【原】【罂粟摘要】血浆τ蛋白与术后谵妄发生率和严重程度的关系：一项前瞻性观察研究

血浆τ蛋白与术后谵妄发生率和严重程度的关系：一项前瞻性观察研究

贵州医科大学 高鸿教授课题组

翻译：牛振瑛    编辑：佟睿    审校：曹莹

背景

术后谵妄与神经细胞损伤生物标记物——神经原纤维素(NFL)的增加有关。本研究验证了另外两个生物标志物，胶质纤维酸性蛋白(GFAP：一种在星形胶质细胞中表达的中间丝蛋白)和tau（τ蛋白：一种微管相关蛋白，它调节轴突微管的稳定性）是否与术后谵妄有关。

方法

共对招募到的114名外科患者评估术后谵妄的严重程度和发病率。采集血浆样本进行生物标志物分析，包括τ蛋白、NfL和GFAP，以及10种细胞因子。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，我们确定了炎症标志物白介素-8（IL-8）的先验值。

结果

GFAP浓度与谵妄无关。从术前到术后第1天谵妄患者血浆τ蛋白的浓度的变化更大（P<0.001），且与谵妄严重程度相关（r=0.39，P<0.001）。血浆τ蛋白的变化与IL-8(P<0.001)和IL-10(P=0.0029)的升高呈正相关。线性回归分析显示，与血浆τ蛋白变化相关的临床预测因素为年龄(P=0.037)、卒中/短暂性脑缺血发作史(P<0.001)和手术出血量(P<0.001)。在线性混合效应模型中，只有τ蛋白(而不是nfl或IL-8)可以预测术后谵妄的恢复(P<0.001)。在调整了年龄、性别、术前认知和IL-8的变化后，血浆τ蛋白仍然与谵妄的严重程度显著相关(P=0.026)。

结论

血浆τ蛋白的变化与术后谵妄的发生率和严重程度有关，并随着时间的推移而缓解。这一围手术期神经元损伤生物标志物对长期认知功能的影响值得进一步研究。

原始文献来源

Ballweg T, et al.Association between plasma tau and postoperative delirium incidence and severity: a prospective observational study[J].  Br J Anaesth. 2021 Feb;126(2):458-466.  doi: 10.1016/j.bja.2020.08.061.

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

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 (r=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.

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