Background: 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. Objective: 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. 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 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. Results: 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). Conclusion: These data suggest that having both diabetes and APOE ε4 increases the risk of dementia, especially for AD and mixed AD.

Context The apolipoprotein E ε4 (APOE ε4) allele is a genetic risk factor for Alzheimer disease. Recently, depression has also become recognized as a risk factor for dementia. However, the possible effect of the APOE genotype on the association between depression and dementia is unexamined. Objective To examine the independent and combined effects of depression and APOE ε4 on the risk of dementia and its subtypes. Design The Honolulu-Asia Aging Study, a population-based prospective cohort study of Japanese American men. Settings and Participants Depressive symptoms and presence of the APOE ε4 allele were assessed between March 1991 and October 1993 in 1932 cognitively healthy men aged 71 to 90 years. Incident cases of dementia were diagnosed during approximately 6 years of follow-up based on neurologic assessment at 2 repeated examinations (April 1994–April 1996 and October 1997–February 1999). Main Outcome Measures Overall dementia, Alzheimer disease, and vascular dementia. Results The interaction of depression and APOE ε4 was statistically significant in the analytical models. Compared with men with neither APOE ε4 nor depression, the risk of dementia in nondepressed men with APOE ε4 was not significant (hazard ratio, 1.1; 95% confidence interval [CI], 0.6–1.8); however, depressed men without APOE ε4 had a 1.6-fold greater risk (95% CI, 0.8–3.0), whereas depressed men with APOE ε4 had a 7.1-fold greater risk (95% CI, 3.0–16.7) of dementia. For subtypes, we found similar increased risks of Alzheimer disease. Conclusions The APOE ε4 status modifies the association between depressive symptoms and dementia in elderly men. Because individuals with depressive symptoms and the APOE ε4 allele had a markedly increased risk of dementia, one might be especially watchful for early signs of dementia in the older person with depression who is also positive for the APOE ε4 allele. Because this cohort includes only men, further investigation in women is required.

In elderly men with poor physical function, increasing general physical activity may potentially confer a protective effect or delay the onset for dementia.

The results indicate that the Injury Severity Score adjusted in-hospital mortality rates for young patients with EDH were 4.8%. Given the limited information on morbidity resulting from EDH, further analysis to examine modifiable factors for better management and to evaluate survivor's long-term health outcomes via a longitudinal follow-up study is warranted.