LAUSR

STUDY OBJECTIVES This study assessed the associations between sleep behaviors with white matter macro and microstructure. METHODS A total of 26354 participants in the UK Biobank (mean [standard deviation], age, 63.7 [7.5] years, 53.4% female) were included in this study. A healthy sleep score integrated sleep behaviors including chronotype, insomnia, sleep duration, daytime sleepiness, and snoring. Linear and non-linear relationships were calculated between individual and aggregate sleep behaviors with white matter hyperintensities (WMH) and microstructural injury. RESULTS A "U-shaped" relationship was revealed between sleep duration and WMH, and the lowest WMH was at 7.7h per night. Four unhealthy sleep behaviors including late chronotype, sleep duration (>8h or <7h), excessive daytime sleepiness, and snoring significantly increased WMH burden. Lower healthy sleep score was linked with increased WMH burden (β=0.164, 95%CI=0.110-0.218), and worse microstructure in association and thalamic white matter tracts. Increased body mass index, glycated hemoglobin A1c, and systolic blood pressure were potential mediators of the relationships between unhealthy sleep behaviors and increased WMH. However, higher BMI and low-density lipoprotein were revealed as protective mediators between snoring and improved white matter integrity including lower MD and higher ICVF. CONCLUSIONS Unhealthy sleep behaviors were associated with increased WMH burden and worse white matter microstructure in specific tracts across middle and older age. These findings provide the potential to improve white matter integrity by reversing unhealthy sleep behaviors.