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

Janina Krell-Roesch, Anna Pink, Rosebud O. Roberts, Gorazd B. Stokin, Michelle M. Mielke, Kathleen A. Spangehl, Mairead M. Bartley, David S. Knopman, Teresa J H Christianson, Ronald C. Petersen, Yonas E. Geda

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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.

Original languageEnglish (US)
JournalJournal of the American Geriatrics Society
StateAccepted/In press - 2016
Externally publishedYes


  • APOE e4
  • Mild cognitive impairment
  • Physical activity

ASJC Scopus subject areas

  • Geriatrics and Gerontology


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