Neurodegeneration and Neuronal Fluctuations in DLB and AD

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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.