The primary goal of this five-year training award is to further the development of the candidate's expertise as a researcher and medical clinician in the following areas: 1) Imaging of functional brain systems in Alzheimer's disease and other dementias; 2) relationships between risk for Alzheimer's Disease (AD), functional brain system patterns, and neuropchycholgical test performance; and 3) clinical research design, methodologies, and statistical analysis techniques used in the evaluation of these relationships. The superceding career goals of this candidate are to improve the understanding of brain systems involved in dementia, develop diagnostic tools for early intervention in degenerative dementing diseases while functioning as a clinician researcher. The proposed training will include structured coursework and expert mentoring in clinical dementia, functional imaging, statistics and neuropsychology. The research project that will be adjunct to this training has an overall aim of conducting a five-year study of non-demented adults over a wide age range (30-50yrs) in an effort to identify reliable patterns of altered brain function and correlate those changes to the underlying hemodynamic response in individuals at higher risk for AD. The primary aims of this study are to answer the following questions: 1) What is the age variances of Blood Oxygen Level Dependency (BOLD) signal in AD risk? 2) Does this BOLD signal correlate to differences in underlying cerebral blood perfusion?, and 3) Does the variance in BOLD signal therefore representative pathology in underlying neuronal activity? The proposed study will evaluate variance in activation BOLD signal in relationship to baseline and activation perfusion, measured by Arterial Spin Labeling Functional MRI. Neuropsychological testing will be performed to evaluate for substantial group differences. Based on our previous pilot studies each participant will be imaged on a 3T MRI scanner while performing a verbal associate episodic memory task. This training program will allow this candidate to transition from a postdoctoral research fellow to an independent investigator and clinician in the field of geriatric neurology in the UCSD Department of Neurosciences, and provide the foundation for a clinical and research career focused on dementia pathology, treatment and diagnosis.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AG024062-02
Application #
6934489
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Molchan, Susan
Project Start
2004-08-15
Project End
2009-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
2
Fiscal Year
2005
Total Cost
$148,770
Indirect Cost
Name
University of California San Diego
Department
Neurosciences
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Wu, Xia; Li, Qing; Yu, Xinyu et al. (2016) A Triple Network Connectivity Study of Large-Scale Brain Systems in Cognitively Normal APOE4 Carriers. Front Aging Neurosci 8:231
Ouyang, Xin; Chen, Kewei; Yao, Li et al. (2015) Independent component analysis-based identification of covariance patterns of microstructural white matter damage in Alzheimer's disease. PLoS One 10:e0119714
Guo, Xiaojuan; Chen, Kewei; Zhang, Yumei et al. (2014) Regional covariance patterns of gray matter alterations in Alzheimer's disease and its replicability evaluation. J Magn Reson Imaging 39:143-9
Wang, Yan; Chen, Kewei; Yao, Li et al. (2013) Structural interactions within the default mode network identified by Bayesian network analysis in Alzheimer's disease. PLoS One 8:e74070
Li, R; Wu, X; Chen, K et al. (2013) Alterations of directional connectivity among resting-state networks in Alzheimer disease. AJNR Am J Neuroradiol 34:340-5
Li, Rui; Wu, Xia; Fleisher, Adam S et al. (2012) Attention-related networks in Alzheimer's disease: a resting functional MRI study. Hum Brain Mapp 33:1076-88
Guo, Xiaojuan; Han, Yuan; Chen, Kewei et al. (2012) Mapping joint grey and white matter reductions in Alzheimer's disease using joint independent component analysis. Neurosci Lett 531:136-41
Zhou, Shan; Chen, Kewei; Reiman, Eric M et al. (2012) A method for generating image-derived input function in quantitative 18F-FDG PET study based on the monotonicity of the input and output function curve. Nucl Med Commun 33:362-70
Miao, Xiaoyan; Wu, Xia; Li, Rui et al. (2011) Altered connectivity pattern of hubs in default-mode network with Alzheimer's disease: an Granger causality modeling approach. PLoS One 6:e25546
Li, Rui; Chen, Kewei; Fleisher, Adam S et al. (2011) Large-scale directional connections among multi resting-state neural networks in human brain: a functional MRI and Bayesian network modeling study. Neuroimage 56:1035-42

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