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: 10598925
• 负责人: Miles Berger
• 金额: $ 21.48万
• 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 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10598925
• 关键词: Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer’s disease biomarker; American; Anesthesia procedures; Attention; Award; Brain; CCL2 gene; Cerebrospinal Fluid; Cognition Disorders; Cognitive; Data; Delirium; Dementia; Development Plans; Elderly; Encephalitis; Functional Magnetic Resonance Imaging; Geroscience; Goals; Grant; Hour; Human; Image; Immunology; Impaired cognition; Individual; Inflammation; K-Series Research Career Programs; Leadership; Link; MAPT gene; Measures; Memory; Memory impairment; Methods; Mission; Mus; National Institute on Aging; Neuraxis; Operative Surgical Procedures; Patients; Physicians; Postoperative Period; Process; Quality of life; Retirement; Risk; Role; Sampling; Spinal Cord; Syndrome; Testing; Thinking; Time; Training; Translational Research; Work; career development; cognitive function; cognitive neuroscience; cognitive testing; fighting; human old age (65+); improved; monocyte; mortality; neuroinflammation; 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.

这是为老年神经麻醉师 Miles Berger 博士颁发的 K76 Beeson 职业发展奖 每年有超过 1600 万美国老年人接受术后认知障碍治疗。 麻醉和手术中，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缺陷的综合征，虽然与谵妄不同，但 POCD 是一种术后思维和记忆缺陷综合征。 （如谵妄）与生活质量下降、长期认知能力下降、提前退休、 死亡率增加，并可能增加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 POCD 的原因。 认为大脑炎症会导致 POCD，但很少有工作直接在人类身上测试这一理论。 我们的初步数据强烈表明，老年患者术后存在明显的神经炎症。 患有 POCD 的成年人在此 K76 奖项中，我们将前瞻性地获得术前和术后的奖项。 对 200 名 65 岁以上的手术患者进行认知测试、功能磁共振成像和脑脊液样本。这将使我们能够 评估 POCD 中特定神经炎症过程的作用及其潜在的大脑连接 脑脊液（CSF）阿尔茨海默病（AD）生物标志物的变化和术后变化， 例如微管相关蛋白 tau，该项目将促进对神经元的理解。 POCD 中的炎症过程，并阐明这些过程与 AD 病理学的术后变化，符合国家老龄化研究所的使命：了解 衰老和对抗 AD 引起的认知能力下降 在 K76 资助期间，Berger 博士还将完成一项研究。 个性化定制的转化研究硕士学位，其中包括免疫学方法的培训， 功能磁共振成像、认知神经科学、老年科学和医生领导力。 计划将为伯杰博士提供跨学科技能，以实现改善术后手术的长期目标 超过 1600 万接受麻醉和手术的美国老年人的认知功能 年。

项目成果

Awake Spinal Fusion Is Associated with Reduced Length of Stay, Opioid Use, and Time to Ambulation Compared to General Anesthesia: A Matched Cohort Study.

• DOI: 10.1016/j.wneu.2023.05.001
• 发表时间: 2023-08
• 期刊: WORLD NEUROSURGERY
• 影响因子: 2
• 作者: Sykes, David A. W.;Tabarestani, Troy Q.;Chaudhry, Nauman S.;Salven, David S.;Shaffrey, Christopher I.;Bullock, W. Michael;Guinn, Nicole R.;Gadsden, Jeffrey;Berger, Miles;Abd-El-Barr, Muhammad M.
• 通讯作者: Abd-El-Barr, Muhammad M.

Intraoperative Anesthetic Probes of Brain Health: Ketamine as a Canary in the Coal Mine?

• DOI: 10.1213/ane.0000000000005965
• 发表时间: 2022-10-01
• 期刊: Anesthesia and analgesia
• 影响因子: 5.7

A Real-Time Neurophysiologic Stress Test for the Aging Brain: Novel Perioperative and ICU Applications of EEG in Older Surgical Patients.

• DOI: 10.1007/s13311-023-01401-4
• 发表时间: 2023-07
• 期刊: NEUROTHERAPEUTICS
• 影响因子: 5.7
• 作者: Berger, Miles;Ryu, David;Reese, Melody;McGuigan, Steven;Evered, Lisbeth A.;Price, Catherine C.;Scott, David A.;Westover, M. Brandon;Eckenhoff, Roderic;Bonanni, Laura;Sweeney, Aoife;Babiloni, Claudio
• 通讯作者: Babiloni, Claudio

Amyloid beta and postoperative delirium: partners in crime or strangers in the dark?

β 淀粉样蛋白和术后谵妄：犯罪同伙还是黑暗中的陌生人？

• DOI: 10.1016/j.bja.2023.05.009
• 发表时间: 2023
• 期刊: British journal of anaesthesia
• 影响因子: 9.8
• 作者: Reekes,TylerH;Devinney,MichaelJ;Berger,Miles
• 通讯作者: Berger,Miles

Response to 'Correlation between bispectral index and age-adjusted minimal alveolar concentration' (Br J Anaesth 2020; 124:e8).

对“双频指数与年龄调整的最小肺泡浓度之间的相关性”的回应（Br J Anaesth 2020；124：e8）。

• DOI: 10.1016/j.bja.2019.12.005
• 发表时间: 2020
• 期刊: British journal of anaesthesia
• 影响因子: 9.8
• 作者: Berger,Miles;Cooter,Mary;Ni,Katherine;Thomas,Jake;Gupta,DhaneshK;Kertai,MiklosD
• 通讯作者: Kertai,MiklosD