Cognitive Function after Major Noncardiac Surgery, Apolipoprotein E4 Genotype, and Biomarkers of Brain Injury

Background: Postoperative cognitive dysfunction (POCD) is a significant cause of morbidity after noncardiac surgery. Identified risk factors are largely limited to demographic characteristics. We hypothesized that POCD was associated with apolipoprotein E4 (APOE4) genotype and plasma biomarkers of brain injury and inflammation. Methods: Three hundred ninety-four patients older than 55 yr undergoing major elective noncardiac surgery were enrolled in this prospective observational study. Apolipoprotein E genotyping was performed at baseline. Plasma was collected at baseline and end of surgery and at 4.5, 24, and 48-h postoperatively. Six protein biomarkers were assayed (B-type natriuretic peptide, C-reactive protein, D-dimer, matrix metalloproteinase-9, neuron-specific enolase, and S-100B). Neurocognitive testing was conducted at baseline and at 6 weeks and 1 yr after surgery; scores were subjected to factor analysis. The association of APOE4 and biomarkers with POCD was tested using multivariable regression modeling. Results: Three hundred fifty patients (89%) completed 6-week neurocognitive testing. POCD occurred in 54.3% of participants at 6 weeks and 46.1% at 1 yr. There was no difference in POCD between patients with or without the APOE4 allele (56.6 vs. 52.6%; P = 0.58). The continuous cognitive change score (mean +/- SD) was similar between groups (APOE4: 0.05 +/- 0.27 vs. non-APOE4: 0.07 +/- 0.28; P = 0.53). Two hundred ninety-one subjects (74%) completed testing at 1 yr. POCD occurred in 45.9% of APOE4 subjects versus 46.3% of non-APOE4 subjects (P = 0.95). The cognitive score was again similar (APOE4: 0.08 +/- 0.27 vs. non-APOE4: 0.05 +/- 0.25; P = 0.39). Biomarker levels were not associated with APOE4 genotype or cognition at 6 weeks or 1 yr. Conclusion: Cognitive decline after major noncardiac surgery is not associated with APOE4 genotype or plasma biomarker levels.