Abstract
BACKGROUND: The choroid plexus (CP) regulates cerebrospinal fluid (CSF) production, neuroimmune monitoring, and glymphatic transport, but its role in glymphatic system and cerebral small vessel disease (CSVD) remains unclear. This study aimed to investigate whether CP enlargement correlates with poor functional status in CSVD and whether glymphatic activity, measured by diffusion tensor imaging along perivascular space (DTI-ALPS), mediates this relationship. METHODS: A total of 70 CSVD participants and 44 age- and sex-matched healthy controls (HCs) underwent 5T ultra-high-field magnetic resonance imaging (MRI). The volumes of CP, lateral ventricles volume, white matter hyperintensities (WMHs), enlarged perivascular spaces (EPVS), and cerebral microbleeds (CMBs) were segmented automatically. Functional status was classified as fair or poor based on modified Rankin Scale (mRS) of <2 or ≥2. Group differences were assessed, and partial correlations, mediation analyses, and logistic regression were performed to quantify associations. RESULTS: Severe CSVD showed a lower global DTI-ALPS index than HCs (1.261 vs. 1.465, P<0.001) and mild to moderate CSVD (1.261 vs. 1.382, P=0.011). Those with poor functional status had larger CP (1.495×10(-3) vs. 1.154×10(-3) cm(3), P=0.006), lateral ventricles volume (41.710 vs. 28.619 cm(3), P<0.001), greater CMB burden (54.071×10(-3) vs. 9.075×10(-3) cm(3), P=0.006), higher Fazekas score {4 [3-4] vs. 4 [2-4], P<0.001}, and lower DTI-ALPS index (1.181 vs. 1.392, P<0.001) compared to those with fair status. The DTI-ALPS index correlated with CP volume (r=-0.271, P=0.036), lateral ventricles volume (r=-0.400, P=0.001), basal ganglia (BG) perivascular space (PVS) volume (r=-0.262, P=0.042), total CSVD score (r=-0.287, P=0.025), and mRS (r=-0.316, P=0.013). Lower DTI-ALPS index partially mediated the relationship between larger CP volume and both larger lateral ventricle volume and higher mRS, with mediation effects accounting for 15.8% and 28.72%, respectively. Logistic regression identified older age [odds ratio (OR) =1.094, P=0.021], increased CP volume (OR =3.165, P=0.045), and lower DTI-ALPS index (OR =0.992, P=0.017) as independent predictors of poor functional status. CONCLUSIONS: CP enlargement is associated with poor functional status in CSVD, and this relationship is partly explained by reduced DTI-ALPS index, suggesting a glymphatic pathway involvement. Quantitative MRI metrics of CP volume and DTI-ALPS index may serve as potential imaging biomarkers for functional status in CSVD.