Cerebrovascular disease, the apolipoprotein e4 allele, and cognitive decline in a community-based study of elderly men.

BACKGROUND AND PURPOSE

Cerebrovascular disease and the apolipoprotein e4 (APOE4) allele are both important risk factors for cognitive decline. We investigated the combined effect of APOE4 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 APOE4 and without a history of cerebrovascular disease, the adjusted OR was 4.7 (1.7 to 12.7) for subjects without APOE4 but with cerebrovascular disease, 3.3 (1.6 to 6.8) for those with APOE4 and no cerebrovascular disease, and 17.2 (2.7 to 110.0) for those with both risk factors. The risk for cerebrovascular disease and APOE4 combined was more than expected from the separate effects. The combined risk of coronary heart disease and APOE4 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 APOE4 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.