The Aging Brain Under General Anesthesia: Neurophysiology, Neuroimaging Biomarkers of Aging and Alzheimer's Disease, and Post-Operative Cognitive Outcomes

在美国，每天有近10万名患者接受全身麻醉和镇静， 接受外科和非外科手术。接受麻醉护理的患者中， 老年人，此外可能有预先存在的条件，如阿尔茨海默病或脑血管疾病 疾病因此，老年患者术后谵妄和认知功能障碍的风险较高。 麻醉学家知道，与老年患者相比，老年患者的管理需要不同的方法。 年轻患者例如，老年患者达到相同麻醉状态所需的剂量可以 比年轻患者低50%。不幸的是，目前我们对基本的 麻醉药物如何影响衰老大脑的神经生理学。这是一个重大的知识差距 这阻碍了我们开发新的方法来更安全地实施麻醉和镇静， 老年患者。近年来，在非侵入性成像方法的帮助下， 在理解人体麻醉作用的系统水平神经生理学方面取得了进展。同时，成像 生物标志物已经发展到能够鉴定两种最常见的“沉默”病理， 使老年人在麻醉后/手术后结果不佳的风险更高：阿尔茨海默病（AD）和 脑血管病（CVD）。我们在这里建议将这两条研究路线结合起来， 采用临床前AD（淀粉样蛋白PET，皮质萎缩）和CVD（FLAIR MRI，DTI）的成像标志物 同时对术中EEG进行复杂的计算分析，目的是使用这些措施 更好地了解麻醉反应和术后结果的变异性。当我们完成 这项赠款的目的，所产生的数据应该导致对神经生理学的基本新见解， 老年患者的麻醉这些见解将推进关于如何评估患者的风险的知识， 麻醉，并通过改善大脑监测，改善药物剂量和精确度来降低这些风险， 根据个人大脑定制麻醉的医学方法。

In the United States, nearly 100,000 patients receive general anesthesia and sedation daily to safely undergo surgical and non-surgical procedures. A high proportion of the patients receiving anesthesia care are elderly, and in addition may have pre-existing conditions such as Alzheimer's disease or cerebrovascular disease. As such, elderly patients have a higher risk of post-operative delirium and cognitive dysfunction. Anesthesiologists know that management of older patients requires different approaches compared with that of younger patients. For example, the dose required to achieve the same anesthetic state in elderly patients can be 50% lower than that for younger patients. Unfortunately, at present we know little about the fundamental neurophysiology of how anesthetic drugs influence the aging brain. This represents a major knowledge gap that prevents us from developing novel approaches to more safely administer anesthesia and sedation in elderly patients. In recent years, aided largely by non-invasive imaging methods, significant progress has been made in understanding systems-level neurophysiology of anesthetic effects in humans. In parallel, imaging biomarkers have advanced to enable the identification of two of the most common “silent” pathologies that may put older adults at higher risk for poor post-anesthesia/surgical outcomes: Alzheimer's disease (AD) and cerebrovascular disease (CVD). We propose here to bring these two lines of research together with a study employing imaging markers of preclinical AD (amyloid PET, cortical atrophy) and CVD (FLAIR MRI, DTI) alongside sophisticated computational analysis of intra-operative EEG, with the goal of using these measures to better understand variability in response to anesthesia and post-operative outcomes. As we accomplish the aims of this grant, the data generated should lead to fundamental new insights into the neurophysiology of anesthesia in aging patients. These insights will advance knowledge about how to assess patients for risks of anesthesia and reduce those risks through improved brain monitoring, improved drug dosing, and a precision- medicine approach to tailoring anesthesia to the individual's brain.