The most common neurodegenerative pathologies underlying age associated cognitive decline, mild cognitive impairment (MCI) and dementia are Alzheimer's disease (AD) and Lewy body disease (LBD) pathologies. Evidence from proton MR Spectroscopy (MRS) and diffusion tensor MRI (DTI) suggest that these techniques are sensitive to early events in the neurodegenerative disease process at the cellular or molecular level. These MR markers may be more sensitive to degenerative changes preceding atrophy, and may provide additional information over structural MRI especially early in the disease course. Although the recent findings in clinically diagnosed patients are promising, the pathologic underpinnings of MRS and DTI alterations in neurodegenerative dementia are not well understood. Our goal is to validate MRS and DTI measures as surrogate markers of AD and LBD pathologies, because they are the most common neurodegenerative changes found in the elderly population. Our objective is to identify the biological correlates of antemortem MRS and DTI changes in specific cortical regions and white matter tracts associated with the paired helical filament (PHF)-tau, amyloid-? and alpha-synuclein mediated pathology. The overarching goal is to translate the MR markers into clinically valid measures of AD and LBD pathologies. The antemortem MRS and DTI changes associated with postmortem PHF-tau, amyloid-b and alpha-synuclein mediated neurodegenerative pathology will be identified using ROI-based quantitative methods for correlating antemortem imaging with postmortem histology. Finally, we will translate MRS and DTI markers to clinically valid measures of pathological severity.

Public Health Relevance

As an outcome of the proposed investigations, we will identify the pathologic basis of magnetic resonance spectroscopy and diffusion tensor imaging changes associated with neurodegeneration in a spectrum of Alzheimer's disease and Lewy body disease pathologies. The proposal is relevant because, with the development of disease modifying treatments, imaging markers of neurodegenerative dementia pathologies will be required for early diagnosis, treatment decisions and monitoring treatment response.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG040042-02
Application #
8331451
Study Section
Clinical Neuroscience and Neurodegeneration Study Section (CNN)
Program Officer
Hsiao, John
Project Start
2011-09-15
Project End
2016-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$321,789
Indirect Cost
$86,302
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Madhavan, Ajay; Schwarz, Christopher G; Duffy, Joseph R et al. (2016) Characterizing White Matter Tract Degeneration in Syndromic Variants of Alzheimer's Disease: A Diffusion Tensor Imaging Study. J Alzheimers Dis 49:633-43
Walton, Ronald L; Soto-Ortolaza, Alexandra I; Murray, Melissa E et al. (2016) TREM2 p.R47H substitution is not associated with dementia with Lewy bodies. Neurol Genet 2:e85
Graff-Radford, Jonathan; Madhavan, Malini; Vemuri, Prashanthi et al. (2016) Atrial fibrillation, cognitive impairment, and neuroimaging. Alzheimers Dement 12:391-8
Petersen, Ronald C; Wiste, Heather J; Weigand, Stephen D et al. (2016) Association of Elevated Amyloid Levels With Cognition and Biomarkers in Cognitively Normal People From the Community. JAMA Neurol 73:85-92
Sarro, Lidia; Tosakulwong, Nirubol; Schwarz, Christopher G et al. (2016) An investigation of cerebrovascular lesions in dementia with Lewy bodies compared to Alzheimer's disease. Alzheimers Dement :
Raman, Mekala R; Schwarz, Christopher G; Murray, Melissa E et al. (2016) An MRI-Based Atlas for Correlation of Imaging and Pathologic Findings in Alzheimer's Disease. J Neuroimaging 26:264-8
Graff-Radford, Jonathan; Lesnick, Timothy G; Boeve, Bradley F et al. (2016) Predicting Survival in Dementia With Lewy Bodies With Hippocampal Volumetry. Mov Disord 31:989-94
Kantarci, Kejal; Lowe, Val J; Lesnick, Timothy G et al. (2016) Early Postmenopausal Transdermal 17β-Estradiol Therapy and Amyloid-β Deposition. J Alzheimers Dis 53:547-56
Gungor, Ipek; Sarro, Lidia; Graff-Radford, Jonathan et al. (2015) Frequency and topography of cerebral microbleeds in dementia with Lewy bodies compared to Alzheimer's disease. Parkinsonism Relat Disord 21:1101-4
Chiang, G C; Cruz Hernandez, J C; Kantarci, K et al. (2015) Cerebral Microbleeds, CSF p-Tau, and Cognitive Decline: Significance of Anatomic Distribution. AJNR Am J Neuroradiol 36:1635-41

Showing the most recent 10 out of 40 publications