Risk of Alzheimer's Disease in People with Diabetes Mellitus

Background Diabetes mellitus (DM) may increase the risk of Alzheimer dementia (AD) in a number of biologically conceivable ways, although it is still uncertain how DM and the development of AD are related. Objective To assess the risk of AD in subjects with and without DM. Design: Prospective community-based cohort study. Participants: Framingham Research Participants (n = 2210; 1325 women; mean age, 70 years) who were part of the first cohort and did not have dementia and participated in the biennial test. Main Outcome Measures: Relative risk of incident Alzheimer disease within the overall group and within subgroups defined by plasma homocysteine levels and apolipoprotein E genotype (based on criteria from the National Institute of Neurological and Communicative Diseases and Stroke/Association for Alzheimer’s Disease and Related Disorders); models were adjusted for age, sex, and cardiovascular risk factors. Results At baseline, 202 people (9.1%) in total had DM. During the follow-up period (mean, 12.7 years; range, 1–20 years), the development of AD created a relative risk of 1.15 (95% confidence interval, 0.65–2.05) in 17 of 202 persons with diabetes (8.1%) and 220 of 2008 people without diabetes (11.0%). Of the 684 participants, 44 (6.4%) did not have elevated plasma homocysteine levels or an apolipoprotein E 4 allele; the relative risk of AD was 2.98 (95% confidence range, 1.06–8.39; P = .03) in patients with diabetes compared to those without diabetes. The effect was greatest among individuals 75 years of age or older, with a relative risk of 4.77 (95% confidence interval, 1.28–17.72; P = .02). Conclusion Overall, diabetes mellitus did not increase the incidence of incident AD in the Framingham cohort; however, in the absence of other major risk factors for AD that are known to exist, diabetes mellitus may be a risk factor for AD.