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 (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.