Application of Multiple Omics to Understand Postoperative Delirium Pathophysiology in Humans

Delirium, an acute change in cognition, is common, morbid, and costly, particularly among hospitalized older adults. Despite growing knowledge of its epidemiology, far less is known about delirium pathophysiology. Initial work understanding delirium pathogenesis has focused on assaying single or a limited subset of molecules or genetic loci. Recent technological advances at the forefront of biomarker and drug target discovery have facilitated application of multiple "omics" approaches aimed to provide a more complete understanding of complex disease processes such as delirium. At its basic level, "omics" involves comparison of genes (genomics, epigenomics), transcripts (transcriptomics), proteins (proteomics), metabolites (metabolomics), or lipids (lipidomics) in biological fluids or tissues obtained from patients who have a certain condition (i.e., delirium) and those who do not. Multi-omics analyses of these various types of molecules combined with machine learning and systems biology enable the discovery of biomarkers, biological pathways, and predictors of delirium, thus elucidating its pathophysiology. This review provides an overview of the most recent omics techniques, their current impact on identifying delirium biomarkers, and future potential in enhancing our understanding of delirium pathogenesis. We summarize challenges in identification of specific biomarkers of delirium and, more importantly, in discovering the mechanisms underlying delirium pathophysiology. Based on mounting evidence, we highlight a heightened inflammatory response as one common pathway in delirium risk and progression, and we suggest other promising biological mechanisms that have recently emerged. Advanced multiple omics approaches coupled with bioinformatics methodologies have great promise to yield important discoveries that will advance delirium research.