Physical Activity Initiated from Midlife on Risk of Dementia and Cognitive Impairment: The Health and Retirement Study

Background: Physical activity is associated with lower risk of dementia and cognitive impairment, but existing randomized controlled trials have shown conflicting results. As cognitive decline occurs decades before the onset of dementia, physical activity interventions initiated in late life may have missed the potential window for prevention. An ideal trial of physical activity initiated from midlife and lasts till incident dementia and cognitive impairment in late life is not feasible. We aimed to estimate the effectiveness of a hypothetical physical activity intervention initiated from midlife on reducing dementia and cognitive impairment by emulating target trials using observational data. Methods: The Health and Retirement Study was used to emulate target trials among noninstitutionalized participants aged 45 to 65 years with normal cognition who were physically inactive in the previous 2 years. Cognitive status was determined based on Langa–Weir classification of cognitive function (including immediate and delayed word recall tests, serial sevens subtraction, counting backward). Individuals were categorized as initiating physical activity or not, based on the self-reported physical activity. Intention-to-treat and per-protocol analysis were conducted with pooled logistic regression models with inverse-probability of treatment and censoring weights to estimate risk ratios (RRs), and 95% confidence intervals (95% CIs) were calculated with 200 sets of bootstrapping. Results: Among 1505 participants (average age 57.6 ± 4.8 years, 67% women, 76.5% White), 72 cases of dementia and 409 cases of cognitive impairment occurred. After 12 years of follow-up, physical activity reduced dementia (RR = 0.70, 95% CI: 0.43, 0.99) for intention-to-treat analysis, and reduced dementia (RR = 0.51, 95% CI: 0.19, 0.99) and cognitive impairment (RR = 0.77, 95% CI: 0.61, 0.92) for per-protocol analysis. No significant reduction was found among older adults. Conclusions: Physical activity initiated during midlife may reduce dementia and cognitive impairment in late life, which highlights the importance of preventing cognitive outcomes at an earlier stage of life.