Targeted profiling of the serum proteome associates increased FGF-23 levels with postoperative delirium in cardiac surgical patients

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.