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- Title
Development of a Dynamic Multi-Protein Signature of Postoperative Delirium.
- Authors
Vasunilashorn, Sarinnapha M; Ngo, Long H; Chan, Noel Y; Zhou, Wenxiao; Dillon, Simon T; Otu, Hasan H; Inouye, Sharon K; Wyrobnik, Iris; Kuchel, George A; McElhaney, Janet E; Xie, Zhongcong; Alsop, David C; Jones, Richard N; Libermann, Towia A; Marcantonio, Edward R
- Abstract
<bold>Background: </bold>Delirium is common, morbid, and costly, yet its biology is poorly understood. We aimed to develop a multi-protein signature of delirium by identifying proteins associated with delirium from unbiased proteomics and combining them with delirium biomarkers identified in our prior work (interleukin [IL]-6 and IL-2).<bold>Methods: </bold>We used the Successful Aging after Elective Surgery (SAGES) Study of adults age ≥70 undergoing major noncardiac surgery (N = 560; 24% delirium). Plasma was collected preoperatively (PREOP) and on postoperative day 2 (POD2). In a nested matched case-control study involving 12 pairs of delirium cases and no-delirium controls, isobaric tags for relative and absolute quantitation-based (iTRAQ) mass spectrometry proteomics was applied to identify the top set of delirium-related proteins. With these proteins, we then conducted enzyme-linked immunosorbent assay (ELISA) confirmation, and if confirmed, ELISA validation in 75 matched pairs. Multi-marker conditional logistic regression was used to select the "best" PREOP and POD2 models for delirium.<bold>Results: </bold>We identified three proteins from iTRAQ: C-reactive protein (CRP), zinc alpha-2 glycoprotein (AZGP1), and alpha-1 antichymotrypsin (SERPINA3). The "best" multi-protein models of delirium included: PREOP: CRP and AZGP1 (Bayesian information criteria [BIC]: 93.82, c-statistic: 0.77); and POD2: IL-6, IL-2, and CRP (BIC: 87.11, c-statistic: 0.84).<bold>Conclusion: </bold>The signature of postoperative delirium is dynamic, with some proteins important before surgery (risk markers) and others at the time of delirium (disease markers). Our dynamic, multi-protein signature for delirium improves our understanding of delirium pathophysiology and may identify patients at-risk of this devastating disorder that threatens independence of older adults.
- Subjects
DELIRIUM; COGNITION disorders; BIOLOGICAL tags; PROTEOMICS; ENZYME-linked immunosorbent assay
- Publication
Journals of Gerontology Series A: Biological Sciences & Medical Sciences, 2019, Vol 74, Issue 2, p261
- ISSN
1079-5006
- Publication type
journal article
- DOI
10.1093/gerona/gly036