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: 9898206
• 负责人: Miles Berger
• 金额: $ 23.68万
• 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/9898206
• 关键词: Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer’s disease biomarker; American; Anesthesia procedures; Anesthesiology; Attention; Award; Biological Markers; Brain; Brain region; CCL2 gene; 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; Intervention Trial; K-Series Research Career Programs; Lead; Leadership; Link; MAPT gene; Measures; Memory; Memory impairment; Mentors; Methods; Mission; Modeling; Mus; National Institute on Aging; 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; human old age (65+); 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.

这是为 Miles Berger 博士颁发的 K76 Beeson 职业发展奖，他是一名老年神经科医师 专注于术后认知障碍的麻醉师每年超过 1600 万人。 美国人接受麻醉和手术，其中高达 40% 的患者出现 术后认知功能障碍（POCD），一种术后思维和记忆综合征 尽管与谵妄不同，POCD（如谵妄）与质量下降相关。 寿命缩短、长期认知能力下降、提前退休、死亡率增加以及可能增加的 患阿尔茨海默病等痴呆症的风险，我们需要预防 POCD 的策略， 但首先，我们需要了解导致这种情况的原因，一种主流理论认为是大脑炎症。 导致 POCD，但很少有工作直接在人类身上测试这一理论。 强烈表明老年人术后存在明显的神经炎症 在这个 K76 奖项中，我们将前瞻性地获得术前和术后认知。 对 200 名 65 岁以上的手术患者进行测试、功能磁共振成像和脑脊液样本。这将使我们能够 评估 POCD（其底层大脑）中特定神经炎症过程的作用 阿尔茨海默病的连通性变化以及脑脊液 (CSF) 术后变化 该项目将研究疾病 (AD) 生物标志物，例如微管相关蛋白 tau。 对 POCD 神经炎症过程的理解进展并阐明潜在联系 这些过程与 AD 病理学术后变化之间的关系，符合国家标准 衰老研究所的使命是了解衰老并对抗 AD 引起的认知能力下降。 K76 资助期间，Berger 博士还将完成单独定制的转化硕士学位 研究将包括免疫学方法、功能磁共振成像、认知神经科学、 该职业发展计划将为伯杰博士提供以下机会： 跨学科技能，以追求改善术后认知功能的长期目标 每年有超过 1600 万美国老年人接受麻醉和手术。