This is a resubmission for a K01 Mentored Research Scientist Award for Dr. Hannes Devos, an Early Career, Tenure Track Faculty of Physical Therapy and Rehabilitation Science at the University of Kansas Medical Center. While I have received clinical research training in my postdoctoral years, I seek to expand my scientific foundation in becoming an independent researcher in applied neurophysiology of Alzheimer's disease (AD). My primary goal is to attain independence, capable of leading a multidisciplinary group in investigating neurophysiological markers ?event-related potentials (ERP), heartbeat-evoked potentials (HEP), and task- evoked pupillary response (TEPR)? of early neurodegenerative decline in pre-clinical AD. I am at a critical point in my career to make this transition after gaining initial experience with pupillometry in Parkinson's disease. Thus, I am proposing a career development plan in which I will train with renowned experts in clinical methods (Dr. Burns), neurophysiology (Dr. Gustafson), neuro-imaging (Dr. Brooks and Dr. Burns), and research independence (Dr. Burns, Dr. Brooks, and Dr. Mahnken). From these experts' mentoring I will learn: (1) Expertise in clinical methods, including the study of cognitive changes due to normal aging and neurodegeneration on molecular, cellular, and systems level; (2) Expertise in neurophysiology of non-invasive brain activity measures such as ERP, HEP, and TEPR; (3) Experience in neuro-imaging, including the ability to read and analyze MRI and PET data; (4) Advanced experience in research independence, especially complex statistical analyses, scholarly productivity, and research funding. The proposed research offers a unique opportunity to (1) compare neurophysiological responses to cognitive demand between healthy aging, pre-clinical AD, and MCI/AD; (2) correlate neurophysiological responses to structural brain changes; and (3) examine the intrasubject variability of neurophysiological responses in the short- and long-term. The central hypothesis is that neurophysiological changes will manifest prior to decrements in neuropsychological performance in pre-clinical AD, reflecting a compensatory mechanism for excessive neural recruitment to cope with cognitive task demand. The knowledge gained from my career development and research training will enable me to compete for R01 funding to investigate neurophysiological markers of early neurodegenerative, cognitive, and functional decline in pre-clinical AD. This project will capitalize on KUMC's major research strengths: the NIH-designated Alzheimer's Disease Center, the Hoglund Brain Imaging Center, and the Clinical and Translational Science Unit (NIH CTSA). In summary, this K01-award will bring together my clinical research experience and my new skills in applied neurophysiology of AD. The mentor team and research environment will provide essential support on my track towards research independence.

Public Health Relevance

Non-invasive neurophysiological measures, including event-related potentials, heartbeat-evoked potentials, and task-evoked pupillary response, have the potential to detect early neurodegenerative changes in pre- clinical Alzheimer's disease (AD), even prior to showing up in neuropsychological tests. The relationship between neurophysiological changes, molecular and structural changes, and neuropsychological tests in pre- clinical AD is currently unknown. We propose a cohort study involving older adults with different severities of cognitive decline (cognitively normal healthy adults, cognitively normal pre-clinical AD, mild cognitive impairment, and AD) to (1) test the hypothesis that neurophysiological changes occur prior to the presence of neuropsychological changes in preclinical AD; (2) test the hypothesis that neurophysiological changes are a manifestation of early structural changes in pre-clinical AD; and (3) to examine the psychometric properties of the neurophysiological measures in the short and long term.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Scientist Development Award - Research & Training (K01)
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Neuroscience of Aging Review Committee (NIA)
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Wagster, Molly V
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University of Kansas
Other Health Professions
Sch Allied Health Professions
Kansas City
United States
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