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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Clinical Neuroscience and Neurodegeneration Study Section (CNN)
Program Officer
Hsiao, John
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Mayo Clinic, Rochester
United States
Zip Code
Raman, Mekala R; Tosakulwong, Nirubol; Zuk, Samantha M et al. (2017) Influence of preeclampsia and late-life hypertension on MRI measures of cortical atrophy. J Hypertens 35:2479-2485
Zeydan, Burcu; Lowe, Val J; Schwarz, Christopher G et al. (2017) Pittsburgh compound-B PET white matter imaging and cognitive function in late multiple sclerosis. Mult Scler :1352458517707346
Zeydan, Burcu; Deelchand, Dinesh K; Tosakulwong, Nirubol et al. (2017) Decreased Glutamate Levels in Patients with Amnestic Mild Cognitive Impairment: An sLASER Proton MR Spectroscopy and PiB-PET Study. J Neuroimaging 27:630-636
Kantarci, Kejal; Murray, Melissa E; Schwarz, Christopher G et al. (2017) White-matter integrity on DTI and the pathologic staging of Alzheimer's disease. Neurobiol Aging 56:172-179
Jones, David T; Graff-Radford, Jonathan; Lowe, Val J et al. (2017) Tau, amyloid, and cascading network failure across the Alzheimer's disease spectrum. Cortex 97:143-159
Kantarci, Kejal; Lowe, Val J; Boeve, Bradley F et al. (2017) AV-1451 tau and ?-amyloid positron emission tomography imaging in dementia with Lewy bodies. Ann Neurol 81:58-67
Raman, Mekala R; Shu, Yunhong; Lesnick, Timothy G et al. (2017) Regional T1 relaxation time constants in Ex vivo human brain: Longitudinal effects of formalin exposure. Magn Reson Med 77:774-778
Sarro, Lidia; Tosakulwong, Nirubol; Schwarz, Christopher G et al. (2017) An investigation of cerebrovascular lesions in dementia with Lewy bodies compared to Alzheimer's disease. Alzheimers Dement 13:257-266
Kantarci, Kejal; Goldberg, Terry E (2016) MR spectroscopy, APOE genotype, and evolving ?-amyloid pathology: What is being detected and when. Neurology 86:1750-1
Kantarci, Kejal; Lowe, Val J; Lesnick, Timothy G et al. (2016) Early Postmenopausal Transdermal 17?-Estradiol Therapy and Amyloid-? Deposition. J Alzheimers Dis 53:547-56

Showing the most recent 10 out of 50 publications