White 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.
Linear mixed models examined the relationship between risk factors, WMHs, and cognition in males and females.
Males 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.
Controlling 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.

Hypertension is the main vascular risk factor associated with WMH in males
A combination of vascular risk factors contributes to WMH burden in females
Only small WMH burden differences were observed between sexes
Females’ cognition was more negatively impacted by WMH burden than males
Females with WMHs may have less resilience to future pathology

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This post is Copyright: Cassandra Morrison,
Mahsa Dadar,
Donald Louis Collins,
for the Alzheimer’s Disease Neuroimaging Initiative | September 22, 2023

Wiley: Alzheimer’s & Dementia: Table of Contents