# The neurobiology of two distinct types of progressive apraxia of speech

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2020 · $475,360

## Abstract

The primary goal of this R01 is to improve understanding of the neurobiology and clinical utility of recognizing
two distinct types of primary progressive apraxia of speech (PAOS). Phonetic PAOS is characterized
predominantly by distorted sound substitutions and additions, whereas Prosodic PAOS is characterized
predominantly by slow, prosodically segmented speech (previously referred to as type 1 and 2, respectively; a
third type is characterized by a relatively equal combination of the Phonetic and Prosodic characteristics). Little
is known about these PAOS types; however, pilot data suggest biological and clinically meaningful differences
between PAOS types. Specifically, Phonetic PAOS seems to be related to degeneration of neocortex, while
Prosodic PAOS appears to be more subcortically and brainstem mediated. Pathological underpinnings may
also differ across PAOS types. There is some evidence that Prosodic, and not Phonetic, PAOS is associated
with the development of a devastating extrapyramidal syndrome and shortened survival. Our approach to the
understanding of PAOS types will involve a comprehensive longitudinal assessment of clinical,
neuroanatomical, functional, molecular and histopathological data for these patients. By the end of the R01, we
expect to have collected and analyzed clinical data - including demographic, speech and language (perceptual
and acoustic), neurological, and neuropsychological variables - for 80 PAOS patients. Of these 80, 33 have
already been recruited and 47 will be recruited via this R01 mechanism. All 47 new patients will complete the
identical volumetric brain MRI protocol which will allow us to assess grey matter atrophy on structural MRI,
white matter tract degeneration on diffusion tensor imaging, and functional network disruption on task free
fMRI. All new patients to be recruited via this R01 mechanism will also complete a dopamine transporter
SPECT scan to assess for striatal dopamine receptor integrity. All tests will be completed annually.
Postmortem brain examinations and additional histological analyses of specific brain regions will also be
performed on the PAOS patients who are expected to die during this R01. This will be the first study to
systematically investigate PAOS types, as well as follow the course of disease longitudinally, and hence is
highly novel. The PI of this grant, Dr. Josephs, will be working with a team of experts in AOS (Drs. Duffy and
Utianski), structural neuroimaging (Dr. Whitwell), functional neuroimaging (Dr. Jones), molecular neuroimaging
(Dr. Lowe), neuropsychology (Drs. Machulda and Butts), and neuropathology (Dr. Dickson) who will work
among state of the art facilities and equipment to collectively to reach the aims. At the completion of the R01,
we will 1) better understand the neurobiology of PAOS and 2) validate the clinical validity and utility of PAOS
types through perceptual consensus, acoustic correlates, and data driven analysis to support prognostication
and...

## Key facts

- **NIH application ID:** 9982934
- **Project number:** 5R01DC014942-04
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Keith A Josephs
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $475,360
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982934

## Citation

> US National Institutes of Health, RePORTER application 9982934, The neurobiology of two distinct types of progressive apraxia of speech (5R01DC014942-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9982934. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*