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Health Protocols

Age Related Cognitive Decline

Dietary and Lifestyle Consideration for Brain Health

An approach that includes healthy diet, physical activity, adequate sleep, and mentally and socially stimulating activities is more important for preserving cognitive health with age than any individual intervention.1,4,143

Physical Activity

Staying physically active throughout life is critical to maintaining healthy cognitive function. Exercise has been linked to slower rates of age-related brain atrophy in key areas of the brain involved in cognitive decline, and being physically active in midlife is associated with slower cognitive decline and reduced risk of cognitive impairment and dementia later in life.144

Preclinical research suggests exercise can stimulate production of growth factors such as brain-derived neurotrophic factor (BDNF), which promote neuroplasticity. Exercise also improves cerebrovascular function, supports formation of new blood vessels in the brain, and increases blood flow.144

A large body of evidence indicates that any type and amount of physical activity is better than none when it comes to cognitive health. It is clear that both aerobic exercise and strength training can prevent or delay cognitive decline in older adults, regardless of their current cognitive status.145 Even seated exercises have cognitive benefits for older patients who are unable to exercise upright.146

Mental Activity

Engaging in activities that are mentally stimulating has been shown in numerous studies to be important for cognitive health during all life stages. It is thought that education and other forms of mental stimulation build cognitive reserve (ie, the brain’s ability to use alternative neuronal pathways to accomplish cognitive tasks) over a lifetime. Having greater cognitive reserve may delay the onset of symptoms related to aging or pathological changes in the brain.6,147

Higher education level and bilingualism over a lifetime have protective effects on cognitive function, and early research suggests educational pursuits and language acquisition at older ages may still benefit some aspects of cognition.6,148,149 A meta-analysis of studies found that musical practice is associated with preservation of a variety of aspects of cognitive function, including those affected by aging. The effect is strongest in those with long-term musical training, but is also observed after short-term musical training later in life.150

Mentally stimulating leisure activities have been linked to cognitive benefits in multiple studies. For example, in one study in 100 cognitively healthy older adults, long-term jigsaw puzzlers were found to have higher function in all aspects of cognitive ability examined.151 There is some evidence that doing Sudoku and crossword puzzles can benefit the aging brain.152,153 A study in 16,572 participants aged 65–100 years found that higher frequency of engagement in word or number games was associated with better cognitive performance on tests of memory, numeracy, and verbal fluency both at baseline and after two years. Even those who began playing word or number games after the beginning of the study demonstrated better cognitive function at the end than those who did not play word or number games regularly. The effect was equally strong in participants of all ages, and was more pronounced in those with a lower level of education.154 Another study found that activities such as computer use, crossword puzzles, handicrafts, and educational courses were each associated with reduced cognitive decline over one year.155 Early research suggests mentally stimulating computerized programs may be useful for improving cognitive performance in patients with mild cognitive impairment and dementia.156

Stress Reduction

Chronic stress, anxiety, depression, and sleep disturbance are often inter-related. These conditions have well-established detrimental effects on brain structure and function, and are associated with increased risk of dementia.157 Stress reduction techniques, such as meditation and yoga, may have a role in slowing age-related cognitive decline and preventing cognitive impairment.157,158 Mindfulness meditation, for example, has consistently been found to positively affect brain structure, function, and plasticity, including in regions of the brain associated with cognitive dysfunction.6 Long-term yoga practitioners have been found to be less likely to have age-related brain atrophy and perform better on some cognitive tests compared with those not practicing yoga.159,160 Other research found similar effects in long-term meditators.161 Looking at cognitive function in subjects with a wide age range, one study determined that long-term yoga practitioners and meditators had slower cognitive decline and more resilient neuronal networks than those with neither practice.162

Preliminary studies have indicated that meditation practice can improve memory, attention, and executive function in older adults,158,163 and may mitigate age-related cognitive decline.164 Mindful movement therapies such as tai chi, yoga, and walking meditation also have positive effects on quality of life, mood, and cognitive function.165 In one randomized controlled clinical trial in 118 participants with an average age of 62, an eight-week Hatha yoga program involving postures, breathing, and meditation exercises improved performance on tests of attention and information processing speed.166

Social Engagement

Social engagement, like physical and mental activity, may be an important mediator of healthy brain function throughout life.167 A growing number of studies indicate high social engagement and strong social networks are correlated with reduced age-related cognitive decline, mild cognitive impairment, and dementia.167,168 On the other hand, progressive loss of cognitive function, as well as physical function, can lead to diminished strength of social networks and increased isolation, contributing to further cognitive losses.169-171

Strong social networks have been correlated with better cognitive function in older adults and reduced likelihood of experiencing anxiety and depression symptoms in those with mild cognitive impairment.172 One study found that cognitive decline in older men and women over an eight-year period was mitigated by regular engagement in social activities, regardless of cognitive status at the beginning of the study.173 Similarly, social engagement was correlated with slower cognitive decline in 543 cognitively healthy 67-year-old participants who were monitored for eight years.174 Volunteering was identified in one study as a particular predictor of cognitive resiliency with aging, which may be due in part to the combined social and cognitive aspects of many volunteer activities.175

Participating in group social activities may become more important to cognitive health at older ages.176 Even in the very old, social engagement appears to be beneficial; participation in art, craft, and social activities were all noted as protective against mild cognitive impairment in a group of 256 people aged 85 years and older who were cognitively normal at the beginning of the study and were monitored for approximately four years.177

Sleep

Sleep is a critical time for brain rest and repair, and both acute and chronic sleep disturbances have measurable negative impacts on physical, emotional, and cognitive health. Long-term sleep deprivation and chronic sleep restriction or fragmentation damages neuronal function and contributes to stress, mood symptoms, and cognitive dysfunction.178 In healthy older adults, subjective cognitive symptoms are reported more often in those also reporting sleep disturbances.179

Aging is naturally associated with diminished sleep quantity and quality,180,181 which may influence cognitive function by disrupting circadian regulation and stress hormone signaling, and promoting systemic inflammation, metabolic disturbance, and fat deposition.182,183 Furthermore, poor sleep may influence cognition through epigenetic changes affecting neuroplasticity.183

According to large meta-analyses of research into this relationship, the optimum amount of sleep for healthy cognitive function appears to be 7–8 hours per night, with both shorter and longer sleep durations associated with increasing risks of cognitive decline, mild cognitive impairment, and dementia.184,185

Sufficient daily activity and a nighttime environment that promotes sleep may help older people struggling with sleep disorders. Strategies that have demonstrated some effectiveness include181,186,187:

  • Daytime activities. Because too little or too much activity during the day can contribute to sleep problems at night, maintaining a balanced schedule of daily activities and engagements may help prevent daytime napping and facilitate better nighttime sleep.
  • Meditation. Mind-body therapies and meditations promote relaxation and may increase time asleep.
  • Cognitive behavioral therapy. Cognitive behavioral interventions for insomnia focus on reframing negative thought patterns around sleep.
  • Sleep-enhancing devices. Use of devices that improve the sleep environment (eg, earplugs, eye masks, white noise machines, weighted blankets, and devices that play sleep-inducing music) have all demonstrated some effectiveness in reducing sleep disturbance.
  • Daytime bright-light therapy. Bright light therapy may help increase daytime activity, reduce daytime napping, and reset the circadian clock, thereby assisting in restoring normal sleep patterns.

A variety of other important considerations for healthy sleep are reviewed in Life Extension’s Insomnia protocol.

Obstructive Sleep Apnea and Cognitive Dysfunction

Obstructive sleep apnea is a common form of sleep-disordered breathing characterized by periodic episodes of complete or partial airway closure, resulting in apnea (lack of breathing) or hypopnea (insufficient breathing), during sleep. Falling blood levels of oxygen and rising levels of carbon dioxide as a result of apnea and hypopnea cause brain arousal that triggers the resumption of sufficient breathing.188 Frequent cycling between apnea and arousal causes sleep fragmentation that, when chronic, can lead to disrupted circadian signaling, dysregulation of the stress response, systemic inflammation, and increased oxidative stress.189,190 Obstructive sleep apnea can be a major contributing factor in metabolic and cardiovascular diseases, as well as cognitive dysfunction.190,191

The relationship between obstructive sleep apnea and cognitive decline, mild cognitive impairment, and dementia has been observed in numerous studies.188,192 According to a large meta-analysis that included 14 studies with over 4 million participants, sleep-disordered breathing is associated with a 26% increased likelihood of developing cognitive impairment.26 A growing body of evidence suggests treatment of sleep apnea with continuous positive airway pressure (CPAP) can reduce sleep apnea-related cognitive decline.193-195

More information is available in Life Extension’s Sleep Apnea protocol.

Diet

An eating pattern based on the traditional Mediterranean diet has been shown to have anti-aging effects on brain, cardiovascular, and metabolic functions, and on overall longevity.143,196-198 Findings from a variety of studies suggest eating a Mediterranean-style diet can slow cognitive decline and may reduce risk of dementia.199

Mediterranean diet. With its emphasis on fruits, vegetables, unrefined whole grains, legumes, and extra virgin olive oil, as well as moderate amounts of seafood, fermented dairy products, and red wine with meals,200 the traditional Mediterranean diet provides ample amounts of critical nutrients such as mono- and polyunsaturated fatty acids, antioxidants, vitamins, minerals, and phytonutrients. It can be used as a template that can be adapted to favor local and seasonal availability of specific foods.143,198

A study including 832 participants examined every two to three years for up to 18 years found that those whose diets most closely reflected a Mediterranean diet experienced significantly less cognitive decline than those whose diets least reflected a Mediterranean diet.201 A study based on data collected over 16 years from 27,842 men participating in the Health Professionals’ Follow-up Study found that those whose diets were most Mediterranean-like were 36% less likely to report poor subjective cognitive function than those whose diets were least Mediterranean-like.202 Examining the brains of cognitively normal older-age subjects has revealed that adherence to a Mediterranean-like dietary pattern is associated with reduced β-amyloid accumulation. The components of the diet most closely linked to this effect were high fruit and vegetable consumption and moderate wine consumption.203,204

Table 2. Strategies for Transitioning from a Western-style Diet to a Mediterranean-style Diet200

Staples of a Mediterranean Diet

Staples of a Western Diet

Incorporating Mediterranean Eating Patterns

Olive oil

Solid fats;

Corn, soybean, canola and sunflower oils

Use extra virgin olive oil on vegetables, legumes, salads, stir-fries, and sautés;

Flavor food with herbs, spices, garlic, onion, and lemon

Vegetables

Mainly starchy vegetables

(Low consumption)

Have vegetables with both lunch and dinner;

Use vegetables as a main dish often;

Have some raw, dressed with olive oil and vinegar, every day

Fruits

Fruit products often contain added sugar

(Low consumption)

Eat raw fruits as dessert most days;

Include a variety of seasonally appropriate fruits

Unrefined whole grains

Refined white flour;

Processed cereals with added sugars;

White flour bread, pasta, pastries

Use whole grain bread, pasta, and flour;

Include whole unrefined grains often

Legumes

Canned beans high in added salt and sugar

(Low consumption)

Include a variety of beans, lentils, and peas;

Cook dried beans or choose canned beans without additives

Nuts and olives

Processed snack foods and condiments;

High-fat, high-sugar sauces and dips

Have nuts and olives as snacks;

Eat a handful of raw nuts daily;

Choose a variety of nuts

Moderate seafood intake

Low consumption

White fish (cod, flounder, tilapia) once or more weekly;

Fatty fish (tuna, salmon, sardines) twice or more weekly;

Shellfish (oysters, clams, squid, shrimp) occasionally

Moderate fermented dairy (yogurt and cheese)

High intake of milk, processed cheeses, ice cream

Use unsweetened yogurt and flavor with fruit;

Have small amounts of fresh or cured cheese occasionally;

Avoid ice cream

Limited intake of homemade baked goods

Processed baked goods (high in sugar, processed fats, and additives)

Bake at home;

Use olive oil instead of butter;

Eat baked goods only occasionally

Little meat and limited poultry

High intake of red and processed meats;

Large portions

(Daily consumption)

Choose lean poultry;

Have moderate portions, not daily

Red wine

Beer, liquor, and sugar-sweetened soft drinks

Include moderate amounts (up to 1 glass per day for women and 2 glasses per day for men) of wine, preferably red, always with meals;

Drink water instead of soft drinks

  • Extra virgin olive oil. While it appears that the combination of eating habits comprising the Mediterranean diet is the key to its efficacy, the high consumption of extra virgin olive oil featured in the diet is thought to be an important reason for its protective effect on cognition. Several preclinical studies indicate polyphenols in extra virgin olive oil can reduce β-amyloid and tau accumulation and toxicity, and may modulate microRNA profiles.205-207 One clinical trial in 285 older adults compared three diets: Mediterranean diet supplemented with as much as 1 liter per week (more than ¼ cup per day) of extra virgin olive oil; Mediterranean diet including 30 grams per day of mixed nuts; and a low-fat diet. After 6.5 years, the olive-oil-supplemented group had better cognitive performance than the other two groups.208

Coffee

Numerous preclinical and clinical studies have examined the potential for drinking coffee to help prevent cognitive decline. Caffeine and coffee are recognized to improve short-term memory and cognition, and some research indicates long-term coffee consumption could protect against dementia and cognitive decline. Furthermore, preclinical models have demonstrated plausible biological mechanisms for bioactive components in coffee to be neuroprotective.209 For instance, in a three-year study in 145 cognitively healthy elderly participants, moderate-to-heavy coffee drinking was linked to reduced cognitive decline, as well as better preservation of brain white matter and cerebral blood flow.210 Similarly, an analysis of 11 prospective studies found that the highest levels of coffee consumption were associated with a 27% lower risk of Alzheimer disease.211 However, some studies have found that smaller amounts also appear to protect cognitive function. An analysis of nine prospective studies concluded that optimal protection resulted from 1‒2 cups of coffee per day,212 while other studies suggest coffee’s effects on cognition and the brain are complex and require further study.213-215

Caloric Restriction

Caloric restriction, a dietary intervention in which calorie intake is reduced but adequate nutrient intake is preserved, has been shown to delay the onset of age-related diseases and extend lifespan in many organisms.216 This effect is thought to be due to a triggering of resilience mechanisms that enhance cellular resistance to stress.217,218 This effect is known as hormesis.

In rodent models, caloric restriction was associated with decreased neural stem cell senescence, increased neuroplasticity, and better cognitive performance.218 Specifically, caloric restriction has been found in animal models to stimulate neural stem cell activity,219 promote normal metabolism of phospholipids needed for myelin production,220 lower stress reactivity and stress-related changes in brain structure,221 and induce epigenetic changes that support youthful gene expression in aging brains.222 Some of the same metabolic and molecular changes and health benefits associated with caloric restriction in animals have been demonstrated in humans engaging in 25% caloric restriction or through an intermittent fasting strategy, combined with physical activity.216

More information is available in Life Extension’s Caloric Restriction protocol.

Celiac Disease, Gluten Sensitivity, and Cognitive Decline

Celiac disease is a chronic condition caused by an autoimmune response to gluten, a protein found primarily in wheat. Patients with celiac disease typically have a high degree of systemic and gastrointestinal inflammation, as well as a marked imbalance of gut microorganisms (dysbiosis).223 It is estimated that 10% of celiac disease patients also experience neurological symptoms related to the condition, such as headaches, lack of muscle coordination, numbness or tingling of extremities, depression, and cognitive impairment ranging from mild reversible cognitive symptoms (such as “brain fog”) to permanent neurological damage and dementia.223-225

Non-celiac gluten sensitivity is a gastrointestinal disorder caused by an inflammatory reaction to gluten that does not appear to involve autoantibodies. It can lead to similar consequences as celiac disease, including gut and systemic inflammation and dysbiosis, potentially leading to neuroinflammation and cognitive symptoms.226

In older individuals, neurological manifestations of celiac disease and non-celiac gluten sensitivity are frequently attributed to age-related cognitive decline or misdiagnosed as cognitive impairment or even Alzheimer dementia, yet with accurate diagnosis and implementation of a gluten-free diet, these symptoms often resolve.223,227

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