Longitudinal Multi-Modality Imaging in Progressive Apraxia of Speech

  • STATUS
    Recruiting
  • End date
    Jun 1, 2023
  • participants needed
    50
  • sponsor
    Mayo Clinic
Updated on 24 January 2022

Summary

The study is designed to determine the relationship between structural and functional changes in the brain on imaging and progression of speech and language, neurological and neuropsychological features in patients with neurodegenerative apraxia of speech (AOS).

Description

Apraxia of Speech (AOS) is a disorder of speech motor planning and/or programming that affects the production of speech, characterized by slow speaking rate, abnormal prosody and distorted sound substitutions, additions, repetitions and prolongations, sometimes accompanied by groping, and trial and error articulatory movements. While AOS is commonly associated with vascular insults, it can be the predominant manifestation of neurodegenerative disease. Apraxia of speech can be the only manifestation of a neurodegenerative disorder. However, AOS very often co-occurs with aphasia, particularly a non-fluent aphasia (NFA) of the Broca's type; a language disorder, typically characterized by agrammatic, telegraphic or truncated spoken language, often accompanied by similar difficulties with written language. Patients with neurodegenerative AOS can have varying degrees of NFA, with the aphasia considered more severe than the AOS in some patients, but with the AOS dominant in others. It is extremely rare to have a patient that presents with NFA that does not also have AOS. Patients with isolated AOS can develop NFA over time, although in some patients the AOS remains isolated for as many as 8-10 years.

Patients with AOS can also develop dysarthria and other non-speech motor symptoms, such as extrapyramidal features, postural instability, extra ocular eye movement abnormalities and limb apraxia. Cognitive impairment can also develop, although is rarely an early feature of the disease. The syndrome is progressive with many patients eventually becoming mute.

Studies have shown that patients with neurodegenerative AOS can be pathologically heterogeneous, with some cases showing deposition of the microtubule associated protein tau, while others have deposition of the TAR DNA binding protein of 43kDa (TDP-43). Typical tau pathologies that are observed include corticobasal degeneration, progressive supranuclear palsy (PSP) and Pick's disease. Clinical features are currently unhelpful in predicting the underlying pathology in these cases, although there is a suggestion that cases with isolated or dominant AOS may be more likely to show tau pathology, particularly PSP.

This project will be the first to assess longitudinal multi-modality neuroimaging in subjects with neurodegenerative AOS. It will allow us to assess all aspects of disease progression in these subjects, including changes on neuroimaging, speech and language, neurological, and neuropsychological assessments, to get a complete picture of dysfunction and progression in these subjects. This project will also be the first to apply DTI and the recently developed technique of resting state fMRI to the study of this disease. These techniques are of great current interest to the field and provide, for the first time, a way of assessing underlying functional and structural connectivity across the brain. Both techniques provide important information about how disease progresses through the brain tissue and have huge potential to be important future biomarkers of many different neurodegenerative diseases.

Details
Condition PPA, Non-fluent Aphasia, Apraxia of Speech, Primary Progressive Non-fluent Aphasia, Primary Progressive Aphasia
Treatment FDG Fluorodeoxyglucose 18, AV-1451
Clinical Study IdentifierNCT01818661
SponsorMayo Clinic
Last Modified on24 January 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

We will study subjects that fulfill clinical inclusion criteria for neurodegenerative AOS that have been seen and diagnosed at Mayo Clinic

Exclusion Criteria

Subjects with concurrent illnesses that could account for speech and language deficits, such as traumatic brain injury, strokes or developmental syndromes will be excluded
Women that are pregnant or post-partum and breast-feeding will be excluded. All women who can become pregnant must have a pregnancy test no more than 48 hours before the PET scan
Subjects will also be excluded if MRI is contraindicated (metal in head, cardiac pace maker, e.t.c.), if there is severe claustrophobia, if there are conditions that may confound brain imaging studies (e.g. structural abnormalities, including subdural hematoma or intracranial neoplasm), or if they are medically unstable or are on medications that might affect brain structure or metabolism,(e.g. chemotherapy)
Subjects will also be excluded if they do not have an informant, or do not consent to research
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