Association between plasma tau and postoperative delirium incidence and severity: a prospective observational study

Abstract

Background: Postoperative delirium is associated with increases in the neuronal injury biomarker, neurofilament light (NfL). Here we tested whether two other biomarkers, glial fibrillary acidic protein (GFAP) and tau, are associated with postoperative delirium.

Methods: A total of 114 surgical patients were recruited into two prospective biomarker cohort studies with assessment of delirium severity and incidence. Plasma samples were sent for biomarker analysis including tau, NfL, and GFAP, and a panel of 10 cytokines. We determined a priori to adjust for interleukin-8 (IL-8), a marker of inflammation, when assessing associations between biomarkers and delirium incidence and severity.

Results: GFAP concentrations showed no relationship to delirium. The change in tau from preoperative concentrations to postoperative Day 1 was greater in patients with postoperative delirium (P<0.001) and correlated with delirium severity (ρ=0.39, P<0.001). The change in tau correlated with increases in IL-8 (P<0.001) and IL-10 (P=0.0029). Linear regression showed that the relevant clinical predictors of tau changes were age (P=0.037), prior stroke/transient ischaemic attack (P=0.001), and surgical blood loss (P<0.001). After adjusting for age, sex, preoperative cognition, and change in IL-8, tau remained significantly associated with delirium severity (P=0.026). Using linear mixed effect models, only tau (not NfL or IL-8) predicted recovery from delirium (P<0.001).

Conclusions: The change in plasma tau was associated with delirium incidence and severity, and resolved over time in parallel with delirium features. The impact of this putative perioperative neuronal injury biomarker on long-term cognition merits further investigation.

Clinical trial registration: NCT02926417 and NCT03124303.

Keywords: biomarker; delirium; glial fibrillary acidic protein; inflammation; neuronal injury; postoperative; surgery; tau.

Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Figures

Fig 1

Perioperative time course of GFAP and tau divided by delirium status. GFAP and tau, from the preoperative visit through the fourth postoperative day are plotted by whether patients were delirious postoperatively or not. Tau and GFAP were normalised by log10-transforming the postoperative value and the baseline value, and then subtracting the transformed baseline value from the transformed postoperative value. n=114. GFAP, glial fibrillary acidic protein; Post-op, postoperative.

Fig 2

Receiver operating curves for classifying delirium. Postoperative Day 1 (POD1) values were used for all biomarkers. Empirical receiver operating characteristic (ROC) curves were generated by calculating the true positive rates (TPR) and false positive rates (FPR) using each observed value of a biomarker as a classification threshold. Prediction performance was assessed using the area under the ROC (AUROC) and statistically tested against chance performance (0.5) using a two-tailed Z-test as described for GraphPad Prism 8.0. The sample sizes for each plot are: (a) and (b): n=107, (c): n=108, and (d): n=104. Six patients are missing POD1 biomarker data as a result of surgery not being completed (n=3) or blood sample not being collected (n=3). For plots (a), (b), and (d), additional patients are missing because of a sample processing error resulting in incomplete/invalid assay runs. GFAP, glial fibrillary acidic protein; IL-8, interleukin-8; NfL, neurofilament light.

Fig 3

Correlations of preoperative-POD1 change in tau or GFAP with peak delirium severity. Plots show the difference between log10-transformed preoperative and log10-transformed POD1 concentrations of tau or GFAP vs the highest delirium severity recorded postoperatively as measured by the Delirium Rating Scale-98. The plots are colour-coded by whether patients were delirious postoperatively. Spearman's rank correlation rho and P-value for the tau plot are ρ=0.39, P<0.001, and for the GFAP plot are ρ=0.13, P=0.20. N=103. Four patients are missing preoperative biomarker data as a result of a blood sample not being collected preoperatively. Seven patients are missing POD1 biomarker data as a result of a blood sample not being collected on POD1 (n=3), surgery not being completed (n=3), or because of a sample processing error resulting in incomplete/invalid assay runs (n=1). DRS, Delirium Rating Scale-98 score; GFAP, glial fibrillary acidic protein; POD1, postoperative Day 1.