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Can Exercise Protect Against Alzheimer’s?

LOS ANGELES — A higher level of daily physical activity was tied to slower amyloid-beta (Aβ)-related cognitive decline, a longitudinal observational study presented here showed.

In clinically normal older adults, higher levels of baseline activity attenuated the relationship between elevated Aβ with cognitive decline and gray matter volume over time, reported Jennifer Rabin, PhD, of Sunnybrook Research Institute in Toronto, Canada, at the Alzheimer’s Association International Conference (AAIC) 2019. The findings were published simultaneously in JAMA Neurology.

“The effects were over and above vascular risk factors,” Rabin told MedPage Today. “Vascular risk also independently predicted slower rates of cognitive decline and brain volume loss. If you were to target both of those, you would see greater benefit than targeting one alone.”

Even modest levels of physical activity had “quite robust protective effects,” she added, but they were most prominent in people who took about 8,900 steps a day.

“This study shows that physical exercise allows persons to tolerate a higher burden of amyloid pathology,” said David Knopman, MD, of the Mayo Clinic in Rochester, Minnesota, who was not involved with the research.

“Even though there was no association between how much people exercised and whether they had elevated amyloid, physical activity affected the downstream clinical expression of the Alzheimer’s process,” Knopman told MedPage Today.

In some ways, this is similar to cognitive reserve: “These people didn’t start exercising the day they joined the study. Their degree of physical activity is probably a proxy for attention to other cardiovascular risk factors,” Knopman said.

“Even if we couldn’t reduce Alzheimer’s pathology — but we could improve brain reserve — we could effectively delay the appearance of overt cognitive impairment and lessen the symptomatic burden of Alzheimer’s disease,” he added.

In this study, Rabin and colleagues assessed baseline physical activity of 182 clinically normal older adults from the Harvard Aging Brain Study who wore waistband pedometers for 7 consecutive days. Participants had an average age of about 73 when they started the study, and 57% were female.

Beta-amyloid burden was assessed at baseline with PET imaging; in this study, amyloid was a continuous variable. “By conventional standards, we would expect around 25% to have elevated amyloid,” Rabin said.

Vascular risk also was quantified at baseline. Cognition was measured annually with the Preclinical Alzheimer Cognitive Composite for a median of 6 years.

After adjusting for age and sex, there was no association of physical activity with Aβ burden. Greater physical activity was linked to slower Aβ-related cognitive decline (β 0.03, 95% CI 0.02-0.05; P<0.001) and gray matter volume loss (β 482.07, 95% CI 189.40-774.74; P=0.002). Beneficial effects were seen at even modest levels of physical activity, and while the study did assess a threshold minimum, “we did see an effect at around 8,900 steps per day,” Rabin noted.

Adjusting for vascular risk did not alter the associations. Lower vascular risk was independently tied to slower Aβ-related cognitive decline (β−0.04, 95% CI−0.06 to −0.02; P<0.001) and volume loss (β−483.41, 95% CI−855.63 to−111.20; P=0.01).

“We can’t really speak to the mechanisms involved; that’s an open question,” Rabin said. “We don’t know what’s preserving the brain tissue over time.”

But the study — one of the first to assess activity and amyloid levels — suggests “we shouldn’t wait until people are symptomatic,” she added. “These are lifestyle changes we should make early on.”

The research has several limitations, Rabin and co-authors noted. The Harvard Aging Brain Study excludes people who are likely to have very high levels of cerebrovascular disease. Most people in the cohort have at least some advanced education and may have high cognitive reserve. Activity was assessed only once in this study (at baseline); its duration and intensity could not be determined.

This work was supported by the National Institute on Aging, the Canadian Institutes of Health Research, the Alzheimer’s Association, the National Health and Medical Research Council, and the National Institutes of Health.

Rabin had no disclosures to report. Co-authors reported relationships with Biogen, Eli Lilly and Company, Janssen Pharmaceuticals, Neurotrack Technologies, Eisai, Merck Sharp & Dohme, Alnylam Pharmaceuticals, Roche, and Takeda.