Circulating and cerebrospinal fluid soluble TREM2 levels and risk of perioperative neurocognitive disorders in surgical patients: a systematic review and meta-analysis

Background Perioperative neurocognitive disorders (PND), including postoperative delirium (POD) and cognitive dysfunction (POCD), are common surgical complications in older adults. Neuroinflammation from microglial activation is a key mechanism. Soluble TREM2 (sTREM2) is a blood/CSF biomarker reflecting microglial activity. Existing studies on sTREM2 and PND risk have been inconsistent. We conducted the first meta-analysis to quantify this association. Methods We searched PubMed, Web of Science, Scopus, APA PsycInfo, Embase, the Cochrane Library (CENTRAL), and https://www.ClinicalTrials.gov , CNKI, and Wanfang Data up to August 2026 for observational studies reporting perioperative sTREM2 levels in surgical patients with/without PND. Primary outcome was standardized mean difference (SMD) in sTREM2 between PND cases and controls, using a random-effects model. Heterogeneity was assessed via I 2 . Subgroup and sensitivity analyses were performed. PROSPERO: CRD420261386903. Results Eight studies (1,154 patients) were included; seven with quantitative data (1,072 patients) were meta-analyzed. Patients with PND had higher sTREM2 levels than controls (SMD = 0.44, 95% CI: 0.02 to 0.87, p = 0.040; I 2 = 86.5%). Subgroup analyses showed a positive direction of effect in CSF (SMD = 0.61, 95% CI: −0.02 to 1.23) but not in peripheral blood (SMD = 0.18, 95% CI: −0.13 to 0.49). Leave-one-out sensitivity analysis showed that the pooled estimate became non-significant after excluding the largest study, warranting cautious interpretation. One additional study reported that postoperative CSF sTREM2 elevation independently predicted POCD (adjusted OR = 1.07, 95% CI: 1.01–1.13). Conclusion Elevated perioperative sTREM2 concentrations in cerebrospinal fluid, but not in peripheral blood, showed a modest positive association with PND risk. sTREM2 represents a candidate biomarker for perioperative cognitive complications; however, the very low certainty of the underlying evidence precludes definitive conclusions. Large-scale standardized studies are needed to validate its clinical utility. Systematic review registration The systematic review was prospectively registered in PROSPERO (Unique Identifier: CRD420261386903), https://www.crd.york.ac.uk/prospero/ .