Background A pre-existing neurocognitive disorder (NCD) is a relevant factor for the outcome of surgical patients. To improve understanding of these conditions, we investigated the association between parameters of the cholinergic system and NCD. Methods This investigation is part of the BioCog project (www.biocog.eu), which is a prospective multicenter observational study including patients aged ≥ 65 years scheduled for elective surgery. Patients with a Mini-Mental-State-Examination (MMSE) score ≤ 23 points were excluded. NCD was assessed according to the 5th Diagnostic and Statistical Manual of Mental Disorders criteria. The basal forebrain cholinergic system volume (BFCSV) was assessed with Magnetic Resonance Imaging, the peripheral cholinesterase (ChE) activities with point-of-care measurements, and anticholinergic load by analyzing the long-term medication with anticholinergic scales (ADS, ARS, ACBS). The associations of BFCSV, ChE activities, and anticholinergic scales with NCD were studied with logistic regression analysis, adjusting for confounding factors. Results A total of 797 participants (mean age 72 years, 42% females) were included. 111 patients (13.9%) fulfilled criteria for mild NCD and 82 patients (10.3%) major NCD criteria. We found that AcetylChE activity was associated with major NCD (Odds Ratio (95%-Confidence Interval); [U/gHB] 1.061 (1.101;1.115)), as well as ADS score ([Points] 1.353 (1.063;1.723)) or ARS score respectively ([Points] 1.623 (1.100;2.397)) with major NCD. However, we found no association between BFCSV or ButyrylChE activity with mild or major NCD. Conclusions AcetylChE activity and anticholinergic load were associated with major NCD. Future research should focus on the association of the cholinergic system and the development of postoperative delirium and postoperative NCD.

Objective Studies have suggested that inflammation contributes to the pathogenesis of postoperative delirium, but previous results on the proinflammatory cytokine IL-8 in plasma are contradictory. Additionally, a significant fraction of IL-8 is bound to erythrocytes, but the relevance of whole blood IL-8 in delirium has not been studied. In this work, we analyzed the association of postoperative delirium with levels of unbound IL-8 in plasma and levels of IL-8 in whole blood in patients from two studies which were conducted in our department and have not been presented previously. We assessed the prognostic value of whole blood IL-8. Methods Plasma/whole blood IL-8 was measured at least once in N ​= ​504 patients preoperatively, on day one (d1) and/or three months after surgery in the BioCog observational study. Whole blood IL-8 was measured in N ​= ​64 patients from the PHYDELIO trial preoperatively, on d1 and d7 after surgery. For the determination of whole blood IL-8, EDTA-preserved blood samples underwent lysis by adding Triton-X100 surfactant. Plasma and whole blood IL-8 levels were assessed with two different immunoassay kits. Delirium was appraised systematically for seven postoperative days according to DSM criteria using two comparable protocols consisting of validated screening tools. Results Delirium occurred in 25% of BioCog and 14% of PHYDELIO patients. In BioCog, IL-8 was elevated on d1 and in delirious patients. A steeper postoperative increase in delirium was confounded by surgery-related factors. A crescendo-decrescendo pattern of whole blood IL-8 levels was observed in non-delirious patients with a peak on d1. This pattern was more distinct in delirious BioCog patients, but inverted in delirious PHYDELIO patients. Preoperative whole blood IL-8>318.4 ​pg/mL (reference <150 ​pg/mL) had adequate sensitivity (0.79/0.78) and specificity (0.53/0.67) for delirium in both samples. Conclusion Our results contribute to an inflammatory hypothesis of postoperative delirium.