• Prashanthi Vemuri, Timothy G Lesnick, Scott A Przybelski, Mary Machulda, David S Knopman, Michelle M Mielke, Rosebud O Roberts, Yonas E Geda, Walter A Rocca, Ronald C Petersen, and Clifford R Jack.
• Department of Radiology, Mayo Clinic, Rochester, Minnesota.
• JAMA Neurol. 2014 Aug 1; 71 (8): 1017-24.

ImportanceIntellectual lifestyle enrichment throughout life is increasingly viewed as a protective strategy against commonly observed cognitive decline in the older population.ObjectivesTo investigate the association of lifetime intellectual enrichment with baseline cognitive performance and rate of cognitive decline in an older population without dementia and to estimate the years of protection provided against cognitive impairment by these factors.Design, Setting, And ParticipantsProspective analysis of individuals enrolled from October 1, 2004, and in 2008 and 2009 in the Mayo Clinic Study of Aging, a longitudinal, population-based study of cognitive aging in Olmsted County, Minnesota. We studied 1995 individuals without dementia (1718 cognitively normal individuals and 277 individuals with mild cognitive impairment) who completed intellectual lifestyle enrichment measures at baseline and underwent at least 1 follow-up visit.Main Outcomes And MeasuresWe studied the effect of lifetime intellectual enrichment by separating the variables into 2 nonoverlapping principal components: education/occupation score and mid/late-life cognitive activity based on self-report questionnaires. A global cognitive z score served as the summary cognition measure. Linear mixed-effects models were used to investigate the associations of demographic and intellectual enrichment measures with global cognitive z score trajectories.ResultsBaseline cognitive performance was lower in older individuals; individuals with lower education/occupation score, lower mid/late-life cognitive activity, and APOE genotype; and men (P < .001). The interaction between the 2 intellectual enrichment measures was significant (P < .03) such that the beneficial effect of mid/late-life cognitive activity on baseline cognitive performance was reduced with increasing education/occupation score. Only baseline age, mid/late-life cognitive activity, and APOE4 genotype were significantly associated with longitudinal change in cognitive performance from baseline (P < .05). For APOE4 carriers with high lifetime intellectual enrichment (75th percentile of education/occupation score and midlife to late-life cognitive activity), the onset of cognitive impairment was approximately 8.7 years later compared with low lifetime intellectual enrichment (25th percentile of education/occupation score and mid/late-life cognitive activity).Conclusions And RelevanceHigher education/occupation scores were associated with higher levels of cognition. Higher levels of mid/late-life cognitive activity were also associated with higher levels of cognition, but the slope of this association slightly increased over time. Lifetime intellectual enrichment might delay the onset of cognitive impairment and be used as a successful preventive intervention to reduce the impending dementia epidemic.

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