Postoperative Delirium and Neurocognitive Disorders Associated With Inflammatory and Neuronal Injury Biomarkers: A Prospective, Longitudinal, Cohort Study.

Abstract

Older adults undergoing surgery frequently experience postoperative delirium and postoperative neurocognitive disorders (NCD), but the neuropathophysiology of these conditions remains obscure. A postoperative inflammatory cascade with subsequent neuronal injury is one theory that requires further investigation. We report the incidence of delirium and postoperative NCD using updated nomenclature and investigate changes in inflammatory and neuronal injury biomarkers associated with these conditions. We performed a prospective, longitudinal, cohort study with older adults aged 60 years or more undergoing major elective noncardiac surgery. Patients completed cognitive assessments preoperatively and at 3 and 28 months postoperatively, alongside twice-daily delirium assessments during hospital admission. Plasma was obtained before surgical incision and at 30 minutes, 6, 24, and 48 hours postoperatively and assayed for cytokines (interleukin [IL]-6, IL-10, IL-18, tumor necrosis factor [TNF]α) and neuronal injury markers (neurofilament light [NfL], total Tau, and pTau181). We enrolled 79 patients (mean age: 69 [standard deviation {SD}: 6.5]; female: 45.6%). Thirteen patients (15.2%) experienced postoperative delirium. At 3 months, 18 of 63 (28.6%) had postoperative NCD, and at long-term follow-up, 17 of 46 (37.0%) had NCD. IL-6, IL-10, total Tau, p-Tau181, and NfL levels were 10.3, 1.9, 1.3, 1.2, and 1.6 times higher at 48 hours postsurgery compared to baseline (all P <.05). IL-18 levels were 1.1 times lower. TNFα remained unchanged. Linear mixed-effects models revealed that greater elevations in IL-6 levels were associated with increased delirium risk (β = 22.23, standard error {SE} = 9.48, P =.02) and long-term NCD (β = 12.46, SE = 6.02, P =.04). Using updated nomenclature, postoperative delirium and postoperative NCD affect a third of surgical patients and inflammatory and neuronal injury markers are elevated after surgical intervention. Increases in IL-6 and pTau181 at the time of surgery are associated with postoperative delirium; increases in IL-6 are also associated with long-term NCD. Specific biomarkers follow unique time courses after anesthesia and surgery.