The significance of S100β and neuron-specific enolase (NSE) in postoperative cognitive dysfunction following cardiac surgery: a systematic review and meta-analysis

Mehdi Hassani Ahangar(Tehran University of Medical Sciences), Komeil Aghazadeh-Habashi(Tabriz University of Medical Sciences), A H Rahi(University of Isfahan), Armina Torabian(Islamic Azad University Kazeron), Iltifat A. Alavi(University of Louisville), Kamran Shayesteh(Islamic Azad University, Mashhad), S Mozaffari(Shahid Beheshti University of Medical Sciences), Amirreza Khalaji(Tabriz University of Medical Sciences), Mahsa Rostami Ghezeljeh(Kerman University of Medical Sciences), Seyyed Kiarash Sadat Rafiei(Shahid Beheshti University of Medical Sciences), Alireza Mohebbi(Ardabil University of Medical Sciences), Sadaf Salehi(Iran University of Medical Sciences), Athena Fahami(Islamic Azad University Medical Branch of Tehran), Mahsa Asadi Anar(Shahid Beheshti University of Medical Sciences), Pooya Eini(Shaheed Rajaei Cardiovascular Medical and Research Center), Mastooreh Sagharichi(Shahid Beheshti University of Medical Sciences), Fatemeh Khosravi(Shahid Beheshti University of Medical Sciences)
European journal of medical research
August 26, 2025
Cited by 6Open Access
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Abstract

BACKGROUND: Postoperative cognitive dysfunction (POCD) significantly affects recovery, hospitalization duration, and quality of life following cardiac surgery. Identifying reliable biomarkers for predicting POCD could improve patient outcomes and perioperative care. Among these, S100 calcium-binding protein beta (S100β) and neuron-specific enolase (NSE) have emerged as promising indicators of cerebral injury and neurocognitive dysfunction. OBJECTIVES: This systematic review and meta-analysis aimed to assess within-subject perioperative changes in S100β and NSE levels among patients who developed POCD after cardiac surgery, to evaluate whether these biomarkers consistently rise in association with POCD. METHODS: Following PRISMA guidelines, we searched PubMed, Scopus, and Web of Science up to October 2024. Studies included peer-reviewed articles evaluating S100β and NSE levels in relation to POCD in cardiac surgery patients. Two reviewers independently extracted data and assessed the quality using the ROBINS-I tool. Meta-analyses were conducted using a random-effects model. RESULTS: = 88.7%) for NSE, indicating large effect sizes. Sensitivity analyses confirmed the robustness of these findings despite substantial heterogeneity. CONCLUSIONS: Among patients who developed POCD, S100β and NSE levels significantly increased from preoperative to postoperative measurements, indicating a potential association with cerebral injury. However, as non-POCD patients were not analyzed for the same biomarker changes, causality or specificity to POCD cannot be confirmed and future research should be directed toward between group changes.


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