Background: Choroid plexus (CP) regulates cerebrospinal fluid (CSF) production, neuroimmune monitoring, and glymphatic transport, but its specific contribution to glymphatic system and functional status in cerebral small vessel disease (CSVD) remains unclear.

Purpose: 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: 70 CSVD participants [median 67 (IQR 53-73) years; 55.7% male] and 44 age- and sex-matched healthy controls (HCs) [61 (51-66) years; 41.9% male] underwent 5T ultra-high-field magnetic resonance imaging (MRI). The volumes of CP, 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. Differences in these indicators between groups were analyzed. Partial correlations and mediation analyses were performed to evaluate the role of DTI-ALPS in the relationship between CP volume and mRS.

Results: Severe CSVD showed a lower global DTI-ALPS index compared to HCs (p < 0.001) and those with mild to moderate CSVD (p = 0.001). Those with poor functional status had larger CP volume, great CMB burden, higher Fazekas score, and lower DTI-ALPS index (all p < 0.05). The DTI-ALPS index correlated with CP volume (r = -0.304, p = 0.011), basal ganglia (BG) PVS volume (r = 0.314, p = 0.008), total CSVD score (r = -0.254, p = 0.034), and mRS (r = -0.506, p < 0.001). Mediation analysis indicated that lower DTI-ALPS index partial mediated the relationship between larger CP volume and higher mRS (indirect effect β = 0.191, 95% CI 0.058-0.375; proportion mediated 44.1%) .

Conclusion: 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.