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Enhanced Risk for Alzheimer Disease in Persons With Type 2 Diabetes and APOE 4

The Cardiovascular Health Study Cognition Study

Fumiko Irie, MD, PhD, MPH; Annette L. Fitzpatrick, PhD; Oscar L. Lopez, MD; Lewis H. Kuller, MD, DrPH; Rita Peila, PhD; Anne B. Newman, MD, MPH; Lenore J. Launer, PhD

Arch Neurol. 2008;65(1):89-93.

Background  Diabetes and the apolipoprotein E 4 allele (APOE 4) increase the risk for Alzheimer disease (AD). We hypothesize that APOE 4 may modify the risk for AD in individuals with diabetes.

Objective  To examine the joint effect of type 2 diabetes and APOE 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 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 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 4 increases the risk of dementia, especially for AD and mixed AD.

Author Affiliations: Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, Maryland (Drs Irie, Peila, and Launer); Department of Epidemiology, University of Washington, Seattle (Dr Fitzpatrick); and Departments of Neurology and Psychiatry, School of Medicine (Dr Lopez), Department of Epidemiology, Graduate School of Public Health (Drs Kuller and Newman), and Department of Medicine (Dr Newman), University of Pittsburgh, Pittsburgh, Pennsylvania.