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Objectives: To examine sex differences in the associations between vascularrisk factors and 6-year changes in the volume of white matter hyperintensities(WMH), and between changes in WMH volumes and changes in cognitive performance,in a cohort of non-demented older adults.  Methods: WMH volumes at 3 time-points (baseline, and 2- and 6-year follow-up)were automatically quantified in participants of Sydney Memory and Ageing Study(N = 605; age range = 70-92 years; 54.78% female). Linear mixed models wereapplied to examine the effects of vascular risk factors and cognitiveconsequences of the progression of WMH, as well as the sex moderation effectsin the associations.  Results: Total (TWMH), periventricular (PVWMH), and deep (DWMH) WMH volumesincreased by 9.47%, 7.70%, and 11.78% per year, respectively. No sexdifferences were found in WMH progression rates. After Bonferroni correction,increases in PVWMH volumes over time were associated with decline in globalcognition, especially in visuospatial and memory domains. Men with moreincreases in PVWMH volumes over time had greater declines in visuospatialabilities. Moreover, higher average TWMH volumes across time-points wereassociated with poorer average performance in processing speed and executivefunction domains across time. Higher average PVWMH volumes across time-pointswere also associated with worse average performance in the executive functiondomain over time, among women but not men.  Conclusion: The findings highlighted sex differences in the associationsbetween WMH progression and cognition decline over time, suggestingsex-specific strategies in managing WMH accumulations in ageing.  Keywords: Cerebral small vessel disease, white matter hyperintensities, sexdifferences, brain ageing, cognitive decline.

Sex Differences in 6-Year Progression of White Matter Hyperintensities in Non-Demented Older Adults: Sydney Memory and Ageing Study