Original Scientific Articles

Exploratory associations between APOE genotype, biochemical markers, and postoperative cognitive outcomes after colorectal cancer surgery: preliminary results from Bosnia and Herzegovina

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Abstract

Introduction. Postoperative cognitive dysfunction (POCD) is a common complication after major surgery. Genetic susceptibility, particularly the APOE ε4 allele, and systemic metabolic status may influence its development. This study investigated associations between biochemical markers of hepatic and renal function and postoperative cognitive outcomes according to APOE ε4 status.
Methods. This prospective multicenter study included 113 cognitively healthy adults undergoing elective colorectal cancer surgery under general anesthesia. Cognitive function was assessed using 
the Mini-Mental State Examination (MMSE) preoperatively, on postoperative day 7, and at three months. APOE genotyping was performed by PCR-RFLP. Urea, creatinine, AST, ALT, GGT, ALP, CK, LDH, and amylase were measured preoperatively and on postoperative day 7. POCD was defined as an MMSE score ≤23. Associations were assessed using nonparametric tests and multivariate logistic regression adjusted for age, sex, education, and baseline MMSE.
Results. Genotyping was successful in 109 patients. Early POCD occurred in 105 patients (92.9%), and persistent POCD at three months in 45 (39.8%). Among genotyped patients, 94 (86.2%) were APOE ε4 carriers and 15 (13.8%) were non-carriers. In non-carriers, preoperative urea, creatinine, and amylase were independently associated with persistent POCD. In ε4 carriers, postoperative creatinine and 
GGT were independently associated with persistent POCD. Early POCD was associated with preoperative CK and LDH and postoperative ALT in non-carriers.
Conclusion. Biochemical correlates of POCD may differ according to APOE genotype. Baseline metabolic status may be more relevant in non-carriers, whereas postoperative disturbances may be more important in ε4 carriers. Larger studies using standardized POCD definitions are warranted.

Keywords: postoperative cognitive dysfunction, APOE ε4, colorectal surgery, renal function, gamma‑glutamyl transferase

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