Diabetes mellitus and risk of developing Alzheimer disease: Results from the Framingham study

Background: Diabetes mellitus (DM) could increase the risk of Alzheimer disease (AD) through several biologically plausible pathways, but the relationship between DM and the development of AD remains uncertain. Objective: To compare the risk of developing AD in subjects with and without DM. Design: Prospective community-based cohort study. Participants: Framingham Study Original cohort participants who were dementia free and attended the 16th biennial examination (n = 2210 persons, 1325 women; mean age, 70 years). Main Outcome Measures: Relative risk of incident AD (criteria from the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association) associated with baseline DM (casual plasma glucose ≥200 mg/dL [≥11.1 mmol/L] or use of insulin or a hypoglycemic drug) in overall group and within subgroups defined by apolipoprotein E genotype and plasma homocysteine levels; models were adjusted for age, sex, and cardiovascular risk factors. Results: At baseline, 202 participants (9.1%) had DM. During the follow-up period (mean, 12.7 years; range, 1-20 years), 17 of 202 persons with DM (8.4%) and 220 of 2008 persons without DM (11.0%) developed AD, yielding a relative risk of 1.15 (95% confidence interval, 0.65-2.05). Among subjects without an apolipoprotein E ε4 allele or elevated plasma homocysteine levels, 44 of 684 persons (6.4%) developed AD; relative risk for AD comparing diabetic patients with nondiabetic patients was 2.98 (95% confidence interval, 1.06-8.39; P = .03). The effect was strongest in persons aged 75 years or older with a relative risk of 4.77 (95% confidence interval, 1.28-17.72; P = .02). Conclusion: Diabetes mellitus did not increase the risk of incident AD in the Framingham cohort overall; however, DM may be a risk factor for AD in the absence of other known major AD risk factors.