Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Harvard Medical School, Boston, Massachusetts, USA.
J Gerontol A Biol Sci Med Sci. 2022 Mar 3;77(3):484-493. doi: 10.1093/gerona/glaa326.
Delirium (an acute change in cognition) is a common, morbid, and costly syndrome seen primarily in aging adults. Despite increasing knowledge of its epidemiology, delirium remains a clinical diagnosis with no established biomarkers to guide diagnosis or management. Advances in proteomics now provide opportunities to identify novel markers of risk and disease progression for postoperative delirium and its associated long-term consequences (eg, long-term cognitive decline and Alzheimer's disease [AD]).
In a nested matched case-control study (18 delirium/no-delirium pairs) within the Successful Aging after Elective Surgery study (N = 556), we evaluated the association of 1305 plasma proteins preoperatively [PREOP] and on postoperative day 2 [POD2]) with delirium using SOMAscan. Generalized linear models were applied to enzyme-linked immunosorbant assay (ELISA) validation data of one protein across the full cohort. Multi-protein modeling included delirium biomarkers identified in prior work (C-reactive protein, interleukin-6 [IL6]).
We identified chitinase-3-like-protein-1 (CHI3L1/YKL-40) as the sole delirium-associated protein in both a PREOP and a POD2 predictor model, a finding confirmed by ELISA. Multi-protein modeling found high PREOP CHI3L1/YKL-40 and POD2 IL6 increased the risk of delirium (relative risk [95% confidence interval] Quartile [Q]4 vs Q1: 2.4[1.2-5.0] and 2.1[1.1-4.1], respectively).
Our identification of CHI3L1/YKL-40 in postoperative delirium parallels reports of CHI3L1/YKL-40 and its association with aging, mortality, and age-related conditions including AD onset and progression. This highlights the type 2 innate immune response, involving CHI3L1/YKL-40, as an underlying mechanism of postoperative delirium, a common, morbid, and costly syndrome that threatens the independence of older adults.
谵妄（认知的急性改变）是一种主要发生在老年人群中的常见、病态且昂贵的综合征。尽管对其流行病学的了解不断增加，但谵妄仍然是一种临床诊断，没有确定的生物标志物来指导诊断或管理。蛋白质组学的进步现在为识别术后谵妄及其相关长期后果（例如，长期认知能力下降和阿尔茨海默病[AD]）的风险和疾病进展的新标志物提供了机会。
在“选择性手术后成功老龄化研究”（N=556）的嵌套匹配病例对照研究（18 例谵妄/无谵妄对）中，我们使用 SOMAscan 评估了术前[PREOP]和术后第 2 天[POD2]的 1305 种血浆蛋白与谵妄的关联。广义线性模型应用于整个队列中单蛋白的酶联免疫吸附试验（ELISA）验证数据。多蛋白模型包括以前工作中确定的谵妄生物标志物（C 反应蛋白、白细胞介素 6 [IL6]）。
我们发现几丁质酶 3 样蛋白 1（CHI3L1/YKL-40）是 PREOP 和 POD2 预测模型中唯一与谵妄相关的蛋白，这一发现通过 ELISA 得到了证实。多蛋白模型发现，高 PREOP CHI3L1/YKL-40 和 POD2 IL6 增加了谵妄的风险（相对风险[95%置信区间]四分位数[Q]4 与 Q1：2.4[1.2-5.0]和 2.1[1.1-4.1]）。
我们在术后谵妄中发现 CHI3L1/YKL-40 的结果与 CHI3L1/YKL-40 的报告以及它与衰老、死亡率和与年龄相关的疾病（包括 AD 发病和进展）的关联相吻合。这突出了涉及 CHI3L1/YKL-40 的 2 型固有免疫反应作为术后谵妄的潜在机制，术后谵妄是一种常见、病态且昂贵的综合征，威胁着老年人的独立性。
