Kapila Ayush K, Watts Helena R, Wang Tianlong, Ma Daqing
Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK.
Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China.
J Alzheimers Dis. 2014;41(1):1-13. doi: 10.3233/JAD-132258.
Alzheimer's disease (AD) is a major social and clinical burden in the elderly, affecting 5% of people aged over 65 and 20% aged over 80. Despite improved management, a cure has not been found and hence analysis of predisposing factors to identify preventive strategies has become increasingly important. Surgery and anesthesia have been proposed to increase the incidence of post-operative cognitive decline (POCD) and AD. This is hypothesized to be the result of a malignant neuroinflammatory response and subsequent synaptic impairment in the elderly and susceptible individuals. As a result, strategies are being explored to prevent surgery and anesthesia induced cognitive impairment. Whereas previously the diagnosis of AD was primarily dependent on clinical examination, biomarkers such as inflammatory cytokines, amyloid-β, and tau deposition in the cerebrospinal fluid have received increased attention. Nonetheless, AD is currently still treated symptomatically with acetylcholinesterase inhibitors and NMDA antagonists to improve cholinergic transmission and prevent glutamatergic excitotoxicity. Therapeutic success is, however, often not achieved, since these treatment methods do not address the ongoing neuroinflammatory processes and hence novel therapeutic and protective strategies are urgently needed. This review provides an insight into the current understanding of age-related cognitive impairment post-surgery and reflects on novel markers of AD pathogeneses exploring their use as targets for treatment. It gives a summary of recent efforts in preventing and treating POCD or AD with regards to the choice and depth of anesthesia, surgical strategy, and peri-operative medication, and discusses the mechanism of action and therapeutic prospects of novel agents.
阿尔茨海默病（AD）是老年人面临的一项重大社会和临床负担，影响着5%的65岁以上人群以及20%的80岁以上人群。尽管管理有所改善，但尚未找到治愈方法，因此分析易感因素以确定预防策略变得越来越重要。手术和麻醉被认为会增加术后认知功能下降（POCD）和AD的发生率。据推测，这是老年人和易感个体发生恶性神经炎症反应及随后突触损伤的结果。因此，人们正在探索预防手术和麻醉引起的认知障碍的策略。以前，AD的诊断主要依赖于临床检查，而脑脊液中的炎症细胞因子、淀粉样β蛋白和tau蛋白沉积等生物标志物受到了越来越多的关注。尽管如此，目前AD仍采用乙酰胆碱酯酶抑制剂和N-甲基-D-天冬氨酸（NMDA）拮抗剂进行对症治疗，以改善胆碱能传递并防止谷氨酸能兴奋性毒性。然而，治疗往往并不成功，因为这些治疗方法并未解决持续的神经炎症过程，因此迫切需要新的治疗和保护策略。本综述深入探讨了目前对术后与年龄相关的认知障碍的理解，并思考了AD发病机制的新标志物，探索将其用作治疗靶点。它总结了近期在预防和治疗POCD或AD方面在麻醉选择和深度、手术策略及围手术期用药方面所做的努力，并讨论了新型药物的作用机制和治疗前景。
