Enhanced risk for Alzheimer disease in persons with type 2 diabetes and APOE epsilon4: the Cardiovascular Health Study Cognition Study.
BACKGROUND
Diabetes and the apolipoprotein E epsilon4 allele (APOE epsilon4) increase the risk for Alzheimer disease (AD). We hypothesize that APOE epsilon4 may modify the risk for AD in individuals with diabetes.


OBJECTIVE
To examine the joint effect of type 2 diabetes and APOE epsilon4 on the risk of AD, AD with vascular dementia (mixed AD), and vascular dementia without AD.


METHODS
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 epsilon4 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 epsilon4, 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).


CONCLUSIONS
These data suggest that having both diabetes and APOE epsilon4 increases the risk of dementia, especially for AD and mixed AD.
Irie
Fumiko
F
Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, 7201 Wisconsin Ave, Bethesda, MD, USA.
Fitzpatrick
Annette L
AL
Lopez
Oscar L
OL
Kuller
Lewis H
LH
Peila
Rita
R
Newman
Anne B
AB
Launer
Lenore J
LJ
D001741:Black or African American; D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics* / Q000523:psychology; D053327:Apolipoprotein E4 / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D016001:Confidence Intervals; D015140:Dementia, Vascular / Q000453:epidemiology* / Q000235:genetics* / Q000523:psychology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics* / Q000523:psychology; D005260:Female; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D044465:White People
D053327:Apolipoprotein E4