Diffusion Tensor Imaging along the Perivascular Space and Choroid Plexus Volume in Assessing Brain Glymphatic System in Overt Hypothyroidism

Background The neurocognitive impairment in overt hypothyroidism (OH) is well-recognized, but its underlying mechanisms remain unclear. The glymphatic system, a recently discovered brain waste-clearance pathway, represents a promising yet unexplored target in this context. This study aimed to non-invasively assess glymphatic function in OH patients using the DTI-ALPS index and choroid plexus (CP) volume, and to investigate their relationships with thyroid function and cognitive performance. Methods We enrolled 40 patients with overt hypothyroidism (OH) and 42 healthy controls. All participants underwent 3D-T1 weighted imaging (3D-T1WI) and diffusion tensor imaging (DTI). Glymphatic activity was assessed using the DTI-ALPS index, and choroid plexus (CP) volume was segmented from 3D-T1WI images. After adjusting for covariates, correlations between these imaging markers and thyroid hormones as well as neuropsychological scale scores were analyzed. Results After confounder adjustment, OH patients demonstrated a significantly reduced DTI-ALPS index and enlarged CP volume compared to controls. Critically, a lower DTI-ALPS index was associated with a larger CP volume. Serum FT3 levels and MoCA scores showed strong positive correlations with the DTI-ALPS index but negative correlations with CP volume. Conclusion Our study provides the first direct evidence of glymphatic system dysfunction in OH, linking it to thyroid hormone levels and cognitive deficits. The DTI-ALPS index and CP volume emerge as novel and promising neuroimaging biomarkers, offering new insights into the pathophysiology of hypothyroidism-related neurocognitive decline and potential targets for future interventions. Clinical trial number: Not applicable.