Parallel neuroinflammatory pathways to cerebrovascular burden and amyloid beta in Alzheimer's disease.

In 2018, an international working group recommended perioperative neurocognitive disorders as an overarching term for cognitive changes associated with surgery and anesthesia. The framework includes pre-existing neurocognitive disorder, postoperative delirium within 7 days, delayed neurocognitive recovery within 30 days, and postoperative neurocognitive disorder from 30 days to 12 months after surgery []. Because the included trials used heterogeneous historical definitions, the term POCD is retained in this review to reflect the terminology reported by the original studies. Despite significant advancements in surgical techniques, anesthesia management, and perioperative care that have markedly improved patient safety, surgery and anesthesia continue to pose risks of both structural and functional injury to the central nervous system []. POD is one of the most common yet frequently underdiagnosed complications, particularly among elderly patients undergoing general anesthesia. General anesthetics can influence the central nervous system by altering neurotransmission and suppressing cortical activity. Clinical manifestations of POD include impaired attention, disorientation, perceptual disturbances, and behavioral changes. However, atypical presentation, limited physician awareness, lack of standardized screening tools, and fluctuating symptoms make POD difficult to identify []. These diagnostic difficulties often delay timely recognition and treatment []. Previous studies have reported that the incidence of postoperative delirium ranges from 26 to 52%, while the incidence of POCD ranges from 35 to 60% []. The development of POD significantly diminishes patients’ postoperative quality of life, increases the burden on healthcare providers, and contributes to elevated healthcare costs. Affected patients face a heightened risk of complications, including aspiration, nosocomial pneumonia, pulmonary embolism, and pressure injuries. In mechanically ventilated patients, POD may lead to unplanned extubation, necessitating reintubation or delayed extubation, which prolongs hospital stays, escalates medical expenditures, and increases both ICU readmission and mortality rates []. Furthermore, POD is linked to persistent cognitive decline and serves as a critical risk factor for the development of POCD within the first month following surgery []. A multicenter cohort study by Kirfel et al. reported that elderly patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) experienced a POCD incidence of nearly 60% within seven days postoperatively, which is substantially higher than that observed in patients undergoing non-cardiac surgery []. Several intraoperative factors contribute to this elevated risk, including systemic and cerebral hypoperfusion, microemboli formation during CPB and aortic manipulation, rapid temperature fluctuations, and systemic inflammatory response syndrome (SIRS). These mechanisms can result in cerebral metabolic disturbances, neuroinflammation, and neurotransmitter imbalances, which together underlie the high incidence of POD following cardiac surgery []. Preventing POD and POCD after cardiac surgery remains an urgent clinical challenge. In recent years, both pharmacological and non-pharmacological interventions have been explored to mitigate these complications. Among pharmacological approaches, agents such as esketamine, ifenprodil, mannitol, and dexamethasone have demonstrated efficacy in reducing the incidence of POD and POCD through mechanisms including sedation, anti-inflammatory effects, and neuroprotection []. Other drugs, such as intranasal insulin, valerian, lidocaine, and erythromycin, appear to attenuate postoperative neuroinflammation by enhancing cerebral glucose metabolism, improving neuronal function, and providing analgesic and anti-inflammatory benefits, thereby demonstrating potential in alleviating cognitive dysfunction. Additionally, dexmedetomidine and propofol have been investigated for their potential roles in preserving postoperative cognitive function []. Sevoflurane has also been evaluated as part of anesthetic strategy comparisons in this field []. Compared with pharmacological approaches, non-pharmacological interventions are more diverse and include strategies such as remote ischemic preconditioning (RIPC), music therapy, family involvement, psychological support, cognitive training, and ABCDE bundled care. These interventions are generally low-cost, easy to implement, and offer notable advantages in terms of safety []. Nevertheless, the existing literature is extensive and often presents conflicting findings. Intervention practices aimed at preventing POD and POCD vary significantly across institutions and lack standardized methodologies, which leaves the optimal approach uncertain. Consequently, this study employs a network meta-analysis to systematically compare the effects of various intervention strategies on postoperative cog