Supplementary Material for: Exploring Neuroinflammation and Its Role in Postoperative Cognitive Dysfunction Following Spine Surgery

Abstract: Background: Progress in spine surgery has significantly improved the safety of proce-dures for older patients with disabling spine disease. However, postoperative cognitive dysfunction (POCD) remain a concern due to their link with poorer outcomes and higher long-term care risk. This study aimed to determine if pro-neuroinflammatory states accelerate neurodegeneration, contributing to POCD development, and explore whether specific biomarkers could predict POCD risk. Methods: Patients (aged ≥ 60 years) scheduled for elective spine surgery between February 2018 and March 2020 were enrolled. Biomarkers tested included IL-6, CRP, S100 calcium-binding protein β (S100β), Brain-derived neurotrophic factor (BDNF), Neurofilament light chain protein (sNFL), Gasdermin D, and soluble ectodomain of triggering receptor expressed on myeloid cells 2 (sTREM2), measured pre-operatively and postoperatively. Cognitive outcomes were assessed using the CERAD test battery at baseline and three months postoperatively. Results: Postoperative levels of sTREM2 and Gasdermin D were significantly associated with cognitive performance changes three months after surgery, particularly in memory function. Higher sTREM2 levels were associated with greater cognitive decline, with six out of twelve CERAD items showing an inverse association (e.g., overall β = -0.010, p = 0.0003). Similarly, higher postoperative Gasdermin D levels were linked to worse performance, particularly in recognition memory (e.g., word list recognition β = -0.615, p = 0.032). Additionally, higher preoperative sNFL levels were associated with poorer cog-nitive outcomes across multiple domains. Conclusions: This study highlights potential associations between neuroinflammation and cognitive decline following spine surgery. Targeting neuroin-flammatory pathways could be crucial in mitigating POCD in older patients. Biomarkers may help identify high-risk patients and guide the development of targeted interventions.