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Original Investigation
March 2017

Association Between Mentally Stimulating Activities in Late Life and the Outcome of Incident Mild Cognitive Impairment, With an Analysis of the APOE ε4 Genotype

Author Affiliations
  • 1Mayo Clinic Translational Neuroscience and Aging Program, Mayo Clinic, Scottsdale, Arizona
  • 2Department of Radiology, Mayo Clinic, Rochester, Minnesota
  • 3Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
  • 4Department of Neurology, Mayo Clinic, Rochester, Minnesota
  • 5International Clinical Research Center, Brno, Czech Republic
  • 6Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
  • 7Department of Psychiatry and Psychology, Mayo Clinic, Scottsdale, Arizona
  • 8Department of Neurology, Mayo Clinic, Scottsdale, Arizona
JAMA Neurol. 2017;74(3):332-338. doi:10.1001/jamaneurol.2016.3822
Key Points

Question  Does engaging in a mentally stimulating activity in old age associate with neurocognitive function?

Findings  In this population-based cohort study, 1929 cognitively normal participants 70 years or older were followed for approximately 4 years. The following activities were associated with significant decreased risk of new-onset mild cognitive impairment: computer use, craft activities, social activities, and playing games.

Meaning  Engaging in a mentally stimulating activity even in late life may decrease the risk of mild cognitive impairment.


Importance  Cross-sectional associations between engagement in mentally stimulating activities and decreased odds of having mild cognitive impairment (MCI) or Alzheimer disease have been reported. However, little is known about the longitudinal outcome of incident MCI as predicted by late-life (aged ≥70 years) mentally stimulating activities.

Objectives  To test the hypothesis of an association between mentally stimulating activities in late life and the risk of incident MCI and to evaluate the influence of the apolipoprotein E (APOE) ε4 genotype.

Design, Setting, and Participants  This investigation was a prospective, population-based cohort study of participants in the Mayo Clinic Study of Aging in Olmsted County, Minnesota. Participants 70 years or older who were cognitively normal at baseline were followed up to the outcome of incident MCI. The study dates were April 2006 to June 2016.

Main Outcomes and Measures  At baseline, participants provided information about mentally stimulating activities within 1 year before enrollment into the study. Neurocognitive assessment was conducted at baseline, with evaluations at 15-month intervals. Cognitive diagnosis was made by an expert consensus panel based on published criteria. Hazard ratios (HRs) and 95% CIs were calculated using Cox proportional hazards regression models after adjusting for sex, age, and educational level.

Results  The final cohort consisted of 1929 cognitively normal persons (median age at baseline, 77 years [interquartile range, 74-82 years]; 50.4% [n = 973] female) who were followed up to the outcome of incident MCI. During a median follow-up period of 4.0 years, it was observed that playing games (HR, 0.78; 95% CI, 0.65-0.95) and engaging in craft activities (HR, 0.72; 95% CI, 0.57-0.90), computer use (HR, 0.70; 95% CI, 0.57-0.85), and social activities (HR, 0.77; 95% CI, 0.63-0.94) were associated with a decreased risk of incident MCI. In a stratified analysis by APOE ε4 carrier status, the data point toward the lowest risk of incident MCI for APOE ɛ4 noncarriers who engage in mentally stimulating activities (eg, computer use: HR, 0.73; 95% CI, 0.58-0.92) and toward the highest risk of incident MCI for APOE ɛ4 carriers who do not engage in mentally stimulating activities (eg, no computer use: HR, 1.74; 95% CI, 1.33-2.27).

Conclusions and Relevance  Cognitively normal elderly individuals who engage in specific mentally stimulating activities even in late life have a decreased risk of incident MCI. The associations may vary by APOE ε4 carrier status.