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

全身麻醉下老化的大脑：神经生理学、衰老和阿尔茨海默病的神经影像生物标志物以及术后认知结果

• 批准号: 9904463
• 负责人: EMERY N BROWN
• 金额: $ 63.92万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-15 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9904463
• 关键词: Adult; Aging; Alzheimer' s Disease; Amyloid; Anesthesia procedures; Anesthetics; Brain; Brain imaging; Caring; Cerebrovascular Disorders; Clinical; Cognition; Cognitive; Computer Analysis; Data; Diagnostic; Dose; Elderly; Electrodes; Electroencephalography; General Anesthesia; Goals; Grant; Human; Impaired cognition; Individual; Knowledge; Lead; Location; Magnetic Resonance Imaging; Measures; Monitor; Neurodegenerative Disorders; Operative Surgical Procedures; Outcome; Pathology; Patient risk; Patients; Perioperative; Pharmaceutical Preparations; Positron-Emission Tomography; Postoperative Period; Research; Risk; Scalp structure; Sedation procedure; System; Time; Unconscious State; United States; age related neurodegeneration; aging brain; base; cerebral atrophy; cognitive function; cognitive testing; density; high risk; imaging biomarker; imaging modality; improved; insight; neuroimaging; neuroimaging marker; neurophysiology; non-invasive imaging; novel strategies; older patient; post-operative cognitive dysfunction; postoperative delirium; pre-clinical; precision medicine; prevent; response; surgery outcome

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.

在美国，每天有近 100,000 名患者接受全身麻醉和镇静以安全地接受治疗 接受麻醉护理的患者中很大一部分接受外科和非外科手术。 老年人，此外可能患有阿尔茨海默氏病或​​脑血管病等既往疾病 因此，老年患者术后谵妄和认知功能障碍的风险较高。 麻醉师知道，与老年患者相比，老年患者的管理需要不同的方法 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，目前我们对其基本原理知之甚少。 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进行麻醉和镇静 近年来，在非侵入性成像方法的帮助下，老年患者的治疗取得了重大进展。 同时，在理解人类麻醉效果的系统级神经生理学方面取得了进展。 生物标志物已经取得进展，能够识别两种最常见的“沉默”病理，这些病理可能 使老年人面临更高的麻醉后/手术结果不佳的风险：阿尔茨海默病 (AD) 和 我们在此建议将这两项研究结合起来进行一项研究。 采用临床前 AD（淀粉样蛋白 PET、皮质萎缩）和 CVD 的成像标记物（FLAIR MRI、DTI） 同时对术中脑电图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化。 这笔赠款的目的是，所生成的数据应该带来对神经生理学的基本新见解 这些见解将增进有关如何评估患者麻醉风险的知识。 通过改善大脑监测、改进药物剂量和精确的麻醉来降低这些风险 根据个人大脑定制麻醉的医学方法。