Diabetes and the apolipoprotein E ε4 allele (APOE ε4) increase the risk for Alzheimer disease (AD). We hypothesize that APOE ε4 may modify the risk for AD in individuals with diabetes.
To examine the joint effect of type 2 diabetes and APOE ε4 on the risk of AD, AD with vascular dementia (mixed AD), and vascular dementia without AD.
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 ε4 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.
Compared with those who had neither type 2 diabetes nor APOE ε4, 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).
These data suggest that having both diabetes and APOE ε4 increases the risk of dementia, especially for AD and mixed AD.