Although pathology is the underlying cause of cognitive decline seen in Alzheimer's disease (AD), inter- subject variability in reserve mechanisms explains why some subjects have greater capacity to minimize the clinical expression of disease related neuropathological changes. The broad objective of this proposal is to investigate how measures of reserve modify the relationship between pathology and cognition. Pathology will be quantified using multi-modality PET and MRI imaging biomarkers. Mentored Phase:
For Specific Aim 1 of the study, the candidate will extend her published results for automated quantification of neurodegeneration in AD from structural MRI (sMRI) to develop algorithms for quantifying in vivo imaging measures of pathology from other imaging modalities (PiB-PET: indicator of plaque burden;FDG-PET: indicator of neuronal dysfunction;FLAIR: indicator of cerebro-vascular disease along with sMRI: indicator of neurodegeneration). These algorithms will be applied to calculate modality-specific imaging measures of pathology in our non-demented population-based cohort consisting of cognitively normal and mild cognitive impairment subjects. During this time, she will receive direct mentorship from Dr. Clifford Jack in the area of multi-modality imaging methods in AD and Dr. David Knopman in clinical aspects of aging and dementia. As part of the proposed research, the candidate will take courses in cognitive neuroscience and clinical methods to strengthen the skill set necessary for the multi-disciplinary research outlined here. Independent Phase (R00): During this phase, measures of reserve will be identified from functional connectivity metrics derived from resting state fMRI and from other sources such as intellectual lifestyle (education, occupation, cognitive activities) and physical activity measure (physical activity and exercise). These will be applied (Aim 2) to establish the relationships between imaging measures of pathology and cognitive performance and how these relationships are modified by measures of reserve and by interactions with other imaging measures of pathology. And in Aim 3, establish the relationships between imaging measures of pathology and change in cognitive performance over time and how these relationships are modified by measures of reserve and by interactions with other imaging measures of pathology.

Public Health Relevance

Understanding factors that modify the association between cognition and pathology in individual subjects will play a key role in the success of preventive strategies in non-demented elderly and are relevant for improving our understanding of the Alzheimer's disease.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Transition Award (R00)
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No Study Section (in-house review) (NSS)
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Hsiao, John
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Mayo Clinic, Rochester
United States
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Okonkwo, Ozioma C; Vemuri, Prashanthi (2017) Stemming the Alzheimer tsunami: introduction to the special issue on reserve and resilience in Alzheimer's disease. Brain Imaging Behav 11:301-303
Vemuri, Prashanthi; Lowe, Val J; Knopman, David S et al. (2017) Tau-PET uptake: Regional variation in average SUVR and impact of amyloid deposition. Alzheimers Dement (Amst) 6:21-30
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Graff-Radford, Jonathan; Madhavan, Malini; Vemuri, Prashanthi et al. (2016) Atrial fibrillation, cognitive impairment, and neuroimaging. Alzheimers Dement 12:391-8
Vemuri, Prashanthi; Fields, Julie; Peter, Jessica et al. (2016) Cognitive interventions in Alzheimer's and Parkinson's diseases: emerging mechanisms and role of imaging. Curr Opin Neurol 29:405-11
Vemuri, Prashanthi; Knopman, David S (2016) The role of cerebrovascular disease when there is concomitant Alzheimer disease. Biochim Biophys Acta 1862:952-6
Schwarz, Christopher G; Gunter, Jeffrey L; Wiste, Heather J et al. (2016) A large-scale comparison of cortical thickness and volume methods for measuring Alzheimer's disease severity. Neuroimage Clin 11:802-812
Vemuri, Prashanthi; Lesnick, Timothy G; Przybelski, Scott A et al. (2016) Effect of intellectual enrichment on AD biomarker trajectories: Longitudinal imaging study. Neurology 86:1128-35

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