relationship between baseline retinal pigment levels and visual processing speed. Following the intervention, both supplement groups demonstrated a significant increase in retinal pigmentation compared to placebo. Finally, participants in the supplement groups also performed 12 percent better on the critical flicker fusion test and decreased visual motor reaction time by 10 percent, two measures of visual processing.

    The authors conclude that lutein and zeaxanthin supplementation may be an effective way to increase visual processing speed, even in young healthy adults.

    Link to full study.

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  • Decreased brain derived neurotrophic factor, physical activity, and brain volume are associated with greater memory impairment. www.nature.com
    Brain Aging BDNF

    Brain derived neurotrophic factor (BDNF) is a growth factor associated with decreased risk of dementia and improved cognitive function in humans. While BDNF promotes brain cell growth plasticity, its precursor form, called proBDNF, has the opposite effect, promoting cell death. The authors of a recent report investigated the relationship between blood levels of pro-BDNF and memory loss.

    The effects of Alzheimer’s disease on the brain can be observed 10 to15 years before the onset of dementia, which presents the opportunity for early detection. Even though BDNF is known to cross the blood-brain barrier, whether blood levels of BDNF are reflective of BDNF activity in the brain is unclear. Establishing blood biomarkers of dementia risk provides the ability for early intervention.

    The authors recruited 256 older adults (average age, 68 years) without dementia. They analyzed magnetic resonance imaging (MRI) scans of the participants’ brains and measured blood levels of BDNF and proBDNF. Participants completed questionnaires to measure memory and physical activity habits.

    The investigators reported that increased age and decreased physical activity were associated with poorer memory performance. MRI findings showed decreased volume in the hippocampus, the region of the brain associated with memory, in those with worse memory scores. Finally, the authors reported that decreased blood levels of BDNF, but not pro-BDNF, were associated with worse memory performance.

    These results echo earlier findings that exercise is associated with greater BDNF activity and better memory performance. The authors conclude the measuring blood levels of BDNF may be an effective strategy for early detection of dementia.

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  • Neurological effects of COVID-19 still evident six months after recovery. www.scientificamerican.com
    Brain COVID-19

    COVID-19 primarily manifests as a respiratory illness, but cardiovascular, gastrointestinal, and neurological symptoms have been reported in some cases. Although most of these symptoms are acute and resolve within a few weeks, many people experience long-term complications of the illness, a phenomenon referred to as “post-COVID-19 syndrome. A recent report describes the long-term neurological effects of COVID-19.

    Mounting evidence indicates that COVID-19 affects the neurological system. A previous report found that the range of acute neurological symptoms associated with COVID-19 included psychoses, delirium, encephalitis, strokes, and Guillain-Barré syndrome. Other evidence suggests that COVID-19 affects speech. A case report describes a woman who manifested stuttering and word-finding difficulties during her COVID-19 illness. A recent lay article described the occurrence of stutter several weeks after recovering from COVID-19. Neuroscientists posit that the inflammatory response that accompanies COVID-19 perturbs the brain neurocircuitry that controls speech.

    The most recent study investigating neurological phenomena associated with COVID-19 involved 165 people (average age, 65 years) who had been hospitalized for the illness and had recovered. Six months after discharge from the hospital, the patients were assessed for long-term neurological symptoms.

    The assessments revealed that more than one-third of the patients experienced long-term neurological abnormalities after COVID-19 illness. The most common complaints were fatigue, memory and attention problems, sleep disorders, and muscle pains. Others included depression, anxiety, visual disturbances, impaired sense of smell, and tingling or numbness. The patients who reported having cognitive deficits were more likely to have experienced worse respiratory symptoms and required longer hospitalization than those without cognitive problems.

    These findings suggest that COVID-19 is associated with a wide range of neurological disorders and many of these disorders manifest long after the original infection. The authors noted that since their study excluded patients with pre-existing neurological disorders, their findings might underestimate the full burden of neurological symptoms associated with COVID-19.

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  • BDNF variant may mediate degree of brain benefits from exercise. www.sciencedaily.com
    Exercise Brain Memory ADHD BDNF

    Exercise improves cognitive function and reduces the risk neurodegenerative diseases such as Alzheimer’s disease. Some of these benefits are mediated by brain-derived neurotrophic factor (BDNF). Findings from a 2012 study showed that regular exercise improved cognitive function and increased BDNF levels, but a genetic variant in BDNF influenced the degree of these effects.

    BDNF is a protein that acts on neurons in the central and peripheral nervous systems. A single-nucleotide polymorphism (SNP) in the gene that encodes BDNF causes a substitution of the amino acid valine (Val) by methionine (Met) in the BDNF protein. This genetic variant, known as Val66Met, alters exercise-driven release of BDNF and affects learning, memory, and emotion.

    The intervention study involved 75 sedentary, healthy, young adults between the ages of 18 and 35 years. The participants took memory tests and mental health surveys before and after engaging in their randomly assigned respective activities: no exercise; four weeks of exercise with exercise and a test on the last day; four weeks of exercise, without exercise on the final test day; or a single bout of exercise on the last test day.

    The participants who engaged in exercise showed improvements in memory and experienced lower levels of perceived stress, but only if they exercised for four weeks including the final day of testing. Participants who engaged in a single bout of exercise showed no changes in memory performance and demonstrated higher perceived stress levels. The authors of the study noted improvements in the participants' memory only if they did not carry the Val66Met variant, suggesting that the associated reduction in BDNF release attenuated some of the cognitive benefits of exercise. They also noted that the improvements in cognitive function were not correlated to improvements in mental health.

    These findings suggest that the variable effects of exercise on brain function are related to a genetic variant that influences the production of BDNF.

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  • Carriers of a common BDNF genetic variant demonstrate more rapid decline from Alzheimer's disease. www.sciencedaily.com
    Brain Alzheimer's Genetics BDNF Neurodegeneration

    BDNF plays critical roles in many aspects of cognitive function, including learning and memory formation. A single-nucleotide polymorphism (SNP) in the gene that encodes BDNF causes a substitution of the amino acid valine (Val) by methionine (Met) in a specific region of the DNA where the gene is located. Evidence suggests that carrying the Met allele (Met/Met or Val/Met genotype) is associated with lower BDNF expression.. A 2017 study found that amyloid-beta burden impaired BDNF-related learning and memory.

    Amyloid-beta is a toxic 42-amino acid peptide that aggregates and forms plaques in the brain with age. Amyloid-beta is associated with Alzheimer’s disease, a progressive neurodegenerative disease that can occur in middle or old age and is the most common cause of dementia.

    The study involved more than 1,000 adults (approximately 55 years at the beginning of the study) who were enrolled in a larger study of Alzheimer’s disease. Nearly 65 percent of the participants were at high risk for developing Alzheimer’s disease, having at least one parent diagnosed with the condition. Each of the participants underwent cognitive assessment and BDNF genotyping five times over a period of four to 11 years. In addition, a small cohort of participants underwent imaging studies to assess amyloid-beta burden.

    The genotyping revealed that approximately one-third of the participants were carriers of the Met-66 allele. Compared to Val/Val carriers, Met-66 carriers showed steeper declines in cognitive function. In addition, Met-66 carriers with greater amyloid-beta burden showed an even greater cognitive decline, likely due to lower BDNF expression. These findings suggest that a SNP in the gene for BDNF influences cognitive health and could serve as a therapeutic target against Alzheimer’s disease.

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  • From the blood to the brain: BDNF-producing blood cells travels to the hypothalamus in adults, regulating and suppressing appetite [animal research] www.sciencedaily.com
    Brain Obesity BDNF

    From the article:

    We knew that blood cells produced BDNF,“[…] "We didn’t know why it was produced in blood cells.”

    Dr. Hiroshi Urabe and Dr. Hideto Kojima, current and former postdoctoral fellows in Chan’s laboratory respectively, looked for BDNF in the brains of mice who had not been fed for about 24 hours. The bone marrow-derived cells had been marked with a fluorescent protein that showed up on microscopy. To their surprise, they found cells producing BDNF in a part of the brain’s hypothalamus called the paraventricular nucleus.

    “We knew that in embryonic development, some blood cells do go to the brain and become microglial cells,” said Chan. […]“This is the first time we have shown that this happens in adulthood. Blood cells can go to one part of the brain and become physically changed to become microglial-like cells.”

    A new way to affect appetite and obesity?

    When normal bone marrow cells that produce BDNF are injected into the third ventricle (a fluid-filled cavity in the brain) of mice that lack BDNF, they no longer have the urge to overeat, said Chan.

    All in all, the studies represent a new mechanism by which these bone-marrow derived cells control feeding through BDNF and could provide a new avenue to attack obesity, said Chan.

    He and his colleagues hypothesize that the bone marrow cells that produce BDNF fine tune the appetite response, although a host of different appetite-controlling hormones produced by the regular nerve cells in the hypothalamus do the lion’s share of the work.

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  • BDNF mimetic 7,8-dihydroxyflavone protects neurons against cell death. www.sciencedaily.com
    Brain Parkinson's BDNF Stroke

    BDNF’s neuroprotective capacity suggests that it could be useful in preventing or treating neurodegenerative diseases. Circumventing problems with BDNF’s delivery, half-life, and other limitations has proven challenging. A 2010 study found that 7,8-dihydroxyflavone, a BDNF mimetic, exerted neuroprotective qualities similar to those of BDNF.

    7,8-dihydroxyflavone is a type of flavonoid compound present in a variety of plants. Flavonoids exert antioxidant and anti-inflammatory effects, among others. Some evidence indicates that 7,8-dihydroxyflavone might be useful in reversing the damage associated with lead poisoning in children.

    The authors of the study screened 2,000 bioactive compounds to gauge their ability to protect rodent and human neurons from apoptosis and identified five compounds, including 7,8-dihydroxyflavone, that showed potential in protecting the cells. Then they treated the cells with BDNF and the various compounds and deprived the cells of oxygen and glucose.

    They found that none of the compounds was as effective as 7,8-dihydroxyflavone in protecting the cells from apoptosis. In fact, 7,8-dihydroxyflavone was even more protective than BDNF. They also found that 7,8-dihydroxyflavone exerted its protective qualities by activating a receptor called TrkB, to which BDNF binds. They replicated their findings in an in vivo study of mice, indicating that 7,8-dihydroxyflavone enhances neuronal survival.

    These findings demonstrate that flavonoid compounds that mimic the effects of BDNF show potential as therapeutics against neurodegenerative diseases.

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  • Plasma levels of BDNF lower in women with history of suicide attempts. www.sciencedaily.com
    Brain Depression BDNF

    Suicide is a major public health concern, claiming the lives of nearly 800,000 people worldwide each year. A history of a suicide attempt is a robust predictor of a future attempt. Findings from a 2017 study suggest that plasma levels of BDNF are a marker for suicidality.

    BDNF is a protein that plays critical roles in the creation and functioning of neurons and the ability of synapses to strengthen or weaken over time. Low BDNF levels are associated with an increased risk for depression.

    The participants in the study included 34 women with a history of suicide attempt and 39 without (average age, 33 years). The women were matched based on age, ethnicity, family income, body mass index, and cigarette smoking history. The authors of the study assessed the women’s mental health history and current status and took blood samples to determine BDNF levels.

    Thirty (88 percent) of the women who had attempted suicide had a lifetime history of major depressive disorder. Of these, 14 (40 percent) met the criteria for current major depressive disorder. The women with a history of suicide attempt had lower levels of BDNF than women without a history of suicide – a difference that was maintained even after taking into account other potential psychiatric or demographic factors. The authors of the study posited that lower BDNF levels represent a trait-like biochemical indicator of suicide risk and might be relevant for suicide prevention.

    Other biochemical indicators of suicide have been identified, as well. For example, markers of accelerated extrinsic aging have been observed in the blood of suicide completers. Age acceleration is a phenomenon that occurs when an individual’s epigenetic age exceeds their chronological age. Learn more about epigenetic aging in this overview article.

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  • BDNF genetic variant predicts success in alcohol dependence treatment. www.sciencedaily.com
    Brain Alcohol Genetics Addiction BDNF

    Alcohol dependence is a complex disorder that increases a person’s risk of death from all causes. Findings from a 2009 study suggest that variations in certain genes can impact the likelihood of relapsing following treatment.

    BDNF is involved in neuronal growth and survival, as well as influencing neurotransmitters – chemical signals from the nervous system. Low BDNF levels have been linked to the development of depression, anxiety, and alcohol dependence.

    Previous research has demonstrated that alcohol dependence has a genetic component. The current study investigated whether common variations in certain genes would have an effect on post-treatment relapse.

    The prospective study involved 154 participants who met the criteria for alcohol dependence and were admitted to a treatment facility. The patients provided blood samples for genetic analysis and completed self-assessment questionnaires about depression, hopelessness, impulsivity, and the severity of their alcohol use. The authors followed up with participants for approximately one year to assess whether they had relapsed. Relapse was defined as any drinking during the observation period, with heavy drinking considered as more than four drinks per day for more than four consecutive days. During the follow-up period, 59 (48 percent) participants relapsed, with 48 returning to heavy drinking. The average time to relapse was 218 days.

    The authors tested a genetic variant that resides in the BDNF gene, known as Val66Met. They observed that participants with the Val form of this gene were more likely to relapse compared to those with the Met version. Participants with two copies of the Val allele – one from each parent – had higher rates of relapse and shorter times to relapse when compared to carriers of at least one Met allele.

    These findings suggest that BDNF influences a person’s ability to remain abstinent following treatment for alcohol dependence. With further evaluation, these findings may help clinicians to identify people at increased risk for post-treatment relapse and tailor their care plans.

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  • Bipolar disorder patients experience generalized impaired cellular resilience and broad reductions in BDNF that may contribute to the disease www.sciencedaily.com
    Brain Depression Stress BDNF

    From the article:

    Effective neuronal plasticity also depends on neurotrophins, which are regulatory factors that promote development and survival of brain cells. Brain-derived neurotrophic factor (BDNF) is the neurotrophin mostly found in the brain. It has been extensively investigated in bipolar disorder patients and has been suggested as a hallmark of bipolar disorder. Indeed, some studies have shown that the levels of BDNF in the serum of bipolar disorder patients are reduced whenever patients undergo a period of depression, hypomania, or mania. Other studies have shown that regardless of mood state, bipolar disorder patients present reduced levels of BDNF. Overall, changes in BDNF levels seem to be a characteristic found in bipolar disorder patients that may contribute to the pathophysiology of the disease.

    Immediate early genes:

    Immediate early genes (IEGs) are a class of genes that respond very rapidly to environmental stimuli, and that includes stress. IEGs respond to a stressor by activating other genes that lead to neuronal plasticity, the ability of brain cells to change in form and function in response to changes in the environment. Ultimately, it is the process of neuronal plasticity that gives the brain the ability to learn from and adapt to new experiences.

    One type of protein produced by IEGs is the so-called Early Growth Response (EGR) proteins, which translate environmental influence into long-term changes in the brain. These proteins are found throughout the brain and are highly produced in response to environmental changes such as stressful stimuli and sleep deprivation. Without the action played out by these proteins, brain cells and the brain itself cannot appropriately respond to the many stimuli that are constantly received from the environment.

    […]

    in a previous study done by the group in 2016, one type of IEG gene known as EGR3, that normally responds to environmental events and stressful stimuli, was found repressed in the brain of bipolar disorder patients, suggesting that when facing a stressor, the EGR3 in bipolar disorder patients does not respond to the stimulus appropriately. Indeed, bipolar disorder patients are highly prone to stress and have more difficulties dealing with stress or adapting to it if compared to healthy individuals. What the research group is now suggesting is that both EGR3 and BDNF may each play a critical role in the impaired cellular resilience seen in bipolar disorder, and that each of these two genes may affect each other’s expression in the cell. “We believe that the reduced level of BDNF that has been extensively observed in bipolar disorder patients is caused by the fact that EGR3 is repressed in the brain of bipolar disorder patients. The two molecules are interconnected in a regulatory pathway that is disrupted in bipolar disorder patients,”

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  • Decreased exposure to air pollution associated with improved cognitive development and increases BDNF levels in children. www.sciencedaily.com
    Brain Development Pollution BDNF

    Exposure to air pollutants is associated with an increased risk of developing many health disorders, including heart disease, stroke, chronic obstructive pulmonary disease, lung cancer, and acute respiratory infections. Some evidence suggests that exposure to air pollution can impair neurological development in children. A 2014 study showed that reducing exposure to polycyclic aromatic hydrocarbons (PAHs) was associated with improved cognitive development and increased BDNF levels in children.

    Polycyclic aromatic hydrocarbons are produced during the combustion of coal, oil, gasoline, trash, tobacco, and wood. High-temperature cooking, such as grilling, promotes the formation of PAHs in meat and other foods. PAHs promote the formation of DNA adducts – covalent modifications of DNA that can drive carcinogenesis.

    The study involved two cohorts of mother-child pairs who lived near a coal plant in China. One cohort of pairs was made up of 150 women who were pregnant while the coal power plant was operational and the other was made up of 158 women who were pregnant after it closed. None of the women smoked, and they all lived within 2.5 kilometers (about 1.5 miles) from the coal plant.

    The authors of the study analyzed BDNF levels and their relationship to adduct formation and developmental outcomes in the two cohorts. They collected umbilical cord blood and maternal blood samples and measured the amount of DNA adducts in the samples. They also measured plasma levels of BDNF. When the children reached the age of two years, they underwent standardized testing that assessed motor, adaptive, language, and social development.

    The children who were born to women who were pregnant after the plant closed had lower levels of PAH-DNA adducts, higher concentrations of BDNF, and higher developmental scores than those who were born to women who were pregnant when the plant was operational. Higher BDNF levels were associated with developmental scores. The findings suggest that reducing exposure to air pollutants during pregnancy lowers levels of PAH-DNA adducts and increases BDNF levels in infants.

    Interestingly, clinical trials have demonstrated that sulforaphane, a compound derived from cruciferous vegetables (especially broccoli sprouts), can reduce the harmful effects of exposure to air pollutants (including PAHs) in humans. Sulforaphane works by switching on the activity of the body’s in-house detoxication pathways. Learn more about sulforaphane in this podcast featuring Dr. Jed Fahey.

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  • Restoration of BDNF-mediated signaling as a potential therapeutic strategy against Huntington's disease. www.sciencedaily.com
    Brain BDNF Neurodegeneration

    Huntington’s disease is a progressive neurodegenerative disorder characterized by uncontrolled movements, speech problems, personality changes, and dementia. The disease is caused by a single genetic mutation, called a CAG repeat, that drives abnormal protein folding and aggregation of the huntingtin protein and subsequent death of striatal neurons. Findings from a 2010 study demonstrate that modulating pathways involved in BDNF-mediated signaling shows promise as a therapeutic against Huntington’s disease.

    Evidence suggests that normal huntingtin promotes the expression of BDNF, but mutated huntingtin impairs it. Striatal neurons need BDNF for their normal function and survival. A critical component in BDNF’s actions on striatal cells is a receptor called TrkB, to which BDNF binds. Levels of TrkB are diminished in Huntington’s disease.

    The authors of the in vitro cell study investigated the effects of BDNF administration on mutant huntingtin. They found that altered cell-signaling in the Ras/MAPK/ERK1/2 pathway in cells expressing mutant huntingtin drove the loss of TrkB receptors, increased striatal cells' sensitivity to oxidative damage, and promoted cell death. These findings suggest that identifying ways to modulate the Ras/MAPK/ERK1/2 pathway and restore BDNF-related signaling shows promise as a therapeutic strategy against Huntington’s disease.

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  • BDNF genetic variant influences response to exposure therapy among people with PTSD. www.sciencedaily.com
    Brain Behavior Anxiety BDNF

    Exposure therapy is a type of cognitive behavioral therapy commonly used to treat people with posttraumatic stress disorder (PTSD). Some evidence suggests that BDNF mediates the response to exposure therapy, which can vary among people. A 2013 study demonstrated that genetic differences in BDNF expression influences how well a person responds to exposure therapy.

    A single-nucleotide polymorphism (SNP) in the region of the DNA that encodes BDNF causes a substitution of the amino acid valine (Val) by methionine (Met) in the BDNF protein. Evidence suggests that carriers of the Met allele (Met/Met or Val/Met genotype) have reduced hippocampal function, poor episodic memory, and decreased exercise-induced secretion of BDNF.

    The study involved 55 people between the ages of 18 and 65 years who had previously participated in an eight-week exposure therapy program. The participants provided DNA (via saliva samples) for BDNF genotyping.

    The genotyping revealed that 30 participants carried the Val/Val BDNF allele, and 25 participants carried the Met-66 allele. Carriers of the Met-66 allele showed a poorer response to exposure therapy than carriers of the Val/Val allele, suggesting that the SNP influenced BDNF expression and subsequent response to cognitive behavioral therapy.

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  • Low BDNF during pregnancy is associated with depression during pregnancy and subsequent low fetal birth weight. www.sciencedaily.com
    Brain Pregnancy Development BDNF

    Depression is the most common form of mental health condition worldwide, affecting more than 322 million people. The disorder affects women disproportionately and is particularly common during pregnancy. Findings from a 2017 study demonstrated that serum levels of BDNF drop considerably during pregnancy, potentially increasing a woman’s risk for depression.

    BDNF modulates synaptic plasticity and long-term potentiation – critical aspects of memory storage and brain function. Low BDNF levels are associated with increased risk for depression00181-1/fulltext?cc=y=).

    The study involved 139 healthy pregnant women (77 Blacks and 62 whites) who were assessed three times during their pregnancies (once during each trimester) and again at four to 11 weeks postpartum. The authors of the study measured the participants' BDNF and cortisol levels via blood samples, gathered demographic data, and conducted psychosocial assessments. They reviewed the women’s medical records to determine their infants' birth weights.

    The results of their assessments indicated that the women’s BDNF levels dropped considerably over the course of their pregnancies but rebounded during the postpartum period. In general, Black women had higher BDNF levels and lower cortisol levels than white women during pregnancy and postpartum. Lower levels of BDNF during the second and third trimesters were associated with higher risk for depression and lower birthweight babies, regardless of race.

    Interestingly, these findings contradict those of an earlier study in rats and humans. However, the authors of the current study suggested that the conflicting findings may have been due to differences in assays used to measure BDNF.

    Evidence indicates that exercise increases BDNF. Exercise is generally considered safe for pregnant women and may be a way to prevent some of the changes in mood that occur during pregnancy.

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  • Preclinical evidence suggests BDNF may be a potent interventional tool in Alzheimer's and brain aging by directly improving learning and memory www.sciencedaily.com
    Exercise Brain Alzheimer's Aging Memory BDNF

    From the article:

    For these experiments, the researchers injected the BDNF gene or protein in a series of cell culture and animal models, including transgenic mouse models of Alzheimer’s disease; aged rats; rats with induced damage to the entorhinal cortex; aged rhesus monkeys, and monkeys with entorhinal cortex damage.

    In each case, when compared with control groups not treated with BDNF, the treated animals demonstrated significant improvement in the performance of a variety of learning and memory tests. Notably, the brains of the treated animals also exhibited restored BDNF gene expression, enhanced cell size, improved cell signaling, and activation of function in neurons that would otherwise have degenerated, compared to untreated animals. These benefits extended to the degenerating hippocampus where short-term memory is processed, one of the first regions of the brain to suffer damage in Alzheimer’s disease.

    […]

    “In this series of studies, we have shown that BDNF targets the cortical cells themselves, preventing their death, stimulating their function, and improving learning and memory. Thus, BDNF treatment can potentially provide long-lasting protection by slowing, or even stopping disease progression in the cortical regions that receive treatment.”

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  • Brain-derived neurotrophic factor may be able to disrupt cocaine-seeking when applied directly to the nucleus accumbens in the brain [animal research] www.sciencedaily.com
    Brain Behavior Addiction BDNF

    From the article:

    Cocaine relapse was significantly reduced in a preclinical model when brain-derived neurotropic factor (BDNF) was applied to the nucleus accumbens deep in the brain immediately before cocaine-seeking behavior, report investigators at the Medical University of South Carolina (MUSC) in an article published online in June 2018 by Addiction Biology.

    […]

    While other research groups have studied how BDNF administration affects drug self-administration and relapse, no one has looked at what happens if BDNF is given immediately before relapse.

    Since low serum BDNF levels are seen in cocaine-dependent patients compared to non-addicts, the MUSC researchers sought to better understand the connection between BDNF and cocaine relapse. The nucleus accumbens was selected as the focal point for BDNF administration since it is a central component of the brain reward circuit.

    “An important aspect of this study is that while others have shown that BDNF is important for establishing the state of addiction, we find that can also be used to reverse addiction,” says Peter Kalivas, Ph.D., professor and chair in the Department of Neuroscience. “This exemplifies that the primary effect of BDNF is to promote changes in the brain, and that this capacity to change the brain contributes to how people get addicted, but also can be harnessed to remove brain pathologies such as drug addiction.”

    The findings reported in Addiction Biology are the first to show that applying BDNF to the nucleus accumbens immediately before the reinstatement phase, when the rats are once again seeking cocaine due to cue exposure, greatly reduces relapse.

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  • Beta-hydroxybutyrate, a ketone, increases brain-derived neurotrophic factor expression: relevance for neurodegenerative disease www.sciencedaily.com
    Exercise Brain Alzheimer's Diet Ketosis BDNF HDAC Inhibitor

    β-hydroxybutyrate production consequent to exercise induces within the muscle the activities of a key promoter involved in the production of brain-derived neurotrophic factor.

    From the article:

    Studies have shown that BDNF levels in the brains of people with Alzheimer’s or Huntington’s disease are, on average, half that of people without either brain-damaging disease.

    Among the key findings of the current study was that a ketone, a chemical naturally produced in the liver called beta-hydroxybutyrate (DBHB), triggers biological reactions that activate the BDNF gene to produce more of its protein. DBHB has long been known to build up in the body and brain with exercise. Ketones are “by-product” chemicals made when animals break down fat as an alternative energy source after having drained more readily available sugar stores during exercise.

    Specifically, Chao says, the researchers found that DBHB prevents other proteins in the brain known as histone deacetylase complexes, or HDACs, from suppressing BDNF production by altering the environment of the BDNF gene.

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  • Environmental enrichment alone produces browning of fat and enhanced weight control not accountable by exercise alone [animal study]
    Brain Obesity Memory Fat BDNF Thermogenesis

    From the article:

    “Up to now the only known approach to inducing brown fat has been through exposure to chronic cold. Our research reveals a novel way of doing this without cold exposure. We show that animals living in an enriched environment become lean and resistant to diet-induced obesity, even in the presence of unlimited food.”

    […]

    The current study used a similarly designed environment, with 15-20 mice housed in large containers equipped with running wheels, tunnels, huts, wood toys, a maze, and nesting material, in addition to unlimited food and water.

    Key findings include the following:

    • Enriched animals showed a significant reduction in abdominal white fat mass (49 percent less than controls).

    • Exercise (running in a wheel) alone did not account for the changes in body composition and metabolism of enriched animals.

    • Fed a high fat diet (45 percent fat), enriched animals gained 29 percent less weight than control mice and remained lean, with no change in food intake. Enriched animals also had a higher body temperature, suggesting that greater energy output, not suppressed appetite, led to the resistance to obesity.

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  • Increases in brain-derived neurotrophic factor from aerobic exercise associated with appetite suppression, weight loss, and improved blood pressure www.sciencedaily.com
    Exercise Brain Obesity Blood Pressure Aerobic Weight Loss BDNF

    From the article:

    The team evaluated blood levels of BDNF before and after a three-month program of aerobic exercise in 15 overweight or obese men and women. The seven men and eight women, ages 26 to 51, worked out on a treadmill and bicycle. They were asked about their calorie intake and told to continue eating their usual number of calories. The participants were unaware that one of the study’s objectives was to evaluate changes in food intake.

    At the end of the study, the subjects had decreased BMI, waist circumference, and blood pressure, the data showed. They also reported consuming fewer calories than at the beginning of the study. Over the three months, BDNF levels greatly increased. This higher the concentration of BDNF, the less the subject’s intake of calories and the greater the weight loss, Araya said.

    Thus, it is possible that increases in BDNF suppress appetite, she said. They did not test appetite suppression directly, but some past studies have shown that aerobic exercise suppresses appetite.

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  • Increased visceral fat impairs cognition through chronic microglial activation mediated by IL-1 beta release [animal research] www.sciencedaily.com
    Brain Inflammation Memory Fat Dementia Weight Loss NLRP3 Visceral Fat

    Scientists find that visceral fat, a type of adipose tissue that produces high levels of inflammatory signals known as adipokines, impair learning and memory in mice by setting off an inflammatory cascade mediated by the release of IL-1 beta, which crosses the blood-brain barrier leading to chronic activation of microglia.

    From the article:

    “We have identified a specific signal that is generated in visceral fat, released into the blood that gets through the blood brain barrier and into the brain where it activates microglia and impairs cognition.”

    Visceral fat as the ring leader:

    They looked further and found that just transplanting the visceral fat caused essentially the same impact as obesity resulting from a high-fat diet, including significantly increasing brain levels of interleukin-1 beta and activating microglia. Mice missing interleukin-1 beta’s receptor on the microglia also were protected from these brain ravages.

    […]

    To measure cognitive ability, the scientists looked at mice’s ability to navigate a water maze after 12 weeks on a high- or low-fat diet. They found it took the normal, or wild type, mice consuming the higher fat diet as well as the visceral transplant recipients with NLRP3 intact longer to negotiate the water maze. In fact, while they could reach a platform they could see, they had trouble finding one beneath the water’s surface that they had been taught to find. Mice with the interleukin-1 receptor knocked out, could find it just fine, Stranahan says.

    The high-fat diet, transplant mice also had weaker connections, or synapses, between neurons involved in learning and memory. Mice on a high-fat diet but missing NLRP3 were spared these changes, like mice on a low-fat diet.

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  • Greater BDNF expression in brain tied to up to 50% slower decline in memory in older people (for those in top decile of expression) www.sciencedaily.com
    Brain Alzheimer's Memory Dementia BDNF

    A study of BDNF gene expression in post-mortem brain tissue found that BDNF may provide a buffer against dementia, particularly when higher expression is found in the context of the classical Alzheimer’s brain pathology of amyloid-beta plaques and tau tangles.

    From the article:

    For the study, 535 people with an average age of 81 were followed until death, for an average of six years. They took yearly tests of their thinking and memory skills, and after death, a neurologist reviewed their records and determined whether they had dementia, some memory and thinking problems called mild cognitive impairment or no thinking and memory problems. Autopsies were conducted on their brains after death, and the amount of protein from BDNF gene expression in the brain was then measured.

    […]

    The rate of cognitive decline was about 50 percent slower for those in the highest 10 percent of protein from BDNF gene expression compared to the lowest 10 percent. The effect of plaques and tangles in the brain on cognitive decline was reduced for people with high levels of BDNF. In the people with the highest amount of Alzheimer’s disease hallmarks in their brains, cognitive decline was about 40 percent slower for people with the highest amount of protein from BDNF gene expression compared to those with the lowest amount.

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