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: 10449438
• 负责人: Shannon Chiu
• 金额: $ 15.56万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10449438
• 关键词: Address; Advisory Committees; Alzheimer' s Disease; Alzheimer' s disease related dementia; Attention; Biological Markers; Biometry; Brain; Brain imaging; Centers of Research Excellence; Clinical; Clinical Research; Cognitive; Collaborations; Collection; Data; Dementia with Lewy Bodies; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Elderly; Electroencephalography; Enrollment; Environment; Equipment and Supplies; Event; Florida; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Future; Goals; Grant; Image; Impairment; Individual; Inferior; Inflammation; Institutes; Institution; Leadership; Learning; Lewy Body Dementia; Lewy Body Disease; Lewy body pathology; Link; Literature; Long-Term Care; Magnetic Resonance Imaging; Measures; Medial; Mentors; Methods; Modality; Monitor; Motor; Nerve Degeneration; Neurons; Parietal; Parietal Lobe; Parkinsonian Disorders; Participant; Pathway interactions; Patients; Pattern; Postdoctoral Fellow; Process; Prognosis; REM Sleep; Research; Research Design; Research Personnel; Sensitivity and Specificity; Site; Structure; Substantia nigra structure; Symptoms; Techniques; Temporal Lobe; Testing; Thalamic structure; Therapeutic; Therapeutic Intervention; Training; Training Programs; United States National Institutes of Health; Universities; Update; Visual Hallucination; Water; accurate diagnosis; base; career; career development; clinically relevant; cohort; density; disorder control; experience; frontal lobe; grasp; gray matter; imaging approach; improved; in vivo; insight; laboratory equipment; mouse model; multi-ethnic; multi-racial; neurodegenerative dementia; neurophysiology; novel; potential biomarker; preservation; prospective; putamen; racial and ethnic; relating to nervous system; responsible research conduct; secondary outcome; sleep behavior; symposium; visual feedback; water diffusion; white matter

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.

项目总结/摘要 路易体痴呆（DLB）是最常见的神经退行性痴呆之一，也是最常见的神经退行性痴呆之一。 阿尔茨海默病相关性痴呆（ADRD），但对潜在的病理生理学和 DLB的脑结构变化。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的诊断只能在死后证实， 这对帮助治疗、预后和长期护理至关重要。弥散加权MRI（dMRI）和任务- 基于脑电图（EEG）是有前途的神经诊断方式，更好地表征DLB 并可能作为生物标记物，这是一个未满足的需求。虽然EEG监测神经元活动，但dMRI可以评估 体内白色物质通路和神经元变性。这项K23研究的主要目标是表征 病理生理和微结构的变化发生在DLB，并推进我们的理解， 与DLB临床症状相关。我会研究病理生理和微观结构的变化 使用新的dMRI技术（目的1）在DLB中发生，并使用 基于任务的定量EEG（目标2）。拟议的研究解决了目前的重大差距， 与临床相关的基础病理生理学和脑结构变化的文献 DLB的表现。 我的长期职业目标是成为ADRD领域的独立临床研究者和领导者， 专注于路易体痴呆症这项拟议中的研究建立在我在年早些时候完成的MRI研究的基础上。 我的训练，并将允许我扩展到路易体痴呆症。我提议一个严格的训练计划 在结构成像和脑电图技术，生物统计学，研究设计和 执行力、专业精神、领导力和负责任的研究行为。我的主要导师，大卫博士 Vaillancourt是NIH资助的成像和EEG技术方面的知名研究人员。他是一 经验丰富的导师，他成功地将许多年轻的学员训练成独立的，NIH资助的 investigators.佛罗里达大学是这个项目的理想环境，不仅是必要的 完成拟议研究所需的实验室、设备和用品，以及Fixel研究所 路易体痴呆症卓越研究中心之一。集合起来的团队 和环境将允许我用先进的神经诊断技术进行指导研究 这对于理解DLB的病理生理学和改进未来的治疗方法是重要的。