Hypothalamic subunit atrophy and glymphatic dysfunction in idiopathic hypogonadotropic hypogonadism: associations with cognitive impairment
Bibliographic record
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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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".