Sex differences in risk factors for white matter hyperintensities in non-demented older individuals

White matter hyperintensities (WMH) are generally considered to be associated with cerebral small vessel disease, especially, in older age. Although significant sex differences have been reported in the severity of WMH, it is not yet known if the risk factors for WMH differ in men and women. In this study, magnetic resonance imaging brain scans from 2 Australian cohorts were analyzed to extract WMH volumes. The objective of this study is to examine the moderation effect by sex in the association between known risk factors and WMH. The burden of WMH was significantly higher in women compared to men, especially in the deep WMH (DWMH). In the generalized linear model that included the interaction between sex and body mass index (BMI), there was a differential association of BMI with DWMH in men and women in the exploratory sample, that is, the Sydney Memory and Aging Study, n = 432, aged between 70 and 90. The finding of a higher BMI associated with a higher DWMH in men compared to women was replicated in the Older Australian Twins Study sample, n = 179, aged between 65 and 90. The risk factors of WMH pathology are suggested to have a different impact on the aging brains of men and women. •Women have greater deep white matter hyperintensities (DWMH) than men.•The positive association between BMI and DWMH in men was found in two independent cohorts.•The significant moderation analysis was validated in an independent sample.