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

这是为老年神经麻醉师迈尔斯·伯杰博士颁发的K76比森职业发展奖 重点放在术后认知障碍上。每年有1600万美国老年人接受 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障碍的综合征。虽然不同于精神错乱，但POCD (如精神错乱)与生活质量下降、长期认知能力下降、提前退休、 死亡率增加，罹患阿尔茨海默病等痴呆症的风险可能增加。 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POCD。占主导地位的理论 认为脑部炎症会导致POCD，但很少有工作在人类身上直接测试这一理论。 我们的初步数据有力地表明，老年人术后有明显的神经炎症。 患有POCD的成年人。在这个K76奖项中，我们将前瞻性地获得手术前和手术后 对200例65岁以上外科患者进行认知测试、功能磁共振成像和脑脊液标本检测。这将使我们能够 评估特定的神经炎性过程在POCD及其潜在的脑连接中的作用 脑脊液(CSF)阿尔茨海默病(AD)生物标志物的变化和手术后的变化 例如微管相关蛋白tau。这个项目将促进对神经细胞的了解 并阐明这些过程和炎症过程之间的潜在联系(S) AD术后病理的变化，与国家老龄研究所了解的使命一致 抗阿尔茨海默病引起的认知功能衰退。在K76授予期间，Berger博士还将完成一项 个人定制的翻译研究硕士学位，将包括免疫学方法培训， 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 该计划将为伯杰医生提供跨学科的技能，以实现他改善术后状况的长期目标 1600多万美国老年人分别接受麻醉和手术后的认知功能 年。

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.