Diffusion tensor imaging along the perivascular space and choroid plexus volume for assessing the brain glymphatic system in overt hypothyroidism

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Introduction: 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. Discussion: 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.