# Longitudinal multi-modality imaging in progressive apraxia of speech

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2021 · $577,511

## Abstract

PROJECT SUMMARY
Progressive apraxia of speech is a neurodegenerative speech motor planning disorder that affects the
production of speech. In the 1st cycle of the R01 we demonstrated that progressive apraxia of speech is
associated with progressive degeneration of both the grey and white matter of the brain, with degeneration
spreading throughout the brain from a relatively focal starting point, and we showed that regional changes
correlated to clinical decline. However, the neurobiological mechanisms underlying these structural changes
and disease progression remain elusive and represent a gap in knowledge. Understanding disease
mechanisms will be critical for the development of appropriate therapies and for assessing the efficacy of
treatments. The primary goal of our 2nd cycle is, therefore, to utilize advanced neuroimaging techniques to
assess the neurobiological mechanisms underlying disease progression in progressive apraxia of speech. The
first objective of the study is to determine the regional distribution and progressive spread of tau uptake using
tau PET imaging. The second objective is then to using resting-state and task-based functional MRI and
diffusion tensor tractography to characterize how disruptions in functional and structural connectivity within and
across brain networks progress over time, and how these changes are related to regional tau uptake. Our last
objective is then to investigate correlations between these neuroimaging measures and clinical disease
progression. To accomplish these aims we will recruit 50 patients with progressive apraxia of speech, and
each patient will undergo two serial assessments one year apart. At each assessment, patients will have a
neurological and speech-language assessment, tau-PET scan using the [18F]AV-1451 ligand and a 3T
magnetic resonance imaging scan that will include resting-state functional MRI and diffusion tensor imaging
sequences. A subset of patients will also undergo a short task-based fMRI scan to allow us to assess brain
activity related to speech articulation. Our analysis will assess abnormalities in these modalities within the
motor speech network of regions, particularly premotor and motor cortex, and determine how dysfunction
within this network changes over time and whether the disease spreads to involve other networks. We will
calculate tau-PET uptake in a standard set of regions-of-interest and then measure both structural and
functional connectivity between these regions-of-interest. This approach will allow us to assess multi-modal
correlations and determine how these different disease mechanisms are related to each other as well as
clinical decline. This mechanistic approach will increase our understanding of disease progression and the
relationship between pathological processes and brain connectivity in progressive apraxia of speech;
knowledge that may help improve diagnostic specificity and will be critical for the future development of
mechanistically based th...

## Key facts

- **NIH application ID:** 10200748
- **Project number:** 5R01DC012519-09
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Jennifer Louise Whitwell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $577,511
- **Award type:** 5
- **Project period:** 2013-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200748

## Citation

> US National Institutes of Health, RePORTER application 10200748, Longitudinal multi-modality imaging in progressive apraxia of speech (5R01DC012519-09). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10200748. Licensed CC0.

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