Plasma Biomarkers Differentiate Cognitive Impairment in Postmenopausal Women with Insomnia Disorder

Abstract

Background: Sleep disorders are common in postmenopausal women and may contribute to cognitive decline. We investigated whether plasma biomarkers differentiate cognitive impairment (CI) in this population.Methods: In this cross-sectional exploratory study, we recruited 105 outpatients with insomnia disorder (79 women and 26 men) aged 45-60 years with insomnia symptoms (PSQI > 5, ISI > 7). Cognition was assessed using the Chinese Brief Cognitive Test (CBCT) and Auditory Verbal Learning Test. Postmenopausal women were classified as CI or non-CI based on CBCT criteria. Plasma glial fibrillary acidic protein (GFAP), neurofilament light chain, orexin A, total tau, and phosphorylated tau-181 (p-Tau) were measured using enzyme-linked immunosorbent assay. Associations with cognition and exploratory classification performance were examined using correlation and receiver operating characteristic analyses.Results: Postmenopausal women exhibited higher anxiety and poorer cognitive performance despite comparable insomnia severity. Among them (non-CI n=42; CI n=37), the CI group had higher plasma GFAP (14.82 vs. 12.42 ng/mL, P = .004) and p-Tau (1,002.18 vs. 918.27 pg/mL, P = .034). Biomarkercognition correlations were weak. GFAP showed the highest apparent performance among individual biomarkers (area under the curve, AUC = 0.672). The clinical information-adjusted model incorporating orexin A, GFAP, and p-Tau showed the highest apparent AUC among biomarker combinations (AUC = 0.755), although internally validated performance was more modest.Conclusions: Plasma GFAP and p-Tau, with potential incremental contribution from orexin A, may provide exploratory information for identifying cognitive vulnerability in postmenopausal women with insomnia disorder. These exploratory findings require validation in larger and independent cohorts.