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 精神错乱是一种警觉性和注意力波动变化的综合征，发生在高达40%的老年人中 外科病人(即65岁)。精神错乱与患痴呆症的风险增加有关， 逐渐丧失思维和记忆技能，最终导致无法照顾自己和 独立生活。美国老年人痴呆症最常见的原因是阿尔茨海默病(AD) 这与两种蛋白质-tau和tau在大脑中的异常沉积有关 淀粉样β蛋白。淀粉样β蛋白沉积通常在脑内发育多年，如果不是几十年的话 记忆缺陷和其他阿尔茨海默病症状。有这些早期或临床前的淀粉样β沉积的患者，甚至 如果他们看起来精神正常，手术后发展为精神错乱的风险往往会增加。在这里，我们将 检查这些淀粉样β沉积，或大脑结构和活动的其他“临床前”变化， 容易使患者对麻醉药物的反应表现出比正常更大的脑活动变化 在手术期间。这一提议的中心思想是，改变(或夸大)的大脑活动对 麻醉药物是大脑不健康的标志，即大脑有“临床前”阿尔茨海默病的迹象，并且处于 增加术后精神错乱的风险。首先，我们将检查有脑淀粉样蛋白证据的患者 β病理(以脊髓液淀粉样β蛋白水平来衡量)改变了大脑活动对 麻醉药。其次，我们将使用大脑成像来确定早期AD样变化是否在 大脑结构和连接与麻醉药物引起的大脑活动反应改变有关。第三, 我们将确定麻醉药物引起的大脑活动反应改变是否与 术后精神错乱的发生和严重程度。这项工作将帮助我们理解潜在的机制 术后妄想与阿尔茨海默病及相关痴呆及其之间的联系。此外，这项工作将 为麻醉师(和外科医生)提供一种使用脑活动记录数据的方法，这些数据已经在 美国手术室预测哪些患者可能会出现术后精神错乱和/或AD， 这可能会让这些患者被选为预防这些疾病的干预措施。