Longitudinal Multi-Modality Imaging in Progressive Apraxia of Speech

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.

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.