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Condition Age-Related Cognitive Decline

Condition groupAging, Mental Disorder, Nervous System

Link
https://www.lifeextension.com/protocols/neurological/age-related-cognitive-decline

Condition information

Aging is associated with a gradual decline in cognitive function. As such, it is common for aging individuals to find that mental tasks take longer to complete and that their memory and attention may be diminished. Age-related cognitive decline is a complex process with numerous contributing factors, including cellular senescence, disturbances of the circadian rhythm, and neuroinflammation, among others.

If age-related cognitive decline progresses to where cognitive changes are more than expected for the person’s age but not debilitating, the condition is called mild cognitive impairment. Dementia refers to cognitive decline that is severe enough that it becomes debilitating, interfering with the person’s ability to function independently.

Fortunately, proactive lifestyle changes, cognitive training, and nutritional interventions such as bacopa and huperzine A have been shown to decrease the rate of intellectual decay and potentially reverse age-related cognitive decline.

What are Risk Factors for Age-Related Cognitive Decline?

• • Age
• • Female gender
• • Sedentary lifestyle
• • Low level of education
• • Smoking
• • Obesity
• • Insulin resistance/type 2 diabetes
• • High blood pressure
• • High cholesterol
• • Depression
• • Sleep disorders
• • Sleep apnea
• • Diseases such as chronic kidney disease and cardiovascular disease

What are Symptoms of Cognitive Decline?

Those who experience cognitive decline will have difficulty with various aspects of cognition, including:

• • Planning and organizing
• • Following changes in conversation
• • Finding words
• • Focusing
• • Losing items
• • Loss of empathy or judgement
• • Inappropriate behavior

What are Novel Therapies for Cognitive Decline?

There are not currently any medications specifically for age-related cognitive decline. Anti-dementia medications do not appear to prevent progression from mild cognitive impairment to dementia. However, certain medications have been found to have brain-protective or enhancing effects:

• • Piracetam and levetiracetam (anti-seizure medications)
• • Selegiline (medication used for Parkinson’s, Alzheimer’s, and major depressive disorder)
• • Zileuton (asthma medication)

What Dietary and Lifestyle Changes Can Be Beneficial to Preserve Brain Health?

• • Switch from a Western-style diet (high in simple sugars and saturated fats) to a Mediterranean-style diet (high in mono- and polyunsaturated omega-3 fats, fiber, and polyphenols)
• • Caloric restriction may improve learning and memory
• • Cognitive stimulation and training, including playing chess and speaking more than one language, can enhance cognitive reserve and convey protection against loss of brain function
• • Manage stress and get enough quality sleep
• • Engage in social activities—strong social networks are protective for cognitive health
• • Exercise is known to increase levels of brain-derived neurotrophic factor, which can lead to enhanced cognitive function
• • Moderate caffeine and coffee consumption (1‒2 cups/day) may convey protection against cognitive decline

What Natural Interventions May Be Beneficial for Age-Related Cognitive Decline?

• Ginkgo. Numerous clinical trials and meta-analyses have demonstrated Ginkgo biloba’s ability to slow cognitive decline. An expert consensus paper from 2019 concluded that ginkgo is safe and effective and can be recommended alone or in combination with conventional therapies to treat mild cognitive impairment and dementia.
• Bacopa. Bacopa monnieri, a plant used in Ayurvedic medicine for centuries, has been shown in many clinical trials to improve several aspects of cognition.
• Huperzine A. Huperzine A, a compound from the medicinal herb Huperzia serrata, has been shown to inhibit acetylcholinesterase, an enzyme that breaks down the neurotransmitter acetylcholine. Patients with dementia and Alzheimer’s disease improved their scores on standard cognitive tests after supplementing with huperzine A.
• Acetyl-L-carnitine. Decreasing levels of acetyl-L-carnitine have been associated with a decline in cognitive function. A meta-analysis of data from over 21 studies showed supplementation with acetyl-L-carnitine improved cognitive deficits in patients with mild cognitive impairment and Alzheimer disease.
• Magnesium-L-threonate. Magnesium-L-threonate is a form of magnesium found to effectively raise brain magnesium levels. Preclinical research indicates it can protect brain function and preserve neural connections.
• Phosphatidylserine. Phosphatidylserine is a phospholipid that is an important part of myelin and cell membranes. Clinical trials indicate supplementing with phosphatidylserine can improve cognitive function in aging subjects with cognitive impairment.
• Alpha-glyceryl phosphoryl choline (α-GPC). α-GPC serves as a precursor to the neurotransmitter acetylcholine. Acetylcholine precursors, alone or in combination with acetylcholinesterase inhibitors, are promising for treating dementia.
• Other natural interventions that may benefit brain health and overall cognitive function include polyphenols, melatonin, B vitamins, colostrinin, lithium, and more.

Introduction

Cognitive function appears to peak around age 20 and diminish steadily over the remaining years of life. With life expectancies increasing dramatically in the last century, cognitive decline and dementia have become major contributors to disability and mortality.

Aging is associated with gradual changes in the brain that slow and reduce its function. As a result of these changes, it is common for elderly people, even those without neurological disease, to find it takes longer to perform mental tasks and to experience diminished memory, attention, and abilities to learn, reason, and solve problems. Although some cognitive decline occurs during normal aging, its rate of progression is affected by lifestyle, environmental, and genetic factors, some of which may be modifiable.

Aging is a complex process, and age-related conditions like cognitive decline are multifactorial. Some factors that likely contribute to age-related cognitive decline are:

• • stem cell senescence,
• • brain oxidative stress and mitochondrial dysfunction,
• • neuroinflammation (inflammation in the brain),
• • circadian rhythm and metabolic disturbances,
• • vascular dysfunction,
• • abnormal protein accumulation,
• • disordered homocysteine metabolism,
• • changing hormone levels, and
• • epigenetic factors—changes in the way genes are expressed.

These same mechanisms also appear to contribute to dementia and neurodegenerative diseases like Alzheimer disease and Parkinson disease.

Currently, much is known about lifestyle factors that work together to promote healthy brain aging, such as eating a nutrient-dense diet (eg, Mediterranean-style diet), being physically active, reducing stress, getting adequate sleep, and regularly engaging in mentally and socially stimulating activities. In addition, a number of integrative interventions have been identified as having protective effects on brain function.

This protocol will review many underlying factors that contribute to cognitive decline, and describe several novel medical strategies, lifestyle and dietary habits, and integrative interventions that can support healthy cognitive function and brain health throughout life.

Background

The brain contains approximately 100 billion interconnected neurons, which collectively assimilate information received from nerves throughout the body and external stimuli. In addition to neurons, the brain is home to specialized cells known as glial cells, mainly astrocytes and microglia, which play numerous essential support roles. Glial cells also participate in vital signaling processes within the brain.

The Aging Brain

With age, the number of brain neurons decreases and the cells and tissues that support them deteriorate slowly after age 20 and more rapidly after age 60. By age 90, brain mass has been found to be decreased by 11% compared with individuals in their 50s. The majority of neuronal loss is in the cerebral cortex, where most information processing occurs, and the hippocampus, a brain structure involved in memory and learning.

Aging is associated with functional brain changes as well. For instance, cerebral blood flow decreases and production of neurotransmitters is reduced. Also, the integrity of the blood‒brain barrier, which controls movement of cells and molecules into and out of blood vessels in the brain, weakens, and the phospholipid-rich myelin sheaths that protect neurons and facilitate signal transmission deteriorate.

These age-related brain changes manifest in the diminished mental abilities typically associated with older age, namely reduced short-term and episodic memory, difficulty recalling words, slower reaction times, and possibly depressed mood.

From Age-Related Cognitive Decline to Mild Cognitive Impairment and Dementia

Age-related cognitive decline is the term used to describe the natural diminishment in ability to learn, remember, and process information. Mild cognitive impairment is the condition characterized by cognitive changes that are more than expected for age, but are not debilitating. It is estimated that 10–20% of adults aged 65 years and older have mild cognitive impairment.

When cognitive decline becomes severe enough to interfere with social and occupational function and the ability to live independently, the condition is called dementia. Dementia affects approximately 5–10% of US adults age 65 and older. Alzheimer disease is the number one cause of dementia in the elderly, followed by cerebrovascular dysfunction. Importantly, most people with age-related losses in cognitive function never develop these more advanced conditions.

Distinguishing between normal age-related cognitive change and mild cognitive impairment is challenging, but a comprehensive assessment that includes a history of cognitive changes, physical exam, neurological exam, and cognitive function testing is the basis of accurate diagnosis.

Risk Factors Associated with Cognitive Decline

Older age is the number one risk factor for age-related cognitive decline, as well as mild cognitive impairment and dementia. Women have a higher risk of dementia than men. Furthermore, a number of potentially modifiable risk factors for late-life dementia have been identified, many of which have their strongest impact on late-life cognitive function when they occur in midlife.21-23 These risk factors include:

• • Sedentary lifestyle
• • Low educational attainment
• • Smoking
• • Obesity
• • Insulin resistance and type 2 diabetes
• • Hypertension
• • High cholesterol levels
• • Chronic kidney disease
• • Atrial fibrillation (a type of arrhythmia)
• • Cardiovascular disease
• • Depression
• • Sleep disorders
• • Sleep apnea
• • High homocysteine levels
• • Heavy metal toxicity

Sleep Medications and Cognitive Dysfunction

Although sleep disorders are a common contributor to both acute and chronic cognitive problems, some medications used to treat sleep disorders have been linked in some studies to increased risk of dementia. This includes prescription sleep medications, such as benzodiazepines, as well as some over-the-counter sleep aids.

Benzodiazepines are a class of sedative medications that alter neurotransmission and are indicated for short-term treatment of anxiety and insomnia; nevertheless, chronic use of benzodiazepines is common. Long-acting benzodiazepines, like clonazepam (Klonopin) and diazepam (Valium), are more likely to contribute to dementia risk than those with a shorter action, such as triazolam (Halcion) and midazolam (Versed). A newer class of sedatives known as Z-drugs is approved for long-term treatment of insomnia, but some evidence suggests their use may also contribute to dementia risk. Examples of Z-drugs are zolpidem (Ambien), zopiclone (Imovane), and eszopiclone (Lunesta).

Mechanisms Involved in Age-Related Cognitive Decline

Age-related cognitive decline is a complex process with multiple overlapping mechanisms that are not fully understood. Below is a discussion of current understandings regarding some of the processes that contribute to cognitive decline in older age.

Stem Cell Senescence

Groundbreaking studies in the 1990s revealed specialized regions of the human brain harbor stem cells, known as neural stem cells, that may continue to repair and regenerate brain tissue throughout life. Growth factors such as brain-derived neurotrophic factor (BDNF) and other signaling factors in the brain environment appear to stimulate neural stem cell proliferation and the formation of neurons and neuronal connections. The ability of the brain to form new neurons and connections and rearrange neural networks in response to signals from the environment is known as brain plasticity, or neuroplasticity.

With age, neural stem cells become less responsive to stimulation and stem cell signaling can become dysregulated. This condition, known as stem cell senescence, is thought to be a major contributing factor in the diminishing plasticity that characterizes the aging brain.

Circadian Rhythm Disturbance

The circadian rhythm is a natural cycle that affects the brain and the rest of the body in many important ways. Circadian clocks synchronize metabolic, physiologic, and behavioral rhythms with environmental cycles, such as light-dark cycles and daily eating patterns. Among the many bodily functions regulated by circadian signaling are acquisition of learning and consolidation and recall of memories.40,41 Desynchronization of the circadian clock, such as through shift work, chronic stress, and sleep disorders, can contribute to cognitive decline. Circadian rhythm disruption is thought to interfere with neurogenesis and reduce neuroplasticity.

Cerebrovascular Dysfunction

The term “cerebrovascular” refers to the blood vessels supplying the brain. Cerebrovascular dysfunction, driven by aging and atherosclerosis of the blood vessels in the brain, results in decreased cerebral blood flow. With age, cerebral blood vessels become stiffer and less responsive to changing blood pressures and oxygen and nutrient demands. In addition, capillary beds in the brain become more susceptible to injury and inflammation, increasing risk of developing small blood clots and microbleeds that can destroy neurons and negatively impact cognitive function.

The blood vessels that supply the brain have a unique structural feature called the blood‒brain barrier, made up of specialized junctions between endothelial cells—the cells that form the inner lining of blood vessels. In healthy individuals, these junctions exert tight control over the movement of compounds between the blood and the brain. The blood‒brain barrier has been observed to lose integrity with age, becoming increasingly permeable to potential toxins and pro-inflammatory factors.

Neuroinflammation

Aging is associated with elevated inflammatory signaling involving activated microglia, astrocytes, blood vessel endothelial cells, and other cell types, causing neuroinflammation. This leads to increased production of free radicals and other neurotoxins that damage neurons and trigger neuronal degeneration. Neuroinflammation also degrades the blood‒brain barrier, exposing neurons to more potential toxins. Conditions associated with systemic inflammation, such as lack of physical activity, poor diet, obesity, and type 2 diabetes have all been associated with age-related cognitive decline and dementia. An unhealthy gut microbiome is another possible source of inflammatory signaling that may contribute to deterioration of the blood‒brain barrier and neuroinflammation.

Condition information addendum

Mitochondrial Dysfunction and Oxidative Stress

The brain uses about 20% of the resting body’s oxygen, and roughly 85% of that oxygen is consumed by brain cell mitochondria. The brain is particularly sensitive to mitochondrial dysfunction, and free radical production in the brain is exceptionally high. Free radical production in a healthy brain is balanced by powerful antioxidant defenses; however, in an aging brain, antioxidant enzymes like glutathione reductase and superoxide dismutase (SOD) are less active, leading to an imbalance that favors free radical production and creates an environment of high oxidative stress.

Oxidative stress damages cellular and mitochondrial DNA, membranes, and proteins, contributing to decreased brain cell activity and increased mitochondrial dysfunction. Mitochondrial dysfunction results in lower ATP production and more free radical generation, and contributes to depletion of neural stem cells.51 Reduced energy for metabolic activity within brain cells leads to their diminished ability to engage in normal neuronal activities, including maintenance of cell membranes and production of myelin, as well as activities related to learning, memory, and cognition.47 In addition, oxidative stress increases inflammatory signaling, exacerbating neuronal damage and loss.

Metabolic Disturbance

Metabolic disturbances like insulin resistance and obesity are implicated as contributors to cognitive impairment and dementia. It is thought that systemic inflammation caused by insulin resistance and obesity may drive neuroinflammation, brain insulin resistance, brain mitochondrial dysfunction, and brain oxidative stress. These conditions eventually lead to neuronal damage and cognitive decline.

Disordered blood lipid levels and high blood glucose levels have consistently been found to correlate with cognitive dysfunction, and type 2 diabetes has been correlated with increased risk of mild cognitive impairment, as well as its progression to dementia.55 In addition, Alzheimer disease increases the risk of developing type 2 diabetes, suggesting a two-directional relationship. Although the mechanism underlying the connection is not fully established, the relationship between insulin resistance and Alzheimer dementia in particular is so compelling that it is sometimes referred to as “type 3 diabetes.”

Concussion and Cognitive Decline

Concussion, also known as mild traumatic brain injury, is now widely recognized as a potential contributor to long-term cognitive dysfunction. Until recently, the effects of concussion were believed to resolve spontaneously in a matter of months in the majority of people. We now know that as many as half of all individuals with a single concussion experience chronic cognitive impairment. Repeated head traumas, which are common in athletes, may further increase long-term risks.

Several mechanisms appear to be at play in the cognitive sequelae of concussion. Laboratory models of head injury suggest mild traumatic brain injury, particularly when repeated, may trigger a cascade of overlapping processes in the brain, such as:

• • altered glucose metabolism and energy production by neuronal mitochondria
• • increased oxidative stress and oxidative damage to critical lipid brain structures
• • decreased cerebral blood flow
• • heightened activity of microglial cells, exacerbating neuroinflammation
• • disrupted blood‒brain barrier function
• • altered neurotransmission
• • decreased removal of amyloid and tau proteins

Furthermore, concussion may trigger neuronal death and initiate long-term degenerative processes. Studies using imaging techniques have revealed structural changes in brain tissue following head injury that are associated with decreases in attention, memory, and executive function. The effects of concussion appear to interact with age-related processes to accelerate loss of cognitive reserve and increase risk of cognitive impairment and dementia years later.

Clinicians and researchers are still exploring strategies for minimizing the short- and long-term problems associated with concussion. In the meantime, protecting the head during high-risk activities is imperative. If you do experience a head injury, following recommendations for protecting the aging brain may be beneficial, whatever your age.

Abnormal Protein Accumulation

Beta [β]-amyloid and tau proteins occur normally in the brain, but when high levels of these proteins accumulate, they can trigger structural changes that disrupt neuronal function and signal transmission. In the aging brain, β-amyloid proteins accumulate in the spaces between neurons due to increased production, reduced clearance, or both. At high concentrations, β-amyloid proteins coalesce and form plaques around neurons.64 Tau proteins become damaged through a chemical process called phosphorylation. Aggregates of phosphorylated tau inside neurons trigger neurofibrillary tangle formation.64 Such plaques and tangles interfere with normal neuron-to-neuron communication, and are the hallmarks of Alzheimer disease, but recent studies reveal β-amyloid and phosphorylated tau may begin to accumulate decades before the onset of clinical dementia.

High levels of β-amyloid and tau in the brain, as well as higher tau levels in the blood, have each been independently correlated with cognitive decline in the elderly and disease progression in those with mild cognitive impairment.65,69,70 While the nature of the relationship between abnormal protein accumulation and cognitive decline is not fully understood, phosphorylated tau proteins in particular appear to interfere with synapse function and induce a neuroinflammatory process leading to neuronal dysfunction even before tangles develop.

Epigenetics

“Epigenetics” is a term used to describe biological phenomena that affect how cells use the information stored in the genetic code. Epigenetic processes emphasize or de-emphasize the information contained in sections of the genome. Sections emphasized by epigenetic processes are said to be “expressed,” and de-emphasized sections are “silenced.” Epigenetic processes do not change the genetic code, but rather how cells “read” the code. Factors such as lifestyle habits, nutrition, and the environment (eg, exposure to air pollution) can influence epigenetic gene expression and silencing.

There is increasing evidence that epigenetics play a crucial role in learning, memory, and cognition in older adults and influence development of cognitive impairment and dementia. For example, epigenetic alterations affecting the brain’s circadian clock have been noted to impact function in key brain regions associated with cognitive decline. Factors that may trigger epigenetic changes associated with cognitive decline and dementia include disordered breathing patterns (such as hyperventilation syndrome), poor diet, alcohol overconsumption, and sleep deprivation.

Disrupted Homocysteine Metabolism

Homocysteine is an amino acid derivative that has detrimental effects on blood vessels, contributing to vascular inflammation, thickening of the vessel walls, and endothelial dysfunction. It is a contributing factor in atherosclerosis and increases the risk of stroke. Homocysteine’s effects on brain function may be related to its impact on cerebral blood vessels, but some evidence also suggests homocysteine increases oxidative stress and neuroinflammation, and may have direct neurotoxic effects.

A consensus statement by a panel of experts published in the Journal of Alzheimer’s Disease in 2018 stated that moderately elevated blood homocysteine levels (>11 micromoles per liter) are a contributing cause of age-related cognitive decline. High homocysteine levels have been linked to brain atrophy, and have consistently been associated with increased risk of cognitive impairment, dementia, and Alzheimer disease. Homocysteine is converted into cysteine via a pathway requiring pyridoxine (B6), or into methionine through a chemical process called methylation that is dependent on the B vitamins folate (B9) and cobalamin (B12). Folate and B12 deficiencies are common in the elderly and are the main cause of hyperhomocysteinemia. Treatment with these B vitamins has been shown to reduce homocysteine levels, slow brain atrophy, inhibit cognitive decline, and improve memory.

Fibrinogen and Cognitive Decline

In a paper published in 2019, scientists at the Gladstone Institutes in San Francisco demonstrated that the blood-clotting protein fibrinogen, which can enter the brain after vascular damage weakens the blood‒brain barrier, may contribute to cognitive decline. Once fibrinogen enters the brain, the researchers found, it forms deposits that activate certain types of microglial cells (the immune cells of the central nervous system). Microglial activation generates reactive oxygen species and damages the dendritic spines, destroying the synaptic connections between neurons and causing cognitive decline. The scientists demonstrated that even very small quantities of fibrinogen in healthy brains caused a loss of synapses as seen in Alzheimer disease—and even in the absence of amyloid plaques. Blocking fibrinogen from binding microglia reduced synaptic deficits and cognitive decline in a mouse model of Alzheimer disease. The vascular component of Alzheimer pathology could be a reason why clinical trials aimed solely at reducing amyloid plaque have been unsuccessful. Combination therapies that address vascular changes as well as amyloid deposits may prove to be more successful in the future.

Several earlier studies established the connection between fibrinogen levels and cognitive decline. In a study of over 2,300 middle-aged to elderly subjects, higher plasma fibrinogen levels at baseline were predictive of cognitive decline after five years. Another study by the same research group linked a specific genotype associated with cognitive decline to higher fibrinogen levels.80 Higher fibrinogen levels after ischemic stroke have also been associated with poorer cognitive outcomes.

Hormone Imbalance

The brain is an integral part of the body’s hormonal network, regulating hormone production and responding to hormone signals. The hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis demonstrate the integrated relationship between the brain and hormone-producing glands. Hormones such as cortisol, dehydroepiandrosterone (DHEA), estrogen, and testosterone affect brain structure and function. Age-related diminishment in levels of these hormones and dampening of the brain’s responsiveness to hormone signaling may impact susceptibility to cognitive decline and dementia.

Estrogen. Estrogen modulates brain function by enhancing cerebral blood flow, activating nerve growth factors, and preventing neuronal damage. It also appears to have a critical impact on mitochondrial energy production. In women, the drop in estrogen levels that occurs during perimenopause may be a contributing factor in age-related cognitive decline. Indeed, many women report changes in cognitive function around the time of menopause, although objective measures suggest this may be more profound with surgical menopause than natural menopause. Clinical trials in women suggest initiating estrogen therapy soon after menopause may have the greatest benefit in lowering dementia risk later in life. In fact, initiating estrogen therapy at an older age has been associated with no effects or detrimental effects on cognitive function. One complicating factor in clinical trials is the use of progesterone in combination with estrogen: while natural progesterone may augment the neuroprotective effects of estrogen, synthetic progestins such as medroxyprogesterone acetate (MPA) (which are typically used with estrogen in postmenopausal hormone therapy) appear to have the opposite effect.

Testosterone. Testosterone is an important regulator of cognition and mood, and lower levels in middle-aged and elderly men have been associated with depressive symptoms, worse cognitive performance, and increased risk of dementia in some studies. In men 70 years and older, greater reductions in testosterone levels have been correlated with increased cognitive decline. Some research suggests testosterone therapy may improve mental health, quality of life, and aspects of cognitive function in men with low levels. In women, however, higher testosterone levels in older age appear to be associated with more rapid cognitive decline, but this finding is complicated by other data suggesting testosterone replacement therapy may benefit cognitive function in the short-term in women whose ovaries have been surgically removed. More research is needed to clarify the potential role of testosterone replacement on cognitive function in women.

Cortisol. Cortisol, a glucocorticoid hormone produced by the adrenal glands in response to HPA axis activation, is a critical moderator of the stress response. Cortisol also affects mood, attention, and memory, as well as immune, metabolic, and other physiologic functions. The HPA axis and resulting cortisol release are normally regulated by circadian signals; under healthy conditions, cortisol levels show a clear diurnal cycle, peaking in the morning and dipping at night.

In older adults, average cortisol levels are higher and the circadian rhythm of cortisol release is blunted. This may be partly related to diminished negative-feedback control over adrenal stimulation. Chronic or repetitive stress can add to persistent dysregulation of HPA axis signaling and cortisol release, and is linked to depression and anxiety, brain atrophy, cognitive impairment, and dementia. Exercise and mindfulness training may help reduce stress, repair cortisol regulation, and slow cognitive decline.

Dehydroepiandrosterone (DHEA). DHEA is a precursor to other steroidal hormones such as estrogen, progesterone, and testosterone. In addition, DHEA has a range of direct hormonal actions. Most DHEA in blood is in the form of DHEA-sulfate (DHEA-s). DHEA is produced mainly in the adrenal glands, but smaller amounts are produced in the ovaries and testes. Levels of both DHEA and DHEA-s drop with age, such that levels in elderly individuals may be
80–90% lower than in younger individuals. A large research review concluded higher blood levels of DHEA-s are associated with better cognitive performance in men and women. Brain DHEA and DHEA-s concentrations are substantially higher than blood concentrations, and it has recently been proposed that DHEA may also be synthesized in the brain. Preclinical evidence suggests DHEA may contribute to cortisol regulation, reduce neuroinflammation and brain oxidative stress, and promote neuronal growth.

Note 1: Dietary and Lifestyle Consideration for Brain Health
Note 2: Healthy Brain: Integrative Approaches - Part 1
Note 3: Healthy Brain: Integrative Approaches - Part 2
Note 4: Subclinical carotid artery atherosclerosis and cognitive function in older adults
Note 5: Association of Low Muscle Mass With Cognitive Function During a 3-Year Follow-up Among Adults Aged 65 to 86 Years in the Canadian Longitudinal Study on Aging
Note 6: Understanding cognitive control in aging: A brain network perspective
Note 7: [A prospective cohort study on the association between grip strength and cognitive function in adults aged 50 years and above]
Note 8: Therapeutic approaches for improving cognitive function in the aging brain
Note 9: Longitudinal Examination of Body Mass Index and Cognitive Function in Older Adults: The HELIAD Study
Note 10: Kicking Back Cognitive Ageing: Leg Power Predicts Cognitive Ageing after Ten Years in Older Female Twins
Note 11: Aerobic exercise reverses aging-induced depth-dependent decline in cerebral microcirculation
Note 12: Age-Related Cognitive Decline, Focus on Microbiome: A Systematic Review and Meta-Analysis
Note 13: Dietary amino acid intake and sleep duration are additively involved in future cognitive decline in Japanese adults aged 60 years or over: a community-based longitudinal study
Note 14: The relationship between handgrip strength and cognitive function among older adults in China: Functional limitation plays a mediating role
Note 15: Association Between Mid-arm Muscle Circumference and Cognitive Function: A Longitudinal Study of Chinese Adults
Note 16: The mediating role of lower body muscle strength and IGF-1 level in the relationship between age and cognition. A MIDUS substudy
Note 17: Neurovascular Mechanisms of Cognitive Aging: Sex-Related Differences in the Average Progression of Arteriosclerosis, White Matter Atrophy, and Cognitive Decline
Note 19: Age-Related Macular Degeneration: A Disease of Cellular Senescence and Dysregulated Immune Homeostasis
Note 20: Physical Exercise Inhibits Cognitive Impairment and Memory Loss in Aged Mice, and Enhances Pre- and Post-Synaptic Proteins in the Hippocampus of Young and Aged Mice

Updated: 2022-10-10