Postoperative cognitive dysfunction (POCD) is cognitive decline after surgery. The authors hypothesized that gene-level changes could be involved in the pathogenesis of POCD. The present study evaluated the incidence of POCD and its associated differentially expressed genes. This was a prospective cohort study conducted on high-risk coronary artery bypass graft patients aged 40 to 75 years. POCD classification was based on a one standard deviation decline in the postoperative scores compared to the preoperative scores. The differentially expressed genes were identified using microarray analysis and validated using quantitative RT-PCR. Forty-six patients were recruited and completed the study. The incidence of POCD was identified using a set of neurocognitive assessments and found to be at 17% in these high-risk CABG patients. Six samples were selected for the gene expression analyses (3 non-POCD and 3 POCD samples). The findings showed five differentially expressed genes in the POCD group compared to the non-POCD group. The upregulated gene was ERFE, whereas the downregulated genes were KIR2DS2, KIR2DS3, KIR3DL2, and LIM2. According to the results, the gene expression profiles of POCD can be used to find potential proteins for POCD diagnostic and predictive biomarkers. Understanding the molecular mechanism of POCD development will further lead to early detection and intervention to reduce the severity of POCD, and hence, reduce the mortality and morbidity rate due to the condition.

The inability to accurately predict the occurrence of postoperative cognitive dysfunction (POCD) among open-heart surgery patients leads to concerning increases in POCD cases. Preoperative circulating biomarkers are important to identify as they are non-invasive and could provide an early prediction of POCD development, allowing for earlier and more strategized interventions. However, to date, no robust circulating biomarkers have proven effective for preoperative POCD prediction. This systematic review aims to synthesize current evidence on preoperative protein profiling among POCD patients following open-heart surgery. Thus, a thorough literature search employing PubMed, EBSCOhost, Scopus, and Science Direct was carried out. This combination of keywords was used as part of the search strategy: (“Postoperative cognitive decline” OR “Postoperative cognitive disorders” OR “Postoperative cognitive dysfunction” OR “Postoperative cognitive complications”) AND (“Thoracic Surgery” OR “Cardiac Surgery” OR “Heart Surgery”) AND (“Protein expression” OR proteomic OR “Protein profiling”). Eight hundred and twenty-nine studies were retrieved and only clinical studies reporting the circulating preoperative differentially expressed Proteins (DEPs) in the POCD patients were selected. Six studies were selected following the inclusion and exclusion criteria. Only one preoperative DEP and four immediate postoperative DEPs were extracted from the studies. All four proteins were selected for analysis using DAVID, STRING, and Cytoscape software. Due to the very low number of proteins, no clusters have been identified. This systematic review demonstrates the lack of POCD preoperative biomarkers for open-heart-surgery patients. Thus, it is suggested that more studies can be conducted to fill this gap.