Apraxia of speech (AOS) is a disorder affecting the motor planning of speech and can be associated with neurodegenerative diseases. It can occur in isolation or in the presence of a language disorder whereby patients have problems with grammar and spoken language, known as non-fluent aphasia (NFA). It is unclear how longitudinal structural and functional changes in the brain are related to the heterogeneous clinical features of the disorder. Characterizing progression in neurodegenerative AOS will be critical for patient prognosis and for further defining these disorders for future research and clinical trials. The objectives of the studies outlined in this application are to determine the relationship between structural and functional changes in the brain and progression of speech and language, neurological and neuropsychological features in patients with AOS. To accomplish our aims we will utilize a well characterized cohort of neurodegenerative AOS subjects that were evaluated at the Mayo Clinic, Rochester MN, and have undergone standardized speech and language, neurological and neuropsychological evaluations, a magnetic resonance imaging (MRI) scan and a [18-F]-fluoro-deoxy-glucose (FDG) positron emission tomography (PET) scan. In this study, we will perform two additional serial assessments of each patient, with the first performed 2.5 years after their original assessment, and the second performed one year later. Each assessment will include identical speech and language, neurological and neuropsychological evaluations and an MRI and FDG-PET scan. Therefore, three serial assessments will be available for analysis in this study. We will assess the rate of brain tissue loss, and examine which specific brain regions and white matter tracts change over time. Changes in brain metabolism and functional connectivity will also be assessed. We will then investigate associations between these imaging measures and different aspects of clinical decline, as well as develop imaging-based models that predict clinical outcomes, such as worsening of AOS and the development of NFA in patients with isolated AOS. Importantly, since we would have followed patients for a number of years, we anticipate that some subjects will die during the study and hence we will be able to perform brain autopsies to determine what disease(s) are present in the brain and develop neuroimaging models to predict brain pathology. The application focuses on neuroimaging and will be led by a Principal Investigator with 10 years experience in neuroimaging research involving these neurodegenerative disorders. She will also have support from a team of world renowned scientists including dementia, movement disorders and speech pathology specialists, a nuclear medicine scientist, neuropsychologists, and biostatisticians. The long term goal of our research is to develop neuroimaging biomarkers in neurodegenerative AOS and provide results that will help improve predictions about the course of clinical decline.

Public Health Relevance

This study will determine the association between imaging changes in the brain over time and symptom characteristics in patients that present with progressive apraxia of speech with and without aphasia. In addition, the study will assess, with autopsy examinations, the relationship between imaging changes and specific brain diseases that cause patients to present with these speech and language problems. The study will improve our understanding of disease progression in such patients, improve prognosis, and lead to better targeted future treatment trials and treatments for patients with apraxia of speech.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Language and Communication Study Section (LCOM)
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Shekim, Lana O
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Mayo Clinic, Rochester
United States
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Koga, Shunsuke; Parks, Adam; Kasanuki, Koji et al. (2017) Cognitive impairment in progressive supranuclear palsy is associated with tau burden. Mov Disord 32:1772-1779
Duffy, Joseph R; Hanley, Holly; Utianski, Rene et al. (2017) Temporal acoustic measures distinguish primary progressive apraxia of speech from primary progressive aphasia. Brain Lang 168:84-94
Whitwell, Jennifer L; Duffy, Joseph R; Machulda, Mary M et al. (2017) Tracking the development of agrammatic aphasia: A tensor-based morphometry study. Cortex 90:138-148
Höglinger, Günter U; Respondek, Gesine; Stamelou, Maria et al. (2017) Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Mov Disord 32:853-864
Respondek, Gesine; Kurz, Carolin; Arzberger, Thomas et al. (2017) Which ante mortem clinical features predict progressive supranuclear palsy pathology? Mov Disord 32:995-1005
Whitwell, Jennifer L; Höglinger, Günter U; Antonini, Angelo et al. (2017) Radiological biomarkers for diagnosis in PSP: Where are we and where do we need to be? Mov Disord 32:955-971
Koga, Shunsuke; Josephs, Keith A; Ogaki, Kotaro et al. (2016) Cerebellar ataxia in progressive supranuclear palsy: An autopsy study of PSP-C. Mov Disord 31:653-62
Whitwell, Jennifer L; Weigand, Stephen D; Duffy, Joseph R et al. (2016) Clinical and MRI models predicting amyloid deposition in progressive aphasia and apraxia of speech. Neuroimage Clin 11:90-8
Josephs, Keith A; Whitwell, Jennifer L; Tacik, Pawel et al. (2016) [18F]AV-1451 tau-PET uptake does correlate with quantitatively measured 4R-tau burden in autopsy-confirmed corticobasal degeneration. Acta Neuropathol 132:931-933
Duffy, Joseph R; Strand, Edythe A; Clark, Heather et al. (2015) Primary progressive apraxia of speech: clinical features and acoustic and neurologic correlates. Am J Speech Lang Pathol 24:88-100

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