Exercise - Types, Lengths, and Benefits

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There is no researched-based consensus as to the best type(s) of exercise or its length of practice for cognitive health. (See Physical Activity and Alzheimer's Disease: A Systematic Review (2017).) However, it is known that exercise is good for the brain as well as the body. This page attempts to broadly address the different types of exercise with their benefits to assist an individual in determining a regimen that best meets their needs.

Why ApoE4s should Exercise

Exercise is good for many reasons, but especially APOE4s.

  • It can reduce, even reverse, hippocampal atrophy in the brain. The hippocampus is part of the brain that is the center for emotion, memory, and the autonomic nervous system. See Physical activity reduces hippocampal atrophy in elders at genetic risk for Alzheimer's disease (2014).
  • Exercise increases BDNF – Brain Derived Neurotrophic Factor. BDNF is the most active neurotrophin. Neurotrophins induce survival, development, and function of neurons. See BDNF Responses in Healthy Older Persons to 35 Minutes of Physical Exercise, Cognitive Training, and Mindfulness: Associations with Working Memory Function. (2017) also The Effects of Aerobic Exercise Intensity and Duration on Levels of Brain-Derived Neurotrophic Factor in Healthy Men (2013).
  • Increases insulin sensitivity, which benefits the body all over, but is particularly critical in the brain. The brain needs insulin, so insulin sensitivity is imperative for healthy cognition. It has been concluded that basically everyone who has Alzheimer’s has brain insulin resistance, whether or not they have insulin resistance elsewhere in the body. See Insulin Resistance
  • When done regularly while incorporating allowances for recovery, exercise lowers inflammation. Low levels of inflammation correspond with maintaining cognitive function and longevity.
  • Aids mitochondrial health. Mitochondria are the powerhouses of the cell. The brain is highly dependent on mitochondrial activity for energy production from glucose. ApoE4 has been found to have detrimental effects on mitochondria, but exercise boosts mitochondria.
  • Exercise works hand in hand with diet to encourage ketosis, providing an alternative source of energy (ketones) for the brain. The brain prefers to use glucose for energy, but in Alzheimer’s this energy source is impaired, and this impairment begins decades before symptoms manifest. Ketosis enables a brain to easily switch between energy sources thus staving off cognitive impairment. See Ketosis and Ketogenic Diet
  • Can enhance sleep. Good, quality sleep is very important for ApoE4s. According to this study, Sleep Drives Metabolite Clearance from the Adult Brain “The restorative function of sleep may be a consequence of the enhanced removal of potentially neurotoxic waste products that accumulate in the awake central nervous system.” In other words, sleep takes out the brain’s trash.
  • Can reduce stress. Stress affects the brain with its many nerve connections. In this article, Exercise Fuels the Brain’s Stress Buffers The American Psychological Association says exercise gives the body a chance to practice dealing with stress, thereby enhancing its ability to respond to it. It forces the body's physiological systems: cardiovascular, renal, muscular, central and sympathetic nervous systems — all of which are involved in the stress response — to communicate much more closely than usual. This workout of the body's communication system enables our bodies to be more efficient in dealing with stress.
  • Exercise helps keep your fat cells fit. Fat cells aren’t merely storage units, and fat isn’t merely a reserve source of body energy. Fat is a necessary part of our body, called adipose tissue, and this tissue is comparable to an organ that serves important body functions. Exercise aids with the blood flow and oxygen delivery to fat cells. This helps hold inflammation at bay which occurs in the fat cells with insulin resistance. And as discussed above and in Insulin Resistance there is a strong link between insulin resistance and Alzheimer’s Disease.
  • Exercise is often accompanied by sweating and sweat can help release toxins/metals in the body.
  • Exercise increases endocannabinoids and according to this articleCannabinoids Remove Plaque Forming Alzheimers Proteins from Brain Cells "It was the study of J147 [Alzheimer’s drug candidate] that led the scientists to discover that endocannabinoids are involved in the removal of amyloid beta and the reduction of inflammation.

Types of Exercise

Aerobic or “Cardio” Exercise – Running, cycling, swimming, rowing, cross-country skiing, etc.

Aerobic refers to a level of exercise where oxygen use meets the energy demands of the body. Aerobic exercise is performed at a moderate level of intensity over a relatively long period of time. For example, running a long distance at a moderate pace is an aerobic exercise; however, sprinting hard for a short distance is not. Aerobic exercise can take many forms: running, walking, hiking, cycling, swimming, rowing, cross-country skiing, roller blading, kayaking, on and on.

Dr Bredesen recommends 150 minutes of moderate aerobic exercise in the form of brisk exercise or something more vigorous in his book The End of Alzheimer's. In this video https://www.youtube.com/watch?v=2HFs0GyIR2M from December 2013, he recommends starting slowly but to incorporate aerobic exercise of at least 30 minutes a day, 5 times a week, starting slowly to get your heart rate up without hurting yourself, to around the 70% max heart beat range. See Bredesen Protocol on Exercise.

The benefits of aerobic exercise are many. From a neurological standpoint, this quote was taken from the Wikipedia page Neurobiological effects of physical exercise accessed 16 August 2017

A large body of research in humans has demonstrated that consistent aerobic exercise (e.g., 30 minutes every day) induces persistent improvements in certain cognitive functions, healthy alterations in gene expression in the brain, and beneficial forms of neuroplasticity and behavioral plasticity; some of these long-term effects include: increased neuron growth, increased neurological activity (e.g., c-Fos and BDNF signaling), improved stress coping, enhanced cognitive control of behavior, improved declarative, spatial, and working memory, and structural and functional improvements in brain structures and pathways associated with cognitive control and memory.[1][2][3][4][5][6][7][8][9][10] The effects of exercise on cognition have important implications for improving academic performance in children and college students, improving adult productivity, preserving cognitive function in old age, preventing or treating certain neurological disorders, and improving overall quality of life.[1][11][12]

High Intensity Interval Training (HIIT or HIT) – Sprint Interval Training, Tabatas, Nitric Oxide Dump

High Intensity Interval Training or HIIT is where one performs a short burst of high-intensity exercise followed by a period of low-intensity activity, then repeating this cycle by going back to a burst of high intensity. There is no universal amount of time to do HIIT, but a routine typically lasts no more than 30 minutes, and for a non-athlete just working on general fitness, often far less, just a few minutes.

This type of exercise has been gaining in general popularity largely because it’s not a major time commitment and it shouldn’t be done more than three times a week. Plus, it is more effective than longer, slower cardio workouts for certain benefits.

Dr Michael Mosely suggests that HIIT (which he refers to as HIT) practiced for just three minutes can reap benefits, particularly with insulin sensitivity. Results do vary, however, based on genetics (not ApoE4), so while 15% of people made huge strides, 20% showed no real improvement. This link tells more: Can three minutes of exercise a week help make you fit?

According to this study, Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans published in Cell Metabolism in March 2017, “High-intensity interval training improved age-related decline in muscle mitochondria” and “HIIT revealed a more robust increase in gene transcripts than other exercise modalities, particularly in older adults,…”

Dr Joe Mercola, an osteopathic physician who through his website http://fitness.mercola.com/ discusses alternative medicine approaches, advocates a particular type of HIIT called the Nitric Oxide Dump. He says it is easier than other HIIT practices, requires no equipment, can be done by anyone regardless of fitness level, and only takes three minutes two or three times a day. He says controlling Nitric Oxide formation has a number of influences on one’s health, including stimulating the brain. You can read more about this at New exercise dumps nitric oxide, relaxes blood vessels in 3 minutes

Strength training - Weight lifting, resistance training (flex bands, body weight), cross-fit

Being strong is a part of general health and well-being. Exercising for strength has many benefits, but those of particular interest to ApoE4s:

  • Improves insulin sensitivity. See An Introduction to ApoE4, biochemistry and possible prevention strategies and Insulin Resistance
  • Reduces inflammation. Muscles, when worked, help ameliorate the effects of fat and reduce inflammation. Fat tissue secretes the pro-inflammatory cytokine TNF- α (TNF stands for tumor necrosis factor, and immune cells secrete it in the presence of tumor cells). Muscle derived IL-6 is anti-inflammatory. IL-6 is interesting; it is a cytokine that causes inflammation, but it is also a myokine that according to wikipedia has many positive effects. Muscle contraction releases large amounts of IL-6, which sensitizes our cells to its effect, resulting in less inflammation causing IL-6 circulating to rest. So why not just do aerobic exercise to get muscles to secrete IL-6? Different muscle fiber types release different clusters of myokines, so different types of exercise offer different myokine benefits.
  • Resistance training can produce better sleep, see Optimize sleep as discussed in Bredesen’s protocol.
  • High-intensity workouts and exercises that involve muscle contraction activates AMPK (AMP-activated protein kinase). Per http://ampkactivator.net/ AMPK acts as the “master regulator” of the cellular energy homeostasis. It is activated in response to the stimuli and stresses that use up the ATP supplies (e.g. low glucose, ischemia, hypoxia, heat shock). Activating AMPK positively regulates the signaling pathways (such as autophagy, see Enhance autophagy, ketogenesis in Bredesen’s Protocol, and fatty acid oxidation) that replenish the cellular ATP supplies.
  • Feeling strong gives a person a sense of well being, and it can boost self-confidence and mood.

Resistance training and Cognition

There aren’t many studies correlating strength exercise specifically to cognitive health, but here are two:

In Australia, a University of Sydney study, Mediation of Cognitive Function Improvements by Strength Gains After Resistance Training in Older Adults with Mild Cognitive Impairment: Outcomes of the Study of Mental and Resistance Training linked stronger muscles with improved cognitive function. Published in the Journal of American Geriatrics in October 2016, the trial was done on a group of 100 patients age 55 to 68, suffering MCI (mild cognitive impairment). The participants were divided into four groups, and each assigned a particular activity:

  1. weightlifting exercises
  2. seated stretching exercises
  3. real cognitive training on a computer
  4. placebo training on a computer

Only the weight training activity demonstrated a measured improvement in brain function. From the conclusion of the study:

High-intensity PRT [Progressive Resistance Training] results in significant improvements in cognitive function, muscle strength, and aerobic capacity in older adults with MCI. Strength gains, but not aerobic capacity changes, mediate the cognitive benefits of PRT. Future investigations are warranted to determine the physiological mechanisms linking strength gains and cognitive benefits.

Another study, Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise published March 2016 found that PRT [progressive resistance training] improved global cognition. From the study:

Here we report for the first time that resistance training can conserve and even increase cortical thickness in the posterior cingulate. This mechanism may be salient to long-term protection from further cognitive decline and impairment because loss of PC gray matter is a biomarker of AD,71, 72 most likely because of neuronal loss in specific cortical laminae.73, 74

Aim for Healthy muscles, not Big muscles

After saying that maintaining strong muscles can be of great benefit, now some cautions. The key to success is likely to work the muscles without overdoing it.

Protein, IGF-1, and longevity

Body builders who want large, pronounced muscles eat a high protein diet to aid in achieving this. Protein raises Insulin Like Growth Factor 1 or IGF-1. As the name suggests, IGF-1 stimulates cells, like muscle cells, to grow. But IGF-1 doesn’t discriminate. In addition to muscle cells, it can also stimulate cancer cell growth and affect other factors that affect longevity. A lower IGF-1 is connected with longer, more healthful aging. It should be noted plant protein doesn’t have the same effect on IGF-1. Excess animal protein is especially more likely to raise IGF-1. Some studies:

Low Protein Intake is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population published March 2014:

Respondents (n=6,381) aged 50–65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer and diabetes mortality during an 18 year follow up period. These associations were either abolished or attenuated if the source of proteins was plant-based.

Growth hormone modulates hypothalamic inflammation in long-lived pituitary dwarf mice Published Dec 2015:

Mice in which the genes for growth hormone (GH) or GH receptor (GHR(-/-) ) are disrupted from conception are dwarfs, possess low levels of IGF-1 and insulin, have low rates of cancer and diabetes, and are extremely long-lived.

Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans Published Oct 2008:

Reduced function mutations in the insulin/IGF-I signaling pathway increase maximal lifespan and health span in many species…. These findings demonstrate that, unlike in rodents, long-term severe CR does not reduce serum IGF-1 concentration and IGF-1 : IGFBP-3 ratio in humans. In addition, our data provide evidence that protein intake is a key determinant of circulating IGF-1 levels in humans, and suggest that reduced protein intake may become an important component of anticancer and anti-aging dietary interventions.
Exercise Intensity can lead to cardiovascular damage

In his presentation at the Ancestral Health Symposium in August 2016, AHS16 - Steven Gundry - Dietary Management of the Apo E 4 at 26:10, Dr Steven Gundry said, “that the last thing ApoE4s should be doing is Cross Fit.” CrossFit is a program of aerobic exercise, calisthenics and Olympic weightlifting. It is typically very intense, emphasizing competition as well as exercise. When later asked to elaborate on his statement, Dr Gundry indicated that that the indictment was not just on cross-fit but all intense, stressful workouts. He cautioned that ApoE4s have to be mindful of their greater potential to develop small vessel disease. Small blood vessels exist in the brain and heart as well as elsewhere in the body. He stated that almost every one of his patients who are intense cross-fitters, or marathoners, or other high-intensity participants have elevated Cardiac Troponin-I markers. Cardiac Troponin-I is a test that is a hundred more times sensitive than the test in the emergency room looking for heart attacks. But he also stated that when his patients back off from the intensity, this marker goes back to normal.

Another potential result of excess intense exercise is Atrial fibrillation (AFib). AFib is an abnormal or rapid heart rate, a common but serious arrhythmia. Two groups are at high risk for AFib: Obese, sedentary people, and thin, active people who over exercise. From this article, An "Iron" response by Dr. John Mandrola, a cardiac electrophysiologist: “There are hundreds of citations documenting the risk of atrial fibrillation in long-term endurance athletes.” He then went on to cite six specific references.

Just moving - strolling in the park, tai chi, dancing, gardening, etc.

There’s a lot to be said for just moving. As a society, we sit a lot: working on the computer, video games, desk work, driving, watching television. Our ancestors didn’t do that, but they did keep very active.

According to this study, Exercise, APOE genotype, and the evolution of the human lifespan

Our hypothesis suggests that increased selection for exercise and physical activity served to ameliorate the effects of APOE ε4, supporting the evolution of longer human lifespans and achieving the potential for successful advanced aging. Thus, changes induced by modern-day environmental constraints and human behavior may have led to greater vulnerability to the effects of APOE ε4 in subgroups of elderly in which high levels of physical activity throughout life are no longer required.

In other words, physical activity helped man extend its overall lifespan, but now, modern day lifestyle has far less demand for physical activity and this is exposing the ApoE4 gene’s health vulnerabilities.

According to Dr Joe Mercola in his post Two Key Strategies to Help Your Fitness Soar in 2017

The scientific literature also clearly shows that sitting for extended periods is a major, independent risk factor for chronic disease, even if you exercise regularly, so daily non-exercise movement is likely one of the most important fitness strategies for many — especially if you’re currently not exercising on a regular basis.
The reason for this is because sitting blocks a number of insulin-mediated systems, including muscular and cellular pathways that process blood sugar, triglycerides and cholesterol. Standing up — bearing your own body weight on your legs — activates all of these systems at the molecular level.

So move often. Better yet, do it outside, walk around the park or do some gardening. The sunshine will provide a nice dose of Vitamin D, see 25OH-D3 = 50-80ng/ml in the Bredesen Protocol discussion. Among its many benefits, Vitamin D supports the health of the immune system, brain and nervous system.

Also, being outside will likely expose a person to M. vaccae, a bacteria that lives naturally in the soil. According to this article Dirt has a microbiome, and it may double as an antidepressant

In a 2007 paper published in the journal Neuroscience, Lowry and his team wrote that the bacteria activated groups of neurons in the mouse brains responsible for producing serotonin—a neurotransmitter that, when impaired, can cause depression.

The article also said:

Papers published since (2007) have described feeding mice M. vaccae-laced peanut butter sandwiches, and watching them race through challenging mazes far faster than their counterparts, suggesting the bacteria gave them a significant brain boost, in addition to apparently elevating their mood.

So get moving and do it outside as much as possible for some beneficial fresh air, sunshine, and bacteria.


Yoga may be lower on the benefit scale for ApoEs when compared to other exercises, but shouldn’t be discounted entirely. There are many types of yoga, from “Power Yoga” which is a high-intensity practice designed to build muscle to “Yoga Nidra” or yogic sleep where the yogi (a person who practices yoga) typically just lies on the floor and is guided verbally into a relaxed state.

Yoga helps promote vagal tone. From 6 ways to Stimulate your Vagus Nerve to reduce Inflammation, Depression, Migranes, and More:

High vagal tone improves the function of many body systems, causing better blood sugar regulation, reduced risk of stroke and cardiovascular disease, lower blood pressure, improved digestion via better production of stomach basic and digestive enzymes, and reduced migraines. The higher vagal tone is also associated with better mood, less anxiety, and more stress resilience.

For more information, see Vagus Nerve. Yoga classes often open and close with a chant of “om” this stimulates the vagus nerve. Yoga can also be meditative and meditation also improves vagal tone.

Yoga can be a good stress reducer. Stress increases risk factors for cognitive decline and cardiovascular disease, but yoga lowers cortisol which results from stress, protects the hippocampus from atrophy, and increases the thickness of the cerebral cortex.

If new to exercise, a very gentle program of yoga, coupled with a light aerobic activity like walking or swimming may be the best way to start. Even if suffering from arthritis, yoga helps with staying flexible and strong. All good yoga instructors are sensitive to the fact that every person’s body is different and insist that a pose only be performed to the ability of that person. Many community recreation centers, “active adult” centers, and yoga studios offer yoga classes for novices or those with physical issues.