Neuro-inflammation in Postoperative Cognitive Dysfunction: CSF and fMRI Studies

术后认知功能障碍中的神经炎症：脑脊液和功能磁共振成像研究

• 批准号: 9390592
• 负责人: Miles Berger
• 金额: $ 24.3万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9390592
• 关键词: Aging; Alzheimer' s Disease; American; Anesthesia procedures; Anesthesiology; Attention; Award; Biological Markers; Brain; Brain region; Cerebrospinal Fluid; Cognition; Cognition Disorders; Cognitive; Data; Delirium; Dementia; Development Plans; Elderly; Encephalitis; Functional Magnetic Resonance Imaging; Funding; Future; General Anesthesia; Geriatrics; Geroscience; Goals; Grant; Headache; Health; Hour; Human; Image; Immune; Immunology; Impaired cognition; Individual; Inflammation; Institutes; Intervention Trial; K-Series Research Career Programs; Lead; Leadership; Link; MAPT gene; Measures; Memory; Memory impairment; Mentors; Methods; Mission; Modeling; Monocyte Chemoattractant Protein-1; Mus; Neuraxis; Operative Surgical Procedures; Outcome; Pain; Pathogenesis; Pathologic Processes; Pathology; Patients; Peripheral; Physicians; Play; Postoperative Period; Process; Quality of life; Research; Retirement; Risk; Role; Sampling; Spinal; Spinal Cord; Spinal Puncture; Syndrome; Testing; Thinking; Time; Training; Translational Research; United States National Institutes of Health; Work; base; career development; cognitive function; cognitive neuroscience; cognitive testing; cohort; cytokine; experience; fighting; functional MRI scan; improved; inattention; insight; molecular marker; monocyte; mortality; neuroinflammation; neuropathology; post-operative cognitive dysfunction; prevent; prospective; skills; tau Proteins; theories

This is a K76 Beeson career development award for Dr. Miles Berger, a geriatric neuro- anesthesiologist with a focus on postoperative cognitive disorders. Each year >16 million older Americans undergo anesthesia and surgery, and up to 40% of these patients develop postoperative cognitive dysfunction (POCD), a syndrome of postoperative thinking and memory deficits. Although distinct from delirium, POCD (like delirium) is associated with decreased quality of life, long term cognitive decline, early retirement, increased mortality, and a possible increased risk for developing dementia such as Alzheimer’s disease. We need strategies to prevent POCD, but first, we need to understand what causes it. A dominant theory holds that brain inflammation causes POCD, but little work has directly tested this theory in humans. Our preliminary data strongly suggest that there is significant postoperative neuro-inflammation in older adults who develop POCD. In this K76 award, we will prospectively obtain pre- and post-operative cognitive testing, fMRI imaging and CSF samples in 200 surgical patients over age 65. This will allow us to evaluate the role of specific neuro-inflammatory processes in POCD, its underlying brain connectivity changes, and postoperative changes in cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers, such as the microtubule-associated protein tau. This project will advance understanding of neuro-inflammatory processes in POCD and clarify the potential link(s) between these processes and postoperative changes in AD pathology, in line with the National Institute of Aging’s mission to understand aging and fight cognitive decline due to AD. During this K76 grant period, Dr. Berger will also complete an individually tailored MS degree in Translational Research that will include training in immunology methods, fMRI imaging, cognitive neuroscience, geroscience, and physician leadership. This career development plan will give Dr. Berger the transdisciplinary skills to pursue his longer term goal of improving postoperative cognitive function for the more than 16 million older Americans who have anesthesia and surgery each year.

这是迈尔斯·伯杰（Miles Berger）博士的K76 Beeson职业发展奖， 麻醉师专注于术后认知障碍。每年> 1600万年龄较大 美国人接受麻醉和手术，其中多达40％的患者发展 术后认知功能障碍（POCD），术后思维和记忆综合征 不足。尽管与del妄不同，但pocd（如del妄）与质量提高有关 生活，长期认知能力下降，提前退休，死亡率增加以及可能增加 患痴呆症（例如阿尔茨海默氏病）的风险。我们需要防止POCD的策略， 但是首先，我们需要了解导致它的原因。主要理论认为脑注射 导致POCD，但很少有工作直接在人类中测试了这一理论。我们的初步数据 强烈表明，老年人有明显的后神经炎症 开发POCD。在这个K76奖中，我们可能会获得术前和术后认知 在65岁以上的200名手术患者中进行测试，fMRI成像和CSF样品。这将使我们能够 评估特定神经炎症过程在POCD（其潜在的大脑）中的作用 连通性的变化以及脑脊液（CSF）阿尔茨海默氏症的术后变化 疾病（AD）生物标志物，例如微管相关的蛋白质TAU。这个项目将 提前了解POCD中神经炎症过程并阐明潜在的联系 在这些过程和AD病理学术后变化之间，与国家一致 老龄化研究所的使命是了解衰老和与AD引起的认知能力下降。在此期间 K76赠款期，Berger博士还将完全量身定制的MS翻译学位 研究将包括免疫学方法培训，fMRI成像，认知神经科学， Geroscience和身体领导。该职业发展计划将为Berger博士提供 跨学科技能追求他改善术后认知功能的长期目标 每年有1600万年龄较大的美国人。