APOE ε4 and risk for Alzheimer's disease: Do regionally distributed white matter hyperintensities play a role?

Background: We previously demonstrated that parietal lobe white matter hyperintensities (WMH) increase the risk for Alzheimer's disease (AD). Here, we examined whether individuals with apolipoprotein E gene (APOE epsilon 4) have increased parietal WMH volume. Methods: Participants were from the Washington Heights-Inwood Columbia Aging Project (WHICAP; n = 694, 47 with dementia) in northern Manhattan and the Etude Sante Psychologique Prevalence Risques et Traitement study (ESPRIT; n = 539, 8 with dementia) in Montpellier. The association between regional WMH and APOE epsilon 4 was examined separately in each group and then in a combined analysis. Results: In WHICAP, epsilon 4 carriers had higher WMH volume particularly in parietal and occipital lobes. In ESPRIT, epsilon 4 carriers had elevated WMH particularly in parietal and temporal lobes. In the combined analysis, epsilon 4 carriers had higher WMH in parietal and occipital lobes. Increased WMH volume was associated with increased frequency of dementia irrespective of APOE epsilon 4 status; those with the epsilon 4 were more likely to have dementia if they also had increased parietal WMH. Conclusions: APOE epsilon 4 is associated with increased parietal lobe WMH. (C) 2014 The Alzheimer's Association. All rights reserved.