Sex differences in the causes and consequences of white matter hyperintensities

Objective: To examine sex differences in white matter hyperintensities (WMHs) on T2-weighted magnetic resonance imaging (MRI), reported to be more severe in older women. Methods: A random community sample of 228 men and 204 women, aged 60-64, underwent brain MRI scans. WMHs on T2-weighted FLAIR MRI scans were measured using an automated procedure. Subjects were assessed for physical health, cognitive function, vascular risk factors and Apolipoprotein E (APOE) genotyping. Results: Women had more WMHs in both deep and periventricular regions. Hypertension, heart disease and high homocysteine were significant determinants in men and current smoking in women. Hormone replacement therapy and APOE*E4 allele did not have an association with WMHs. WMHs were related to reduced processing speed in men, and had an association with poor physical health and lowered grip strength in both sexes. Conclusion: WMHs are more common in women, with somewhat different putative causes and consequences than men., but >80% of the variance in their causation remains unexplained. The focus in the investigation of WMHs should move beyond the examination for cerebrovascular disease. (C) 2007 Elsevier Inc. All rights reserved.