The association of pre-operative biomarkers of endothelial dysfunction with the risk of post- operative neurocognitive disorders: Results from BioCog study

Abstract Introduction: Endothelial dysfunction (ED) promotes atherosclerosis development, and studies suggest an association with age-related neurocognitive disorders. Nonetheless, it is unclear whether ED is associated with the risk of neurocognitive disorders. Method: We included 788 participants aged ≥65 years in the BioCog study. Blood was collected before surgery for measurement of 5 biomarkers of ED including asymmetric and symmetric dimethylarginine (ADMA; SDMA), intercellular and vascular adhesion molecule (ICAM-1, VCAM-1), and von Willebrand factor (vWF). Patients were examined for the occurrence of postoperative delirium (POD) daily until the 7th postoperative day. 537 (68.1%) patients returned for a 3-month follow-up. Post-operative cognitive dysfunction (POCD) was defined from the change in results on 6 neuropsychological tests between baseline and 3 months, compared to the change in results of a control group during a 3-month interval. The associations of each of the 5 ED biomarkers with POD and POCD respectively were determined using multiple logistic regression analyses with adjustment for age, sex, surgery type, pre-morbid IQ, body mass index, hypertension, diabetes, HbA1C, triglyceride, total and HDL cholesterol. Results: 19.8% of 788 patients developed POD; 10.1% of 537 patients developed POCD. Concentrations of ED biomarkers were not significantly associated with a POD (all p>0.05). A higher VCAM-1 concentration was associated with a reduced POCD risk (odds ratio 0.64; 95% CI: 0.43-0.95). No further statistically significant results were found. Conclusion: Pre-operative concentrations of ED biomarkers are not associated with POD risk. We unexpectedly found higher VCAM-1 to be associated with a reduced POCD risk. Further studies are needed to confirm or refute these findings.