Department of Neurosciences Psychiatric and Anesthesiological Sciences, University of Messina, Policlinico Universitario 'G.Martino', Italy.
Anaesthesia. 2010 Apr;65(4):388-95. doi: 10.1111/j.1365-2044.2010.06244.x. Epub 2010 Feb 5.
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.
随着寿命的延长，老年人术后认知功能下降已成为一个主要的健康问题，有几个因素与之相关，其中最近的一个是麻醉剂的作用。麻醉剂的相互作用及其不同的靶点已在分子、细胞和结构解剖学水平上进行了研究。最近的体外核磁共振波谱研究表明，几种麻醉剂作用于淀粉样β肽的寡聚化。淀粉样β肽的失控产生、寡聚化和沉积，以及随后的淀粉样斑块的形成，是阿尔茨海默病发生的基本步骤。淀粉样β肽在中枢神经系统中自然存在，在老年人的组织中浓度更高。我们认为，给老年患者使用某些全身麻醉剂可能会加重淀粉样β肽的寡聚化和沉积，从而增加术后认知功能障碍的风险。本综述的目的是强调术后认知功能障碍的临床方面，并找到可能的麻醉作用与阿尔茨海默病的分子病理机制之间的合理联系。希望我们的假设将激发进一步的研究，特别是引发对那些在认知功能障碍特别关注时可能更合适的麻醉剂的研究。
