Right-hemisphere glymphatic dysfunction is associated depressive symptoms in subacute stroke: A diffusion tensor imaging-along the perivascular space index study.

BACKGROUND

Depressive symptoms are common in patients with subacute stroke, yet the underlying mechanisms remain unclear. We aimed to investigate the relationship between "along the perivascular space" (ALPS) indices, a measure of glymphatic dysfunction, and depressive symptoms in ischemic stroke patients, considering infarct laterality.

METHODS

A prospective cohort of 104 patients with acute ischemic stroke underwent 3.0-T MRI and clinical assessments at their 3-month follow-up. The 24-item Hamilton Depression Rating Scale (HAMD) was used to assess depressive symptoms (HAMD ≥8). ALPS indices including left (L-ALPS), right (R-ALPS), infarct (I-ALPS), and non-infarct hemispheres (N-ALPS), average across L-ALPS and R-ALPS, and I-ALPS to N-ALPS ratio (I-to-N) were calculated. Logistic regression and mediation analyses were conducted to evaluate associations between ALPS indices and depressive symptoms.

RESULTS

At follow-up, 32.7 % (n = 34) of patients experienced depressive symptoms. R-ALPS, but not I-ALPS or N-ALPS, was the strongest predictor of depressive symptoms (odds ratio = 0.032, 95 % confidence interval: 0.002-0.567, p = 0.019). Additionally, higher fractional anisotropy (p = 0.02) and lower fractional anisotropy (p = 0.049) in the left superior cerebellar peduncle (SCP) were correlated with depressive symptoms. Glymphatic dysfunction was directly linked to depressive symptoms, independent of left SCP metrics (p > 0.05).

CONCLUSION

In subacute stroke patients, glymphatic dysfunction, particularly in the right hemisphere, is independently associated with depressive symptoms, which suggests a lateralized role in subacute mood regulation. Therefore, the ALPS index may serve as a non-invasive biomarker for stratifying patients according to risk of depressive symptoms.