The Relationship between Glymphatic Dysfunction and Post-stroke Cognitive Impairment

Background: Glymphatic dysfunction is proposed as a final common pathway to dementia. Cognitive impairment following ischemic stroke can gradually worsen, potentially leading to post-stroke dementia. This study aimed to examine the changes in glymphatic function in post-stroke patients and explore its relationship with cognition. Methods: A total of thirty-two post-stroke patients and twenty-seven healthy controls (HCs) matched for age, sex, and educational level were enrolled in this study. All participants underwent neurological MRI scans and comprehensive cognitive assessments six months following the onset of the stroke. Three glymphatic markers derived from MRI were quantified, including diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, choroid plexus volume (CPV), and enlarged perivascular spaces (PVS) volume. The changes in glymphatic markers and their correlations with cognitive scores were analyzed. Results: Post-stroke patients exhibited a significantly decreased DTI-ALPS index (p < 0.001) and an increased CPV (p < 0.001) compared to HCs, while no significant difference was observed in PVS volume. Correlation analysis revealed that the DTI-ALPS index was positively correlated with Digit Span Test (r = 0.426, p = 0.015) and Digit Symbol Substitution Test (rs = 0.363, p = 0.041) scores, and PVS volume showed a positive correlation with Trail Making Test-B scores (rs = 0.391, p = 0.027). After adjusting for confounding factors, multiple linear regression analyses indicated that enlarged PVS volume was independently associated with worse performance in Trail Making Test-B (β = 0.428, p = 0.010). Discussion: The findings demonstrated that glymphatic dysfunction, as indicated by a reduced DTI-ALPS index and increased CPV volume, was evident in post-stroke patients and significantly linked to impairments in specific cognitive domains, including working memory, processing speed, and executive function. These observations supported the hypothesis that glymphatic impairment may represent a key mechanistic pathway underlying post-stroke cognitive impairment (PSCI). To further elucidate the causal relationships and identify potential therapeutic targets, future studies incorporating larger cohorts, longitudinal designs, and region-specific PVS analyses are warranted. Conclusion: Post-stroke patients exhibited a reduced DTI-ALPS index and an increased CPV, potentially reflecting impaired glymphatic function. Furthermore, these metrics were associated with specific cognitive domains.