Apolipoprotein E genotype, atherosclerosis, and cognitive decline: the Rotterdam Study.
Slooter AJ., van Duijn CM., Bots ML., Ott A., Breteler MB., De Voecht J., Wehnert A., de Knijff P., Havekes LM., Grobbee DE., Van Broeckhoven C., Hofman A.
The apolipoprotein E4 allele (APOE epsilon 4) and atherosclerosis are risk factors for cognitive decline. We investigated whether the effects of APOE epsilon 4 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 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 for APOE epsilon 4 in the absence of atherosclerosis. APOE epsilon 4 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-APOE epsilon 4 carriers with no evidence of atherosclerosis. Our findings suggest that the consequences of APOE epsilon 4 and atherosclerosis are not independent, and that particularly APOE epsilon 4 carriers with atherosclerosis are at increased risk of cognitive decline.