Advanced Topics: Preventing Cognitive Decline - The Role of Exercise




Prevention of Cognitive Decline and Dementia: The Role of Exercise


migraine Unlike the skimpy data that support the use of most nutritional supplements for prevention/reversal of cognitive decline and dementia, with exercise we have far better data. The studies also include both observational and clinical intervention studies tracking measures of mental function and volumetric brain imaging. The latter, in particular, generate “hard” findings of brain anatomy that are especially powerful, less subject to interpretation or bias.




Overview

Exercise increases brain volume, specifically the dentate gyrus of the hippocampus, consistent with the concept that neuronal plasticity is preserved; increases overall white and gray matter volumes; increases brain-derived neurotrophic factor (BDNF), with increased IGF-1 alpha with strength training; and improves psychometric measures including memory and executive function. One pivotal study demonstrated that exercise increased hippocampal volume by 2% over one year.   Exercise has also been shown to reverse mild cognitive impairment and improve some psychometric measures in dementia, as well as reduce the likelihood of developing either over time.

Given the expected loss of hippocampal volume of 1-2% per year, the magnitude of increased hippocampal volume appears to be a one-to-one tradeoff: One year of consistent exercise achieves the equivalent of one year of reversed brain atrophy.

Exercise exerts its benefits through a variety of means that includes reduced insulin resistance in the liver, muscle, and in brain tissue; reduced blood sugar and thereby endogenous glycation; reduced inflammatory phenomena; reduced blood pressure; and direct effects on increasing levels of brain neurotrophic factors that cultivate neuronal richness and plasticity. For instance, one experience demonstrated a 400% increase in blood levels of BDNF (an indirect index of brain BDNF) in cognitively normal males exercising over 3 months. While strength training does not raise serum BDNF, it raises levels of another hormone with neurotrophic effects, IGF-1 alpha. In another study, elderly non-cognitively impaired people reduced inflammatory markers, c-reactive protein and interleukin-6 (but not TNF-alpha), by engaging in 180 minutes/week exercise. By itself, exercise can only accomplish so much in preserving cognitive health. But, when added to the collection of other strategies we apply, exercise amplifies the cognitive benefits of grain and sugar elimination, vitamin D and omega-3 fatty acid supplementation, and cultivation of bowel flora.

Exercise should therefore be a cornerstone of your cognition-preserving efforts. Given the variety of forms of exercise and exercise intensities studied, a “magic formula” for exercise has not yet been worked out. But the bulk of data suggest that most benefits occur at moderate levels of exercise, e.g., walking while maintaining a heart rate in the 90-120 beats per minutes (bpm) range or 75% of age-predicted maximum heart rate (age-predicted max heart rate = 220 - age in years). For a 60-year old, for example, this means a heart rate of 120 bpm. Exercise should be sustained for at least 30 minutes 4 or more days per week. While bouts of high-intensity exercise (e.g., Tabatas) interspersed within lesser levels of effort have been successful in abbreviating the amount of time required to achieve benefits such as reversing insulin resistance and allowing modest weight loss, this has not been examined in the setting of cognitive preservation. It is likely, however, that the time savings generated via high-intensity exercise can still preserve the benefits on cognitive health provided by longer duration, less intense exercise.

Strength training appears to add a modest additional benefit in preserving cognitive health, although the evidence is limited. However, strength training provides benefits in other areas of health (improved bone density, improved insulin sensitivity that facilitates reduction of blood sugar and weight management, reduced falls) and any exercise program should include some component of strength training.

A Summary of the Evidence

Biomarker studies:

Ahlskog JE, Geda YE, Graff-Radford NR et al. Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Mayo Clin Proc 2011 Sep; 86(9): 876–84.

Colbert LH, Visser M, Simonsick EM et al. Physical activity, exercise, and inflammatory markers in older adults: findings from the Health, Aging and Body Composition Study. J Am Geriatr Soc 2004 Jul;52(7):1098-104.

Seifert T, Brassard, Wissenberg M et al. Endurance training enhances BDNF release from the human brain. Am J Physiol Regul Integr Comp Physiol 2010 Feb;298(2):R372-7.

Observational data:

Regular mid-life aerobic exercise reduces incidence of dementia by approximately 30%: Hamer M, Chida Y. Physical activity and risk of neurodegenerative disease: a systematic review of prospective evidence. Psychol Med 2009 Jan;39(1):3-11.

Women (n = 9300) who exercised at various times along their life course reduced incidence of mild cognitive impairment by about 50%: Middleton LE, Barnes DE, Lui LY, Yaffe K. Physical activity over the life course and its association with cognitive performance and impairment in old age. J Am Geriatr Soc 2010 Jul;58(7):1322-6.

Clinical intervention studies:

A large Chinese experience (n = 15,000+) demonstrating that aerobic exercise, but not stretching or toning, reduces development of dementia by about 20% in cognitively normal people over 6 years. Exercise involved 45 minutes per day, 7 days per week (!). Lee AT, Richards M, Chan WC et al. Intensity and types of physical exercise in relation to dementia risk reduction in community-living older adults. J Am Med Dir Assoc 2015 Oct 1;16(10):899.

Cognitively normal people with pre-diabetes and type 2 diabetes experienced improved executive function, but not memory, over 6 months of aerobic exercise (45-60 minutes x 4 days/week): Baker LD, Frank LL, Foster-Schubert K et al. Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer’s disease. J Alzheimers Dis 2010;22(2):569-79.

6 months of aerobic exercise in cognitively normal, sedentary adults increased white and gray matter brain volumes: Colcombe SJ, Erickson KI, Scalf PE et al. Aerobic exercise training increases brain volume in aging humans. J Gerontol A Biol Sci Med Sci 2006 Nov;61(11):1166-70.

Hippocampal volume (specifically the dentate gyrus) increased by 2% over one year in people engaged in aerobic exercise compared to a similar magnitude of loss of brain volume in people not engaged in exercise, changes that correlated with increased serum BDNF levels. Memory also improved: Erickson KI, Voss MW, Prakash RS et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci USA 2011 Feb 15; 108(7): 3017–22.

Meta-analysis showing improved cognitive function with exercise in people with mild cognitive impairment: Wang C, Yu JT, Wang HF et al. Non-pharmacological interventions for patients with mild cognitive impairment: a meta-analysis of randomized controlled trials of cognition-based and exercise interventions. J Alzheimers Dis 2014;42(2):663-78.

A meta-analysis of intervention studies that suggests that, once established, exercise does not impact on dementia although it can reduce depression that accompanies dementia: Barreto PS, Demougeot L, Pillard F et al. Exercise training for managing behavioral and psychological symptoms in people with dementia: A systematic review and meta-analysis. Ageing Res Rev 2015 Nov;24(Pt B):274-85.

Another meta-analysis of aerobic exercise in people with dementia (Alzheimer's and other forms) that showed improved cognitive function: Groot C, Hooghiemstra AM, Raijmakers PG et al. The effect of physical activity on cognitive function in patients with dementia: A meta-analysis of randomized control trials. Ageomg Res Rev 2016 Jan;25:13-23.

One year of walking at 60% max heart rate in non cognitively impaired people improved MRI-measured "functional connectivity," the intensity of neuronal interaction between various brain regions (frontal, temporal, posterior): Voss MW, Prakash RS, Erickson KI et al. Plasticity of brain networks in a randomized intervention trial of exercise training in older adults. Front Aging Neurosci 2010; 2: 32

Go to Forum discussion.

Transcript:

This is another discussion in our series on preventing cognitive decline, or reversing early cognitive dysfunction. In this conversation we're going to emphasize the role of exercise. Exercise is a really powerful way to preserve mental and cognitive function. Now, exercise by itself is insufficient, right? If all you did was bike and run and lift weights — that's not enough to prevent dementia, because if that was true, anybody who's athletic would never have dementia, right?

Exercise takes on its power when it's thrown into the context of the other things we do: the diet of the Undoctored Wild-Naked-Unwashed strategies, the replacement of vitamin D, and omega 3 fatty acids, and cultivation of bowel flora, and then some of the other pieces we're going to add on in our cognitive preservation program. Exercise really amplifies a lot of these effects, and there's good science to tell use why that is.

When you exercise, you reduce blood pressure a little bit. Blood pressure's a big player in dementia, both Alzheimer's dementia as well as vascular dementia (essentially dementia from mini-strokes). Blood pressure reduces inflammation. Inflammation is a huge driver of dementia, particularly in people with the ApoE4 genetic marker. So, exercise reduces inflammatory markers dramatically. It's worth adding for that purpose.

Exercise also amplifies your response to insulin; reverses insulin resistance. Insulin resistance is a key factor in causing dementia, and exercise helps counter that, in the brain, as well as in the liver, and muscles.

Exercise also increases neurotrophic factors, that is factors that cause the nerve system cells in your brain to grow and to connect with each other (neuronal plasticity). You can actually change brain structure over time, with consistent exercise efforts. One of the reasons why that happens is because exercise increases the levels of BDNF (Brain-Derived Neurotrophic Factor), a very potent growth factor in the brain. Now we can't measure brain BDNF concentration very easily (because no one wants to have their brain biopsied), but the blood levels can reflect brain levels. In one recent study, for instance, showed a 400% increase in BDNF levels in the blood with a consistent exercise program.

Strength training does not seem to increase BDNF, but it seems to increase another neurotrophic growth factor called IGF-1α, and that also adds to these effects. In other words, there'a whole constellation of beneficial effects of exercise that yield positive effects on preserving your cognitive health.

The clinical data, in humans (not just in animals, and not just in experimental models, in humans) has for the most part borne this out. People who exercise are protected from dementia — typically 20 to 50% less risk for dementia, less risk for mild cognitive impairment. The key here is to do this as early as possible, before even mild cognitive impairment sets in, because that's where you have the most power over preventing these kinds of things.

If you have early cognitive decline, exercise still is beneficial. If you have dementia established to the extent that exercise is not so helpful, it might be helpful for boosting mood, and other beneficial effects on health, but it may not be that helpful. The key is to start early — not wait for dementia to seize hold on your brain.

How much exercise, and what kind? Well, the studies are kind of all over the place. There is no magic formula for exercise, but several patterns seem to fall out. It appears that about 30 minutes of exercise, 4 days a week, provides the bulk of benefits. In other words, if you exercise for 4 days a week for 60 minutes, you don't double the benefits. You just get a little bit more benefits. The bulk of benefits occur with very modest efforts.

Most of us, that is most of us in our 40s, 50s, 60s and 70s, only have to achieve a heart rate of around 90 to 120 beats per minute, or to be more precise, about 60 to 75% of your age-predicted maximum heart rate. How to calculate that is below in the text (above this transcript on the Advanced Topic page). Which means, that a brisk walk will do it. Casual biking will do it. Lawn work will do it. Really, any kind of moderate activity where your heart rate goes up somewhat, and you sweat a little bit, that's enough to provide you with cognitive benefit. You do not have to become a triathelete. You don't have to run marathons. It just takes modest levels of physical exercise, plus you all the other benefits of exercise, right; reductions in blood sugar and blood pressure, better mood, anti-inflammatory effects, etc.

It is worth adding strength training, even though it doesn't increase BDNF levels, it has other benefits, like the increase in that other neurotrophic factor, the IGF-1α, as well as increased muscle mass gives you better control over weight, and insulin, and blood sugar, and decreases falls, and can increase bone mass and protect you from osteoporosis. So strength training is worth including for a lot of reasons, and perhaps for its contribution also to maintaining cognitive health.