Choroid Plexus Enlargement Exacerbates White Matter Hyperintensity Growth through Glymphatic Impairment

Objective Choroid plexus (CP) is a key regulator in cerebrospinal fluid production, but its contribution to glymphatic clearance function and association with white matter hyperintensity (WMH) remains unclear. Methods This retrospective study included 2 prospective 3.0‐T magnetic resonance imaging (MRI) cohorts. In cohort 1, patients with indications for lumbar puncture underwent 3‐dimensional T1‐weighted sequence (3D‐T1) before and at 39 hours after intrathecal administration of contrast agent (glymphatic MRI). In cohort 2, patients with WMH were enrolled from the CIRCLE study and had a median follow‐up time of 1.4 years. WMH and CP of the lateral ventricles were automatically segmented on T2 fluid‐attenuated inversion recovery (FLAIR) and 3D‐T1, respectively. CP volume was expressed as a ratio to intracranial volume. Glymphatic clearance was measured as signal percentage change from baseline to 39 hours at 8 brain locations based on glymphatic MRI in the first cohort, or as noninvasive diffusion tensor image analysis along the perivascular space (DTI‐ALPS) index based on DTI in the second cohort. Results In cohort 1, a total of 52 patients were included. Higher CP volume was correlated with slower glymphatic clearance rate in all brain locations. In cohort 2, a total of 197 patients were included. Baseline CP volume was positively associated with WMH volume and its growth. Furthermore, DTI‐ALPS index partially mediated the association of CP with both WMH load and growth. Interpretations Enlarged CP volume could be an indicator for larger growth of WMH, potentially involving impaired glymphatic clearance function. The exploration of CP may provide a novel perspective to clarify the mechanism of WMH pathogenesis, as well as other glymphatic‐related disorders. ANN NEUROL 2023;94:182–195