Table_1_Correlation of Serum BACE1 With Emergence Delirium in Postoperative Patients: A Preliminary Study.DOCX

Background: The mechanism underlying delirium, a common acute fluctuating mental state, may be related to the activation of a neuroinflammatory response. In this study, we attempted to investigate whether plasma inflammatory response markers, vascular and cerebrovascular injury-related markers, and neurodegeneration-associated markers were associated with emergence delirium (ED).
Methods: Patients aged 50 years or above who underwent elective laparoscopic surgery under general anesthesia were included in this study. Delirium was assessed postoperatively with the Richmond Agitation Sedation Scale (RASS) and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) scale. Plasma samples were collected from ED patients and non-ED patients to test concentrations of inflammation markers, including interleukin 6 (IL-6), chitinase 3-like 1 (CHI3L1), S100 calcium-binding protein B (S100B), lipoprotein-associated phospholipase-A2 (Lp-PLA2), and macrophage migration inhibitory factor (MIF); vascular and cerebrovascular injury-related markers, including intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1); and neurodegeneration-associated markers, including alpha-synuclein (α-Syn) and β-secretase 1 (BACE1). Binary logistic regression analysis was performed to analyze the relationship between biomarkers and ED, and receiver operating characteristic (ROC) curves were used to analyze the diagnostic value of biomarkers.
Results: A total of 104 patients were included in this study, with an average age of 63.69 ± 7.21. IL-6 (OR = 2.73, 95% CI: 1.66–6.44, P = 0.022), S100B (OR = 4.74, 95% CI: 1.88–11.95, P = 0.001), and BACE1 (OR = 6.54, 95% CI: 2.57–16.65, P < 0.000) were independent biological indicators for the occurrence of ED.CHI3L1, Lp-PLA2, MIF, ICAM-1, VCAM-1, and α-Syn were unrelated to ED. Plasma BACE1 level had a possible diagnostic value for ED [area under curve (AUC) = 0.75, 95% CI: 0.66–0.85], whereas plasma IL-6 (AUC = 0.62, 95% CI: 0.51–0.73) and S100B (AUC = 0.65, 95% CI: 0.54–0.76) levels had little diagnostic value for distinguishing ED vs. non-ED.
Conclusion: Higher levels of systemic inflammation marker IL-6, cerebral inflammation marker S100B, and neurodegeneration-associated marker BACE1 are related to ED. Plasma BACE1 may be a potential diagnostic biomarker for ED.

背景：谵妄是一种常见的急性波动性精神状态，其潜在发病机制可能与神经炎症反应激活相关。本研究旨在探讨血浆炎症反应标志物、血管及脑血管损伤相关标志物、神经退行性变相关标志物是否与苏醒期谵妄（emergence delirium, ED）相关。

方法：本研究纳入50岁及以上、接受全身麻醉下择期腹腔镜手术的患者。术后采用里奇蒙德躁动镇静量表（Richmond Agitation Sedation Scale, RASS）及重症监护病房意识模糊评估法（Confusion Assessment Method for the Intensive Care Unit, CAM-ICU）对谵妄进行评估。采集苏醒期谵妄患者与非苏醒期谵妄患者的血浆样本，检测以下标志物浓度：炎症标志物，包括白细胞介素6（interleukin 6, IL-6）、几丁质酶3样蛋白1（chitinase 3-like 1, CHI3L1）、S100钙结合蛋白B（S100 calcium-binding protein B, S100B）、脂蛋白相关磷脂酶A2（lipoprotein-associated phospholipase-A2, Lp-PLA2）及巨噬细胞移动抑制因子（macrophage migration inhibitory factor, MIF）；血管及脑血管损伤相关标志物，包括细胞间黏附分子1（intercellular cell adhesion molecule-1, ICAM-1）及血管细胞黏附分子（vascular cell adhesion molecule, VCAM-1）；神经退行性变相关标志物，包括α-突触核蛋白（alpha-synuclein, α-Syn）及β-分泌酶1（β-secretase 1, BACE1）。采用二元logistic回归分析探讨生物标志物与苏醒期谵妄的关联，并通过受试者工作特征（receiver operating characteristic, ROC）曲线分析生物标志物的诊断价值。

结果：本研究共纳入104例患者，平均年龄为63.69±7.21岁。白细胞介素6（OR=2.73，95%CI：1.66~6.44，P=0.022）、S100钙结合蛋白B（OR=4.74，95%CI：1.88~11.95，P=0.001）及β-分泌酶1（OR=6.54，95%CI：2.57~16.65，P<0.000）是苏醒期谵妄发生的独立生物标志物。几丁质酶3样蛋白1、脂蛋白相关磷脂酶A2、巨噬细胞移动抑制因子、细胞间黏附分子1、血管细胞黏附分子及α-突触核蛋白与苏醒期谵妄无关联。血浆β-分泌酶1水平对苏醒期谵妄具有一定诊断价值[曲线下面积（area under curve, AUC）=0.75，95%CI：0.66~0.85]，而血浆白细胞介素6（AUC=0.62，95%CI：0.51~0.73）与S100钙结合蛋白B（AUC=0.65，95%CI：0.54~0.76）水平在区分苏醒期谵妄患者与非苏醒期谵妄患者时诊断价值有限。

结论：全身炎症标志物白细胞介素6、脑炎症标志物S100钙结合蛋白B及神经退行性变相关标志物β-分泌酶1的水平升高与苏醒期谵妄相关。血浆β-分泌酶1可能成为苏醒期谵妄潜在的诊断生物标志物。