Apolipoprotein E genotype, atherosclerosis, and cognitive decline: The Rotterdam study

Abstract

The apolipoprotein E4 allele (APOEε4) and atherosclerosis are risk factors for cognitive decline. We investigated whether the effects of APOEε4 and atherosclerosis on cognitive decline are independent. A population-based follow-up study was performed on 838 subjects who were non-demented at baseline. The Mini Mental State Examination (MMSE) score at follow-up was studied as a function of APOEε4 and atherosclerosis. Mild, non-significant effects on the MMSE score were found for atherosclerosis in the absence of APOEε4 and for APOEε4 in the absence of atherosclerosis. APOEε4 carriers with two or more indicators of atherosclerosis positive, had a significantly lower MMSE score at follow-up (mean difference -0.7 points; 95% confidence interval -1.1 to -0.2) relative to non-APOEε4 carriers with no evidence of atherosclerosis. Our findings suggest that the consequences of APOEε4 and atherosclerosis are not independent, and that particularly APOEε4 carriers with atherosclerosis are at increased risk of cognitive decline.