Circulating Biomarkers to Predict Post-Operative Cognitive Decline in Patients Undergoing Coronary Artery Bypass Grafting.

Abstract

Post-operative cognitive decline (POCD) is characterized by impairments in cognitive functions. Coronary artery bypass grafting (CABG) is associated with a high risk of POCD due to its impact on neuroinflammation and oxidative stress. In this study, we investigated the dynamics of neurotrophic, inflammatory, and oxidative stress markers in a cohort of post-CABG patients to identify potential biomarkers for POCD. Blood samples were collected at baseline (immediately post-surgery) and at 3-month follow-up. Expression levels of NRF2 and other regulators of oxidative stress (GST, GSS, HMOX1, CAT, HSP27, and LOX-1), inflammatory mediators (IL-6, IP-10, and NFκB), and neuroprotective factor (BDNF) were analyzed. Cognitive assessments were performed using RBANS, TMT, TIB and MMSE. POCD patients exhibited an initial upregulation of NRF2-related antioxidant genes, which failed to sustain at 3-months follow-up, leading to a decline in HMOX1, IP-10 and BDNF protein levels, along with increased LOX-1 protein level and NFκB expression, indicating persistent oxidative stress and inflammation. In contrast, non-POCD patients demonstrated a sustained increase in antioxidant and neuroprotective markers, suggesting a more effective compensatory response. ROC analysis identified HMOX1 and BDNF as significant predictors of POCD, with LOX-1 and IP-10 emerging as diagnostic markers at follow-up. In conclusion, our findings highlight the dynamic regulation of oxidative stress and inflammatory pathways in POCD, emphasizing the failure of sustained neuroprotection in affected patients. Further large-scale studies are necessary to validate these findings, and biomarker-based screening could facilitate early risk stratification and targeted interventions to improve cognitive outcomes after cardiac surgery.