Cerebrovascular disease, the apolipoprotein e4 allele, and cognitive decline in a community-based study of elderly men.
OBJECTIVE
Cerebrovascular disease and the apolipoprotein e4 (APOE*4) allele are both important risk factors for cognitive decline. We investigated the combined effect of APOE*4 and cerebrovascular disease on cognitive decline.


METHODS
Data are from a cohort of 353 men, aged 69 to 89 years at baseline, living in Zutphen, Netherlands. The 30-point Mini-Mental State Examination (MMSE) was used to measure cognitive decline (drop of > 2 points) from 1990 to 1993 (14% of the sample). Odds ratios (OR [95% confidence interval]) for cognitive decline were adjusted for age, education, and baseline MMSE score.


RESULTS
Compared with those without APOE*4 and without a history of cerebrovascular disease, the adjusted OR was 4.7 (1.7 to 12.7) for subjects without APOE*4 but with cerebrovascular disease, 3.3 (1.6 to 6.8) for those with APOE*4 and no cerebrovascular disease, and 17.2 (2.7 to 110.0) for those with both risk factors. The risk for cerebrovascular disease and APOE*4 combined was more than expected from the separate effects. The combined risk of coronary heart disease and APOE*4 was 6.1 (1.7 to 22.3). The analysis of cardiovascular risk factors showed that the risk of cognitive decline was highest in subjects with both APOE*4 and a high cholesterol level, high fibrinogen level, normal blood pressure, or diabetes mellitus.


CONCLUSIONS
Cerebrovascular disease and APOE*4 may have a synergistic effect on cognitive decline.
Kalmijn
S
S
Department of Chronic Diseases and Environmental Epidemiology, National Institute of Public Health and the Environment, Bilthoven, Netherlands. kalmijn@epib.fgg.eur.nl
Feskens
E J
EJ
Launer
L J
LJ
Kromhout
D
D
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D002561:Cerebrovascular Disorders / Q000453:epidemiology* / Q000235:genetics / Q000523:psychology; D002784:Cholesterol / Q000097:blood; D003072:Cognition Disorders / Q000453:epidemiology* / Q000209:etiology; D015331:Cohort Studies; D015897:Comorbidity; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology; D004198:Disease Susceptibility; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D012307:Risk Factors
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D005340:Fibrinogen; D002784:Cholesterol