Anaesthetics and postoperative cognitive dysfunction: a pathological mechanism mimicking Alzheimer’s disease

Abstract

SummaryWith longevity, postoperative cognitive decline in the elderly has emerged as a major health concern for which several factors have been implicated, one of the most recent being the role of anaesthetics. Interactions of anaesthetic agents and different targets have been studied at the molecular, cellular and structural anatomical levels. Recent in vitro nuclear magnetic resonance spectroscopy studies have shown that several anaesthetics act on the oligomerisation of amyloid b peptide. Uncontrolled production, oligomerisation and deposition of amyloid b peptide, with subsequent development of amyloid plaques,

Postoperative Cognitive Dysfunction (POCD) and Markers of Brain Damage After Big Joints Arthroplasty

“…The interactions between anesthetics and amyloid peptide have been discussed above. Thus, it is possible that general anesthesia could be a factor in the pathogenesis of POCD (Fodale, et al, 2010). However, in his study, Hudetz et al (J. Hudetz et al, 2009;J.…”

“…Such was the conclusion from both statistic and bibliographic data. However, the central cholinergic system has been identified as the basic system of neurotransmitters taking part in the regulation of the level of conscience, memory and learning (Fodale, et al, 2010), and the interactions between anesthetic drugs and this system may be important in the pathogenesis and development of POCD. There are two main classes of cholinergic receptors: nicotinic and muscarinic.…”

“…Nicotinic acetylcholine receptors (nAChRs) are ligandgated cation channels and muscarinic acetylcholine receptors (mAChRs) are ligand-gated K + channels, divided into five subtypes (M1 -M5). The agonists of central mAChRs and nAChRs may improve, while the antagonists might impair performance in cognition, learning and memory (Fodale, et al, 2010). Volatile anesthetics and ketamine are potent inhibitors of nAChRs.…”

“…Some authors discussed the role of genetic factors in the pathogenesis of neurodegenerative disorders. They found an association between the apolipoprotein ε4 (APO-ε4) allele and Alzheimer's disease (Blaise, et al, 2007), so the APO-ε4 gene could be a predictor of postoperative cognitive disorders (Fodale, et al, 2010).…”

On the issue of transmissibility of Alzheimer disease

“…32,45-48 Among these, general anesthesia had been suspected to be associated with an increased risk for AD, since long-term cognitive decline was observed after anesthesia in various studies. [49][50][51][52][53][54][55] To discuss general anesthesia in this context is important, as it may act as a major confounder when researching surgery or (intraoperative) blood transfusions as risk factors for potential transmission of AD in epidemiological studies. Molecular mechanisms were hypothesized and especially volatile anesthetics were demonstrated to be associated with Aβ production, Aβ oligomerization, Tau formation and Tau phosphorylation as described thoroughly in a review by Papon et al 56 Several observational studies were designed to substantiate these experimental theories with epidemiological data.…”