Low Neurophysiologic Resistance to Anesthetics as a Marker of Preclinical/Prodromal Alzheimer's Disease and Neurovascular Pathology, Delirium risk and Inattention

对麻醉药的神经生理学抵抗力低是临床前/前驱阿尔茨海默病和神经血管病理学、谵妄风险和注意力不集中的标志

• 批准号: 10671023
• 负责人: Miles Berger
• 金额: $ 74.98万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10671023
• 关键词: Age; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Alzheimer' s disease risk; American; Amyloid beta-Protein; Anesthesia procedures; Anesthetics; Attention; Biological Markers; Brain; Brain Pathology; Brain imaging; Brain region; Caring; Cerebrospinal Fluid; Clinical; Cognitive; Data; Delirium; Dementia; Deposition; Development; Disease; Dose; Elderly; Electroencephalography; Exercise; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Image; Impaired cognition; Incidence; Intervention; Link; Magnetic Resonance Imaging; Measures; Medial; Memory; Memory impairment; Monitor; Myocardial dysfunction; Neurocognitive; Operating Rooms; Operative Surgical Procedures; Outcome; Parietal; Pathology; Patients; Pattern; Perioperative; Phase; Proteins; Psyche structure; Resistance; Rest; Risk; Severities; Signal Transduction; Spinal Puncture; Stress Tests; Structure; Surgeon; Symptoms; Syndrome; Temporal Lobe; Thalamic structure; Thallium Myocardial Perfusion Imaging Stress Test; Thinking; Thoracic Surgical Procedures; Time; Vascular Dementia; Waxes; White Matter Hyperintensity; Work; aging brain; alertness; beta amyloid pathology; brain abnormalities; brain dysfunction; cognitive testing; dosage; follow-up; functional MRI scan; human old age (65+); inattention; indexing; neurocognitive disorder; neuroimaging; neuropathology; neurophysiology; neurovascular; neurovascular injury; observational cohort study; older patient; pharmacologic; postoperative delirium; pre-clinical; prevent; prodromal Alzheimer' s disease; prospective; response; screening; skills; standard of care; stressor; tau Proteins; tau-1

Project Summary/Abstract Delirium is a syndrome of fluctuating changes in alertness and attention that occurs in up to 40% of older surgical patients (i.e. age >65. Delirium is associated with an increased risk of developing dementia, a progressive loss of thinking and memory skills that eventually results in an inability to care for oneself and to live independently. The most common cause of dementia in older Americans is Alzheimer’s disease (AD) which is associated with a progressive buildup of abnormal deposits in the brain of two proteins, tau and amyloid beta. Amyloid beta deposits typically develop in the brain for years if not decades before the start of memory deficits and other AD symptoms. Patients with these early or “pre-clinical” amyloid beta deposits, even if they appear mentally normal, are often at increased risk of developing delirium after surgery. Here, we will examine whether these amyloid beta deposits, or other “pre-clinical” changes in brain structure and activity, predispose patients to show larger than normal brain activity changes in response to anesthetic drugs given during surgery. The central idea of this proposal is that an altered (or exaggerated) brain activity responses to anesthetic drugs is a marker of an unhealthy brain, i.e. a brain with signs of “pre-clinical” AD and which is at increased risk of postoperative delirium. First we will examine whether patients with evidence of brain amyloid beta pathology (as measured by spinal fluid amyloid beta levels) have altered brain activity responses to anesthetic drugs. Second, we will use brain imaging to determine whether changes early AD-like changes in brain structure and connections are associated with altered brain activity responses to anesthetic drugs. Third, we will determine whether altered brain activity responses to anesthetic drugs are associated with increased postoperative delirium occurrence and severity. This work will help us understand mechanisms underlying postoperative delirium and AD and related dementias, and the links between them. Further, this work will provide a way for anesthesiologists (and surgeons) to use brain activity recording data already in wide use in American operating rooms to predict which patients are likely to develop postoperative delirium and/or AD, which could allow these patients to be selected for interventions to prevent these disorders.

项目概要/摘要 谵妄是一种警觉性和注意力波动性变化的综合征，高达 40% 的老年人会出现这种症状 手术患者（即年龄 >65 岁）。谵妄与患痴呆症的风险增加有关，痴呆症是一种 思维和记忆能力逐渐丧失，最终导致无法照顾自己和 独立生活导致美国老年人痴呆的最常见原因是阿尔茨海默病（AD）。 这与大脑中两种蛋白质 tau 和 tau 蛋白异常沉积物的逐渐积累有关。 β 淀粉样蛋白沉积物通常在大脑中形成数年（甚至数十年）。 记忆缺陷和其他 AD 症状的患者，甚至患有这些早期或“临床前”淀粉样蛋白沉积的患者。 如果他们看起来精神正常，手术后发生谵妄的风险往往会增加。 检查这些β淀粉样蛋白沉积物或大脑结构和活动的其他“临床前”变化是否， 使患者对麻醉药物的反应容易表现出比正常大脑活动更大的变化 该提案的中心思想是改变（或夸大）大脑活动对手术的反应。 麻醉药物是大脑不健康的标志，即大脑具有“临床前”AD 的迹象，并且处于 首先，我们将检查患者是否有脑淀粉样蛋白的证据。 β 病理学（通过脊髓液淀粉样蛋白 β 水平测量）具有大脑活动反应 其次，我们将使用脑成像来确定早期AD的变化是否类似。 大脑结构和连接与大脑活动对麻醉药物的反应有关。 我们将确定大脑活动对麻醉药物的反应是否与增加 这项工作将帮助我们了解术后谵妄的发生和严重程度。 术后谵妄和 AD 及相关痴呆，以及它们之间的联系。 为麻醉师（和外科医生）提供一种使用已广泛使用的大脑活动记录数据的方法 美国手术室预测哪些患者可能出现术后谵妄和/或 AD， 这可以让这些患者被选择进行干预措施以预防这些疾病。