Abstract

Primary progressive aphasia (PPA) is a devastating neurodegenerative syndrome that involves relentless development of aphasia with relative sparing of other cognitive functions, at least early in its course. There are multiple subtypes as well as multiple underlying pathologies. PPA and its subtypes can be difficult to differentiate from other neurodegenerative disorders and from each other, particularly early in their course. There are currently few clinical tools to assist in the early specific diagnosis of PPA and its subtypes. We have recently made substantial preliminary progress toward the development of novel imaging techniques that could be extremely valuable in early specific diagnosis of the molecular basis of specific pathologies underlying PPA. We propose to use tau and amyloid imaging tracers to attempt to discriminate these underlying molecular pathologies, and FDG-PET, functional connectivity MRI, and morphometric structural MRI to measure and longitudinally monitor markers of neurodegeneration in the language network(s) and other brain regions. In addition to more accurate diagnosis, these measures will likely be important for prognostication and monitoring of decline and the effects of putative therapies. The overall goal of this proposal is to translate these methods from new scientific technologies into clinically useful tools that can be used by clinicians around the country and internationally to improve the diagnostic specificity and assessment capabilities for PPA and its subtypes.

Public Health Relevance

Primary progressive aphasia (PPA), a devastating neurodegenerative syndrome that involves relentless development of language impairment, is currently not treatable in part because of a lack of tools available for identifying the underlying molecular diagnosis and for monitoring patients. This project aims to employ and validate new imaging methods for use as markers in clinical research and care, one goal of which is to serve as markers to determine whether potential therapies are effective.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC014296-04
Application #
9753727
Study Section
Clinical Neuroscience and Neurodegeneration Study Section (CNN)
Program Officer
Cooper, Judith
Project Start
2016-09-01
Project End
2021-08-31
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114

  Publications

Chen, Kevin T; Salcedo, Stephanie; Chonde, Daniel B et al. (2018) MR-assisted PET motion correction in simultaneous PET/MRI studies of dementia subjects. J Magn Reson Imaging 48:1288-1296
Makaretz, Sara J; Quimby, Megan; Collins, Jessica et al. (2018) Flortaucipir tau PET imaging in semantic variant primary progressive aphasia. J Neurol Neurosurg Psychiatry 89:1024-1031
Lois, Cristina; Gonzalez, Ivan; Johnson, Keith A et al. (2018) PET imaging of tau protein targets: a methodology perspective. Brain Imaging Behav :
Das, Sandhitsu R; Xie, Long; Wisse, Laura E M et al. (2018) Longitudinal and cross-sectional structural magnetic resonance imaging correlates of AV-1451 uptake. Neurobiol Aging 66:49-58
Veronelli, Laura; Makaretz, Sara J; Quimby, Megan et al. (2017) Geschwind Syndrome in frontotemporal lobar degeneration: Neuroanatomical and neuropsychological features over 9 years. Cortex 94:27-38
Cordella, Claire; Dickerson, Bradford C; Quimby, Megan et al. (2017) Slowed articulation rate is a sensitive diagnostic marker for identifying non-fluent primary progressive aphasia. Aphasiology 31:241-260
Dickerson, Bradford C; Brickhouse, Michael; McGinnis, Scott et al. (2017) Alzheimer's disease: The influence of age on clinical heterogeneity through the human brain connectome. Alzheimers Dement (Amst) 6:122-135
Darby, R Ryan; Brickhouse, Michael; Wolk, David A et al. (2017) Effects of cognitive reserve depend on executive and semantic demands of the task. J Neurol Neurosurg Psychiatry 88:794-802
Xia, Chenjie; Dickerson, Bradford C (2017) Multimodal PET Imaging of Amyloid and Tau Pathology in Alzheimer Disease and Non-Alzheimer Disease Dementias. PET Clin 12:351-359
Xia, Chenjie; Makaretz, Sara J; Caso, Christina et al. (2017) Association of In Vivo [18F]AV-1451 Tau PET Imaging Results With Cortical Atrophy and Symptoms in Typical and Atypical Alzheimer Disease. JAMA Neurol 74:427-436

Showing the most recent 10 out of 14 publications