The Significance of Perioperative Changes in CSF tau levels in the Elderly

老年人围手术期脑脊液 tau 水平变化的意义

基本信息

批准号：
9123506
负责人：
Miles Berger
金额：
$ 10.93万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-15 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9123506
关键词：
Acute Address Adverse effects Affect Age Alzheimer&apos s Disease Alzheimer&apos s Disease Pathway Alzheimer&apos s disease risk American Amyloid beta-Protein Anesthesia procedures Animal Model Animals Axon Biological Markers Brain Cerebrospinal Fluid Clinical Research Cognitive deficits Complication Data Delirium Dementia Development Disease Elderly Environmental Risk Factor Epidemiologic Studies Functional disorder Goals Health Hospitals Hour Human Impaired cognition Knowledge Memory Memory impairment Microtubule-Associated Proteins Modeling Neurocognitive Neurological outcome Neuronal Injury Neurons Operative Surgical Procedures Outcome Outcomes Research Pathogenesis Pathology Patient-Focused Outcomes Patients Perioperative Perioperative Care Quality of life Research Research Personnel Rest Risk Risk Factors Subarachnoid Hemorrhage Syndrome Thinking Time Traumatic Brain Injury United States Visit Work cognitive function follow-up functional status high risk improved mortality mouse model multidisciplinary neuropathology older patient postoperative delirium prevent prospective relating to nervous system stem tau Proteins

项目摘要

DESCRIPTION (provided by applicant): Tau is a microtubule-associated protein found in neuronal axons, and is released after neuronal injury. Increased cerebrospinal fluid (CSF) tau levels predict the development of Alzheimer's disease, and increased CSF tau levels also predict worsened outcomes after subarachnoid hemorrhage and traumatic brain injury. We have found increased CSF tau levels in patients after surgery and anesthesia, and numerous investigators have found that anesthesia and surgery increase tau levels and cause memory deficits in animal models (6-8). Taken together, these findings suggest the possibility that changes in CSF tau levels may also be associated with neurocognitive changes after anesthesia and surgery in our patients. Indeed, multiple studies have found neurocognitive changes (i.e. post-operative delirium and cognitive dysfunction) occur in a substantial fraction of patients after surgery and anesthesia, and a major risk factor for these disorders is age >60. Post-operative delirium and cognitive dysfunction are major complications in elderly patients: they are associated with decreased ability to perform IADLs, decreased quality of life, early exit from the work force, and increased one year mortality. Yet, the underlying pathophysiology of post-operative delirium and/or cognitive dysfunction is unclear, which impedes our ability to treat these syndromes and improve patient outcomes. In this application, we will extend our preliminary work demonstrating significant increases in CSF tau levels after anesthesia and surgery by determining the long-term trajectory of these perioperative CSF tau increases, and whether they are associated with delirium, cognitive dysfunction, or altered functional neural connectivity in elderly surgical patients vs age-matched controls. We will also obtain data on the relationship between changes in CSF tau levels, IADLs and quality of life in these patients' vs controls. This study is the first, adequately powered prospective clinical study to determine the long-term trajectory of perioperative changes in CSF tau levels, and to correlate these changes with changes in cognitive function, brain connectivity and functional status. Understanding these relationships could help develop strategies to prevent adverse effects of anesthesia and surgery in the elderly and to improve neurocognitive function for the millions of patients over age 60 who undergo perioperative care each year in the United States.

描述（由申请人提供）：Tau 是一种在神经元轴突中发现的微管相关蛋白，在神经元损伤后释放，脑脊液 (CSF) tau 水平升高可预测阿尔茨海默病的发展，而 CSF tau 水平升高也可预测病情恶化。我们发现，在蛛网膜下腔出血和创伤性脑损伤后，患者的脑脊液 tau 水平升高，并且许多研究人员发现，麻醉和麻醉后患者的脑脊液 tau 水平升高。手术会增加动物模型中的 tau 水平并导致记忆缺陷 (6-8)。事实上，多项研究表明，脑脊液 tau 水平的变化也可能与患者麻醉和手术后的神经认知变化有关。发现神经认知变化（即术后谵妄和认知功能障碍）发生在很大一部分患者中手术和麻醉后的患者，这些疾病的主要危险因素是年龄 > 60 岁。术后谵妄和认知功能障碍是老年患者的主要并发症：它们与执行 IADL 的能力下降、生活质量下降、提前退出有关。然而，术后谵妄和/或认知功能障碍的潜在病理生理学尚不清楚，这阻碍了我们的治疗能力。在本申请中，我们将通过确定这些围手术期脑脊液 tau 增加的长期轨迹以及它们是否与谵妄相关，来扩展我们的初步工作，证明麻醉和手术后脑脊液 tau 水平显着增加。与年龄匹配的对照相比，老年手术患者的认知功能障碍或功能性神经连接发生改变。我们还将获得有关这些患者与对照的 CSF tau 水平、IADL 和生活质量之间关系的数据。首先，进行充分有力的前瞻性临床研究，以确定围手术期脑脊液tau蛋白水平变化的长期轨迹，并将这些变化与认知功能、大脑连接和功能状态的变化联系起来，了解这些关系有助于制定预防不良反应的策略。旨在改善老年人的麻醉和手术，并改善美国每年数百万接受围手术期护理的 60 岁以上患者的神经认知功能。