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

The apolipoprotein E4 allele (APOEe4) and atherosclerosis are risk factors for cognitive decline. We investigated whether the effects of APOEe4 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 APOEe4 and atherosclerosis. Mild, non-significant effects on the MMSE score were found for atherosclerosis in the absence of APOEe4 and for APOEe4 in the absence of atherosclerosis. APOEe4 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-APOEe4 carriers with no evidence of atherosclerosis. Our findings suggest that the consequences of APOEe4 and atherosclerosis are not independent, and that particularly APOEe4 carriers with atherosclerosis are at increased risk of cognitive decline.