How staying physically active may protect the ageing brain

Staying physically active as we age substantially drops our risk of developing dementia during our lifetimes, and it does not require prolonged exercise. Walking or moving about, rather than sitting, may be all it takes to help bolster the brain, and a new study of octogenarians from Chicago may help to explain why.

The study — which tracked how often older people moved or sat, then looked deep inside their brains after they died — found that certain vital immune cells worked differently in the brains of older people who were active compared with their more sedentary peers. Physical activity seemed to influence their brain’s health, their thinking abilities and whether they experienced the memory loss of Alzheimer’s disease. The findings add to growing evidence that when we move our bodies, we change our minds, no matter how advanced our age.

Already, plenty of scientific evidence indicates that physical activity bulks up our brains. Older, sedentary people who begin walking for about an hour most days, for instance, typically add volume to their hippocampus, the brain’s memory centre, reducing or reversing the shrinkage that otherwise commonly occurs there over the years. Active people who are middle-aged or older also tend to perform better on tests of memory and thinking skills than people of the same age who rarely exercise, and are nearly half as likely eventually to be diagnosed with Alzheimer’s disease. Almost as heartening, active people who do develop dementia usually show their first symptoms years later than inactive people do.

But precisely how movement remodels our brains is still mostly mysterious, although scientists have hints from animal experiments. When adult lab mice and rats run on wheels, for example, they goose production of hormones and neurochemicals that prompt the creation of new neurons, as well as synapses, blood vessels and other tissues that connect and nurture those young brain cells.

Rodent exercise also slows or halts ageing-related declines in the animals’ brains, studies show, in part by strengthening specialized cells called microglia. Little understood until recently, microglial cells are now known to be the brain’s resident immune cells and hall monitors. They watch for signs of waning neuronal health and, when cells in decline are spotted, release neurochemicals that initiate an inflammatory response. Inflammation, in the short term, helps to clear away the problem cells and any other biological debris. Afterward, the microglia release other chemical messages that calm the inflammation, keeping the brain healthy and tidy and the animal’s thinking intact.

But as animals age, recent studies have found, their microglia can start to malfunction, initiating inflammation but not subsequently quieting it, leading to continuous brain inflammation. This chronic inflammation can kill healthy cells and cause problems with memory and learning, sometimes severe enough to induce a rodent version of Alzheimer’s disease.

Unless the animals exercise. In that case, post-mortem exams of their tissues show, the animals’ brains typically teem with healthy, helpful microglia deep into old age, displaying few signs of continuous brain inflammation, while the elderly rodents themselves retained a youthful ability to learn and remember.

We are not mice, though, and while we have microglia, scientists had not previously found a way to study whether being physically active as we age — or not — would influence the inner workings of microglial cells. So for the new study, which was published in November in the Journal of Neuroscience, scientists affiliated with Rush University Medical Center in Chicago; the University of California, San Francisco; and other institutions turned to data from the ambitious Rush Memory and Aging Project. For that study, hundreds of Chicagoans, most in their 80s at the start, completed extensive annual thinking and memory tests and wore activity monitors for at least a week. Few formally exercised, the monitors showed, but some moved around or walked far more often than others.

Many of the participants died as the study continued, and the researchers examined stored brain tissues from 167 of them, searching for lingering biochemical markers of microglial activity. They wanted to see, in effect, whether people’s microglia appeared to have been perpetually overexcited during their final years, driving brain inflammation, or been able to dial back their activity when appropriate, blunting inflammation. The researchers also looked for common biological hallmarks of Alzheimer’s disease, like the telltale plaques and tangles that riddle the brain. Then they cross-checked this data with information from people’s activity trackers.

They found a strong relationship between being in motion and healthy microglia, especially in portions of the brain involved in memory. Microglia from the most active elderly men and women contained biochemical markers indicating the cells knew how to be quiet when needed. But microglia from sedentary participants showed signs of having become stuck in unhealthy overdrive during their final years. Those inactive men and women also generally scored lowest on cognitive tests.

Perhaps most interesting, though, these effects were greatest in people whose brains showed signs of Alzheimer’s disease when they died, regardless of whether they had serious memory impairments while they were still alive. If these people had been inactive, their microglia tended to look quite dysfunctional, and their memories tended to be spotty. But if people frequently had moved around during late life, their microglia usually appeared healthy after their deaths, and many had not experienced notable memory loss in their later years. Their brains may have showed signs of Alzheimer’s, but their lives and thinking abilities had not.

What these findings suggest is that physical activity may delay or alter memory loss from Alzheimer’s disease in older people, partly by keeping microglia fit, said Kaitlin Casaletto, an assistant professor of neuropsychology at the UCSF Memory and Aging Center, who led the new study.

Encouragingly, the amount of activity needed to see these benefits was not large, Casaletto said. None of the participants had been running marathons in their twilight years. Few had formally exercised. “But there was a linear relationship” between how still they were and their brain health, she said. “The less they sat, the more they stood, the more they moved around, the better their outcomes.”

The study is important, said Mark Gluck, a professor of neuroscience at Rutgers University in New Jersey, who was not involved in the research. The findings are “the first to use post-mortem analyses of brain tissue to show that a marker of inflammation in the brain, microglial activation, appears to be the mechanism through which physical activity can reduce brain inflammation and help protect against the cognitive ravages of Alzheimer’s disease,” he said, though further research in living people is needed.

In addition, no one believes microglia are the only aspect of the brain affected by movement, Casaletto said. Physical activity changes countless other cells, genes and chemicals in the brain, she said, and some of those effects may be more important than microglia in keeping us mentally sharp. This study also does not prove activity causes microglia to work better, only that healthy microglia are common in people who are active. Finally, it does not tell us whether we get extra brain benefits from being physically active when we are far younger than 80-plus. But Casaletto, who is 36, said the study’s results keep her exercising.

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