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

Abstract

With 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 beta peptide. Uncontrolled production, oligomerisation and deposition of amyloid beta peptide, with subsequent development of amyloid plaques, are fundamental steps in the generation of Alzheimer's disease. Amyloid beta peptide is naturally present in the central nervous system, and is found at higher tissue concentrations in the elderly. We argue that administering certain general anaesthetics to elderly patients may worsen amyloid beta peptide oligomerisation and deposition and thus increase the risk of developing postoperative cognitive dysfunction. The aim of this review is to highlight the clinical aspects of postoperative cognitive dysfunction and to find plausible links between possible anaesthetic effects and the molecular pathological mechanism of Alzheimer's disease. It is hoped that our hypothesis will stimulate further enquiry, especially triggering research into elucidating those anaesthetics that may be more suitable when cognitive dysfunction is a particular concern.