Exercise Builds Brain Health

Carl W. Cotman, Ph.D.

Increasingly, it seems, we are besieged in the print media, television and the Internet by advertisements for products to enhance mental and physical health in a relatively fast and painless fashion though miracle elixirs, computer-based training, games or brief exercise programs. While there is little convincing evidence for the efficacy of such claims, one that is well-documented in the scientific literature is the benefit of physical activity and exercise on cognitive and physical health. This idea is not new. In fact, Hippocrates, an ancient Greek physician and founder of Western medicine stated, “If we could give every individual the right amount of nourishment and exercise we would have found the safest way to health.” Ben Franklin, one of our founding fathers, commented, “Exercise invigorates, and enlivens all the faculties of body and of mind… It spreads a gladness and satisfaction over our minds and qualifies us for every sort of business, and every sort of pleasure.” Indeed there is an increasing body of scientific evidence from human and animal studies that reveals numerous health benefits of regular physical exercise, including the health and function of the brain.

Exercise builds neuron health and improves brain function

As recently as the mid-1990s, the prevailing assumption was that exercise improves health by its effect on the body, building skeletal muscle tone and improving cardiovascular function. Within the past several years, however, it has become clear that the brain itself is also directly impacted by exercise. In the mid-1990s, our group at UCI first demonstrated that exercise increases the amounts of a protein called brain derived neurotrophic factor (BDNF) in the brain. This molecule protects neurons from injury and facilitates learning and synaptic plasticity. In a sense, BDNF is like brain fertilizer. With age, BDNF levels fall and this decline is one of the reasons for impaired age-related cognitive function. Exercise counteracts these age-related declines in BDNF, and can restore young levels of BDNF in the aged brain. These basic studies and others catalyzed many follow-up studies, and formed one of the cornerstones for additional animal and human studies aimed at elucidating the impact of exercise on brain structure, chemistry and function.

We now know that exercise acts at multiple levels to build the brain and enhance its function. The circuitry of the brain is dependent on neuron integrity, the connections between neurons (synapses), and the ability of synapses to function normally in network communication and learning. With age, synapses are lost and their function declines. Recently, we discovered in the aged rodent that exercise increases the numbers of synapses, counteracting the synaptic loss that occurs with age. In addition to stimulating an increase in synapse number, exercise stimulates the brain to generate more neurons. Until a few years ago it was believed that the brain cannot make new neurons. This idea was disproven when it was discovered that new neurons are made in specific regions of the brain throughout the lifespan. One key region that manufactures new neurons is the hippocampus, a critical region in learning and memory formation, and a target of massive decline in Alzheimer’s disease. Importantly, after these new neurons are generated (“neurogenesis”), they integrate into the circuitry of the hippocampus and improve learning. Exercise is one of the few known interventions that can enhance neurogenesis. Moreover there is evidence that exercise may increase neurogenesis in the human hippocampus just as we observe in the rodent brain. Finally, In addition to stimulating synapses and neurogenesis, exercise builds systems that help support brain function, such as enhancing brain metabolism and stimulating new blood vessel formation.

Studies in humans also show that exercise benefits the brain and cognitive function, based on both population surveys (“epidemiological studies”) as well as clinical studies. In one epidemiological study, walking 3 or more times per week was found to correlate with a 32% reduced risk for Alzheimer’s disease (AD). In another study, a moderate level of physical activity was associated with slower cognitive decline in aging, equivalent to staying younger by 2-3 years. Clinical trials have validated these observations, demonstrating that elderly subjects who engage in moderate aerobic exercise (vigorous walking) show improved cognitive function, particularly on executive function tasks. Executive function is essential for multi-tasking and working memory, for example, holding facts and events in memory storage while engaging in conversation. Thus the benefits of exercise add practical value to everyday life. At a biological level, human studies also have demonstrated that exercise prevents age-related declines in blood flow, particularly in the vulnerable cortex and hippocampus. In addition, exercise prevents atrophy that occurs in certain brain regions with age. A decrease in the volume of the hippocampus is one the biomarkers which is linked to Alzheimer’s disease. For example, 40 min/day of moderate walking, 3 times per week for 1 year, increases the volume of the hippocampus in normal elderly adults. Further, exercise can reduce the accumulation of pathology in the brain that may trigger Alzheimer’s disease. For example, exercise reduces the brain levels of beta-amyloid, which is the major component of senile plaques (one of the hallmarks of Alzheimer’s disease), first reported by our group in transgenic mouse models of AD. Recent human studies reveal that less brain amyloid accumulates in individuals who are active and fit than those who are sedentary, suggesting that exercise prevents the age-related build up of harmful pathology that impairs brain health and function. It appears that exercise could improve cognitive function even in those with some level of impairment and brain pathology (e.g., persons with MCI or AD). To test this hypothesis, the National Institutes of Health awarded funding to undertake the first clinical trial of exercise as an intervention in MCI as part of the Alzheimer’s Disease Cooperative Study, a national consortium focused on developing treatments and diagnostic tools. The newly funded randomized, controlled clinical trial, led by the author with Laura Baker, Ph.D., of the Wake Forest School of Medicine, will investigate if supervised aerobic exercise can improve cognition, slow brain atrophy, or mitigate Alzheimer’s pathology in older adults with MCI, a condition the often progresses to AD.

Lifestyles and Personalized and Proactive Medicine.

Nearly all of our lifestyle choices affect our health. Lifestyle practices can be effective therapeutic approaches to promote optimal health of the body and brain. While aging is inevitable, aging is also influenced by how we live.

Each person can practice personalized and proactive medicine by including physical activity in their daily routine, maintaining a healthy weight, and eating a healthy diet. These lifestyle practices go a long way toward slowing the effects of aging, and gaining an upper-hand on brain and physical health. The American Heart Association identifies inactivity as one of the five leading risk factors for developing cardiovascular disease. Taking steps to increase physical activity can improve circulation, blood vessel health and heart function, reduce blood pressure, and help control blood sugar and insulin levels. In turn, these physical benefits help promote brain health. In addition to the brain benefiting from improved general body health with exercise, exercise directly affects the brain, stimulating the growth of new blood vessels, enhancing neurogenesis and synapse formation, and improving learning. No other lifestyle or pharmaceutical approach can impact overall health and brain health as significantly as physical activity.

So how do I exercise regularly?

Despite this increasing wealth of knowledge on the relationship of physical activity and health, an estimated 74% of adults do not meet the recommended guidelines of at least 30 minutes of moderate intensity physical activity 3 times/week. As little as 4 – 7 hrs per week of exercise can lower your risk for cognitive decline and prolong your life. It is not uncommon to hear people say, “Okay, it sounds like a convincing argument that exercise is good for me. But I am too busy, do not like to exercise and have no convenient place to exercise….”

Several proven strategies will help you overcome such excuses and incorporate exercise into your lifestyle. The most important factor is that YOU must decide you WANT to try. Just like other priorities, it is essential to set aside dedicated time and to develop a regular schedule for exercise. Think about what time of day you would be happiest to exercise. I personally prefer late in the day, after work but before dinner. This gives me a chance to reflect on my day, to plan ahead, and also to relax. Keep exercise interesting and fun by varying the type of exercise, or learning new skills or sports. Exercising with another person or group is also a great strategy and adds an important social element. The key is to experiment with the best approach for you, make it part of your schedule, and realize that physical activity is the safest and least costly way to practice personalized and proactive medicine.