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.

项目概要/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。 阿尔茨海默病相关痴呆（ADRD），但人们对潜在的病理生理学和认知知之甚少。 DLB 中的大脑结构变化。 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诊断只能通过死后确诊，早期准确诊断是关键 迫切需要帮助治疗、预后和长期护理。弥散加权 MRI (dMRI) 和任务- 基于脑电图 (EEG) 的神经诊断方式有望更好地表征 DLB 并有可能作为生物标志物，这是一个未满足的需求。脑电图 (EEG) 监测神经元活动，而 dMRI 可以评估 白质通路和体内神经元变性。这项 K23 研究的主要目标是表征 DLB 中发生的病理生理学和微观结构变化，并加深我们对它们如何发生的理解 与 DLB 临床症状相关。我将研究病理生理学和微观结构的变化 使用新型 dMRI 技术（目标 1）在 DLB 中发生，并使用以下方法评估 DLB 中的神经元去同步化 基于任务的定量脑电图（目标 2）。拟议的研究解决了当前的重大差距 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 ADRD 领域的独立临床研究者和领导者， 重点关注路易体痴呆。拟议的研究建立在我早些时候完成的 MRI 研究的基础上 我的训练将使我能够将其扩展到路易体痴呆症。我提出严格的培训计划 拥有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 是一位由 NIH 资助的成像和脑电图技术领域知名研究员。他是一个 经验丰富的导师，已成功培训许多年轻学员成为独立的、由 NIH 资助的 调查人员。佛罗里达大学是该项目的理想环境，不仅提供了必要的 完成拟议研究所需的实验室、设备和用品，以及 Fixel 研究所 作为领先的路易体痴呆研究卓越中心之一。聚集在一起的团队 和环境将使我能够利用先进的神经诊断技术进行指导研究 对于理解 DLB 病理生理学和改进未来的治疗方法非常重要。