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老年人大脑脊髓液中阿尔茨海默病生物标志物与术后谵妄的关联

Association of CSF Alzheimer's disease biomarkers with postoperative delirium in older adults.

作者信息

Fong Tamara G, Vasunilashorn Sarinnapha M, Gou Yun, Libermann Towia A, Dillon Simon, Schmitt Eva, Arnold Steven E, Kivisäkk Pia, Carlyle Becky, Oh Esther S, Vlassakov Kamen, Kunze Lisa, Hshieh Tammy, Jones Richard N, Marcantonio Edward R, Inouye Sharon K

机构信息

Department of Neurology Beth Israel Deaconess Medical Center Boston Massachusetts USA.

Aging Brain Center, Institute for Aging Research Hebrew SeniorLife Boston Massachusetts USA.

出版信息

Alzheimers Dement (N Y). 2021 Mar 17;7(1):e12125. doi: 10.1002/trc2.12125. eCollection 2021.

Abstract

INTRODUCTION

The interaction between delirium and dementia is complex. We examined if Alzheimer's disease (AD) biomarkers in patients without clinical dementia are associated with increased risk of postoperative delirium, and whether AD biomarkers demonstrate a graded association with delirium severity.

METHODS

Participants ( = 59) were free of clinical dementia, age 70 years, and scheduled for elective total knee or hip arthroplasties. Cerebrospinal fluid (CSF) was collected at the time of induction for spinal anesthesia. CSF AD biomarkers were measured by enzyme-linked immunosorbent assay (ELISA) (ADX/Euroimmun); cut points for amyloid, tau, and neurodegeneration (ATN) biomarker status were  = amyloid beta (Aβ) <175 pg/mL or Aβ ratio <0.07;  = p-tau >80 pg/mL; and  = t-tau >700 pg/mL. Confusion Assessment Method (CAM) and CAM-Severity (CAM-S) were rated daily post-operatively for delirium and delirium severity, respectively.

RESULTS

Aβ, tau, and p-tau mean pg/mL (SD) were 361.5 (326.1), 618.3 (237.1), and 97.1 (66.1), respectively, for those with delirium, and 550.4 (291.6), 518.3 (213.5), and 54.6 (34.5), respectively, for those without delirium. Thirteen participants (22%) were ATN positive. Delirium severity by peak CAM-S [mean difference (95% confidence interval)] was 1.48 points higher (0.29-2.67),  = 0.02 among the ATN positive. Delirium in the ATN-positive group trended toward but did not reach statistical significance (23% vs. 7%, p = 0.10). Peak CAM-S [mean (SD)] in the delirium group was 7 (2.8) compared to no delirium group 2.5 (1.3), but when groups were further classified by ATN status, an incremental effect on delirium severity was observed, such that patients who were both ATN and delirium negative had the lowest mean (SD) peak CAM-S scores of 2.5 (1.3) points, whereas those who were ATN and delirium positive had CAM-S scores of 8.7 (2.3) points; other groups (either ATN or delirium positive) had intermediate CAM-S scores.

DISCUSSION

The presence of AD biomarkers adds important information in predicting delirium severity. Future studies are needed to confirm this relationship and to better understand the role of AD biomarkers, even in pre-clinical phase, in delirium.

摘要

引言

谵妄与痴呆之间的相互作用很复杂。我们研究了无临床痴呆患者的阿尔茨海默病(AD)生物标志物是否与术后谵妄风险增加相关,以及AD生物标志物是否与谵妄严重程度呈分级关联。

方法

参与者(n = 59)无临床痴呆,年龄≥70岁,计划进行择期全膝关节或髋关节置换术。在脊髓麻醉诱导时收集脑脊液(CSF)。通过酶联免疫吸附测定(ELISA)(ADX/欧蒙免疫)测量脑脊液AD生物标志物;淀粉样蛋白、tau蛋白和神经退行性变(ATN)生物标志物状态的切点分别为:淀粉样β蛋白(Aβ)<175 pg/mL或Aβ比值<0.07;磷酸化tau蛋白(p-tau)>80 pg/mL;总tau蛋白(t-tau)>700 pg/mL。术后每天分别使用谵妄评定法(CAM)和CAM严重程度量表(CAM-S)对谵妄和谵妄严重程度进行评分。

结果

发生谵妄者的Aβ平均pg/mL(标准差)为361.5(326.1)、tau蛋白为618.3(237.1)、p-tau蛋白为97.1(66.1),未发生谵妄者分别为550.4(291.6)、518.3(213.5)和54.6(34.5)。13名参与者(22%)ATN呈阳性。ATN阳性者谵妄严重程度的峰值CAM-S[平均差异(95%置信区间)]高1.48分(0.29 - 2.67),P = 0.02。ATN阳性组的谵妄发生率呈上升趋势但未达到统计学意义(23% 对 7%,P = 0.10)。谵妄组的峰值CAM-S[平均值(标准差)]为7(2.8),而无谵妄组为2.5(1.3),但当根据ATN状态对组进行进一步分类时,观察到对谵妄严重程度有递增效应,即ATN和谵妄均为阴性的患者平均(标准差)峰值CAM-S得分最低,为2.5(1.3)分,而ATN和谵妄均为阳性的患者CAM-S得分为8.7(2.3)分;其他组(ATN或谵妄阳性)的CAM-S得分居中。

讨论

AD生物标志物的存在为预测谵妄严重程度增添了重要信息。未来需要开展研究以证实这种关系,并更好地理解AD生物标志物即使在临床前期在谵妄中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c277/7968120/b383c64042ed/TRC2-7-e12125-g001.jpg

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