Metabolic syndrome and perioperative neurocognitive disorders: epidemiology, mechanisms, and interventions

Perioperative neurocognitive disorders, an umbrella term encompassing preoperative cognitive impairment, acute postoperative delirium, and longer term postoperative neurocognitive disorders, represent significant complications for the growing population of older surgical patients. The rising prevalence of metabolic syndrome, defined by the clustering of abdominal obesity, insulin resistance, hypertension, and dyslipidemia, necessitates a deeper understanding of its impact on the perioperative brain. This comprehensive review elucidates the intricate epidemiological and mechanistic links between metabolic syndrome and the spectrum of cognitive decline. Epidemiologically, we disaggregate the risk profiles of individual components, demonstrating that distinct metabolic phenotypes serve as specific predictors for different phases of impairment. Mechanistically, we propose a sequential pathophysiological cascade where chronic systemic inflammation primes the brain for injury. Surgical stress triggers the failure of a compromised blood brain barrier, leading to the activation of the TLR4/NLRP3 inflammasome and the induction of central insulin resistance. These processes ultimately culminate in mitochondrial energy crises and synaptic degradation. To address these vulnerabilities, we evaluate an integrated perioperative strategy spanning preoperative metabolic optimization, intraoperative management, and emerging pharmacological interventions such as SGLT2 inhibitors and mitochondria targeted antioxidants. Critically, this review identifies a major knowledge gap regarding the absence of dedicated randomized controlled trials targeting the surgical metabolic syndrome population. Ultimately, our findings advocate for a clinical paradigm shift toward phenotype specific metabolic optimization to improve neurocognitive outcomes in these high risk patients.