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.

项目摘要/摘要 Lewy Bodies（DLB）是最常见的神经退行性痴呆症之一，是其中之一 阿尔茨海默氏病有关的痴呆症（ADRDS），但对潜在的病理生理学和 DLB的结构大脑变化。 DLB经常在临床上被误诊，最常见于阿尔茨海默氏症 疾病（AD）。目前，DLB诊断只能在Mortem后确认，并且早期准确的诊断是 有助于治疗，预后和长期护理需要至关重要的。扩散加权MRI（DMRI）和任务 - 基于脑电图（EEG）是有希望的神经诊断方式，可以更好地表征DLB 并有可能用作生物标志物，这是一种未满足的需求。在脑电图监测神经元活动的同时，DMRI可以评估 白质途径和体内神经元变性。这项K23研究的主要目标是表征 DLB中发生的病理生理和微观结构变化，并促进我们对它们如何的理解 与DLB临床症状相关。我将研究病理生理和微观结构的变化 使用新型的DMRI技术（AIM 1）在DLB中发生，并使用DLB中的神经元对异步进行评估 基于任务的定量脑电图（AIM 2）。拟议的研究解决了当前的显着差距 关于与临床相关的潜在病理生理学和大脑结构变化的文献 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， 专注于Lewy身体痴呆症。拟议的研究是基于我之前完成的MRI研究 我的培训将使我能够将其扩展到Lewy身体痴呆症中。我建议一个严格的培训计划 结构成像和脑电图技术，生物统计学，研究设计和 执行，专业精神，领导和负责任的研究行为。我的主要导师大卫博士 Vaillancourt是一位成像和脑电图技术领域的知名研究员。他是一个 经验丰富的导师，他成功地培训了许多年轻的学员，为独立的NIH资助 调查人员。佛罗里达大学是该项目的理想环境，不仅是必要的 完成拟议的研究所需的实验室，设备和用品，但也用于Fixel Institute 作为领先的路易人身体痴呆症研究中心之一。组装团队在一起 环境将使我能够通过高级神经诊断技术进行指导的研究 对于理解DLB病理生理学和未来改善治疗剂的重要性很重要。