Sex Differences in Risk Factors for White Matter Hyperintensities in Non-demented Older Individuals

Abstract White matter hyperintensities (WMH) are generally considered to be associated with cerebral small vessels disease. They are commonly found in the brains of older individuals. While 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, MRI brain scans from two Australian cohorts were analysed to extract WMH volumes. The objective of this study was to examine the moderation effect by sex in the association between known risk factors and WMH using the generalised linear model. The burden of WMH was significantly higher in women compared to men, especially in the deep WMH (DWMH). In the generalised 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, i.e. the Sydney Memory and Ageing Study (MAS), n= 432, aged between 70 to 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 (OATS) sample, n= 179, aged between 65 to 90. The risk factors of WMH pathology are suggested to have a different impact on the ageing brains of men and women.