Abstract
Occurrences of delirium, in the event of cardiac surgical interventions, are often confounded by antecedent metabolic states that may predispose vulnerable elders to early-onset dementia. An in-depth capture of the circulating proteome, ideally suited for discerning patients' metabolic profiles before and after surgery, could thus be of great relevance to the delirium-dementia interface. Using a nested case-control study design, we performed targeted proteomics on serum samples collected from 19 older patients, of whom 8 (42%) experienced delirium post-surgery, and measured the levels of 183 proteins in 2 multiplex panels. Differential expression analyses identified 2 proteins associated with delirium incidence, based on a threshold of 1.5-fold difference between delirious and non-delirious inpatients. Postoperative serum fibroblast growth factor 23 (FGF-23) levels were 3.82-fold higher in patients with delirium and significantly correlated with serum neurofilament light levels. We corroborated these findings in an independent, age- and sex-matched cohort of 16 patients with similar delirium rates (38%), wherein a significant trend toward higher FGF-23 levels was observed amongst delirious patients. A technical validation of the differentially expressed FGF-23 protein via enzyme-linked immunosorbent assays further reinforced the generalizability of our results, suggesting that circulating FGF-23 may serve as a serum biomarker of delirium post-cardiac surgery.