The Neurobiology of Two Distinct Types of Progressive Apraxia of Speech (SLD4T)

The purpose of this study is to identify and distinguish two different types of Progressive Apraxia of Speech through clinical imaging and testing.

Study Overview

• Status: Recruiting
• Conditions: Primary Progressive Aphasia; Apraxia of Speech; Primary Progressive Nonfluent Aphasia; Non-fluent Aphasia
• Intervention / Treatment: Diagnostic test: Testing protocol for the study

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 47

Contacts and Locations

• Study Contact: Name: Sarah M Boland, CCRP; Phone Number: 507-284-3863; Email: boland.sarah@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Sarah M Boland, CCRP; Phone Number: 507-284-3863; Email: boland.sarah@mayo.edu
      • Principal Investigator: Keith A Josephs, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients that have been diagnosed as having Progressive Apraxia of Speech.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Progressive Apraxia of Speech	Diagnostic test: Testing protocol for the study; All patients will see a Neurologist for a neuro exam and consult, see a Speech Pathologist for assessment of speech and language skills, see the Study Coordinator for neuropsych testing (brief tests of thinking, memory, visual spatial skills, etc), undergo an MRI of the brain and a DaTscan of the brain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distinguish types of Progressive Apraxia of Speech	Distinguish types of PAOS using the Apraxia of Speech Rating Scale (ASRS)	1-2 years after baseline imaging

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Keith Josephs, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Anticipated): July 1, 2027
• Study Completion (Anticipated): July 1, 2027

Study Registration Dates

• First Submitted: October 11, 2017
• First Submitted That Met QC Criteria: October 16, 2017
• First Posted (Actual): October 18, 2017

Study Record Updates

• Last Update Posted (Actual): April 11, 2023
• Last Update Submitted That Met QC Criteria: April 10, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: apraxia of speech
• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Neurodegenerative Diseases; Psychomotor Disorders; TDP-43 Proteinopathies; Proteostasis Deficiencies; Dementia; Language Disorders; Communication Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Aphasia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Apraxias; Aphasia, Broca; Primary Progressive Nonfluent Aphasia
• Other Study ID Numbers: 17-002468

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No