Sex differences in risk factors, burden, and outcomes of cerebrovascular disease in Alzheimer & apos;s disease populations

BACKGROUNDWhite matter hyperintensities (WMHs) are associated with cognitive decline and progression to mild cognitive impairment (MCI) and dementia. It remains unclear if sex differences influence WMH progression or the relationship between WMH and cognition.METHODSLinear mixed models examined the relationship between risk factors, WMHs, and cognition in males and females.RESULTSMales exhibited increased WMH progression in occipital, but lower progression in frontal, total, and deep than females. For males, history of hypertension was the strongest contributor, while in females, the vascular composite was the strongest contributor to WMH burden. WMH burden was more strongly associated with decreases in global cognition, executive functioning, memory, and functional activities in females than males.DISCUSSIONControlling vascular risk factors may reduce WMH in both males and females. For males, targeting hypertension may be most important to reduce WMHs. The results have implications for therapies/interventions targeting cerebrovascular pathology and subsequent cognitive decline.HIGHLIGHTSHypertension is the main vascular risk factor associated with WMH in malesA combination of vascular risk factors contributes to WMH burden in femalesOnly small WMH burden differences were observed between sexesFemales' cognition was more negatively impacted by WMH burden than malesFemales with WMHs may have less resilience to future pathology