ArticleBMC medical imaging2025
Hypothalamic subunit atrophy and glymphatic dysfunction in idiopathic hypogonadotropic hypogonadism: associations with cognitive impairment.
Article in BMC medical imaging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Idiopathic hypogonadotropic hypogonadism (IHH), a rare neurodevelopmental and endocrine disorder resulting from defective development or function of gonadotropin-releasing hormone (GnRH) neurons in the brain, is increasingly recognized for its association with cognitive impairment, yet the underlying neural substrates remain largely unexplored. Here, we used 3T MR scanner to investigate brain structural integrity and glymphatic function in 48 adult male IHH patients and 30 healthy controls, and to determine their relationship with cognitive performance. We quantified key structural metrics (volumes of hypothalamic subunits, adenohypophysis, hippocampus; cortical surface metrics) and assessed glymphatic function using the diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index, choroid plexus volume (CPV), and perivascular space (PVS) volume, with all volumes normalized as fractions of total intracranial volume. Global cognition was evaluated using the Montreal Cognitive Assessment (MoCA). Compared to healthy controls, IHH patients exhibited significantly lower MoCA scores. Neuroimaging revealed specific atrophy in the left anterior-superior hypothalamic subunit (asHyp) and adenohypophysis, accompanied by altered cortical curvature in the right precuneus and postcentral gyrus. Furthermore, patients demonstrated glymphatic dysfunction, evidenced by a reduced DTI-ALPS index and an increased CPV fraction. Crucially, atrophy of the left asHyp, a reduced DTI-ALPS index, and an elevated CPV fraction were all significantly associated with worse MoCA scores (all p < 0.05, corrected). Moreover, statistical mediation analysis suggested that the correlation between left asHyp atrophy and cognitive performance was partially explained by glymphatic dysfunction (lower DTI-ALPS index). In conclusion, our findings suggest a significant association among hypothalamic subunit atrophy, glymphatic dysfunction, and poorer cognitive performance.
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