This is an application for the Paul B. Beeson Career Development Award in Aging. Mild cognitive impairment (MCI) is a heterogeneous condition with multiple etiologies, presentations, and outcomes. This prospective study will investigate whether baseline magnetic resonace imaging (MRI) markers can predict conversion of MCI to Alzheimer disease (AD). We propose that entorhinal/parahippocampal, inferior and lateral temporal, posterior cingulate and precuneal gray matter atrophy, hippocampal atrophy and lateral ventricle enlargement will strongly correlate with conversion to AD within 3 years. We will recruit 90 MCI subjects from identified available recourses. They will receive a baseline high-quality structural MRI scan and yearly clinical and neuropsychological testing. The proposed state-of-the-art surface-based algorithms for explicit matching of corresponding morphology will reduce inter-subject variability, and increase the power to detect localized disease effects. The long-term goal of this project is to influence the methods of trial planning and patient selection, and to establish a powerful surrogate marker for MCI therapeutic trials. The candidate, Liana G. Apostolova, M.D., has developed an integrated research/educational plan that will lead to advanced knowledge in structural and functional neuroimaging analysis. In addition, she will pursue a Master of Science in Clinical Research degree at UCLA with structured course work in clinical trial methodology, biostatistics, clinical pharmacology and ethics of patient-oriented research. This multidisciplinary training will facilitate Dr. Apostolova's development into an independent investigator in patient-oriented research in aging. It will allow her to develop an R01 proposal investigating the effects of disease-modifying therapeutic interventions in a selected high-risk MCI cohort predestined to develop AD where MRI markers serve as surrogate marker of disease effect. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AG026803-02
Application #
7111063
Study Section
Special Emphasis Panel (ZAG1-ZIJ-9 (M3))
Program Officer
Buckholtz, Neil
Project Start
2005-08-15
Project End
2010-05-31
Budget Start
2006-07-01
Budget End
2007-05-31
Support Year
2
Fiscal Year
2006
Total Cost
$172,800
Indirect Cost
Name
University of California Los Angeles
Department
Neurology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Chow, N; Hwang, K S; Hurtz, S et al. (2015) Comparing 3T and 1.5T MRI for mapping hippocampal atrophy in the Alzheimer's Disease Neuroimaging Initiative. AJNR Am J Neuroradiol 36:653-60
Apostolova, Liana G; Di, Li Jie; Duffy, Erin L et al. (2014) Risk factors for behavioral abnormalities in mild cognitive impairment and mild Alzheimer's disease. Dement Geriatr Cogn Disord 37:315-26
Hwang, Kristy S; Beyer, Mona K; Green, Amity E et al. (2013) Mapping cortical atrophy in Parkinson's disease patients with dementia. J Parkinsons Dis 3:69-76
Apostolova, Liana G; Babakchanian, Sona; Hwang, Kristy S et al. (2013) Ventricular enlargement and its clinical correlates in the imaging cohort from the ADCS MCI donepezil/vitamin E study. Alzheimer Dis Assoc Disord 27:174-81
Chow, Nicole; Aarsland, Dag; Honarpisheh, Hedieh et al. (2012) Comparing hippocampal atrophy in Alzheimer's dementia and dementia with lewy bodies. Dement Geriatr Cogn Disord 34:44-50
Andrawis, John P; Hwang, Kristy S; Green, Amity E et al. (2012) Effects of ApoE4 and maternal history of dementia on hippocampal atrophy. Neurobiol Aging 33:856-66
Apostolova, Liana G; Green, Amity E; Babakchanian, Sona et al. (2012) Hippocampal atrophy and ventricular enlargement in normal aging, mild cognitive impairment (MCI), and Alzheimer Disease. Alzheimer Dis Assoc Disord 26:17-27
Apostolova, Liana G; Hwang, Kristy S; Medina, Luis D et al. (2011) Cortical and hippocampal atrophy in patients with autosomal dominant familial Alzheimer's disease. Dement Geriatr Cogn Disord 32:118-25
Apostolova, Liana G; Thompson, Paul M; Green, Amity E et al. (2010) 3D comparison of low, intermediate, and advanced hippocampal atrophy in MCI. Hum Brain Mapp 31:786-97
Apostolova, Liana G; Hwang, Kristy S; Andrawis, John P et al. (2010) 3D PIB and CSF biomarker associations with hippocampal atrophy in ADNI subjects. Neurobiol Aging 31:1284-303

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