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术后谵妄的干预措施:生物标志物-3 研究中血浆淀粉样蛋白-β与术后谵妄的前瞻性分析。

Prospective analysis of plasma amyloid beta and postoperative delirium in the Interventions for Postoperative Delirium: Biomarker-3 study.

机构信息

Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Anaesthetics, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, NSW, Australia.

Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.

出版信息

Br J Anaesth. 2023 May;130(5):546-556. doi: 10.1016/j.bja.2023.01.020. Epub 2023 Feb 25.

Abstract

BACKGROUND

The effect of postoperative delirium on the amyloid cascade of Alzheimer's dementia is poorly understood. Using early postoperative plasma biomarkers, we explored whether surgery and delirium are associated with changes in amyloid pathways.

METHODS

We analysed data from 100 participants in the Interventions for Postoperative Delirium: Biomarker-3 (IPOD-B3) cohort study in the USA (NCT03124303 and NCT01980511), which recruited participants aged >65 yr undergoing non-intracranial surgery. We assessed the relationship between the change in plasma amyloid beta ratio (AβR; Aβ42:Aβ40) and delirium incidence (defined by the 3-Minute Diagnostic Confusion Assessment Method) and severity (quantified by the Delirium Rating Scale-Revised-98, the study's primary outcome). We also tested the relationship between plasma amyloid beta and intraoperative variables.

RESULTS

Across all participants, the plasma AβR increased from the preoperative period to postoperative Day 1 (Wilcoxon P<0.001). However, this increase was not associated with delirium incidence (Wilcoxon P=0.22) or peak severity after adjusting for confounders (log[incidence rate ratio]=0.43; P=0.14). Postoperative Day 1 change in plasma AβR was not associated with postoperative Day 1 change in plasma tau, neurofilament light, or inflammatory markers (interleukin [IL]-1β, IL-1Ra, IL-2, IL-4, IL-6, IL-8, IL-10, and IL-12), or with operative time or low intraoperative arterial pressure.

CONCLUSIONS

Perioperative changes in plasma amyloid do not appear to be associated with postoperative delirium. Our findings do not support associations of dynamic changes in amyloid with postoperative delirium.

CLINICAL TRIAL REGISTRATION

.NCT03124303 and NCT01980511.

摘要

背景

术后谵妄对阿尔茨海默病淀粉样蛋白级联的影响知之甚少。我们使用术后早期的血浆生物标志物来探索手术和谵妄是否与淀粉样蛋白途径的变化有关。

方法

我们分析了美国干预术后谵妄:生物标志物-3(IPOD-B3)队列研究中的 100 名参与者的数据(NCT03124303 和 NCT01980511),该研究招募了年龄>65 岁接受非颅内手术的参与者。我们评估了血浆淀粉样蛋白β比值(AβR;Aβ42:Aβ40)变化与谵妄发生率(由 3 分钟诊断性混淆评估方法定义)和严重程度(由谵妄评定量表修订版-98 量化,作为研究的主要结果)之间的关系。我们还测试了血浆淀粉样蛋白β与术中变量之间的关系。

结果

在所有参与者中,血浆 AβR 从术前阶段到术后第 1 天增加(Wilcoxon P<0.001)。然而,在调整混杂因素后,这种增加与谵妄发生率(Wilcoxon P=0.22)或峰值严重程度无关(对数[发生率比]=0.43;P=0.14)。术后第 1 天的血浆 AβR 变化与术后第 1 天的血浆 tau、神经丝轻链或炎症标志物(白细胞介素[IL]-1β、IL-1Ra、IL-2、IL-4、IL-6、IL-8、IL-10 和 IL-12)的变化无关,也与手术时间或术中低动脉压无关。

结论

围手术期血浆淀粉样蛋白的变化似乎与术后谵妄无关。我们的研究结果不支持淀粉样蛋白动态变化与术后谵妄之间的关联。

临床试验注册

NCT03124303 和 NCT01980511。

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