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

Abstract

Postoperative delirium (POD) following cardiac surgery is a severe complication. 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 (p < 0.001). Preoperative IL-6 and p-tau181 levels independently predicted POD [IL-6: area under the curve (AUC) = 0.605, p < 0.005; p-tau181: AUC = 0.641, p < 0.0001)]. 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, p < 0.0001) 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 = 0.672, p < 0.0001; validation data: AUC = 0.642, p < 0.05). The LASSO regression showed an increased AUC in the training (0.751, p < 0.0001) and validation dataset (0.652, p < 0.05). 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.