Neurodegeneration and Neuronal Fluctuations in DLB and AD

DLB 和 AD 中的神经变性和神经元波动

• 批准号: 10881500
• 负责人: Shannon Chiu
• 金额: $ 14.57万
• 依托单位: MAYO CLINIC ARIZONA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-05 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10881500
• 关键词: Neurodegeneration; Neuronal; Fluctuations; DLB; AD

Project Summary/Abstract Dementia with Lewy bodies (DLB) is one of the most common neurodegenerative dementias and one of the Alzheimer disease related dementias (ADRDs), but much less is known about underlying pathophysiology and structural brain changes in DLB. DLB is frequently misdiagnosed clinically, most commonly as Alzheimer disease (AD). Currently, DLB diagnosis can only be confirmed post mortem, and early accurate diagnosis is critically needed to aid treatment, prognosis and long-term care. Diffusion-weighted MRI (dMRI) and task- based electroencephalography (EEG) are promising neurodiagnostic modalities for better characterizing DLB and potentially serving as biomarkers, an unmet need. While EEG monitors neuronal activity, dMRI can assess white matter pathways and neuronal degeneration in vivo. The primary goal of this K23 study is to characterize pathophysiologic and microstructural changes occurring in DLB, and advance our understanding of how they correlate with DLB clinical symptoms. I will investigate the pathophysiologic and microstructural changes occurring in DLB using a novel dMRI technique (Aim 1), and evaluate neuronal desynchronization in DLB using task-based quantitative EEG (Aim 2). The proposed research addresses a significant gap in the current literature on the underlying pathophysiology and brain structural changes associated with clinical manifestations of DLB. My long-term career goal is to become an independent clinician investigator and leader in the field of ADRDs, with a focus on Lewy body dementias. The proposed study builds on MRI research that I completed earlier in my training and will allow me to expand this into Lewy body dementias. I propose a rigorous training program with advanced coursework in structural imaging and EEG techniques, biostatistics, research design and execution, professionalism, leadership, and responsible conduct of research. My primary mentor, Dr. David Vaillancourt, is a well-established NIH-funded researcher in imaging and EEG techniques. He is an experienced mentor who has successfully trained many young trainees into independent, NIH-funded investigators. The University of Florida is an ideal environment for this project, not only for the necessary laboratories, equipment and supplies needed to complete the proposed studies, but also for the Fixel Institute as one of the leading Lewy body dementia Research Centers of Excellence. Together, the assembled team and environment will allow me to conduct mentored research with advanced neurodiagnostic techniques important for understanding DLB pathophysiology, and improving therapeutics in the future.

项目摘要/摘要 路易体痴呆是最常见的神经退行性痴呆之一，也是最常见的痴呆之一。 阿尔茨海默病相关痴呆(ADRD)，但对潜在的病理生理学和 DLB脑结构改变。DLB在临床上经常被误诊，最常见的是阿尔茨海默病。 疾病(AD)。目前，DLB的诊断只能在尸检后确认，早期准确的诊断是 急需帮助治疗、预后和长期护理。弥散加权磁共振成像(DMRI)和任务- 脑电(EEG)是一种很有前途的神经诊断方法，可以更好地描述DLB 并有可能成为生物标记物，这是一个尚未得到满足的需求。虽然脑电监测神经元的活动，但dMRI可以评估 体内白质通路和神经元变性。这项K23研究的主要目标是 DLB的病理生理和微结构改变，并加深我们对它们是如何发生的理解 与DLB临床症状相关。我将研究病理生理和显微结构的变化。 使用一种新的dMRI技术(AIM 1)在DLB中发生，并使用 基于任务的定量脑电(目标2)。这项拟议的研究解决了当前 与临床相关的潜在病理生理学和脑结构改变的文献 DLB的表现。 我的长期职业目标是成为ADRDS领域的独立临床研究员和领导者， 重点关注路易体痴呆症。这项拟议的研究是在我早些时候完成的MRI研究的基础上进行的 我的训练，并将使我扩大到路易体痴呆。我提出了一个严格的培训计划 在结构成像和脑电技术、生物统计学、研究设计和 执行力、专业性、领导力和负责任的研究行为。我的主要导师，大卫博士 Vaillancourt是美国国立卫生研究院资助的成像和脑电技术方面的知名研究员。他是一个 经验丰富的导师，成功地将许多年轻的实习生培养成由NIH资助的独立的 调查人员。佛罗里达大学是这个项目的理想环境，不仅是为了 完成拟议研究所需的实验室、设备和用品，以及Fixel研究所 作为领先的路易体痴呆症研究中心之一的卓越。团结在一起，集结的团队 环境将允许我用先进的神经诊断技术进行有指导的研究 对于了解DLB的病理生理学，并在未来改进治疗方法具有重要意义。