• Sarinnapha M Vasunilashorn, Simon T Dillon, Noel Y Chan, Tamara G Fong, Marie Joseph, Bridget Tripp, Zhongcong Xie, Long H Ngo, Chun Geun Lee, Jack A Elias, Hasan H Otu, Sharon Inouye, Edward R Marcantonio, and Towia A Libermann.
• Beth Israel Deaconess Medical Center.
• J. Gerontol. A Biol. Sci. Med. Sci. 2021 Feb 4.

BackgroundDelirium (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 (e.g., long term cognitive decline and Alzheimer's disease [AD]).MethodsIn 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 1,305 plasma proteins preoperatively [PREOP] and on postoperative day 2 [POD2]) with delirium using SOMAscan. Generalized linear models were applied to 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]).ResultsWe 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).ConclusionsOur 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.© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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