Primary progressive aphasia (PPA) is a brain disease that causes a gradual and increasingly more debilitating impairment of word usage and comprehension. Although it is being recognized with increasing frequency, PPA remains underserved with respect to research and patient services. This application seeks continued funding for a project that is the centerpiece of a comprehensive PPA Research Program at Northwestern University. The goal is to make maximal use of a unique cohort that has been recruited during the first 5 years of the project and to enroll new patients for hypothesis-driven investigations of naming, word comprehension, incidental memory and sentence processing with novel tasks designed by a multidisciplinary team of investigators with a track record of close collaboration and high productivity in PPA. We believe that this type of research program can best be achieved within the structure of a multidisciplinary approach such as the one we have established for this purpose, led by researchers in neuroimaging (Dr. Emily Rogalski), neurolinguistics (Dr. Cynthia Thompson), event-related potentials (Dr. Ken Paller), neuropsychology (Dr. Sandra Weintraub), neurobehavior (Dr. Marsel Mesulam), biostatistics (Dr. Alfred Rademaker) and Magnetic Resonance physics (Dr. Todd Parrish). For the next cycle, we chose specific aims that address the four core themes of this project: subtyping and temporal evolution of PPA, mechanisms of naming and semantic distortions, characteristics of fluency and grammatical competence, and anatomical substrates of language as inferred from the distribution of peak atrophy sites in patients. Within this framework, our primary aims will be 1. To complete a longitudinal study of a select subset of current participants in order to delineat the natural course of PPA and to characterize the evolution of its initial stages (Experiment 1). 2 To clarify the mechanisms of anomia with a cross-modal ERP experiment (Experiment 2). 3. To investigate dynamic perturbations of verb and sentence processing with on-line tasks using the methodology of ERP and eye movement recording (Experiments 3 and 4). 4. To identify the anatomical basis of material- and modality-specific distortions of learning in PPA (Experiment 5). 5. To foster the continued development of the International PPA Connection (IMPPACT) website, launched through the American Recovery and Reinvestment Act (ARRA), as an international collaborative patient and resource registry (ppaconnection.org).

Public Health Relevance

Primary progressive aphasia (PPA) is a brain disease that causes a gradual and increasingly more debilitating impairment of word usage and comprehension. Although it is being recognized with increasing frequency, PPA remains underserved with respect to research and patient services. This application seeks continued funding for a project that is the centerpiece of a comprehensive PPA Research Program at Northwestern University.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01DC008552-08
Application #
8656321
Study Section
Language and Communication Study Section (LCOM)
Program Officer
Cooper, Judith
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Neurology
Type
Schools of Medicine
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60611
Martersteck, Adam; Murphy, Christopher; Rademaker, Alfred et al. (2016) Is in vivo amyloid distribution asymmetric in primary progressive aphasia? Ann Neurol 79:496-501
Seckin, Mustafa; Mesulam, M-Marsel; Voss, Joel L et al. (2016) Am I looking at a cat or a dog? Gaze in the semantic variant of primary progressive aphasia is subject to excessive taxonomic capture. J Neurolinguistics 37:68-81
Seckin, Mustafa; Mesulam, M-Marsel; Rademaker, Alfred W et al. (2016) Eye movements as probes of lexico-semantic processing in a patient with primary progressive aphasia. Neurocase 22:65-75
D'Anna, Lucio; Mesulam, Marsel M; Thiebaut de Schotten, Michel et al. (2016) Frontotemporal networks and behavioral symptoms in primary progressive aphasia. Neurology 86:1393-9
Kielb, Stephanie; Cook, Amanda; Wieneke, Christina et al. (2016) Neuropathologic Associations of Learning and Memory in Primary Progressive Aphasia. JAMA Neurol 73:846-52
Mack, Jennifer E; Chandler, Sarah D; Meltzer-Asscher, Aya et al. (2015) What do pauses in narrative production reveal about the nature of word retrieval deficits in PPA? Neuropsychologia 77:211-22
Hurley, Robert S; Bonakdarpour, Borna; Wang, Xue et al. (2015) Asymmetric connectivity between the anterior temporal lobe and the language network. J Cogn Neurosci 27:464-73
Mesulam, M-Marsel; Thompson, Cynthia K; Weintraub, Sandra et al. (2015) The Wernicke conundrum and the anatomy of language comprehension in primary progressive aphasia. Brain 138:2423-37
Christensen, Adam; Alpert, Kathryn; Rogalski, Emily et al. (2015) Hippocampal subfield surface deformity in non-semantic primary progressive aphasia. Alzheimers Dement (Amst) 1:14-23
Oboudiyat, Carly; Bigio, Eileen H; Bonakdarpour, Borna et al. (2015) Diffuse leukoencephalopathy with spheroids presenting as primary progressive aphasia. Neurology 85:652-3

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