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

项目概要/摘要 谵妄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， 手术患者（即年龄>65岁。谵妄与患痴呆症的风险增加有关， 思维和记忆能力的逐渐丧失，最终导致无法照顾自己， 独立生活。老年痴呆症的最常见原因是阿尔茨海默病（AD） 这与两种蛋白质tau和 淀粉样蛋白β淀粉样蛋白β沉积通常在大脑中发展数年，如果不是几十年前开始， 记忆缺陷和其他AD症状。患有这些早期或“临床前”淀粉样β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。在这里，我们将 检查这些淀粉样蛋白β沉积，或大脑结构和活动的其他“临床前”变化， 使患者对麻醉药物的反应倾向于表现出比正常更大的大脑活动变化 在手术中。这一提议的中心思想是，改变（或夸大）的大脑活动对 麻醉药物是不健康大脑的标志，即具有“临床前”AD迹象的大脑， 增加术后谵妄的风险。首先，我们将检查是否有证据表明患者脑淀粉样蛋白 β病理学（通过脊髓液淀粉样蛋白β水平测量）改变了大脑活动对 麻醉药第二，我们将使用脑成像来确定是否改变早期AD样变化， 大脑结构和连接与对麻醉药物的改变的大脑活动反应有关。第三、 我们将确定对麻醉药物的脑活动反应的改变是否与增加的 术后谵妄的发生率和严重程度。这项工作将帮助我们了解潜在的机制 术后谵妄和AD及相关痴呆，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）提供了一种使用大脑活动记录数据的方法， 美国手术室，以预测哪些患者可能发生术后谵妄和/或AD， 这可以让这些患者被选择进行干预，以防止这些疾病。

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.