In this K02 Independent Scientist Career Development Award, the candidate seeks to build upon his background in functional and structural neuroimaging and use multimodal neuroimaging to understand the evolution of cognitive disorders, such as Parkinson's disease dementia (PDD) and Alzheimer's disease (AD). The K02 will provide the candidate protected time for research and career development activities that will enhance the clinical applicability of his imaging expertise and assure excellence in the responsible conduct of human subject research. The proposed projects use multimodal magnetic resonance imaging (MRI) to examine structural and functional differences in the brains of patients with PDD and AD relative to elderly controls. The overall goal of the research is to better understand the selective vulnerability of brain regions to synuclein and amyloid pathology and to understand how cognitive deficits in dementia relate to underlying damage in brain structure and circuitry. Specifically, clinically and neuropsychologically characterized controls and subjects with PDD and AD will undergo a baseline and followup resting MRI protocol of around 30 minutes that will allow the following measurements: 1) regional volume of cortical and subcortical structures, 2) white matter integrity in tracts identified using probabilistic atlas-based diffusion tensor tractography, 3) functional connectivity within anatomically-defined regions of the default network, and 4) interval change in volume of cortical and subcortical structures using nonlinear registration of serial image datasets. High throughput processing streams are in place for efficiently capturing the structural measures obtained from each procedure, and the candidate's laboratory has added expertise in functional connectivity analysis. Thus, the proposed research will allow new insight into the structural and functional consequences of neurodegenerative disease.

Public Health Relevance

NARRATIVE: The proposed research aims to improve understanding of the effects of dementia on brain structure using noninvasive brain imaging. Such information may help researchers evaluate disease-modifying effects of new therapies designed to target different causes of dementia. Rapid quantitative assessment of brain structure might be practical in the clinical setting to assist clinicians in making earlier and more accurate diagnoses of neurodegenerative diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02NS067427-03
Application #
8197451
Study Section
NST-2 Subcommittee (NST)
Program Officer
Babcock, Debra J
Project Start
2009-12-01
Project End
2014-11-30
Budget Start
2011-12-01
Budget End
2012-11-30
Support Year
3
Fiscal Year
2012
Total Cost
$190,736
Indirect Cost
$14,129
Name
University of California San Diego
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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