<p>Multivariate logistic regression analysis.</p>

Background Postoperative cognitive dysfunction (POCD) is a frequent complication in older patients undergoing hip and knee arthroplasty. While irisin has demonstrated benefits in neurological disorders associated with cognitive impairment, its role in POCD remains unclear. This study investigated the association between serum irisin levels and POCD and assessed the discriminative value of irisin for POCD development. Methods This prospective observational study employed Spearman correlation and multifactorial logistic regression analyses to investigate the relationships between these biomarkers and POCD. Receiver operating characteristic analyses were then performed to assess the discriminative value of irisin. Result POCD occurred in 37 (31.36%) patients. Serum irisin levels were markedly reduced in patients with POCD relative to those without POCD. T0 irisin (rho = 0.675) levels correlated positively with Montreal cognitive assessment-Basic (MoCA-B) scores. Logistic regression analysis identified T0 irisin, T1 irisin, T0 Tumor necrosis factor-α (TNF-α), and hypertension as independent factors associated with the development of POCD (all P < 0.05). T0 irisin showed significant discriminative value for POCD, with a cutoff value of 302.840 ng/mL (Area Under the Curve [AUC]: 0.817; sensitivity: 0.757; specificity: 0.765). Conclusion Irisin may serve as an early warning biomarker for POCD, offering new insights for its prevention and treatment.