Joseph R Duffy

Mayo Foundation for Medical Education and Research | MMS · Department of Neurology

Purpose Speakers with primary progressive apraxia of speech (PPAOS) have an insidious onset of motor speech planning/programming difficulties. As the disease progresses, the apraxia of speech (AOS) becomes more severe and a co-occurring dysarthria often emerges. Here, longitudinal data from speakers with phonetic- and prosodic-predominant PPAOS are...

Introduction Transcribing disordered speech can be useful when diagnosing motor speech disorders such as primary progressive apraxia of speech (PPAOS), who have sound additions, deletions, and substitutions, or distortions and/or slow, segmented speech. Since transcribing speech can be a laborious process and requires an experienced listener, using...

Background and Objective No epidemiologic studies have formally assessed the incidence of primary progressive aphasia (PPA) and primary progressive apraxia of speech (PPAOS). Thus, we decided to assess the incidence of these disorders in Olmsted County, MN, between 2011 and 2022, and to characterize clinical, radiographic, and pathologic characteri...

Background and objectives: Nonverbal oral apraxia (NVOA) is the inability to plan, sequence, and execute voluntary oromotor movements in the absence of weakness. In the context of neurodegenerative disease, it remains unclear whether it is linked to a specific underlying pathologic, clinical, or neuroimaging finding. Thus, we aimed to assess the c...

Primary progressive aphasia (PPA) variants present with distinct disruptions in speech-language functions with little known about the interplay between affected and spared regions within the speech-language network and their interaction with other functional networks. The Neurodegenerative Research Group, Mayo Clinic, recruited 123 patients with PP...

Purpose We describe the communication challenges of four patients with a neurodegenerative disorder consistent with behavioral variant frontotemporal dementia (bvFTD), characterized by early behavioral and personality changes. By describing their clinical profiles, we identify common barriers to functional communication in this population and provi...

Progressive apraxia of speech (PAOS) is a 4R tauopathy characterized by difficulties with motor speech planning. Neurodegeneration in PAOS targets the premotor cortex, particularly the supplementary motor area (SMA), with degeneration of white matter (WM) tracts connecting premotor and motor cortices and Broca's area observed on diffusion tensor im...

Purpose Systematically improving voice therapy outcomes is challenging as the clinician actions (i.e., active ingredients) responsible for improved patient functioning (i.e., targets) are relatively unknown. The theory-driven Rehabilitation Treatment Specification System (RTSS) and standard, voice-specific terminology based on the RTSS (RTSS-Voice)...

Purpose: Systematically improving voice therapy outcomes is challenging as the clinician actions (i.e., active ingredients) responsible for improved patient functioning (i.e., targets) are relatively unknown. The theory-driven Rehabilitation Treatment Specification System (RTSS) and standard, voice-specific terminology based on the RTSS (RTSS-Voice...

Background and objectives Nonfluent variant primary progressive aphasia (nfvPPA) and primary progressive apraxia of speech (PPAOS) can be precursors to corticobasal syndrome (CBS). Details on their progression remain unclear. We aimed to examine the clinical and neuroimaging evolution of nfvPPA and PPAOS into CBS. Methods We conducted a retrospect...

Progressive supranuclear palsy is a neurodegenerative disease characterized by the deposition of four-repeat tau in neuronal and glial lesions in the brainstem, cerebellar, subcortical and cortical brain regions. There are varying clinical presentations of progressive supranuclear palsy with different neuroimaging signatures, presumed to be due to...

Two variants of semantic dementia are recognized based on the laterality of temporal lobe involvement: a left-predominant variant associated with verbal knowledge impairment and a right-predominant variant associated with behavioral changes and non-verbal knowledge loss. This cross-sectional clinicoradiologic study aimed to assess whole hippocampal...

Background Primary progressive aphasia (PPA) defines a group of neurodegenerative disorders characterised by language decline. Three PPA variants correlate with distinct underlying pathologies: semantic variant PPA (svPPA) with transactive response DNA-binding protein of 43 kD (TDP-43) proteinopathy, agrammatic variant PPA (agPPA) with tau depositi...

Objectives To introduce the first case in which primary progressive apraxia of speech (PPAOS) is associated with TAR DNA-binding protein 43 (TDP-43) instead of 4-repeat tau. Methods This patient was identified through a postmortem autopsy. Following an initial diagnostic evaluation, he participated in 3 annual research visits during which speech,...

Background Large curated data sets are required to leverage speech-based tools in health care. These are costly to produce, resulting in increased interest in data sharing. As speech can potentially identify speakers (ie, voiceprints), sharing recordings raises privacy concerns. This is especially relevant when working with patient data protected u...

Purpose Apraxia of speech (AOS) is a motor speech disorder affecting articulatory planning and speech programming. When AOS is the sole manifestation of neurodegeneration, it is termed primary progressive apraxia of speech (PPAOS). Recent work has shown that there are distinct PPAOS subtypes: phonetic, prosodic, and those that do not clearly align...

Progressive apraxia of speech is a neurodegenerative motor-speech disorder that most commonly arises from a 4-repeat tauopathy. Recent studies have established that progressive apraxia of speech is not a homogenous disease, but rather there are distinct subtypes: the phonetic subtype is characterized by distorted sound substitutions, the prosodic s...

Background Progressive apraxia of speech (PAOS) is characterized by difficulties with motor speech programming and planning. PAOS targets gray matter (GM) and white matter (WM) microstructure that can be assessed using diffusion tensor imaging (DTI) and multishell applications, such as neurite orientation dispersion and density imaging (NODDI). In...

Background Patients with a yes‐no reversal verbally and non‐verbally respond “yes” when they mean “no” and vice versa. They are typically aware of the error and able to correct it given additional time. This symptom commonly, but not exclusively, occurs in patients with primary progressive apraxia of speech (PPAOS). PPAOS is a form of frontotempora...

Background The spectrum of what is referred to as nonfluent/agrammatic primary progressive aphasia includes patients with isolated apraxia of speech (PPAOS), progressive agrammatic aphasia (PAA), or a combination thereof (AOS‐PAA). When AOS is present, there is typically an underlying 4R tauopathy (corticobasal degeneration; progressive supranuclea...

Background: The agrammatic variant of primary progressive aphasia (PAA), primary progressive apraxia of speech (PPAOS), or a combination of both (AOS-PAA) are neurodegenerative disorders characterized by speech-language impairments and together compose the AOS-PAA spectrum disorders. These patients typically have an underlying 4-repeat tauopathy, a...

Primary progressive aphasia (PPA) and primary progressive apraxia of speech (PPAOS) are neurodegenerative syndromes characterized by progressive decline in language or speech. There is a growing number of studies investigating speech-language interventions for PPA/PPAOS. An updated systematic evaluation of the treatment evidence is warranted to inf...

Most recent studies of progressive apraxia of speech (PAOS) have focused on patients with phonetic or prosodic predominant PAOS to understand the implications of the presenting clinical phenotype. Patients without a clearly predominating speech quality, or mixed AOS, have been excluded. Given the implications for disease progression, it is importan...

Background The semantic fluency task involves naming as many items as possible in a given category (e.g., animals) in one minute. It is often interpreted as a measure of word retrieval, but also draws on executive function abilities to organize responses and develop task‐specific strategies. Indeed, both language skills and dementia severity rating...

Purpose: To describe qualitative and quantitative longitudinal changes in dopamine transporter uptake (DaT) scan findings in progressive apraxia of speech (PAOS) patients. Methods: DaTQUANT software was used to quantify uptake in the left and right caudate and putamen in DaT scans of 39 patients with PAOS, 19 with repeat scans. Clinical radiolog...

Posterior cortical atrophy and logopenic progressive aphasia are atypical clinical presentations of Alzheimer’s disease. Resting-state functional connectivity studies have shown functional network disruptions in both phenotypes, particularly involving the language network in logopenic progressive aphasia and the visual network in posterior cortical...

Speech rate can be judged clinically using diadochokinetic (DDK) tasks, such as alternating motion rates (AMR) and sequential motion rates (SMR). We evaluated whether acoustic AMR/SMR speech rates would differentiate primary progressive apraxia of speech (PPAOS) from healthy controls, and determined how DDK rates relate to phonetic and prosodic spe...

Objective: Primary progressive apraxia of speech (PPAOS) is associated with imaging abnormalities in lateral premotor cortex (LPC) and supplementary motor area (SMA). It's unknown whether relatively greater involvement of these regions in either hemisphere is associated with demographics, presenting, and/or longitudinal features. Methods: In 51...

Purpose: Progressive apraxia of speech (PAOS) is a neurodegenerative disorder affecting the planning or programming of speech. Little is known about its magnetic susceptibility profiles indicative of biological processes such as iron deposition and demyelination. This study aims to clarify (1) the pattern of susceptibility in PAOS patients, (2) the...

Purpose: The purpose of this study was to describe, compare, and understand speech modulation capabilities of patients with varying motor speech disorders (MSDs) in a paradigm in which patients made highly cued attempts to speak faster or slower. Method: Twenty-nine patients, 12 with apraxia of speech (AOS; four phonetic and eight prosodic subty...

Purpose: Prior studies have shown that communication-related participation restrictions in patients with degenerative disease do not always match clinician judgment or objective indices of symptom severity. Although there is a growing body of literature documenting that discrepancies between patients with dementia and their care partners' percepti...

Purpose The purpose of this study was to examine the interrater reliability and validity of the Apraxia of Speech Rating Scale (ASRS-3.5) as an index of the presence and severity of apraxia of speech (AOS) and the prominence of several of its important features. Method Interrater reliability was assessed for 27 participants. Validity was examined...

Prior studies have shown communication‐related participation restrictions in patients with degenerative disease do not always match clinician judgment of symptom severity. Relatedly, there is a growing body of literature documenting discrepancies between patients with dementia and care partner perception of participation restrictions. However, it i...

Background: Globular glial tauopathy (GGT) has been associated with frontotemporal dementia syndromes; little is known about the clinical and imaging characteristics of GGT and how they differ from other non-globular glial 4-repeat tauopathies (N4GT) such as progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). Methods: For th...

UNSTRUCTURED Large, curated datasets are required to leverage speech-based tools in healthcare. These are costly to produce, resulting in increased interest in data sharing. As speech can potentially identify speakers (i.e., voiceprints), sharing recordings raises privacy concerns. We examine the re-identification risk for speech recordings, withou...

Primary progressive apraxia of speech (PPAOS) is a neurodegenerative motor speech disorder affecting the ability to produce speech. If agrammatic aphasia is present, it can be referred to as the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA). We investigated whether resting-state functional MRI (rs-fMRI) connectivity from dis...

Background: The hippocampus and temporal lobe are atrophic in typical amnestic Alzheimer's disease (tAD) and are used as imaging biomarkers in treatment trials. However, a better understanding of how temporal structures differ across atypical AD phenotypes and relate to cognition is needed. Objective: Our goal was to compare temporal lobe region...

A 57‐year‐old man presented with dynamic aphasia with evolving agrammatism and anomia. Additionally, he exhibited emerging atypical parkinsonism and features of behavioral variant frontotemporal dementia. Insights pertinent to this complex clinical presentation are discussed.

Introduction: Progressive agrammatic aphasia (PAA) can be associated with abnormal behaviors; however, it is unknown whether behaviors occur and/or are different in patients with primary progressive apraxia of speech (PPAOS). We aimed to compare baseline and longitudinal behavioral symptomatology between PPAOS, patients with PAA, and patients with...

Background Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy with neurodegeneration typically observed in the superior cerebellar peduncle (SCP) and dentatorubrothalamic tracts (DRTT). However, it is unclear how these tracts are differentially affected in different clinical variants of PSP. Objectives To determine whether diffusion trac...

Background Speech-induced action myoclonus may occur as a component of a generalized myoclonus syndrome. However, it may also present in isolation, or with a paucity of other findings, and be diagnostically challenging. Objectives To report a retrospective case series of restricted speech-induced action myoclonus. Methods We reviewed cases of spe...

Purpose Functional speech disorders (FSDs), a subtype of functional neurological disorders, are distinguishable from neurogenic motor speech disorders based on their clinical features, clinical course, and response to treatment. However, their differential diagnosis and management can be challenging. FSDs are not well understood, but growing eviden...

The objective of this study was to characterize network-level changes in nonfluent/agrammatic Primary Progressive Aphasia (agPPA) and Primary Progressive Apraxia of Speech (PPAOS) with graph theory (GT) measures derived from scalp electroencephalography (EEG) recordings. EEGs of 15 agPPA and 7 PPAOS patients were collected during relaxed wakefulnes...

This study compared orofacial muscle strength between normal and dysarthric speakers and across types of dysarthria, and examined correlations between strength and dysarthria severity. Participants included 79 speakers with flaccid, spastic, mixed spastic–flaccid, ataxic, or hypokinetic dysarthria and 33 healthy controls. Maximum pressure generatio...

Progressive apraxia of speech (AOS) is a motor speech disorder affecting the ability to produce phonetically or prosodically normal speech. Progressive AOS can present in isolation or co-occur with agrammatic aphasia and is associated with degeneration of the supplementary motor area. We aimed to assess breakdowns in structural connectivity from th...

Functional speech and voice disorders represent a common subtype of functional movement disorder (FMD). This chapter reviews the epidemiology of functional speech and voice disorders, the general approach to their diagnosis, and the characteristics of specific functional speech and voice disorders that allow them to be distinguished from other neur...

Background: Magnetic resonance brainstem measurements are useful structural biomarkers in the Richardson's syndrome variant of progressive supranuclear palsy (PSP). However, it is unclear how these biomarkers differ across the phenotypic spectrum of PSP and how they relate to underlying pathology. Objective: The aim of this study was to compare...

We describe two individuals with progressive verbal difficulty who exhibited impairment of propositional language, with relatively well-preserved auditory comprehension, naming, and repetition—a profile that is consistent with dynamic aphasia. By providing a brief review of pertinent literature and the results from our neurologic, speech and langua...

Background Progressive apraxia of speech (PAOS) is a neurodegenerative disorder of speech programming distinct from aphasia and dysarthria, most commonly associated with a 4-repeat tauopathy. Our objective was to better understand the reasons for possible delays or diagnostic errors for patients with PAOS.Methods Seventy-seven consecutive PAOS rese...

Background Logopenic progressive aphasia (LPA) and posterior cortical atrophy (PCA) have distinct patterns of hypometabolism and atrophy. However, these clinical syndromes overlap: visuospatial impairment has been documented in LPA and aphasia in PCA. Rey‐Osterrieth Complex Figure – Copy (Rey‐O Copy) performance is correlated with parietal‐occipita...

Background The Neurodegenerative Research Group (NRG) at Mayo clinic has followed patients with degenerative speech and/or language disorders for over a decade. In this presentation I will present data from this cohort to inform a broader discussion about the importance of apraxia of speech (AOS) and its subtypes, heterogeneity within the agrammati...

Background Individuals with Primary Progressive Apraxia of Speech (PPAOS) have AOS as the initial and predominant symptom. Many develop aphasia and/or dysarthria later in the disease course. Past research has shown that patients with neurodegenerative AOS experience reduced participation in communication that is further exacerbated by co‐occurring...

Background The apolipoprotein ε4 ( APOE4 ) allele is the most common and well established risk factor for typical late‐onset amnestic Alzheimer’s dementia. Less is known about the role of APOE in patients with atypical clinical presentations of AD, with studies often disagreeing on APOE4 frequencies in these cohorts. We aimed to assess relationship...

Purpose This study compared performance on three-word fluency measures among individuals with primary progressive aphasia (PPA) and primary progressive apraxia of speech (PPAOS), and examined the relationship between word fluency and other measures of language and speech. Method This study included 106 adults with PPA and 30 adults with PPAOS. PPA...

Background: Progressive supranuclear palsy (PSP) may present as a speech/language disorder (PSP-SL). Objective: We assessed pathological correlates of patients with PSP-SL who retained the suggestive of PSP-SL (s.o. PSP-SL) diagnosis versus those who progressed to possible/probable (poss./prob.) PSP. Methods: Thirty-four prospectively recruite...

Purpose Individuals with primary progressive apraxia of speech have apraxia of speech (AOS) as the initial and predominant symptom. Many develop aphasia and/or dysarthria later in the disease course. It was previously demonstrated that patients with neurodegenerative AOS experience reduced participation in communication that is further exacerbated...

Purpose Clinical trials have demonstrated that standardized voice treatment programs are effective for some patients, but identifying the unique individual treatment ingredients specifically responsible for observed improvements remains elusive. To address this problem, the authors used a taxonomy of voice therapy, the Rehabilitation Treatment Spec...

Introduction Progressive supranuclear palsy (PSP) variants other than PSP-Richardson Syndrome (PSP-RS) have been recognized, including PSP with speech and language problems (PSP-SL). Given the reported sleep disruptions in PSP-RS, we investigated sleep abnormalities in PSP-SL. Methods Four sleep-related screening questions were given to the caregi...

The apolipoprotein E (APOE) ε4 allele is the most well-established risk factor for Alzheimer's disease (AD), although its relationship to age at onset and clinical phenotype is unclear. We aimed to assess relationships between APOE genotype and age at onset, amyloid-beta (Aβ) deposition and typical versus atypical clinical presentations in AD. Freq...

Objective: To characterize and compare the neuropsychological profiles of patients with primary progressive apraxia of speech (PPAOS) and apraxia of speech with progressive agrammatic aphasia (AOS-PAA). Method: Thirty-nine patients with PPAOS and 49 patients with AOS-PAA underwent formal neurological, speech, language, and neuropsychological evalu...

Background: Posterior cortical atrophy (PCA) is an atypical variant of Alzheimer's disease (AD) that presents with visuospatial/perceptual deficits. PCA is characterized by atrophy in posterior brain regions, which overlaps with atrophy occurring in logopenic variant of primary progressive aphasia (lvPPA), another atypical AD variant characterized...

Communication problems (eg, dysphonia, dysfluency and language and articulation disorders), swallowing disorders (dysphagia and globus), cough and upper airway symptoms, resulting from functional neurological disorder (FND), are commonly encountered by speech and language professionals. However, there are few descriptions in the literature of the m...

Progressive apraxia of speech is a neurodegenerative syndrome affecting spoken communication. Molecular pathology, biochemistry, genetics, and longitudinal imaging were investigated in 32 autopsy-confirmed patients with progressive apraxia of speech who were followed over 10 years. Corticobasal degeneration and progressive supranuclear palsy (4R-ta...

Objective To assess and compare demographic, clinical, neuroimaging and pathologic characteristics of a cohort of patients with right versus left hemisphere-predominant logopenic progressive aphasia (LPA). Methods This is a case-control study of patients with LPA who were prospectively followed at Mayo Clinic and underwent an [ ¹⁸ F]-fluorodeoxygl...

A 67‐year‐old right‐handed woman presented with an approximate 3‐year history of word‐finding difficulty. She was initially diagnosed with progressive fluent aphasia, characterized by isolated anomia (mainly during confrontation naming) without explicit semantic or phonological impairment1. Her anomia was attributed to the left medial temporal lobe...

Purpose This study investigated the relationship between word production rates (WPRs) and phonological error rates (PERs) in generative and responsive tasks in logopenic progressive aphasia (lvPPA). We examined whether a portion of the reduced WPR during generative tasks related directly to phonological impairments affecting PER on all tasks, irres...