Sex differences in risk factors, burden, and outcomes of cerebrovascular disease in Alzheimer’s disease populations

Abstract

AbstractBackgroundWhite matter hyperintensity (WMH) accumulation is associated with vascular risk factors such as hypertension, diabetes, smoking, and obesity. Increased WMH burden results in increased cognitive decline and progression to mild cognitive impairment (MCI) and dementia. However, research has been inconsistent when examining whether sex differences influence the relationship between vascular risk factors, WMH accumulation, and cognition.MethodsA total of 2119 participants (987 females) with 9847 follow-ups from the Alzheimer’s Disease Neuroimaging Initiative met inclusion criteria for this study. Linear regressions were used to examine the association between vascular risk factors (individually and as a composite score) and WMH burden in males and females. When controlling for vascular risk factors, linear mixed models were also used to investigate whether the relationship between WMHs and longitudinal cognitive scores differed between males and females.ResultsMales had overall increased occipital (p<.001), but lower frontal (p<.001), total (p=.01), and deep (p<.001) WMH burden compared to females. For males, history of hypertension was the strongest contributor to WMH burden. On the other hand, the vascular composite score was the strongest factor for WMH in females. Greater increase in WMH accumulation was observed in males with a history of hypertension in the frontal region (p=.014) and males with high systolic blood pressure in the occipital region (p=.029) compared to females. With respect to cognition, WMH burden was more strongly associated with longitudinal decreases in global cognition, executive functioning, and functional activities of daily living in females compared to males.DiscussionThese findings show that controlling hypertension is important to reduce WMH burden in males. Conversely, minimizing WMH burden through vascular risk factors requires controlling many factors for females (e.g., hypertension, diabetes, smoking, alcohol abuse, etc.). The results have implications for therapies and interventions designed to target cerebrovascular pathology and the subsequent cognitive decline.