Citations

ObjectivesThe four‐repeat (4R) tauopathies are a group of neurodegenerative diseases, including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and globular glial tauopathy (GGT). This study aimed to characterize spatiotemporal atrophy progression using structural magnetic resonance imaging (MRI) and to examine its relationship with clinical course and neuropathology in a cohort of autopsy‐confirmed 4R tauopathies.MethodsThe study included 85 autopsied patients (54 with PSP, 28 with CBD, and 3 with GGT) who underwent multiple 3T MRI scans, as well as neuropsychological, neurological, and speech/language examinations, and standardized postmortem neuropathological evaluations. An unsupervised machine‐learning algorithm, Subtype and Stage Inference (SuStaIn), was applied to the cross‐sectional brain volumes to estimate spatiotemporal atrophy patterns and data‐driven subtypes and stages in each patient. The relationships among estimated subtypes, pathological diagnoses, and longitudinal changes in clinical testing were examined.ResultsThe SuStaIn algorithm identified 2 distinct subtypes: (1) the subcortical subtype, in which atrophy progresses from the midbrain to the cortex, and (2) the cortical subtype, in which atrophy progresses from the frontal cortex to the subcortical regions. The subcortical subtype was more associated with typical PSP, whereas the cortical subtype was more associated with atypical PSP with a cortical distribution of pathology and CBD (p < 0.001). The cortical subtype had a faster rate of change on the PSP Rating Scale than the subcortical subtype (p < 0.05).InterpretationSuStaIn analysis revealed 2 MRI‐driven subtypes with distinct spatiotemporal atrophy patterns, clinical courses, and neuropathology. Our findings contribute to a comprehensive and improved understanding of disease progression and its relationship to tau pathology in 4R tauopathies. ANN NEUROL 2025;98:492–507

ABSTRACTIndividuals with primary progressive apraxia of speech (PPAOS) often develop parkinsonism and dysphagia. To evaluate the clinical correlates and impact of dysphagia in this population, we compared enrollment visit data between individuals with (n = 12) versus individuals without (n = 44) dysphagia symptoms. The group with dysphagia had more motor speech symptoms and parkinsonism. Longitudinal analysis revealed that almost everyone developed dysphagia before dying; the average time to death after developing dysphagia was 5.43 years and complications of dysphagia resulted in mortality for 35% of the individuals for whom data were available. These results emphasize the need for dysphagia management and provide useful prognostic estimates.

Background and Objectives: Hearing loss is relatively common in older individuals, and individuals with frontotemporal lobar degeneration (FTLD) are no exception; this can exacerbate communication difficulties stemming from speech-language impairments. The co-occurrence of these symptoms can contribute to increased frustration and isolation for patients and their communication partners. The objective of this study was to evaluate the feasibility of self-administered hearing testing. Ultimately, this could be administered remotely, which would increase access to assessment and inform management for this population. Method: Seventeen patients with underlying FTLD, clinically presenting with progressive apraxia of speech with and without agrammatic aphasia, independently completed the Home Hearing Test supervised while in office. Results: Three patients self-reported hearing loss, but results for 100% recommended formal evaluation. Eleven patients demonstrated good test accuracy. Six patients had “poor” or not computable accuracy; among them, five had evidence of cognitive impairment and/or behavioral changes, and one had known severe hearing loss, although differences between those with good and poor test accuracy were not significant. Patients with poor test accuracy had more difficulty with limb praxis. Conclusions: Most participants independently completed the test, though some had reduced test accuracy that may have been associated with cognitive impairment and/or limb apraxia. This study supports the need for hearing screenings in all patients with progressive apraxia of speech and aphasia and highlights both the feasibility and caution required in implementing self-administered testing protocols. Further work should evaluate the feasibility of in-home hearing screenings in a broader range of FTLD phenotypes and directly compare sensitivity and specificity of hearing loss detection with in-clinic administration. Supplemental Material: https://doi.org/10.23641/asha.28306613

AbstractBackgroundDiscussion surrounding the nomenclature of the “nonfluent/agrammatic” spectrum of progressive speech‐language disorders has largely focused on the clinical‐pathological and neuroimaging correlations, with some attention paid to the prognostication afforded by differentiating clinical phenotypes. Progressive apraxia of speech (AOS), with or without agrammatic aphasia, is generally associated with an underlying tauopathy; however, patients have offered a unique perspective on the importance of distinguishing between difficulties with speech and language that extends beyond pathological specificity. This study aimed to provide insight into the experience of patients with primary progressive AOS (PPAOS), with particular attention to their diagnostic journey.MethodA qualitative research approach was used. Structured interviews were conducted with three prosodic and one phonetic predominant PPAOS patients, judged representative of our research cohort, who were previously received other diagnoses, including primary progressive aphasia (PPA). A current PPAOS diagnosis and willingness to discuss the details of their diagnostic workup and reflect upon their experience were the inclusion criteria. One patient preferred to provide written responses. Each interview was reviewed, and the collective contents were examined using thematic analysis.ResultThe primary themes were identity, community, and planning. Patients expressed: 1) the importance of the alignment of AOS with their difficulties, specifically that they had no difficulty with thinking of words or with comprehension (i.e., no aphasia); 2) not sharing attributes with PPA patients and their observed clinical presentations; and 3) the desire to capitalize upon their retained skills for treatment, for example “I intend to retain my ‘voice’ even as I lose my speaking ability.”ConclusionUnderstanding the experiences of PPAOS patients may inform future iterations of progressive speech‐language spectrum diagnostic criteria and the consistency of their use, along with intervention recommendations. The specificity of a PPAOS diagnosis is meaningful to patients as it relates to their identity, sense of community, and approach to future planning. Further work will evaluate the experience of patients with a broader spectrum of progressive speech‐language disorders along with their care partners. More work is underway to outline the predictive value of an AOS diagnosis, relative to co‐occurring aphasia severity, to inform better prognostication.

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 used to characterize the progression of their motor speech impairment, including the development of dysarthria and mutism. Method: Data are presented from 52 speakers who had PPAOS at enrollment (i.e., progressive AOS in the absence of aphasia, cognitive, or other neurologic symptoms). Twenty-one had predominantly phonetic features, whereas 31 had primarily prosodic features. All participants underwent a comprehensive motor speech evaluation at their enrollment visit and each annual return visit, with a median of three visits per participant. Results: Almost 25% of the speakers with PPAOS presented with dysarthria at their enrollment visit (median disease duration of 3.65 years), whereas more than 70% of them had developed dysarthria by their last visit (median disease duration of 6.85 years). Neither the likelihood to develop dysarthria nor the disease duration at which it was detected differed significantly between the phonetic and prosodic groups. However, muteness emerged sooner for speakers with phonetic-predominant PPAOS; the median disease duration at which they became mute was 1.5 years shorter than for their prosodic counterparts. Conclusions: Clinically, these results facilitate more accurate prognostication of motor speech symptoms in speakers with PPAOS, allowing for timely introduction of alternative means of communication. The results also support the differentiation between progressive AOS and dysarthria as distinct motor speech disorders that often co-occur in these individuals.

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 automatic speech recognition (ASR) systems for diagnosis and treatment monitoring is appealing. This study evaluated the efficacy of a readily available ASR system (wav2vec 2.0) in transcribing speech of PPAOS patients to determine if the word error rate (WER) output by the ASR can differentiate between healthy speech and PPAOS and/or among its subtypes, whether WER correlates with AOS severity, and how the ASR's errors compare to those noted in manual transcriptions. Method: Forty-five patients with PPAOS and 22 healthy controls were recorded repeating 13 words, 3 times each, which were transcribed manually and using wav2vec 2.0. The WER and phonetic and prosodic speech errors were compared between groups, and ASR results were compared against manual transcriptions. Results: Mean overall WER was 0.88 for patients and 0.33 for controls. WER significantly correlated with AOS severity and accurately distinguished between patients and controls but not between AOS subtypes. The phonetic and prosodic errors from the ASR transcriptions were also unable to distinguish between subtypes, whereas errors calculated from human transcriptions were. There was poor agreement in the number of phonetic and prosodic errors between the ASR and human transcriptions. Conclusions: This study demonstrates that ASR can be useful in differentiating healthy from disordered speech and evaluating PPAOS severity but does not distinguish PPAOS subtypes. ASR transcriptions showed weak agreement with human transcriptions; thus, ASR may be a useful tool for the transcription of speech in PPAOS, but the research questions posed must be carefully considered within the context of its limitations. Supplemental Material: https://doi.org/10.23641/asha.26359417