Lighter sleep is associated with higher enlarged perivascular spaces burden in middle-aged and elderly individuals

Background: While healthy sleep is suggested to promote glymphatic clearance in the brain, poorer sleep may be associated with higher enlarged perivascular spaces (ePVS) burden, potentially representing impaired perivascular drainage. This study aims to evaluate the association between ePVS burden and polysomnographic sleep characteristics in a large community-based sample. Methods: 552 dementia and stroke-free Framingham Heart Study participants (age: 58.6 ± 8.9 years; 50.4% men) underwent a full-night in-home polysomnography. Three years later on average, participants underwent a brain MRI. ePVS were rated in the basal ganglia and centrum semiovale, and dichotomized as low burden (<20 counts, grades 1 and 2) or high burden (>20 counts, grades 3 and 4). Logistic regression analyses relating sleep variables to subsequent ePVS burden were used, adjusted for age, sex, time interval between polysomnography and MRI, ApoE ε4 allele carrier status, hypertension, and smoking. Results: Longer N1 sleep and shorter N3 sleep duration were associated with higher ePVS burden in the centrum semiovale. When stratifying these associations by subpopulations, longer N1 sleep duration with ePVS burden was observed especially in older individuals and hypertensive participants. Associations between ePVS burden and other sleep characteristics such as total sleep time and REM sleep duration varied according to ApoE ε4 allele carrier status. Conclusions: Lighter sleep, as characterized by longer N1 sleep and shorter slow-wave sleep, is associated with higher ePVS burden. These findings suggest that sleep architecture may be involved in glymphatic clearance and cerebral small vessel disease, which could be an important biological link between sleep and dementia risk.