Timing of Physical Activity, Apolipoprotein E ε4 Genotype, and Risk of Incident Mild Cognitive Impairment

Objectives: To investigate the timing (mid- vs late life) of physical activity, apolipoprotein (APO)E ε4, and risk of incident mild cognitive impairment (MCI). Design: Prospective cohort study. Setting: Mayo Clinic Study of Aging (Olmsted County, MN). Participants: Cognitively normal elderly adults (N = 1,830, median age 78, 50.2% female). Measurements: Light, moderate, and vigorous physical activities in mid- and late life were assessed using a validated questionnaire. An expert consensus panel measured MCI based on published criteria. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) with age as a time scale after adjusting for sex, education, medical comorbidity, and depression. Results: Light (HR = 0.58, 95% CI = 0.43–0.79) and vigorous (HR = 0.78, 95% CI = 0.63–0.97) physical activity in midlife were associated with lower risk of incident MCI. The association between moderate activity and incident MCI was not significant (HR = 0.85, 95% CI = 0.67–1.09). In late life, light (HR = 0.75, 95% CI = 0.58–0.97) and moderate (HR = 0.81, 95% CI = 0.66–0.99) but not vigorous physical activity were associated with lower risk of incident MCI. A synergistic interaction was also observed between mid- and late-life activity in reducing risk of incident MCI. Furthermore, APOE ε4 carriers who did not exercise had a higher risk of incident MCI than noncarriers who reported physical activity. Conclusion: Physical activity reduced the risk of incident MCI. Exercising in mid- and late life had an additive synergistic interaction in reducing the risk of MCI.