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From the Departments of Neurological Sciences (Drs. Wilson, Bennett, Aggarwal, Schneider, and Evans), Psychology (Dr. Wilson), Internal Medicine (Drs. Bienias, Mendes de Leon, Morris, and Evans), and Preventive Medicine (Drs. Mendes de Leon and Morris), Rush Alzheimer’s Disease Center and Rush Institute for Healthy Aging, Rush-Presbyterian-St. Luke’s Medical Center, Chicago, IL.
Address correspondence and reprint requests to Dr. Robert S. Wilson, Rush Alzheimer’s Disease Center, 1645 West Jackson Blvd., Suite 675, Chicago, IL 60612; e-mail: rwilson{at}rush.edu
Background: Participation in cognitively stimulating activities is hypothesized to be associated with risk of AD, but knowledge about this association is limited.
Methods: A biracial community in Chicago was censused, persons aged 65 years and older were asked to participate in an interview, and 6,158 of 7,826 (79%) eligible persons did so. As part of the interview, persons rated current frequency of participation in seven cognitive activities (e.g., reading a newspaper) and nine physical activities (e.g., walking for exercise) from which composite measures of cognitive and physical activity frequency were derived. Four years later, 1,249 of those judged free of AD were sampled for a detailed clinical evaluation of incident disease and 842 (74% of those eligible) participated.
Results: The composite measure of cognitive activity ranged from 1.28 to 4.71 (mean 3.30; SD 0.59), with higher scores indicating more frequent activity. A total of 139 persons met National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria for AD on clinical evaluation. In a logistic regression model adjusted for age, education, sex, race, and possession of the APOE 
4 allele, a one-point increase in cognitive activity score was associated with a 64% reduction in risk of incident AD (OR 0.36; 95% CI 0.20 to 0.65). By contrast, weekly hours of physical activity (mean 3.5; SD 5.1) was not related to disease risk (OR 1.04; 95% CI 0.98 to 1.10). Education was associated with risk of AD and a similar trend was present for occupation, but these effects were substantially reduced when cognitive activity was added to the model.
Conclusion: Frequency of participation in cognitively stimulating activities appears to be associated with risk of AD and may partially explain the association of educational and occupational attainment with disease risk.
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