Comparative analysis of neuropsychological impairments between Cushing's disease and non-functioning pituitary adenoma patients: the roles of HPA axis hormones and inflammatory markers in a prospective cohort study.

Abstract

Introduction: This prospective cohort study systematically compared neuropsychological impairments in Cushing's disease (CD),non-functioning pituitary adenomas (NFPA), and healthy controls (HCs), and investigated the roles of HPA axis hormones (ACTH, cortisol)and inflammatory markers in cognitive dysfunction.

Material and methods: A total of 107 CD patients, 110 NFPA patients, and 84 HCs were enrolled from the Chinese PLA General Hospital.Participants underwent preoperative comprehensive neuropsychological assessments, including the Mini-Mental State Examination(MMSE) and Montreal Cognitive Assessment (MoCA), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), PittsburghSleep Quality Index (PSQI), and Quality of Life (QOL) Scale. Clinical data were also collected. Longitudinal neuropsychological changeswere evaluated in 90 CD patients post-surgery. Statistical analyses included FDR-corrected group comparisons, correlation analyses,and multivariable regression.

Results: Cushing's disease patients exhibited significantly greater deficits in global cognition (MMSE/MoCA, q < 0.001), depression/anxiety (SDS/SAS, q < 0.006), and quality of life compared with NFPA and HCs. Critically, morning ACTH levels (8 A.M.) predicted cognitive decline, whereas cortisol showed no significant correlation. Paradoxically, inflammatory markers (WBC, neutrophils, lymphocytes) positively correlated with MMSE scores (q < 0.024), suggesting compensatory neuroprotection, which needs further investigation. Postoperatively, significant improvements occurred in affective symptoms and cognition, with maximal recovery in memory and attention.

Conclusions: The CD-specific neuropsychological impairments exceed tumor mass effects in NFPA, driven by HPA hyperactivation. ElevatedACTH is an associated predictor of cognitive decline, advocating for its prioritization in clinical monitoring. Surgical remission partiallyreverses deficits, while neuroendocrine-immune crosstalk bidirectionally modulates cognition. Adrenocorticotropic hormone-centricmanagement and targeted rehabilitation may optimize long-term outcomes.