Vascular brain injury modifies the relationship between sleep duration, cognition, and white matter hyperintensity burden in the Alzheimer's disease continuum

INTRODUCTION: Self-reported sleep duration is associated with dementia-risk and vascular brain injury markers, including white matter hyperintensities (WMHs), yet how additional cerebrovascular pathology alters these relationships remains unclear. METHOD: In a deeply phenotyped cohort (735) including healthy and Alzheimer's disease (AD) continuum individuals (subjective and mild cognitive impairment [MCI], dementia [AD], MCI and AD with high vascular burden [+V]), sleep was assessed using the Pittsburgh Sleep Quality Index. Individuals were classified as WMH-only or WMH+ (WMHs with microbleeds, infarcts, or cerebral amyloid angiopathy). Linear models tested interactions between sleep duration, WMH+ status, and diagnostic group on WMH burden and cognition. RESULTS: In MCI+V and AD, WMH+ significantly amplified the association between shorter sleep and greater WMH burden. In AD, longer sleep related to better cognition in WMH+ but worse cognition in WMH-only (exploratory). DISCUSSION: Additional vascular brain injury modifies how sleep relates to WMH burden and cognition across the AD continuum, highlighting the importance of moving beyond WMHs alone.