Physical Exercise, APOE E4 Genotype And Cognitive Trajectories: The Mayo Clinic Study Of Aging

Abstract

PURPOSE: To investigate whether physical exercise (PE) is differentially associated with global and domain-specific cognitive trajectories (memory, language, visuospatial skills, attention) among Apolipoprotein E (APOE) ε4 carriers and non-carriers. METHODS: We included 2,060 community-dwelling individuals aged 70 years and older (50.5% males, 26.6% APOE ε4 carriers). Participants were cognitively unimpaired at baseline, and underwent serial cognitive testing and self-reported assessment of PE engagement in midlife (between 50-65 years of age) and late-life (within one year prior to assessment). We calculated linear mixed-effect models comparing three PE groups (light intensity such as leisurely walking or slowly dancing; at least moderate intensity such as hiking or swimming; at least vigorous intensity such as jogging or tennis singles) versus a none PE reference group (defined as each level of PE carried out less than once per week). Models were adjusted for age, sex, education and medical comorbidities, and run separately for mid- and late-life PE. RESULTS: Among APOE ε4 non-carriers, midlife light PE was associated with less decline in memory (time x PE interaction coefficient 0.044, p = 0.01); midlife vigorous PE was associated with less decline in memory (0.033, p = 0.05); and late-life vigorous PE was associated with less decline in visuospatial skills (0.025, p = 0.03) and global cognition (0.034, p = 0.03). Among APOE ε4 carriers, late-life vigorous PE was associated with less decline in memory (0.067, p = 0.03), attention (0.083, p = 0.01) and global cognition (0.073, p = 0.02); and late-life moderate PE was associated with less decline in global cognition (0.048, p = 0.05). CONCLUSIONS: Engaging in PE (light, moderate and vigorous) is associated with less decline in memory, attention, visuospatial skills and global cognition among community-dwelling older individuals, including those that are APOE ε4 genotype carriers who are at an increased risk of Alzheimer’s disease. Supported by NIH grants R01 AG057708, U01 AG006786, R01 AG034676; Robert Wood Johnson Foundation; Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program; GHR Foundation; Edli Foundation; Arizona Alzheimer’s Consortium.