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There is evidence of a link between neuroinflammation and neurodegeneration in POD. We investigated the preoperative proinflammatory interleukin-6 (IL-6) and neuronal damage marker phosphorylated tau protein 181 (p-tau181) to POD while considering preoperative heart-brain axis related factors. The prospective FINd DElirium RIsk factors (FINDERI) is an observational study in patients undergoing cardiac surgery. Biomarkers IL-6 and p-tau181 were measured in blood samples. For statistics, we utilized multiple logistic regression analyses and advanced machine learning techniques. In 491 patients, 106 (21.6%) developed POD. The age of patients with POD was significantly higher than that of patients without POD (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Preoperative IL-6 and p-tau181 levels independently predicted POD [IL-6: area under the curve (AUC)\u2009=\u20090.605,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.005; p-tau181: AUC\u2009=\u20090.641,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001)]. A multiple logistic regression analysis of preoperative log-transformed biomarkers levels (p-tau181, IL-6), female sex and cognitive performance increased the AUC (0.710,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) in predicting POD. We created a decision tree prediction model including preoperative p-tau181, IL-6, and the severity of mitral valve disease (training data: AUC\u2009=\u20090.672,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001; validation data: AUC\u2009=\u20090.642,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). The LASSO regression showed an increased AUC in the training (0.751,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) and validation dataset (0.652,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Our results demonstrate that the combined assessment of preoperatively measured p-tau181 and IL-6, preoperative mitral valve disease, cognitive performance and female sex, significantly predicts POD. These findings provide evidence that neuroinflammation and neuronal cell damage are associated with POD.\n                  <\/jats:p>","DOI":"10.1038\/s41380-025-03412-3","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T13:35:13Z","timestamp":1766410513000},"page":"2509-2519","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Prediction of postoperative delirium after cardiac surgery by the interplay between preoperative plasma p-tau181 and IL-6 and heart-brain axis related factors: results from the prospective observational study FINDERI"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5785-9594","authenticated-orcid":false,"given":"Niels","family":"Hansen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara Maria","family":"Knopp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5484-9710","authenticated-orcid":false,"given":"Hermann","family":"Esselmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0547-2851","authenticated-orcid":false,"given":"Christopher M.","family":"Celano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9542-4647","authenticated-orcid":false,"given":"Carlotta","family":"Derad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Asendorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Chebbok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3937-5956","authenticated-orcid":false,"given":"Stephanie","family":"Heinemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihtzaz","family":"Malik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Morgado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilda-Marie","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"G\u00fcnther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iryna","family":"Krasiuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Packro\u00df","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina Isabel","family":"Rediske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas Paul","family":"S\u00fcttmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Titsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Kutschka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassina","family":"Baraki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1492-5330","authenticated-orcid":false,"given":"Jens","family":"Wiltfang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8614-2223","authenticated-orcid":false,"given":"Christine A. 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Reference 53 was mistakenly removed from the reference list, although this was not requested in our responses or correction files. Only citation (53) in the main text was to be deleted. To correct this, the supplementary material has been revised. Reference 53 has been reinstated as a written source for Supplementary Table 7.","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"CMC has received funding from the National Heart, Lung, and Blood Institute (grant R01HL155301) and stipends from Elsevier for editorial work for General Hospital Psychiatry. JW has served at scientific advisory boards for Abbot, Biogen, Boehringer-Ingelheim, Eli Lilly, F. Hoffmann-La Roche, Immunogenetics, MSD SHARP & DOHME, he has also received honorarium for lectures sponsored by Eli Lilly, Pfizer, Janssen, MSD SHARP & DOHME, Amgen, Roche Pharma, Actelion Pharmaceuticals, Guangzhou Glorylen Medical Technology Co. (China), Beijing Yibai Science and Technology Ltd. CAFvA has received honoraria from serving on the scientific advisory board of Biogen, Roche, Lilly and Dr. Willmar Schwabe GmbH &Co. CAFvA has also received funding for travel and speaker honoraria from Biogen, Roche diagnostics AG, Novo Nordisk, MedTrixGmbH, Landesvereinigung f\u00fcr Gesundheit und Akademie f\u00fcr Sozialmedizin Niedersachsen e. V., Medical Tribune Verlagsgesellschaft mbH, Novartis, FomF GmbH, Paracelsus\u2013Kliniken Deutschland, Sch\u00f6n Klinik Bad Aibling and Dr. Willmar Schwabe GmbH &Co. NH has received funding support from the DFG (project number 5302297989) and receives travel support from Eli Lilly and Company. MS, HE, CD, TA, MC, SH, AW, JS, FEB, JE, IG, HB report no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The study protocol was approved by the Ethics Committee of the University of G\u00f6ttingen Medical Center on February 16, 2021 (#20\/11\/20). Written informed consent is obtained from each participant before any trial\u2011related procedures are performed and patients receive a copy of the signed and dated written consent form. All methods were performed in accordance with the relevant guidelines and regulations.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consents to participate"}}]}}