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From the Laboratory of Epidemiology, Demography and Biometry (Drs. Peila and Launer), National Institute on Aging, National Institutes of Health, Bethesda, MD; Clinical Epidemiology and Geriatric Division (Drs. Rodriguez and White), Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu; and Pacific Health Research Institute (Dr. White), Manoa, Honolulu, HI.
Address correspondence and reprint requests to Dr. Rita Peila, Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, National Institutes of Health, Room 3C-309 Gateway Building, 7201 Wisconsin Avenue, Bethesda, MD 20892; e-mail: peilar{at}mail.nih.gov
Objective: To evaluate the association of fasting insulin level to incident dementia in a cohort of elderly men.
Methods: Data are from the Honolulu-Asia Aging Study, a community-based study of Japanese-American men, aged 71 to 91 years in 1991. Serum insulin was measured in 1991 and participants were grouped based on their insulin levels. Dementia was ascertained in 1991, 1994, and 1996 according to international guidelines. The 2,568 men dementia-free in 1991 were reexamined in 1994 and 1996; 244 new cases of dementia were diagnosed. Survival analysis with age as the time scale was used to estimate the risk (hazard ratio [HR] and 95% CI) for incident dementia associated with levels of insulin.
Results: The risk of dementia was increased at the two extremes of the insulin distribution (lower and upper 15th percentiles). Compared to the rest of the cohort subjects in the lowest 15th percentile and highest 15th percentile had an increased risk for dementia (HR = 1.54, CI 1.11 to 2.11 and HR = 1.54, CI 1.05 to 2.26). In men with insulin levels <22.2 mIU/L the risk for dementia decreased with increased levels of insulin (HR = 0.76, CI 0.72 to 0.79 for each increase of one logarithmic unit –2.72 mIU/L of insulin). In men with insulin levels 
22.2 mIU/L the risk for dementia increased with increasing levels of insulin (HR = 1.64, CI = 1.07 to 2.52 for each 2.72 mIU/L).
Conclusions: Both low and high levels of insulin are associated with an increased risk of developing dementia.
Received January 30, 2003. Accepted in final form March 22, 2004.
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