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

To investigate the timing (mid- vs late life) of physical activity, apolipoprotein (APO)E ε4, and risk of incident mild cognitive impairment (MCI).

Prospective cohort study.

Mayo Clinic Study of Aging (Olmsted County, MN).

Cognitively normal elderly adults (N = 1,830, median age 78, 50.2% female).

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.

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.

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.