Apolipoprotein E epsilon4 allele genotype and the effect of depressive symptoms on the risk of dementia in men: the Honolulu-Asia Aging Study.
BACKGROUND
The apolipoprotein E epsilon4 (APOE epsilon4) 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 epsilon4 on the risk of dementia and its subtypes.


METHODS
The Honolulu-Asia Aging Study, a population-based prospective cohort study of Japanese American men.


METHODS
Depressive symptoms and presence of the APOE epsilon4 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).


METHODS
Overall dementia, Alzheimer disease, and vascular dementia.


RESULTS
The interaction of depression and APOE epsilon4 was statistically significant in the analytical models. Compared with men with neither APOE epsilon4 nor depression, the risk of dementia in nondepressed men with APOE epsilon4 was not significant (hazard ratio, 1.1; 95% confidence interval [CI], 0.6-1.8); however, depressed men without APOE epsilon4 had a 1.6-fold greater risk (95% CI, 0.8-3.0), whereas depressed men with APOE epsilon4 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 epsilon4 status modifies the association between depressive symptoms and dementia in elderly men. Because individuals with depressive symptoms and the APOE epsilon4 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 epsilon4 allele. Because this cohort includes only men, further investigation in women is required.
Irie
Fumiko
F
Pacific Health Research Institute, Honolulu, Hawaii, USA. f.irie@uq.edu.au
Masaki
Kamal H
KH
Petrovitch
Helen
H
Abbott
Robert D
RD
Ross
G Webster
GW
Taaffe
Dennis R
DR
Launer
Lenore J
LJ
White
Lon R
LR
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D053327:Apolipoprotein E4 / Q000235:genetics*; D001213:Asian / Q000235:genetics / Q000523:psychology; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006254:Hawaii; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D012307:Risk Factors; D012737:Sex Factors; D013223:Statistics as Topic
D053327:Apolipoprotein E4