Sex Differences in White Matter Hyperintensities in the Ageing Brain

Abstract

Cerebral white matter hyperintensities (WMH) appear in the brain magnetic resonance imaging scan at early age and become more prevalent at older age. Despite that old age is known as the main risk factor for WMH accumulation, the literature has shown that many vascular risk factors contribute significantly to the existence and progression of WMH. Women were shown to have higher WMH volume compared to men in the literature. However, the existing literature lacks comprehensive evidence to address why such pattern is noted. Therefore, this thesis aims to examine sex differences in WMH. Specifically, three studies were conducted: (1) investigating sex differences in the associations between vascular risk factors and WMH, (2) examining the contribution of the hormonal risk factors to WMH and their moderation effects on the associations between vascular risk factors and WMH, and (3) examining sex differences in longitudinal associations between vascular risk factors and WMH, and the effects of WMH progression on cognitive decline. Results showed that the pattern of higher WMH in women compared to men was identified across the studies, however, men had stronger contributions of vascular risk factors, especially obesity measures, to WMH. The second study showed that hypertensive postmenopausal women benefited significantly from using hormone replacement therapy, especially when taken early and for longer duration. Diabetic women and women with increased pulse wave velocity had increased deep WMH when post-menopausal duration was one standard deviation below the mean. In men, smokers with higher testosterone levels had significant increase in WMH. In the third study, significant sex differences were found in the association between WMH progression and cognition. Specifically, increases in periventricular WMH volume over time was associated with greater decline in visuospatial abilities in men, but not in women. In women, but not in men, higher average periventricular WMH volumes across time-points was associated with poorer executive function. The thesis comprehensively examined sex differences in vascular and hormonal risk factors associated with WMH, as well as in cognitive consequences of the progression of WMH. The findings highlight the importance of taking sex differences into consideration clinically and for future clinical research of WMH