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

在美国，近10万名患者每天接受全身麻醉和镇静，以确保安全 接受手术和非手术程序。接受麻醉护理的患者中有很高比例是 老年人，此外还可能有阿尔茨海默病或脑血管疾病等既往疾病 疾病。因此，老年患者术后精神错乱和认知功能障碍的风险更高。 麻醉师知道，老年患者的管理需要不同的方法。 更年轻的病人。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，目前我们对基础知识知之甚少。 麻醉药物如何影响老化大脑的神经生理学。这代表着一个重大的知识鸿沟 这阻碍了我们开发新的方法来更安全地给患者提供麻醉和镇静 老年病人。近年来，在非侵入性成像方法的帮助下，取得了显著的进展。 在了解人类麻醉效应的系统水平神经生理学方面取得的进展。同时，成像 生物标记物已经发展到能够识别两种最常见的“沉默”病理，它们可能 使老年人在麻醉后/手术后出现不良结果的风险更高：阿尔茨海默病(AD)和 脑血管疾病(CVD)。我们在这里建议将这两条研究路线与一项研究结合起来 使用临床前AD(淀粉样蛋白PET，皮质萎缩)和CVD(FLAIR MRI，DTI)的成像标记物 同时对手术中的脑电进行复杂的计算分析，目标是使用这些措施 以更好地了解麻醉反应和术后结果的变异性。当我们完成 这笔赠款的目的，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。这些见解将促进对如何评估患者的风险的了解 通过改进大脑监测，改进药物剂量，以及精确度- 为个体大脑量身定做麻醉的医学方法。

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.