Author:
Tripp Bridget A.,Dillon Simon T.,Yuan Min,Asara John M.,Vasunilashorn Sarinnapha M.,Fong Tamara G.,Metzger Eran D.,Inouye Sharon K.,Xie Zhongcong,Ngo Long H.,Marcantonio Edward R.,Libermann Towia A.,Otu Hasan H.
Abstract
AbstractPostoperative delirium is the most common complication among older adults undergoing major surgery. The pathophysiology of delirium is poorly understood, and no blood-based, predictive markers are available. We characterized the plasma metabolome of 52 delirium cases and 52 matched controls from the Successful Aging after Elective Surgery (SAGES) cohort (N = 560) of patients ≥ 70 years old without dementia undergoing scheduled major non-cardiac surgery. We applied targeted mass spectrometry with internal standards and pooled controls using a nested matched case-control study preoperatively (PREOP) and on postoperative day 2 (POD2) to identify potential delirium risk and disease markers. Univariate analyses identified 37 PREOP and 53 POD2 metabolites associated with delirium and multivariate analyses achieved significant separation between the two groups with an 11-metabolite prediction model at PREOP (AUC = 83.80%). Systems biology analysis using the metabolites with differential concentrations rendered “valine, leucine, and isoleucine biosynthesis” at PREOP and “citrate cycle” at POD2 as the most significantly enriched pathways (false discovery rate < 0.05). Perturbations in energy metabolism and amino acid synthesis pathways may be associated with postoperative delirium and suggest potential mechanisms for delirium pathogenesis. Our results could lead to the development of a metabolomic delirium predictor.
Funder
National Institute on Aging
Beth Israel Deaconess Medical Center
Foundation for the National Institutes of Health
Alzheimer's Association
Publisher
Springer Science and Business Media LLC
Cited by
22 articles.
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