Low-grade, systemic inflammation and the risk of perioperative neurocognitive disorders in an observational study of older adults

Aims The neuroinflammatory response to surgery may contribute to the pathogenesis of post-operative delirium (POD) and cognitive dysfunction (POCD), but whether inflammation before surgery enhances the risk of developing these conditions is unclear. Here, we investigate the relationship between preoperative levels of inflammation markers and the risk of POD/POCD. Methods 697 surgical patients aged ≥ 65 years were recruited 2014-2017 in Utrecht, the Netherlands and Berlin, Germany into the BioCog study. C-reactive protein (CRP), S100A12, interleukin-6 (IL-6) and IL-18 were measured immediately before surgery. POD was assessed twice daily up to 7 days/hospital discharge. POCD was determined from neuropsychological testing before surgery and 3 months thereafter. Multiple logistic regression analyses were run adjusted for age, sex, surgery site, and BMI. Results. 140 out of 697 patients (20.1%) developed POD during 7 days/by discharge; 50 out of 469 patients (10.9%) attending the 3-month follow-up developed POCD. CRP ≥ 10 mg/L was found in 149 patients and was not associated with POD/POCD. Among patients with CRP < 10 mg/L, higher S100A12 and higher CRP concentrations were each associated with higher POD risk (OR per SD higher concentrations, S100A12, 1.26, 95% CI 1.03, 1.54; CRP,1.42, 95% CI 1.15, 1.76). Higher S100A12 was associated with higher POCD risk (OR 1.40 per SD, 95% CI 1.04, 1.88). No associations were found for IL-6 and IL-18. Of note, only the result on CRP and POD survived Bonferroni correction with cut-off p < 0.006. Conclusion Low-grade inflammation may influence individual vulnerability to cognitive complications of surgery. Our results warrant further examination. Trial registration NCT02265263.