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 e4 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.