Complement Activation as a Predictor of Postoperative Delirium in Elderly Spine Surgery Patients

Postoperative delirium (POD) is a frequent and serious complication among elderly surgical patients. Despite its clinical relevance, reliable biomarkers for early identification and pathophysiological insight remain limited. Recent evidence implicates systemic immune activation and complements dysregulation as contributors to cognitive decline after surgery. This study investigated the association between perioperative levels of selected complement pathway proteins and both the incidence and severity of POD. Methods: We performed a secondary analysis of 22 patients aged ≥ 60 years from the prospective CONFESS cohort undergoing elective spine surgery. Complement proteins (C1q, C2, C4), mannose-binding lectin (MBL), Factor D [FD], Factor B [FB], Factor I [FI] were quantified from blood samples collected at baseline, preoperatively, and on postoperative days 1 and 2. POD was assessed using the Nursing Delirium Screening Scale (Nu-DESC) and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Delirium severity was rated with the Confusion Assessment Method-Severity (CAM-S) scale. Associations were tested using univariate and multivariate regression analyses. Preoperative levels of FD and C2 were significantly elevated in patients who developed POD (FD: <i>p</i> = 0.023; C2: <i>p</i> = 0.044), while C4 levels trended lower. FD remained an independent predictor of POD in multivariate regression (<i>p</i> = 0.049), although cognitive performance was the only significant predictor when adjusted for surgery duration. Delirium severity was associated with perioperative reductions in C1q, FI, and FB and with increased MBL levels, explaining up to 43% of CAM-S score variance. These findings highlight the role of complement activation-particularly FD, C2, MBL-in the development and clinical expression of POD. Complement profiling may offer a novel approach for risk stratification and therapeutic targeting in perioperative neurocognitive disorders.