Abstract
BACKGROUND: Sleep disorders co-existing with cerebral small vessel disease (CSVD) are prevalent in older adults, both of which are established risk factors for cognitive decline. Here, we aimed to explore the role of glymphatic function in linking CSVD and sleep quality to cognitive decline in community-dwelling older adults from a new perspective. METHODS: This cohort study included participants from the Shanghai Aging Study (SAS) who underwent clinical interviews, neuroimaging, and neuropsychological assessments. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was employed to evaluate the glymphatic function. Mediation and interaction analyses were performed to investigate the potential mediating role of DTI-ALPS in the associations between CSVD burden/sleep quality and cognitive impairment, as well as their interaction effects. RESULTS: 258 participants were included in cross-sectional analysis (mean age 68.5 years, 54.7% female), with 133 followed up after a 7-year interval. At baseline, DTI-ALPS index simultaneously mediated the associations between CSVD score/PSQI and cognitive impairment. Interaction analyses revealed that poor sleep quality had a more significant impact on cognitive impairment among participants at high risk of CSVD. Longitudinally, while no significant mediating effect was observed, both baseline DTI-ALPS and CSVD burden were significantly correlated with longitudinal MMSE changes. CONCLUSIONS: Our study suggested that glymphatic function, as assessed by DTI-ALPS, may play a crucial role in linking CSVD burden and sleep quality to cognitive decline in community-dwelling older adults. We also emphasized the importance of individualized sleep management for individuals at high risk of CSVD.