The Neurobiology of Two Distinct Types of Progressive Apraxia of Speech

Apraxia of speech (AOS) is a motor speech disorder reflecting a problem with the programming
and/or planning of speech. AOS is well recognized in the context of stroke where onset is
acute and the condition improves or is stable and chronic. AOS that is insidious in onset and
progresses over time because of neurodegeneration is less well recognized and understood. For
the past decade the investigators have been studying patients with primary progressive
apraxia of speech (PAOS). They have demonstrated that it can be the earliest manifestation of
an underlying neurodegenerative disease and have recently reported that the profile of PAOS
characteristics can differ among affected patients. In some instances, the speech pattern is
dominated by distorted sound substitutions and additions, and other features attributable to
articulatory difficulty, while in other instances the pattern is dominated by slow,
prosodically segmented speech. We have designated the first profile as Phonetic PAOS
(Ph-PAOS) and the second as Prosodic PAOS (Pr-PAOS; previously referred to in our studies as
type 1 and 2, respectively). Importantly, it appears that the AOS pattern type may have
prognostic implications. In a recent longitudinal study, the investigators observed that in
some PAOS patients, the AOS remained the most salient feature over an average of seven years
of the neurodegenerative disease. Other patients developed a severe extrapyramidal syndrome,
resembling progressive supranuclear palsy, within five years, causing significant morbidity,
including the inability to ambulate and a shortened life span; interestingly, this more
aggressive course was associated with the Pr- PAOS type. At present, little is known about
these types. To address the main aim to better understand the neurobiology and clinical
associations of PAOS types, they will perform longitudinal speech, language, and
neurocognitive testing, acoustic analyses, neuroimaging, and autopsy in a cohort of 47 new
PAOS patients (for 80 PAOS patients total) and healthy controls.

Inclusion Criteria:

1. All enrolled patients must be over the age of 18, speak English as their primary
language, and have an informant who can provide an independent evaluation of
functioning.

2. Each new patient must present with a chief complaint of progressive impairment of
speech and must have evidence of AOS documented by a speech-language pathologist
during routine clinical evaluation.

3. At study entry, all patients must have speech sufficiently intelligible for a
confident diagnosis of AOS, dysarthria, and/or aphasia, and for acoustic analysis.

Exclusion Criteria:

1. Any patient whose speech is not intelligible enough for confident speech-language
diagnosis will be excluded from the study.

2. All patients with concurrent illnesses that could account for speech deficits (e.g.,
traumatic brain injury, strokes, developmental syndromes), and patients meeting
criteria for another neurodegenerative disease (e.g., Alzheimer's type dementia57),
will be excluded.

3. Patients with aphasia or dysarthria who do not have PAOS, or whose aphasia or
dysarthria at study entry is more severe than PAOS, will be excluded.

4. All women who are pregnant, or post-partum and breast-feeding, will be excluded as
they are unable to undergo the required imaging. All women who can become pregnant
must have a pregnancy test no more than 48 hours before the DaTscan.

5. Patients will also be excluded if MRI is contraindicated (e.g., metal in head, cardiac
pace maker), 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).

6. Patients will be excluded if they do not have an informant, or do not consent to the
research.