African American women exercising

Exercise Rewires the Brain to be More Flexible, But Only for Those with the Right Genes

Regular aerobic exercise, which gets your heart beating fast, can literally rewire your brain, enabling key circuits for memory formation to flexibly rearrange their connections to other parts of the brain every few seconds, reports a new publication from researchers at Rutgers University-Newark’s Aging & Brain Health Alliance. In contrast, they showed that people who don’t exercise have more rigid brain connections, where each part of the memory circuit gets stuck communicating, over and over, with the same regions. According to Mark A. Gluck, a professor of neuroscience and public health at the Center for Molecular and Behavioral Neuroscience (CMBN), and senior author on both papers, “It's like comparing two different dinner parties: At the lively party, guests jump around regularly from conversation to conversation, breaking off repeatedly into different groups to talk about various topics. In contrast, at the dull party, you get stuck talking all night long to the same small set of people. Exercise has a similar effect on your brain. It allows the memory circuits to be more flexible, jumping from conversation to conversation with different parts of the brain.”

In their study, the researchers recruited older African Americans, all previously sedentary, to complete twenty weeks of twice-weekly cardio-dance exercise classes held at local churches and senior centers. As compared to the control group comprised of community members of similar age and background who did not exercise, those in the program showed significant improvements in dynamic brain connectivity (or “neural flexibility”) in their hippocampus and surrounding medial temporal lobe, as measured using resting-state functional MRI. “This is especially important,” said lead author Neha Sinha, a Rutgers Faculty Research Associate, “because this is the same brain region where damage from Alzheimer’s disease appears, often years before the onset of noticeable dementia. As such, these studies add to our understanding of how regular aerobic exercise may protect us from Alzheimer’s dementia.”

This increase in neural flexibility in the brains of the people who exercised had clear cognitive benefits, as well. The exercise participants increased their ability to apply old memories to new situations and tasks. That is, they improved their ability to generalize learning from the past which enabled them to more efficiently transfer old knowledge to new problems, suggesting that neural flexibility leads directly to memory flexibility.

However, there’s a catch: not everyone gains the same degree of neurocognitive benefits from exercise; in a second follow-up paper, the team demonstrated that the improvements in generalization occurred only in a subset of the people who exercised. People who had a risk-variant of the ABCA7 gene showed no improvements in their memory abilities, even if they participated in the exercise intervention. Recent genome-wide association studies (GWAS) have identified ABCA7 as an important new susceptibility locus for late-onset Alzheimer's disease, and the gene ranks among the top five known risk genes for Alzheimer’s disease.  

This suggests an important interaction between biology and behavior: to reap the full benefits of exercise in protecting your brain, you need to also have the right genetic profile to take advantage of this exercise. When it comes to preventing Alzheimer’s disease, the potential benefits of aerobic exercise may be limited in carriers of the ABCA7 non-risk genotype. This doesn’t mean these people had no benefit from exercise (they likely experienced many other benefits including improved cardio-vascular function). But it does suggest that there are important genetically-determined individual differences in how exercise affects the brain. Future studies will be needed to determine if people with the ABCA7 risk-genotype can get the same cognitive and brain benefits as others if they exercise more intensely, more often each week, or for a longer duration. If so, that suggests a possible future for personalized exercise prescriptions that are not one-size-fits-all but, rather, based on people’s individual genetics.

It’s notable that these studies were done in African Americans, who suffer from dementia at two to three times the rate as white Americans, and have historically been underrepresented in past research on aging and Alzheimer’s disease. What underlies this minority health disparity? Various behavioral, biological, and lifestyle factors may all play a role, but little is known about the relative importance and interactions among these different risk factors in African Americans. These new studies by Sinha, Gluck, their colleagues, and community partners in Newark are helping to close that knowledge gap. Through their ongoing study, Pathways to Healthy Aging in African Americans, and with support from the National Institutes of Health (National Institute on Aging) and the New Jersey Department of Health, this university-community collaboration is seeking to understand why African Americans suffer from such high rates of Alzheimer’s disease and other forms of dementia, and what interventions (such as exercise) can remediate this health crisis.

A major limitation of the current study, according to Gluck, is that we do not know from these results if the cognitive and neural benefits of exercise are slowing down or reversing the underlying brain damage that occurs in Alzheimer’s disease. It is possible, Gluck notes, that the benefits of exercise are only compensatory, allowing people with Alzheimer’s disease to function at a higher level without changing their underlying brain damage. Gluck and his colleagues at the Rutgers University-Newark’s Aging & Brain Health Alliance are planning future exercise studies that will use newly-developed blood tests for the brain pathologies in Alzheimer’s disease to see whether these interventions are affecting disease progression.


For more information on the Pathways to Healthy Aging in African Americans study, the Rutgers-Newark Aging & Brain Health Alliance, and for copies of the original papers referenced here, see Drs. Gluck and Sinha can be reached directly at and