Whitwell, Jennifer L.

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.

AbstractINTRODUCTIONPrimary age‐related tauopathy (PART) is characterized by neurofibrillary tangles and minimal β‐amyloid deposition, diagnosed postmortem. This study investigates 18F‐flortaucipir (FTP) PET imaging for antemortem PART diagnosis.METHODSWe analyzed FTP PET scans from 50 autopsy‐confirmed PART and 13 control subjects. Temporal lobe uptake was assessed both qualitatively and quantitatively. Demographic and clinicopathological characteristics and voxel‐level uptake using SPM12 were compared between FTP‐positive and FTP‐negative cases. Intra‐reader reproducibility was evaluated with Krippendorff's alpha.RESULTSMinimal/mild and moderate FTP uptake was seen in 32% of PART cases and 62% of controls, primarily in the left inferior temporal lobe. No demographic or clinicopathological differences were found between FTP‐positive and FTP‐negative cases. High intra‐reader reproducibility (α = 0.83) was noted.DISCUSSIONFTP PET imaging did not show a specific uptake pattern for PART diagnosis, indicating that in vivo PART identification using FTP PET is challenging. Similar uptake in controls suggests non‐specific uptake in PART.Highlights 18F‐flortaucipir (FTP) PET scans were analyzed for diagnosing PART antemortem. 32% of PART cases had minimal/mild FTP uptake in the left inferior temporal lobe. Similar to PART FTP uptake was found in 62% of control subjects. No specific uptake pattern was found, challenging in vivo PART diagnosis.

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

Abstract Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy that presents with highly heterogenous clinical syndromes. We perform cross-sectional data-driven discovery of independent patterns of brain atrophy and hypometabolism across the entire PSP spectrum. We then use these patterns to predict specific clinical features and to assess their relationship to phenotypic heterogeneity. We included 111 patients with PSP (60 with Richardson syndrome and 51 with cortical and subcortical variant subtypes). Ninety-one were used as the training set and 20 as a test set. The presence and severity of granular clinical variables such as postural instability, parkinsonism, apraxia and supranuclear gaze palsy were noted. Domains of akinesia, ocular motor impairment, postural instability and cognitive dysfunction as defined by the Movement Disorders Society criteria for PSP were also recorded. Non-negative matrix factorization was used on cross-sectional MRI and fluorodeoxyglucose-positron emission tomography (FDG-PET) scans. Independent models for each as well as a combined model for MRI and FDG-PET were developed and used to predict the granular clinical variables. Both MRI and FDG-PET were better at predicting presence of a symptom than severity, suggesting identification of disease state may be more robust than disease stage. FDG-PET predicted predominantly cortical abnormalities better than MRI such as ideomotor apraxia, apraxia of speech and frontal dysexecutive syndrome. MRI demonstrated prediction of cortical and more so sub-cortical abnormalities, such as parkinsonism. Distinct neuroanatomical foci were predictive in MRI- and FDG-PET-based models. For example, vertical gaze palsy was predicted by midbrain atrophy on MRI, but frontal eye field hypometabolism on FDG-PET. Findings also differed by scale or instrument used. For example, prediction of ocular motor abnormalities using the PSP Saccadic Impairment Scale was stronger than with the Movement Disorders Society Diagnostic criteria for PSP oculomotor impairment designation. Combination of MRI and FDG-PET demonstrated enhanced detection of parkinsonism and frontal syndrome presence and apraxia, cognitive impairment and bradykinesia severity. Both MRI and FDG-PET patterns were able to predict some measures in the test set; however, prediction of global cognition measured by Montreal Cognitive Assessment was the strongest. MRI predictions generalized more robustly to the test set. PSP leads to neurodegeneration in motor, cognitive and ocular motor networks at cortical and subcortical foci, leading to diverse yet overlapping clinical syndromes. To advance understanding of phenotypic heterogeneity in PSP, it is essential to consider data-driven approaches to clinical neuroimaging analyses.

Abstract INTRODUCTION Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype. METHODS Retrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments. RESULTS Common symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word‐finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face‐recognition deficits (60%). Real‐life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations. DISCUSSION This study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real‐life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients. Highlights This project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.