APOLIPOPROTEIN-E GENOTYPE, ATHEROSCLEROSIS, AND COGNITIVE DECLINE - THE ROTTERDAM STUDY

The apolipoprotein E4 allele (APOE epsilon 4) and atherosclerosis are risk factors for cognitive decline. We investigated whether the effect s of APOE epsilon 4 and atherosclerosis on cognitive decline are indep endent. A population-based follow-up study was performed on 838 subjec ts who were non-demented at baseline. The Mini Mental State Examinatio n (MMSE) score at follow-up was studied as a function of APOE epsilon 4 and atherosclerosis. Mild, non-significant effects on the MMSE score were found for atherosclerosis in the absence of APOE epsilon 4 and f or APOE epsilon 4 in the absence of atherosclerosis. APOE epsilon 4 ca rriers with two or more indicators of atherosclerosis positive, had a significantly lower MMSE score at follow-up (mean difference -0.7 poin ts; 95% confidence interval -1.1 to -0.2) relative to non-APOE epsilon 4 carriers with no evidence of atherosclerosis. Our findings suggest that the consequences of APOE epsilon 4 and atherosclerosis are not in dependent, and that particularly APOE epsilon 4 carriers with atherosc lerosis are at increased risk of cognitive decline.