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K76比森职业发展奖授予迈尔斯·伯杰博士，一位老年神经学家