Apolipoprotein E Genotype Is Related to Progression of White Matter Lesion Load

Background and Purpose-The relationship between white matter lesions (WMLs) and the apolipoprotein E genotype has been controversial from cross-sectional studies and no longitudinal finding has been reported. We investigated whether the apolipoprotein E genotype influences baseline and evolution over 4-year follow-up of WML volumes in a population-based sample of 1779 nondemented subjects aged 65 to 80 years old at enrollment. Methods-The sample consisted of 3C-Dijon study participants who had 2 cerebral MRIs, at entry and at 4-year follow-up. WML volumes were estimated using a fully automatic procedure. We performed analysis of covariance to evaluate the relationship between apolipoprotein E genotype and WML load and progression. Results-Multivariable analyses showed that epsilon 4 epsilon 4 individuals had both significantly higher WML volume at baseline and higher WML increase over 4-year follow-up than noncarriers and heterozygous of the epsilon 4 allele for apolipoprotein E genotype. Conclusion-These findings suggest it might be important to take into account WML severity when assessing the relationship between apolipoprotein E and dementia. (Stroke. 2009;40:3186-3190.)