Abstract
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients undergoing abdominal surgery; however, reliable biomarkers for its early identification are limited. Klotho, an anti-aging protein with neuroprotective and anti-inflammatory properties, may play a role in POCD development. This study investigated the association between serum Klotho levels and POCD, as well as their relationships with inflammation and cognitive outcomes. METHODS: A total of 93 patients undergoing abdominal surgery were enrolled and classified into non-POCD (n = 59) and POCD (n = 34) groups based on their postoperative Montreal Cognitive Assessment (MoCA) scores. Serum Klotho, C-reactive protein (CRP), interleukin (IL)-1β, and IL-6 levels were measured preoperatively and postoperatively. Multivariate logistic regression, receiver operating characteristic (ROC) curve analysis, and Pearson correlation analyses were performed to evaluate associations and predictive value. RESULTS: Patients who developed POCD had significantly longer durations of anesthesia than those without POCD (all P < 0.001). While preoperative Klotho levels were comparable between the groups, postoperative serum Klotho levels were significantly reduced in the POCD group (561.07 ± 59.27 vs. 654.66 ± 94.63 pg/mL, P < 0.001). Multivariate analysis identified age (odds ratio [OR] = 1.101, 95% confidence interval [CI] = 1.009-1.201, P = 0.031) and anesthesia duration (OR = 1.059, 95% CI = 1.011-1.109, P = 0.015) as independent risk factors, whereas higher postoperative Klotho levels were independently associated with a reduced risk of poor outcomes (OR = 0.992, 95% CI = 0.985-0.998, P = 0.016). Postoperative Klotho levels were negatively correlated with anesthesia duration and inflammatory markers (C-reactive protein, interleukin [IL]-1 β, and IL-6) (all P < 0.05) and positively correlated with postoperative MoCA scores (r = 0.45, P < 0.001). ROC analysis identified an optimal cutoff value of 630.2 pg/mL for Klotho in distinguishing POCD, demonstrating favorable diagnostic performance. CONCLUSION: Decreased postoperative serum Klotho levels are closely associated with increased inflammation and cognitive impairment following abdominal surgery. Klotho may serve as a promising biomarker for the early identification of POCD and as a potential therapeutic target to improve postoperative cognitive outcomes.