Department of Anesthesiology, University of Wisconsin, Madison, WI, USA.
Department of Medicine, Indiana University School of Medicine, Center for Aging Research, Center for Health Innovation and Implementation, Indianapolis, IN, USA.
Br J Anaesth. 2021 Feb;126(2):458-466. doi: 10.1016/j.bja.2020.08.061. Epub 2020 Nov 20.
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.
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.
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).
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.
NCT02926417 and NCT03124303.
术后谵妄与神经元损伤生物标志物神经丝轻链（NfL）的增加有关。在这里，我们测试了另外两种生物标志物，胶质纤维酸性蛋白（GFAP）和 tau，是否与术后谵妄有关。
共招募了 114 名手术患者，进行了两项前瞻性生物标志物队列研究，评估了谵妄严重程度和发生率。采集血浆样本进行生物标志物分析，包括 tau、NfL 和 GFAP，以及 10 种细胞因子的检测。我们预先确定，在评估生物标志物与谵妄发生率和严重程度之间的关系时，调整白细胞介素 8（IL-8），一种炎症标志物。
GFAP 浓度与谵妄无关。术后第 1 天从术前浓度到术后浓度的 tau 变化在术后谵妄患者中更大（P<0.001），与谵妄严重程度相关（ρ=0.39，P<0.001）。tau 的变化与白细胞介素 8（P<0.001）和白细胞介素 10（P=0.0029）的增加相关。线性回归显示，tau 变化的相关临床预测因素是年龄（P=0.037）、既往卒中/短暂性脑缺血发作（P=0.001）和手术失血量（P<0.001）。在调整年龄、性别、术前认知和白细胞介素 8 变化后，tau 与谵妄严重程度仍显著相关（P=0.026）。使用线性混合效应模型，只有 tau（而非 NfL 或白细胞介素 8）预测谵妄的恢复（P<0.001）。
血浆 tau 的变化与谵妄的发生率和严重程度相关，并随着时间的推移与谵妄的特征同时恢复。这种潜在的围手术期神经元损伤生物标志物对长期认知的影响值得进一步研究。
NCT02926417 和 NCT03124303。
