Abstract Body: Background: The advancement of age is associated with an increased incidence of both cerebral small vessel disease (CSVD) and sleep disorders, which are recognized as risk factors for cognitive decline. Recent studies suggest that the glymphatic system may play an important role in these relationships.
Methods: In this cross-sectional and longitudinal study, participants from Shanghai Aging Study underwent multi-modal MRI, Pittsburgh Sleep Quality Index (PSQI) and neuropsychological assessment. Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was employed to evaluate the function of glymphatic system. Spearman correlation and partial correlation analyses were used to explore the relationships between CSVD burden/sleep disorders, glymphatic dysfunction, and cognition. Furthermore, mediation analysis was conducted to investigate the potential mediating effects of DTI-ALPS in the association between CSVD/PSQI and cognition. We further examined the interaction effects between CSVD burden and sleep disorders on cognitive outcomes.
Results: 258 participants were included in this study (average age, 68.5 years), among which 133 participants were followed up after a 7-year interval. At baseline, DTI-ALPS was significantly correlated with PSQI (r = -0.174, p = 0.005) and various imaging biomarkers of CSVD after adjusting for age, gender, vascular risk factors, and ApoE4. Additionally, DTI-ALPS was significantly correlated with executive function (r = -0.237, p < 0.001), memory (r = 0.146, p = 0.02), and visuospatial ability (r = 0.154, p = 0.014). Mediation analysis indicated that DTI-ALPS simultaneously mediated the association between CSVD burden/sleep disorders and cognitive decline, with a complete mediation effect of 19.22% between CSVD burden and executive function, 13.03% between PSQI and memory. Interaction analysis showed that the impacts of sleep disorders on general cognitive function and executive function were more significant among older adults at high risk of CSVD. Longitudinally, classic imaging biomarkers of CSVD as well as DTI-ALPS were significantly related to long-term changes in cognition.
Conclusion: The study reveals that glymphatic dysfunction serves as a link to closely connect sleep disorders/CSVD with cognitive decline in community-dwelling older adults. Moreover, the interaction effect between two risk factors emphasizes the importance of individualized sleep management in the elderly at high risk of CSVD.