Higher physical activity in midlife and late life reduces dementia risk

Higher levels of physical activity in midlife and late life, but not in early adulthood, are associated with lower risk of all-cause and Alzheimer’s disease (AD) dementia, a cohort study has shown.

“Being physically active is protective against dementia. Yet, it is unknown when during the adult life course physical activity is most associated with dementia risk,” wrote the researchers.

To determine whether higher physical activity levels in early adult life, midlife, or late life are associated with lower risk of all-cause or AD dementia, the researchers conducted a prospective cohort study using data from the original Framingham Heart Study Offspring cohort. Physical activity was divided into quintiles (Q), from lowest (Q1; reference group) to highest (Q5). [JAMA Network Open 2025;8:e2544439]

A total of 1,526 offspring of Framingham Heart Study participants who were dementia-free and had physical activity measured at baseline were included. Participants were categorized into three groups: early adult life (aged 26–44 years; mean age, 36.7 years; female, 53.8 percent), midlife (aged 45–64 years; mean age, 54.0 years; female, 52.0 percent), and late life (aged 65–88 years; mean age, 71.0 years; female, 53.4 percent), and were followed up for a mean duration of 37.2, 25.9, and 14.5 years, respectively, for the development of incident all-cause or AD dementia.

All-cause and AD dementia

Overall, there were 567 cases of all-cause dementia, including 62 in early adult life (4 percent), 273 in midlife (14 percent), and 232 in late life (26 percent).

Compared with low physical activity (Q1), higher physical activity in both midlife and late life was associated with lower risks of all-cause dementia (midlife Q4: hazard ratio [HR], 0.60; 95 percent confidence interval [CI], 0.41–0.89; midlife Q5: HR, 0.59; 95 percent CI, 0.40–0.88) (late-life Q4: HR, 0.64; 95 percent CI, 0.42–1.00; late-life Q5: HR, 0.55; 95 percent CI, 0.35–0.87). However, there was no association between early-life physical activity and risk of all-cause dementia.

There were 35 cases of incident AD dementia among early adult life, 178 in midlife, and 156 in late-life participants. Compared with Q1, physical activity in Q5 was associated with lower risks of AD dementia in both midlife (HR, 0.55; 95 percent CI, 0.33–0.94) and late life (HR, 0.53; 95 percent CI, 0.29–0.95).

“These findings suggest that timing efforts to promote physical activity during midlife or late life may be warranted to help delay or prevent dementia,” wrote the researchers.

APOE ε4 status

Of note, benefits of midlife or late-life physical activity differed by APOE ε4 status.

Among noncarriers, higher physical activity in midlife and late life was associated with lower risks of both all-cause dementia and AD dementia.

In APOE ε4 carriers, only late-life physical activity in Q5 was associated with a reduced risk of all-cause dementia, while no level of physical activity was associated with reduced AD dementia risk vs Q1.