Background: The number of elective surgeries for older individuals is on the rise globally. Machine learning may improve risk assessment with impact on surgical planning and postoperative care. Preoperative cognitive assessment may facilitate early identification of postoperative delirium (POD). This study aim to estimate the predictive ability of machine learning models for POD using pre- and/or perioperative features, with a specific focus on adding neuropsychological assessments prior to surgery. Materials and Methods: This retrospective cohort study analyzed data from the multicenter PAWEL study and its PAWEL-R substudy, encompassing older patients (≥70 years) undergoing elective surgeries across five medical centers from July 2017 to April 2019. A total of 1624 patients were included, with POD diagnosis made before discharge. Data included demographics, clinical, surgical, and neuropsychological features collected pre- and perioperatively. Machine learning model performance was evaluated using the area under the receiver operating characteristic curve (AUC), with permutation testing for significance and SHapley Additive exPlanations (SHAP) for effective neuropsychological assessments identification. Results: In this cohort of 1624 patients, 52.3% (N=850) were male, with a mean [SD] age of 77.9 [4.9] years. Predicting POD before surgery using demographic, clinical, surgical, and neuropsychological features achieved an AUC of 0.79. Incorporating all pre- and perioperative features into the model yielded a slightly higher AUC of 0.82, with no significant difference observed (P= .19). Notably, cognitive factors alone were not strong predictors (AUC=0.61). However, specific tests within neuropsychological assessments, such as the Montreal Cognitive Assessment memory subdomain and Trail Making Test Part B, were found to be crucial for prediction according to SHAP analysis. Conclusion and Relevance: Preoperative risk prediction for POD can increase risk awareness in presurgical assessment and improve postoperative management in patients with a high risk for delirium.

CT received honoraria from serving on the scientific advisory board of Roche, a research grant from the gemeinsame Bundesausschuss der Krankenkassen and has received funding for travel and speaker honoraria from several hospitals for scientific education. GWE has nothing to disclosure. CAFvA received honoraria from serving on the scientific advisory board of Biogen, Roche, Novo Nordisk, Biontech, MindAhead UG and Dr. Willmar Schwabe GmbH &Co. KG and has received funding for travel and speaker honoraria from Lilly, Biogen, Roche diagnostics AG, Novartis, Medical Tribune Verlagsgesellschaft mbH, Landesvereinigung fuer Gesundheit und Akademie fuer Sozialmedizin Niedersachsen e. V., FomF GmbH | Forum fuer medizinische Fortbildung and Dr. Willmar Schwabe GmbH &Co. KG and has received research support from Roche diagnostics AG.

This work was supported by grant VF1_2016-201 from the Innovationsfonds (fund of the Gemeinsamer Bundesausschuss, GBA) as well as the German Research Foundation (DFG) Emmy Noether with reference 513851350 (TW) and the Cluster of Excellence with reference 390727645 (TW). This work was supported by the BMBF-funded de.NBI Cloud within the German Network for Bioinformatics Infrastructure (de.NBI) (031A532B, 031A533A, 031A533B, 031A534A, 031A535A, 031A537A, 031A537B, 031A537C, 031A537D, 031A538A).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was approved by ethical votes under the PAWEL-R study (Patientensicherheit, Wirtschaftlichkeit und Lebensqualitaet bei elektiven Operationen, English: Patient safety, Efficiency and Life quality in elective surgery, R for risk, DRKS-ID: DRKS00012797), and ethical approval (Ethical Committee 233/2017BO1) was provided by the Ethical Committee of Tuebingen University Hospitals, Tuebingen, Germany on 06 June 2017.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

The data can be requested by addressing the PAWEL consortium.