Associations between blood cholin-esterase activity and postoperative basal forebrain cholinergic system atrophy: A secondary analysis of the BioCog cohort with exploration of potential mechanisms

OBJECTIVE: Structural and functional metabolism are closely linked in the cholinergic system, and associations between cholinergic neurotransmission and atrophy of cholinergic nuclei, i.e., the nucleus basalis of Meynert (NBM), have been described for neurodegenerative conditions. Impaired cholinergic neurotransmission, as shown by alterations in cholinesterase (ChE) activity of patients undergoing anaesthesia, may contribute to perioperative disorders of cognition. In this secondary analysis, we evaluated a potential association between perioperative ChE activity and postoperative NBM atrophy and studied its potential role in postoperative delirium (POD) and cognitive dysfunction (POCD). We further explored how postoperative inflammation, liver injury and anaesthetic toxicity may contribute to this relationship. METHODS: We conducted a secondary analysis in a subsample from the BioCog cohort study. N = 170 cognitively healthy (MMSE≥24) patients ≥65 years provided ChE activity, inflammatory markers and transaminase activity before elective surgery and on the first postoperative day, as well as magnetic resonance imaging data before surgery and at follow-up three months after surgery for volumetry of the NBM. Patients were screened for delirium until the 7th postoperative day. POCD was assessed three months after surgery and was defined according to the reliable change index. The data were analysed in linear regression models of postoperative NBM volume adjusted for age, sex, MMSE score and preoperative NBM volume. RESULTS: per U/L). We observed no relationship between BuChE activity, NBM atrophy and POD or POCD. Postoperative inflammatory response was associated with BuChE inhibition, but not NBM atrophy. In patients undergoing anaesthesia maintained with sevoflurane, duration of surgery was significantly associated with BuChE inhibition and NBM atrophy. DISCUSSION: We observed an association between plasma BuChE activity and postoperative NBM atrophy. Our findings point towards a potential neurotoxic effect of sevoflurane on the cholinergic system. However, the involvement of this mechanism in postoperative cognitive disorders will require further well powered studies to evaluate causality.