Preoperative depression as a neuroimmune-cholinergic vulnerability state for postoperative cognitive dysfunction after gastrointestinal cancer surgery

Abstract

Postoperative cognitive dysfunction, a legacy term broadly corresponding to the postoperative spectrum within the contemporary perioperative neurocognitive disorders framework, is a frequent and clinically consequential complication after gastrointestinal (GI) cancer surgery in older adults. Preoperative depression is increasingly recognized as a high-impact risk factor, yet its biological links to perioperative brain vulnerability remain underappreciated. Li et al recently published a study in World Journal of Gastrointestinal Surgery, examining postoperative cognitive outcomes in depressed older adults undergoing GI tumor surgery, with particular emphasis on inflammatory and cholinergic mechanisms. Li et al report a substantial burden of postoperative cognitive impairment and identify a dual-pathway pattern in which postoperative inflammatory signaling - indexed by interleukin-6 as a representative perioperative cytokine - and reduced peripheral cholinesterase activity are associated with excess cognitive risk in patients with preoperative depression. Conceptually, these findings support reframing depression as a neuroimmune-cholinergic vulnerability state that may amplify perioperative susceptibility through interacting inflammatory and neuromodulatory processes. While mechanistic in nature and hypothesis-generating, this framework suggests that preoperative depression screening may inform future risk stratification strategies and motivate investigation of inflammation-aware, cholinergic-sensitive, and psychosocially integrated perioperative care approaches. A neuropsychiatric-immune-cholinergic perspective provides a coherent conceptual framework for understanding heterogeneity in postoperative neurocognitive outcomes after GI cancer surgery and highlights preoperative depression as a biologically relevant vulnerability state warranting further prospective investigation.

Keywords: Postoperative cognitive dysfunction; Preoperative depression; Gastrointestinal tumor surgery; Cholinergic dysfunction; Neuroinflammation; Interleukin-6; Perioperative brain health

Core Tip: Postoperative cognitive dysfunction (POCD) is a frequent yet underappreciated complication in elderly patients undergoing gastrointestinal tumor surgery. This editorial highlight emerging evidence that preoperative depression represents a biologically active vulnerability state that predisposes patients to POCD through synergistic neuroinflammatory activation and cholinergic dysfunction. By integrating findings on interleukin-6-mediated inflammation and impaired cholinergic regulation, the article reframes POCD as a disorder of perioperative brain resilience. This perspective supports earlier risk identification and mechanism-based preventive strategies to preserve cognitive health in aging surgical populations.