年龄是阿尔茨海默病（AD）危险因素之一,65岁以上发病率为13%。麻醉和手术不仅可导致术后认知功能障碍(POCD)，也是AD潜在危险因素，年龄越大发生POCD/AD风险越高。前期工作显示炎症可能在POCD发展中起重要作用，而异氟烷可能造成线粒体功能损伤和casepase-3活化。但麻醉与手术后出现POCD以致AD过程中炎症反应、神经元死亡、和AD相关机制尚不清楚。本研究:1）探讨手术诱导的神经炎性反应与AD和POCD的发生和恶化之间有无直接联系的证据，确定抗炎症反应化合物—Celastrol和Atorvastatin能否预防和治疗从POCD进展到AD。并将对AD小鼠和AD患者做进一步的实验和观察；2）研究麻醉药诱导细胞死亡和Aβ水平增加的上游机制并评估地氟烷在老年人特别是AD患者使用是否较异氟烷更安全。本研究希望找到合适的麻醉用药和新的预防策略减缓麻醉与手术老年人POCD和AD的发生发展。

Age is one of the most important risk factors for Alzheimer’s disease (AD) with an incidence of 13% in people over 65 years old. Anesthesia and surgery not only induce Post-operative cognitive dysfunction (POCD) but also are potential risk factors of AD. Clinically, older patients who receive anesthesia and surgery have a higher risk in POCD/AD. Our previous studies showed that cognitive decline was associated with a hippocampal inflammatory response and that isoflurane could induced casepase-3 activation and mitochondrial dysfunction.However, it remains unclear clear how inflammatory response, neuronal death and AD-related pathogenese following anaesthesia/surgery to the POCD toward AD development. In this application, 1) we will explore evidence for a direct link between surgery-induced neuroinflammation and the development and/or exacerbation of AD and to determine whether the novel strategies of Celastrol or Atorvastatin, anti-inflammatory compounds, can prevent and/or treat the progression from POCD to AD, on the other hand we will do further experiments in mice with AD pathology and in human AD patients; 2) we will study the up-stream mechanism of anesthetic-induced cell death and increases in β-amyloid protein levels to test whether desflurane is a safer anesthetic than isoflurane for AD patients. Ultimately, we wish that the proposed studies will help us to identify safer anesthetics and novel proventive strategies to slow-down the onset development of POCD toward AD for old patients who are at risk for receiving anesthesia/surgery.