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<p>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 <i>NRF2</i> and other regulators of oxidative stress (<i>GST</i>, <i>GSS</i>, <i>HMOX1</i>, <i>CAT</i>, HSP27, and LOX-1), inflammatory mediators (IL-6, IP-10, and <i>NFκB</i>), and neuroprotective factor (BDNF) were analyzed. Cognitive assessments were performed using RBANS, TMT, TIB and MMSE. POCD patients exhibited an initial upregulation of <i>NRF2</i>-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 <i>NFκB</i> 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.</p> Graphical Abstract <p>Potential biomarkers of POCD (post-operative cognitive decline) in the circulatory system. It depicts patients without POCD, and highlights the activation of the <i>NRF2</i> pathway to upregulate downstream genes, which exert antioxidant and anti-inflammatory effects. Central to the scheme is oxidative stress, which causes inflammation and subsequent damage, with protective biomarkers like HSP27, HMOX1, BDNF, and IP-10 counteracting its effects.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月21日

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  • Vitale Miceli,
  • Emanuele Lo Gerfo,
  • Giovanna Russelli,
  • Matteo Bulati,
  • Gioacchin Iannolo,
  • Rosaria Tinnirello,
  • Maura Cimino,
  • Luciano Saso,
  • Federica Avorio,
  • Vincenzina Lo Re

摘要

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.

Graphical Abstract

Potential biomarkers of POCD (post-operative cognitive decline) in the circulatory system. It depicts patients without POCD, and highlights the activation of the NRF2 pathway to upregulate downstream genes, which exert antioxidant and anti-inflammatory effects. Central to the scheme is oxidative stress, which causes inflammation and subsequent damage, with protective biomarkers like HSP27, HMOX1, BDNF, and IP-10 counteracting its effects.