Exercise and Brain Health: Some Good Points to Remember

May 11, 2012 · Posted in Peer-Reviewed Published Data, Risk Factors 


In a review article in the Neuroscientist published in February of this year, Kirk I. Erickson and collaborators wrote that “[m]ajor depressive disorder is considered a risk factor for Alzheimer’s dementia and memory impairment and is associated with less BDNF and greater hippocampal atrophy, possibly through a BDNF pathway. However, exercise and effective treatment for geriatric depression increases BDNF levels, increases serotonin fibers, is associated with greater hippocampal volumes, and reduces the risk for Alzheimer’s dementia.”

Editor’s note: Not a bad set of benefits from exercise! The researchers suggest that exercise is extremely important in reversing the decreases in brain-derived neurotrophic factor (BDNF) associated with depression, helping to improve depressed mood, increasing cardiovascular fitness, and maintaining healthy cognition.

Hippocampal volume and BDNF levels in blood both decrease with age. Yet exercise increases both BDNF and the formation of new neurons (neurogenesis) in animals. New data in humans suggest that aerobic fitness is associated with the size of the hippocampus, both in both children and adults. It is not clear yet whether this increase in hippocampal volume is directly driven by increases in BDNF and/or neurogenesis. However, since a smaller hippocampus is a risk factor both for depression and for mild cognitive impairment progressing to Alzheimer’s dementia, attempting to enhance hippocampal volume in any way possible is probably a good idea.

Methods of increasing hippocampal volume include treatment with antidepressants or with lithium. In the 2012 paper Erickson and collaborators also wrote, “Anaerobic exercise enhances executive and memory function and reduces hippocampal atrophy in late adulthood, and this may be partially mediated through a BDNF pathway.”

Erickson and collaborators conducted a longitudinal study published in 2010 that quantified the amount of physical activity subjects engaged in by calculating the total number of blocks walked per week. Individuals reporting greater amounts of physical activity at the beginning of the study had, upon examination nine years later, greater gray matter volume in several parts of the brain, including the hippocampus. This effect was “dose-dependent,” meaning that only those individuals who walked at least 72 blocks per week (roughly equivalent to 1 mile per day) had significant sparing of brain tissue nine years later. The study found increased gray matter volume in the prefrontal cortex and in the temporal lobe.

After a further follow-up of four more years, greater gray matter volume with physical activity was associated with a two-fold reduced risk of cognitive impairment. The researchers concluded that “physical activity patterns earlier in life were linked to brain volume and cognitive impairment later in life.”

There are a number of important points to remember about cognitive impairment. One is that increasing hippocampal volume and preventing its decrement with aging may help prevent age-related memory loss and potentially the rapidity at which mild cognitive impairment progresses.

A second point is that it is critically important to prevent depressive episodes, since having more prior depressions is associated with experiencing more cognitive dysfunction, and there is some evidence that it may also be associated with decreasing volume of the hippocampus.

A third point is that several different modes of helping protect hippocampal volume are available.

1) Antidepressants: Researcher Yvette Sheline has shown that unipolar depressed patients on antidepressants more of the time compared to less of the time do not experience hippocampal volume loss with aging. These data converge with others that indicate that antidepressants either increase hippocampal volume or prevent its decrement, likely through by increasing BDNF and neurogenesis.

2) Lithium: Lithium increases hippocampal volume in patients with bipolar disorder and is also known to increase BDNF and neurogenesis. Preliminary data from a large population of patients studied in a Danish case registry also suggest that patients who renew their lithium prescriptions are less likely to receive a diagnosis of dementia in old age. A small study published by Forlenza et al. in the British Journal of Psychiatry in 2011 indicated that treatment with lithium at 150mg/day compared to placebo over a period of one year decreased the rate of cognitive decline in psychiatrically well patients in the general population who had mild cognitive impairment (MCI).

3) Long-term maintenance: Long-term preventative treatment is important in both unipolar and bipolar depression.  Antidepressants in unipolar patients not only help prevent depressions (and the associated decreases in BDNF in the brain and the blood), but also protect hippocampal volume. In bipolar patients, effective mood stabilizers for adequate long-term prophylaxis are critically important. These drugs are able to increase BDNF. Lithium in particular also increases hippocampal volume.

4) Exercise: Now it seems that including exercise as part of one’s regular approach to maintaining good health might also lead to benefits in maintaining hippocampal volume and associated memory function with aging. While the literature is mixed about the role of exercise as an antidepressant, a sufficient number of positive controlled studies have indicated that it can be helpful. Exercise-induced increases in BDNF may be important both in helping to ward off depression and preventing hippocampal volume loss with aging.

Previously we have suggested a mantra for long-term prevention of mood disorders: “Prevent episodes, protect the brain.” To this mantra we might add a new one: “Exercise protects the heart and the brain.” Not only is exercise a way of increasing cardiovascular fitness, which itself is associated with increases in hippocampal volume, but exercise has many other potential benefits as well, particularly in the cardiovascular arena. In addition, exercise directly increases BDNF and neurogenesis, and also increases the ratio of beneficial or high-density lipoproteins to problematic or low-density lipoproteins.

Enhancing Motivation For Exercise During A Depression

One common problem for depressed patients is lack of motivation to exercise, even in those who enjoy exercise and are highly committed to it when euthymic. Approaching exercise in small steps may be helpful. A walk around the block may be a good first step, and the distance can gradually be increased. Walking, bicycling, sports, or other forms of exercise that can be done with a friend may increase motivation to exercise while also providing social support. In patients who like dogs, having a dog that insists on a regular walking routine may also be helpful.

Exercise also has benefits in the realm of weight control. Patients who are depressed tend to move less and gain weight accordingly. Exercise, as well as good dietary habits, can be a key element in helping to maintain one’s weight during depression or to reduce it during periods of planned dieting in those who are overweight.

There is another potential benefit to exercise, this one neurobiological. Since exercise helps in the generation of new neurons, it may also increase some higher-level cognitive processes that require fine discrimination between choices. Animal studies by Fred Gage and colleagues have revealed that newly formed cells in the hippocampus are more excitable than older neurons. Older neurons are adequate for discriminating objects that are markedly different, but young neurons can differentiate between two closely related objects or concepts thanks to their hyperexcitability, and this may be an asset in some types of demanding cognitions.

In summary, exercise is good for: the hippocampus, cognition, depression, cardiovascular health, and weight maintenance.

Modern modes of transportation like cars, planes, trains, escalators, moving sidewalks, and even flights of imagination from the sofa while watching TV or from the desk chair while using the internet make it too easy to avoid exercise. Building exercise into one’s general health regimen (or therapeutic regimen in those with depression or mild cognitive impairment) may be a way of overcoming the unintended negative consequences of modern life. So “A mile a day keeps memory loss away” may be a good thought for those of us who want to protect our brains and bodies for as long as possible.


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