How Exercise Helps Protect the Brain Against Alzheimer’s

January 3, 2022

Numerous studies show that exercise is good for the brain, and perhaps even more so for the aging brain. A recent study sheds new light on why. Physical activity appears to modulate the activity of immune cells in the brain, dampening inflammation in the brain’s memory centers.

And it doesn’t take a lot of exercise to help keep the brain healthy. Older adults who simply got up and walked or moved about rather than remaining seated seemed to be better protected than their more sedentary peers.

For the study, researchers looked at 167 older men and women, most in their 80s at the study’s start. All were part of the Rush Memory and Aging Project, a long-term study of brain health.

Every year, study participants wore fitness devices to track their daily movements over a typical week or so. Few of them went to gyms to work out or formally exercised. Rather, the trackers recorded how much of the day they walked or moved about, rather than remaining sedentary.

Study volunteers also got annual medical checkups and tests of memory and thinking skills. The researchers monitored them for years until they died, when most were 90 or older. All had donated their brains to science.

Inspection of their brains revealed that about 60 percent of participants had signs of Alzheimer’s disease in their brains, including the telltale beta-amyloid plaques and neurofibrillary tangles. But only about a third had received a diagnosis of Alzheimer’s disease when they were still alive. Why did some people have brains full of plaques and tangles, yet few or no serious memory problems?

The researchers focused on immune system cells in the brain called microglia. These specialized cells act as a kind of hall monitor for the brain, looking for signs of infection and helping to clear debris or dying cells. In order to do their job, they must switch from a resting to an activated state.

However, as we age, the microglia seem to be activated more easily and can become over-activated, looking as if they were “stuck” in an activated state. Such heightened activation can prompt an excessive inflammatory response in the brain. While the initial response is usually beneficial, the chronic inflammatory state can damage neurons in the brain’s memory centers, very likely contributing to the onset of age-related memory loss and, for some, Alzheimer’s disease.

The researchers found that older men and women who remained the most active tended to have the healthiest microglia, especially in areas of the brain crucial for memory. Their microglia did not appear to be stuck in a constant state of inflammatory overdrive.

Microglia from the least active men and women, however, showed signs of being stuck in an activated state. These inactive men and women also tended to score the lowest on tests of memory and thinking skills.

Interestingly, among the people whose brains showed signs of Alzheimer’s disease, those who were the most active tended to have the healthiest microglia, and they tended to have fewer problems with thinking and memory skills. Those who were inactive and tended to have dysfunctional microglia, however were more likely to have memory problems.

The findings suggest that physical activity may delay the onset of Alzheimer’s disease in part by helping to keep microglia functioning well. The results bolster earlier studies showing that exercise is good for the aging brain, and can help to lower the risk of developing Alzheimer’s disease in old age. Furthermore, this study proposes a mechanism and confirms other studies showing the importance of inflammation for Alzheimer’s disease.

A 2010 study of nearly 300 city dwellers whose average age was 78, for example, found that those who walked about six miles a week had less shrinkage of parts of the brain critical for thinking and memory. Another study of 2,257 older men living in Hawaii who were in their 70s, 80s, and 90s found that those who walked the least, less than a quarter mile a day, had nearly twice the risk for Alzheimer’s than men who walked the most, more than two miles daily. In another large study, women in their 70s who engaged in regular physical activity showed less age-related memory problems than women who were less active.

Many factors go into determining who ultimately develops Alzheimer’s disease, including the genes you inherit. Lifestyle factors like walking and regular exercise are likely just one part of the preventive puzzle. While a daily walk around the mall or neighborhood won’t guarantee a physically and mentally robust old age, it may help you to look, feel and act younger. 

By ALZinfo.org, The Alzheimer’s Information Site. Reviewed by Marc Flajolet, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.

Source: Kaitlin B. Casaletto, Cutter A. Lindbergh, Anna VandeBunte, et al: “Microglial Correlates of Late Life Physical Activity: Relationship With Synaptic and Cognitive Aging in Older Adults.” Journal of Neuroscience, November 22, 2021


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