Post-Operative Cognitive Decline
Postoperative cognitive decline (POCD) is the predominant complication affecting elderly patients following major surgery, yet its prediction and prevention remain challenging. Understanding POCD’s underlying biological processes is essential for identifying mechanistic biomarkers to advance diagnostics and therapeutics. This prospective, longitudinal study involving 26 elderly patients undergoing orthopedic surgery aimed to comprehensively characterize the impact of perioperative peripheral immune cell trajectories on POCD. Unsupervised analysis of single-cell mass cytometry immunological data highlighted early JAK/STAT signaling exacerbation and diminished MyD88 signaling post-surgery in patients who later developed POCD. Further analyses integrating preoperative single-cell and plasma proteomics with clinical data yielded a sparse predictive model that accurately identified patients who would develop POCD (AUC = 0.80, p = 2x10-2, U-test). The resulting POCD immune signature included one plasma and ten single-cell proteomic features, offering a concise list of biomarker candidates for developing point-of-care prognostic tests to personalize perioperative care for at-risk patients