Chronic Glymphatic Dysfunction Modulates Domain-Specific Cognitive Recovery After Stroke: A DTI-ALPS Lesion...

Glymphatic dysfunction may exacerbate post-stroke cognitive impairment (PSCI) via impaired metabolic waste clearance. However, longitudinal dynamics of glymphatic function during the chronic stroke phase (3-12 months) and links to cognitive recovery remain unclear. This study aimed to characterize chronic glymphatic remodeling dynamics using the DTI-ALPS index while exploring its temporal associations with cognitive outcomes and assessing lesion location effects.

In this retrospective cohort study, 51 chronic stroke patients (3-12 months post-stroke) and 27 matched healthy controls underwent DTI scans and neuropsychological assessments (evaluating language, memory, motor, attention) at 3 months (3 M-S) and 1 year (1Y-S) post-stroke. The DTI-ALPS index was calculated for lesioned/contralateral hemispheres. Patients were stratified by lesion location (cortical [n = 17] vs. subcortical [n = 34]). Group comparisons and Spearman correlations (FDR-corrected) were performed.

Stroke patients showed significantly lower DTI-ALPS index versus controls at both 3 M-S and 1Y-S (FDR-p < 0.001). At 3 M-S, the lesioned hemisphere ALPS index was significantly lower than the contralateral hemisphere (FDR-p < 0.05); this difference resolved by 1Y-S. No significant differences existed between cortical/subcortical subgroups. Weak correlations emerged at 3 M-S between lesioned-hemisphere ALPS index and Motor/Memory scores (r = 0.280-0.316, uncorrected p < 0.05), but these did not survive FDR correction and disappeared by 1Y-S. Lesion volume did not correlate with ALPS index.

Chronic stroke patients exhibit persistent glymphatic dysfunction. The affected hemisphere showed more severe impairment at 3 months post-stroke, with partial improvement observed by the 1-year mark. Transient cognitive associations observed at 3 months diminished by the 1-year follow-up, suggesting stabilization of recovery patterns in later stages. Despite study limitations, these findings validate the utility of the DTI-ALPS index for chronic-phase assessments and highlight the importance of targeting glymphatic dysfunction as a therapeutic strategy for PSCI.