APOE and Alzheimer disease: Our results are therefore mostly in line with a generally null association between APOE e4 and cross-sectional brain volumes in middle age (around 60 years), but not WM hyperintensity volumes and this may suggest that at least part of APOE e4’s contribution to worse cognitive ability is via a cerebrovascular-type pathway; although the findings may also to an extent be secondary to prodromal AD.