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: 10521860
• 负责人: Miles Berger
• 金额: $ 78.42万
• 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/10521860
• 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; Cohort Studies; 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; Pharmacology; 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; 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; older patient; postoperative delirium; pre-clinical; prevent; prodromal Alzheimer' s disease; prospective; response; screening; skills; standard of care; stressor; tau Proteins; tau-1; white matter

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.

项目摘要/摘要 妄想是一种综合征，警报和注意力变化的综合征在多达40％的老年人中发生 手术患者（即年龄> 65岁。del妄与患痴呆症的风险增加有关 逐渐丧失思维和记忆技巧，有时导致无法照顾自己和 独立生活。老年人痴呆的最常见原因是阿尔茨海默氏病（AD） 这与两种蛋白质tau和tau和 淀粉样蛋白β。淀粉样蛋白β矿床通常在大脑中发育多年，即使不是在开始之前的几十年 记忆定义和其他广告症状。患有这些早期或“临床前”淀粉样蛋白β矿床的患者，甚至 如果它们在精神上正常，通常会增加手术后del妄的风险。在这里，我们会的 检查这些淀粉样蛋白β沉积物是大脑结构和活动的其他“临床前”变化， 易于症状的患者显示出比正常人的大脑活性大于正常人，以应对麻醉药物的响应 手术期间。该提议的核心思想是，对大脑活动的改变（或夸大）对 麻醉药物是不健康的大脑的标志物，即具有“临床前” AD迹象的大脑，并且在 术后del妄的风险增加。首先，我们将检查有脑淀粉样蛋白证据的患者是否 β病理学（通过脊柱淀粉样β水平测量）的大脑活动反应改变了 麻醉药。其次，我们将使用脑成像来确定是否会更改类似AD的变化 大脑结构和连接与大脑活动对麻醉药物的反应改变有关。第三， 我们将确定大脑活动对麻醉药物的反应是否与增加有关 术后ir妄的发生和严重程度。这项工作将有助于我们了解基本机制 术后del妄和AD和相关痴呆症，以及它们之间的联系。此外，这项工作将 为麻醉师（和外科医生）提供一种使用大脑活动记录数据已广泛使用的方法的方法 美国手术室可以预测哪些患者可能会发展术后del妄和/或广告 这可以允许这些患者进行干预以防止这些疾病。