Enhanced risk for Alzheimer disease in persons with type 2 diabetes and APOE epsilon 4

Background: Diabetes and the.apolipoprotein E epsilon 4 allele (APOE epsilon 4) increase the risk for Alzheimer disease (AD). We hypothesize that APOE epsilon 4 may modify the risk for AD in individuals with diabetes. Objective: To examine the joint effect of type 2 diabetes and APOE epsilon 4 on the risk of AD, AD with vascular dementia (mixed AD), and vascular dementia without AD. Design: The Cardiovascular Health Study (CHS) Cognition Study (1992-2000) is a prospective study designed to identify all existing and new cases of dementia among study participants. Diagnoses were made according to international criteria for dementia and subtypes. There were 2547 dementia-free participants in the CHS Cognition Study cohort with complete information on APOE epsilon 4 and type 2 diabetes status; among these, 411 new cases of dementia developed. Risk of dementia was estimated with a Cox proportional hazard model adjusted for age and other demographic and cardiovascular risk factors. Results: Compared with those who had neither type 2 diabetes nor APOE epsilon 4, those with both factors had a significantly higher risk of AD (hazard ratio, 4.58; 95% confidence interval, 2.18-9.65) and mixed AD (hazard ratio, 3.89; 95% confidence interval, 1.46-10.40). Conclusion: These data suggest that having both diabetes and APOE epsilon 4 increases the risk of dementia, especially for AD and mixed AD.