Effect of Reversal Agents on Postoperative Cognitive Disorders Following General Anesthesia in the Elderly Population: A Systematic Review and Meta-Analysis

Background/Objectives: Perioperative neurocognitive disorders (PND), including postoperative delirium and cognitive dysfunction (POCD), represent significant complications in elderly surgical patients undergoing general anesthesia. The choice of neuromuscular blockade reversal agent may influence POCD risk through different mechanisms and side effects. This systematic review and meta-analysis evaluated the comparative effect of neostigmine versus sugammadex on POCD incidence in elderly patients. Methods: A systematic search of PubMed, Web of Science, Scopus, and Google Scholar was conducted from database inception to September 2025, following PRISMA 2020 guidelines with PROSPERO registration (CRD420251058187). Randomized controlled trials involving elderly patients (≥60 years) undergoing general anesthesia with neuromuscular blockade were included, comparing neostigmine and sugammadex for reversal. Primary outcomes included POCD incidence, assessed using validated cognitive tools, including the Mini-Mental State Examination and Montreal Cognitive Assessment. Meta-analysis was performed using Review Manager 5.4.1, with results expressed as odds ratios (ORs) and 95% confidence intervals (CIs). Results: Six randomized controlled trials involving 795 elderly patients published between 2017 and 2024 met the inclusion criteria. Studies encompassed non-cardiac surgery, robotic-assisted radical cystectomy, and pars plana vitrectomy. Pooled meta-analysis showed neostigmine was associated with a higher risk of POCD than sugammadex (OR 1.74, 95% CI 1.00–3.02, p = 0.05), with low heterogeneity (I2 = 39%). Secondary outcomes, including prevention of POCD, management strategies, and related complications, were inconsistently reported and unavailable across all six RCTs. Subgroup analysis stratified by neostigmine dosage demonstrated that administration of a higher dose (≥0.04 mg/kg) was associated with reduced POCD incidence compared to a lower dose (