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

这是为迈尔斯·伯杰博士颁发的K76比森职业发展奖，他是一名老年神经科医生- 专注于术后认知障碍的麻醉师。每年&>1600万岁的老年人 美国人接受麻醉和手术，其中高达40%的患者 术后认知功能障碍(POCD)--一种术后思维记忆综合征 赤字。虽然与精神错乱不同，但POCD(如精神错乱)与质量下降有关 寿命，长期认知衰退，提前退休，死亡率增加，以及可能增加 罹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，我们需要了解是什么导致了这种情况。一种占主导地位的理论认为，大脑炎症 导致POCD，但很少有研究直接在人类身上测试这一理论。我们的初步数据 强烈提示老年人术后有明显的神经炎症。 发展POCD。在这个K76奖项中，我们将前瞻性地获得手术前和术后的认知 对200例65岁以上的外科患者进行脑脊液检查、功能磁共振成像和脑脊液检查。这将使我们能够 评估特定的神经炎性过程在POCD及其基础脑中的作用 阿尔茨海默病患者脑脊液的连接性改变和术后改变 疾病(AD)生物标志物，如微管相关蛋白tau。这个项目将 进一步了解POCD的神经炎性过程并阐明可能的联系(S) 这些过程与AD术后病理变化之间的关系，符合National 老年研究所的使命是了解衰老和抗击由于AD导致的认知衰退。在此期间 K76授权期内，Berger博士还将完成翻译专业的个人定制硕士学位 研究将包括免疫学方法、功能磁共振成像、认知神经科学、 老年科学和医生领导力。这份职业发展计划将为伯杰博士提供 跨学科的技能，以追求改善术后认知功能的长期目标 为每年接受麻醉和手术的1600多万美国老年人服务。

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.