Investigating the relationship between sleep disturbances and white matter hyperintensities in older adults on the Alzheimer's disease spectrum.

Background: While studies report that sleep disturbance can have negative effects on brain vasculature, its impact on cerebrovascular disease such as white matter hyperintensities (WMHs) in beta-amyloid positive older adults remains unexplored. Methods: Linear regressions, mixed effects models, and mediation analysis examined the crosssectional and longitudinal associations between sleep disturbance, cognition, and WMH burden, and cognition in normal controls (NCs), mild cognitive impairment (MCI), and Alzheimer's disease (AD) at baseline and longitudinally. Results: People with AD reported more sleep disturbance than NC and MCI. AD with sleep disturbance had more WMHs than AD without sleep disturbances. Mediation analysis revealed an effect of regional WMH burden on the relationship between sleep disturbance and future cognition. Conclusion: These results suggest that WMH burden and sleep disturbance increases from aging to AD. Sleep disturbance decreases cognition through increases in WMH burden. Improved sleep could mitigate the impact of WMH accumulation and cognitive decline.