{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:00:36Z","timestamp":1790834436255,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We searched PubMed, Web of Science, Scopus, APA PsycInfo, Embase, the Cochrane Library (CENTRAL), and\n                      <jats:uri>https:\/\/www.ClinicalTrials.gov<\/jats:uri>\n                      , 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\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      . Subgroup and sensitivity analyses were performed. PROSPERO: CRD420261386903.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\u202f=\u202f0.44, 95% CI: 0.02 to 0.87,\n                      <jats:italic>p<\/jats:italic>\n                      =\u202f0.040;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      =\u202f86.5%). Subgroup analyses showed a positive direction of effect in CSF (SMD\u202f=\u202f0.61, 95% CI: \u22120.02 to 1.23) but not in peripheral blood (SMD\u202f=\u202f0.18, 95% CI: \u22120.13 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\u202f=\u202f1.07, 95% CI: 1.01\u20131.13).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      The systematic review was prospectively registered in PROSPERO (Unique Identifier: CRD420261386903),\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1899745","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:42:43Z","timestamp":1790833363000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating and cerebrospinal fluid soluble TREM2 levels and risk of perioperative neurocognitive disorders in surgical patients: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"18","author":[{"given":"Haotian","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Beijing Tsinghua Changgung Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical Data Science Center, Beijing Tsinghua Changgung Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifeng","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Beijing Tsinghua Changgung Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Beijing Tsinghua Changgung Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.ebiom.2018.10.021","article-title":"Surgery, neuroinflammation and cognitive impairment","volume":"37","author":"Alam","year":"2018","journal-title":"EBioMedicine"},{"key":"ref2","author":"Cheng","year":"2022"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1002\/ana.22082","article-title":"Role of interleukin-1beta in postoperative cognitive dysfunction","volume":"68","author":"Cibelli","year":"2010","journal-title":"Ann. 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