November/December 2019 Issue

The Impact of Exercise on the Brain
By Carrie Dennett, MPH, RDN, CD
Today’s Dietitian
Vol. 21, No. 11, P. 30

Research shows physical activity plays a positive role in cognition and mental health.

We know physical activity is good for health, but much of the focus on the benefits of exercise and other nonsedentary activities are on physical health: prevention and treatment of chronic disease, avoidance of age-related muscle loss, and weight management. But there’s substantial research on the effects of physical activity on the structure and function of the brain, and the resulting impact on both mental and cognitive health—factors that could arguably have an even broader impact on well-being, quality of life, and longevity.

Brain Development
Both human and animal studies demonstrate that physical activity habits have a positive influence on brain development during pregnancy and early childhood. Development of the brain and the rest of the central nervous system is a complex process that begins in the third week of gestation, and each stage must be properly completed for the brain structure to develop normally. This process involves both gene expression and environmental stimulation, and physical activity is one environmental stimulus.1

Evidence from human studies shows that maternal physical activity before and during pregnancy improves babies’ cognitive performance in childhood.1 The brain has high levels of plasticity—the ability of neurons to change and reorganize continuously to meet the demands of the internal and external environments—during childhood and adolescence, so environmental stimuli during this time can have significant impact on the developing brain. Human studies have found a positive relationship between physical activity and scores on learning and intelligence tests in school-age children, including improved reading comprehension and attention during tasks.1,2

One likely mechanism is that maternal exercise appears to significantly increase levels of brain-derived neurotrophic factor (BDNF), a nerve growth factor produced and secreted in some regions of the brain—including the hippocampus, which is largely responsible for learning and memory. BDNF protects existing neurons while encouraging new neurons to grow, survive, and proliferate.1 Sangeeta Pradhan, RD, LDN, CDE, a Boston-based diabetes program coordinator, says that exercise plays a key role in enhancing cognitive function and synaptic plasticity, and the intermediary is the BDNF system.

“The majority of the studies done in animal models as well as in human beings have focused on measuring BDNF as the primary outcome to evaluate the effects of exercise either in various disorders or in healthy subjects,” Pradhan says. “BDNF enables neurons to connect with each other through their synapses and thus wire together and form long-lasting relationships with each other. It is this wiring of neural networks that leads to consolidation and formation of memory, promoting learning and higher thinking.”

Rodent studies suggest that maternal exercise during pregnancy may cause a temporary increase in the formation of neurons in the hippocampal region of the brain, which can have a significant long-term impact on the structure of the hippocampus, resulting in improved learning and memory across the lifespan. These studies also have found that maternal exercise improves mitochondrial function and antioxidant defenses in the brains of their offspring, which could benefit brain growth as well as development of specific brain functions. In addition, rodent studies demonstrate that postnatal exercise by offspring increases cell proliferation in the brain, primarily during the earliest stages of postnatal development. It also can alter gene expression in young rodents, including upregulating the gene responsible for BDNF production.1

What remains unclear is the optimal maternal physical activity—including type, intensity, volume, and duration—for promoting brain health. More research also is needed to establish whether the neurobiological mechanisms identified in animal studies can be extrapolated to humans.1

Adolescent Brain Structure
While pregnancy and early childhood are critical windows for brain development, so is adolescence, the period when the hippocampus matures and experiences elevated production of new neurons. Stress during this window can impair hippocampal neurogenesis, and adolescence is generally a stressful time.3 Physical activity may mitigate the effects of stress on the brain, yet only 20% of adolescents get the daily 60 minutes of moderate-to-vigorous physical activity recommended by the 2018 Physical Activity Guidelines for Americans.4 This means not only that adolescents aren’t reaping the physical health benefits of exercise but that they also may be impairing their academic performance and general cognitive function.5

Most studies looking at physical activity and school performance have found a positive association between the two, especially in the areas of reading and math. Increasingly, studies also are finding positive associations between aerobic exercise and a wide range of cognitive abilities, including executive brain functions such as attention, planning, problem-solving, working memory, and inhibitory control. Brain scan studies in older adolescents have found that greater aerobic fitness is associated with larger volumes of the hippocampus and other regions of the brain. Results of experimental studies, in which adolescents or teens are randomized to increase physical activity, or not, have yielded inconsistent results, possibly because genetic differences, including different BDNF genotypes, may influence individual capacity for aerobic fitness and for deriving brain benefits from physical activity.5

Age-Related Cognitive Function
Physical activity may play an important role in both preventing and delaying the progression of dementia. Unfortunately, only 27% of older adults meet recommended physical activity guidelines,4 says Christine Rosenbloom, PhD, RDN, FAND, Atlanta-based author of Food & Fitness After 50: Eat Well, Move Well, Be Well. “The reasons are as varied as they are for the general population; however, older adults may fear falling and choose not to be active,” she says.

A 2009 systematic review found that the risk of developing dementia was 28% less, and the risk of developing Alzheimer’s disease was 45% less among individuals within the highest category of physical activity compared with the lowest.6 While it’s unclear at what time in an individual’s life physical activity is most important for future protection, or what “dose” in terms of frequency, duration, and intensity is optimal, some evidence suggests that midlife physical activity may be especially beneficial.7

“Many people underappreciate the role of physical activity on the brain, but the 2018 Physical Activity Guidelines Advisory Committee Scientific Report clearly demonstrates a consistent association between greater amounts of physical activity and improvements in cognition, including tasks that involve processing speed, memory, and higher executive functions, such as information processing, reasoning, planning, organizing, and problem solving,” Rosenbloom says.8 “There’s strong evidence that physical activity in healthy older adults reduces the risk of cognitive decline and developing cognitive impairment, including Alzheimer’s disease. And there’s moderate evidence that it can improve cognition in those with dementia and in those with other diseases that can impair cognitive function, such as Parkinson’s disease, multiple sclerosis, and stroke.”

Results from the Brain in Motion study published in 2015 found that greater lifetime physical activity—especially recreational activity, vigorous activity, and activity from early childhood to midlife—was associated with better cognitive performance across several measures in middle-aged and older adults. However, other research has shown that children with higher cognitive ability are more likely to choose healthful lifestyles, so it’s unclear whether the increased physical activity actually caused the improved cognitive performance, or if it’s simply an association.9

Possible mechanisms include reduced blood pressure, lipids, and markers of inflammation, as well as improved function of the endothelial cells lining the blood vessels, and increased blood flow and oxygen supply.6,7 With normal aging, cerebral blood flow decreases about 5% per decade.10 “The Alzheimer’s Association cites physical activity as a beneficial strategy to lower the risk of not just Alzheimer’s disease but of vascular dementia,” Rosenbloom says. “Exercise increases blood flow and oxygen not just to working muscles but also to the brain.”

Clinical studies have found that decreased cardiorespiratory fitness in older adults is associated with related declines in cortical tissue density in areas that are responsible for executive function, and that regular exercise is associated with increased volume in the hippocampus.7 The effect of exercise on neural plasticity and BDNF levels also may play a role in preserving cognitive function,1,6 and physical activity also may affect levels of major neurotransmitters.11

“The idea that exercise is medicine is as true for brain health as it is for cardiovascular, muscular, or bone health,” Rosenbloom says. “The research evidence is strong that physical activity in those over 50 improves health-related quality of life or life satisfaction compared to those who are inactive. Active older adults report increased energy levels, emotional well-being, and reduced anxiety and stress. Physical activity also improves sleep quality, something that many older adults complain about. When you add the cognitive benefits of exercise to the physical benefits, it is truly a win-win.”

For dietitians who see older adult patients, Rosenbloom cautions that older adults who have never been active may be intimidated at a gym because the many options can seem overwhelming. “For those who have never been active or want to get back into physical activity, a structured exercise program that includes balance training, strength and endurance training, and gait training are available for the 50-plus population,” she says.

Oxidative Stress
A second theme running through the connection between physical activity and brain health, after BDNF, is oxidative stress. While oxidative stress has long been known to contribute to neurodegenerative disorders such as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease, newer research also is finding that it plays a role in psychiatric disorders, including depression and anxiety.12

“Any form of metabolic dysfunction—for example, metabolic syndrome—in the body itself can lead to increased oxidative stress, the formation of reactive oxygen species/free radicals and membrane damage in the brain,” Pradhan says. “The brain is particularly vulnerable to oxidative stress because of its high polyunsaturated fatty acid content, the fact that it is a huge energy guzzler relative to its small mass, and has relatively low antioxidant defenses.”

Pradhan says any form of oxidative stress can cause BDNF levels to plummet, and, by restoring BDNF, exercise can reduce the negative effects of oxidative stress in the body, including counteracting oxidative stress produced by high-fat diets. “A high-fat diet, especially [one high in] saturated fats, has been shown to increase oxidative stress and reduce BDNF, neuronal plasticity, and learning in animal models.”

Mental Health
Counteracting oxidative stress with physical activity doesn’t just help keep the brain sharp; it also can improve mood. Both animal and human research support the efficacy of physical activity in preventing and relieving mood disorders—including depression—and anxiety disorders. Again, one likely mechanism is by optimizing BDNF levels in the hippocampus. Another is regulation of the hypothalamic-pituitary-adrenal (HPA) axis, which boosts resilience to stress. This is important, because HPA dysregulation causes elevated levels of glucocorticoids—including the “stress hormone” cortisol—which can lead to atrophy of the hippocampus in individuals with mood disorders, contributing to the progression of major depressive disorder (MDD) and anxiety disorder.13,14

Observational and randomized controlled trials in humans have found associations between regular physical activity—both strength training and aerobic exercise—and a reduction in symptoms of depression.11 Evidence shows that physical activity reduces the risk of developing MDD and aids in recovery and relapse prevention in those who already have been diagnosed with it.13

Research has established that low BDNF levels contribute to depression, with low blood levels noted in people with depression compared with healthy controls. Postmortem examinations of people who suffered from MDD and/or completed suicide have found low levels of BDNF in the hippocampus. Results from genetic studies show that symptoms of depression are associated with polymorphisms in the BDNF gene. In animal studies, regular physical activity increases BDNF in the hippocampus for several days and increases levels of muscle-derived proteins that also help regulate BDNF in the brain. Moreover, physical activity optimizes levels and function of several neurotransmitters, including serotonin and dopamine, which can positively affect BDNF levels.13

Blood levels of BDNF tend to normalize after treatment with antidepressants, electroconvulsive therapy, or physical activity. Physical activity also may enhance the efficacy of antidepressants. Animal studies also show that chronic stress and depressive symptoms are associated with reduced BDNF levels, while direct infusion of BDNF into the hippocampus or midbrain regions produces antidepressant effects.13

“In rats that were chronically stressed, those that were made to exercise on running wheels had decreased depressivelike behaviors,” Pradhan says, adding that reduction in depressive symptoms may be due to an increase in BDNF levels, which then leads to increased neuroplasticity and a decrease in the neuronal injury or death that can contribute to depression. She contends that a 1999 Duke University study of 156 older adults with MDD found that a brisk 30-minute walk or jog three times per week was as effective as antidepressants.15 A larger follow-up study that included a placebo group confirmed these findings,16 and despite heterogeneity in subsequent studies, the consensus is that exercise is an effective treatment for depression.17 Overall, the data suggest that moderate physical activity optimizes BDNF and neuronal plasticity, especially in individuals with depression.

Observational studies have found that people who engage in higher levels of physical activity are less likely to be diagnosed with an anxiety disorder and tend to have milder and less frequent symptoms if they have been diagnosed.14 A 2017 meta-analysis of studies compared the benefits of exercise with those of control conditions—treatment as usual or waitlist—in people with anxiety and/or stress-related conditions. These included generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, social phobia, and posttraumatic stress disorder. The results showed that exercise decreased anxiety symptoms significantly more than control conditions. However, the authors said more high-quality randomized controlled trials are needed to determine the optimal exercise type, intensity, duration, and frequency.18

Physical activity also can lower levels of the proinflammatory cytokine C-reactive protein, which, when elevated, can contribute to the development of anxiety. Because exercise produces physical responses that are typical with increased anxiety, such as elevated heart rate, but without the feelings of anxiety, people with anxiety who exercise regularly may associate the physical sensations with something pleasant, and be better able to tolerate them when they do occur in the context of anxiety. They become habituated to anxiety symptoms.14

Since physical activity is low risk, easy to implement, and has no side effects, it’s become part of the basic clinical management protocol for depression and other mood disorders.13 Adding physical activity to interventions for anxiety disorders may be a cost-effective, practical way to improve treatment response. Up to one-third of people with anxiety disorders don’t respond to treatment, and combining drug therapy with forms of cognitive behavioral therapy hasn’t improved those numbers—never mind that many people can’t afford or don’t have access to ongoing therapy. In addition, people with anxiety disorders are 52% more likely to develop CVD than the general population, so including physical activity may have benefits on multiple levels.14

Physical Activity Prescription
While dietitians don’t have to think twice about recommending physical activity for maintaining and improving physical health, the benefits of lifelong movement for mental and cognitive health also are worth factoring into recommendations. No matter where on the lifespan spectrum your clients or patients fall, helping them find ways to incorporate enjoyable forms of exercise or other physical activity into their lives can improve their health and well-being in myriad ways for years, or decades, to come.

— Carrie Dennett, MPH, RDN, CD, is the nutrition columnist for The Seattle Times, owner of Nutrition By Carrie, and author of Healthy for Your Life: A Holistic Guide to Optimal Wellness.


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