Meade, Gabriela

Purpose: Frontotemporal lobar degeneration (FTLD) is the neuropathology that underlies a collection of progressive clinical syndromes typically classified by the initial/primary symptom. For example, individuals with loss of word meaning as a first manifestation are often diagnosed with the semantic variant of primary progressive aphasia. Growing evidence suggests that language and communication can be impacted in all clinical syndromes across the FTLD spectrum, but the functional relevance of these symptoms has yet to be explored. Method: The Frontotemporal Degeneration (FTD) Insights Survey is the largest community survey of individuals affected by FTLD. It was administered online and included questions related to demographics, symptoms, life participation, quality of life, and experiences with and hopes for treatment. Self-reported diagnoses of respondents included the nonfluent/agrammatic, semantic, and unspecified variants of primary progressive aphasia, semantic dementia, corticobasal syndrome, progressive supranuclear palsy, and behavioral variant FTD. Here, we grouped respondents according to whether they had a language-predominant ( n = 43), motor-predominant ( n = 43), or behavior-predominant ( n = 90) variant of FTLD and used descriptive statistics to explore how they perceive their own communication difficulties and gauge their motivation for management. Results: Over 65% of respondents in each group identified changes to communication as a symptom; subsequent analyses focused on the responses of this cohort. Across groups, word finding and speaking were two of the most frequently endorsed difficulties. Over 50% of each group identified improved communication as a treatment priority, reflecting the impact that these symptoms have on their day-to-day life. Speech-language therapy is an important approach to manage these changes and minimize their impact. Whereas 76% of the language and motor groups had attended speech-language therapy, this was true for only 16% of the behavior group. Conclusions: Individuals across the FTLD spectrum experience changes to communication that impact their social engagement and quality of life. Management needs to be tailored to the needs of each individual, but recommendations are provided based on the insights and group-level preferences reported here. Future research is needed to identify current referral practices and how to increase engagement in skilled communication interventions, especially for individuals with the behavioral variant of FTD. Supplemental Material: https://doi.org/10.23641/asha.33940597

Abstract Motor speech disorders (MSDs) are early markers of neurological disease, but expert perceptual analysis is rarely available outside specialized centers. Automated speech analysis offers a scalable alternative, yet prior studies have not systematically compared modeling approaches or assessed clinically relevant metrics in independent datasets. This study compared static acoustic features, articulatory informed Phonet features, and self-supervised pretrained models for binary and multi label MSD classification. We trained and evaluated models on 583 speech samples using speaker level splits. Baseline models included logistic regression and Gated Recurrent Units (GRUs) trained on eGeMAPS and MFCCs. We extracted three types of Phonet derived features and evaluated pretrained HuBERT and SSAST models in frozen, partially fine-tuned, and fully fine-tuned configurations. Binary classification distinguished MSDs from controls, while multi label classification identified six MSD subtypes. Models were assessed using validation AUC, and cut points were tested on two independent datasets. Pretrained and Phonet based models substantially outperformed static acoustic features. In binary classification, HuBERT achieved the highest AUC (0.95), while compact Phonet derived GRUs achieved comparable performance (up to 0.94). These models generalized well to independent datasets, maintaining high sensitivity (0.94) and specificity (0.97). In multi label classification, Phonet models achieved the highest macro average AUC (0.86), but threshold-based subtype performance declined on unseen data. Automated MSD detection is feasible and clinically promising. Binary classification generalized well, whereas multi label classification showed limited threshold stability across datasets.

Background Frontotemporal dementia is an umbrella term that encompasses several clinical syndromes with impaired behavioral, language, and motor functions. These syndromes show considerable overlap in clinical features and imaging patterns. Therefore, there is a need to investigate the syndromic heterogeneity in FTD using unbiased data-driven approaches. Methods We used data-driven clustering analysis of structural magnetic resonance imaging (MRI) data on 400 patients with clinical FTD diagnoses [behavioral variant of frontotemporal dementia (bvFTD), semantic variant of primary progressive aphasia (svPPA), right temporal variant of frontotemporal dementia (rtvFTD), apraxia of speech with agrammatic aphasia (AOS-PAA), primary progressive apraxia of speech (PPAOS), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and primary progressive aphasia who did not fit into the other diagnostic categories (PPA-other)]. MR images were w-scored relative to cognitively unimpaired individuals, and principal component analysis was performed. A clustering ensemble approach, including hierarchical algorithms, was applied to the MR-based principal components, and imaging and clinical characteristics of the clusters were investigated. Various numbers of clusters ( K = 2, 3, or 4) were evaluated. Results The K = 3 solution offered the most clinically meaningful separation of FTD syndromes. The first cluster captured mostly frontal MRI abnormalities related to the speech, language and behavioral clinical dimensions, including patients with AOS-PAA, PPAOS, PPA-other, and bvFTD. The second cluster captured mostly temporal abnormalities and included mainly patients with svPPA and rtvFTD, but also bvFTD, AOS-PAA, and PPA-other. The third cluster captured cortical and subcortical atrophy, particularly in the midbrain, and included atypical Parkinsonian syndromes, with all PSP and CBS patients captured in this cluster, as well as most PPAOS patients. Considerable overlap of clinical syndromes was noted across these clusters, whereby patients with AOS-PAA, svPPA, PPA-other, and bvFTD were captured in more than one cluster. Discussion Our findings highlight heterogeneity in FTD, which mainly exists along three axes: speech, language and behavioral deficits reflecting frontal atrophy, language deficits reflecting temporal atrophy, and motor and motor speech deficits reflecting mostly midbrain and subcortical atrophy, with cortical involvement.

Purpose: This viewpoint addresses the complexity of the nomenclature of progressive speech-language disorders, which often exists at the intersection of descriptive symptoms, clinical syndromes, and underlying neuropathology. Using primary progressive apraxia of speech (PPAOS) as an example, we explore how overlapping diagnostic frameworks employed by speech-language pathologists, neurologists, and other clinicians and researchers can lead to different diagnostic labels that may evolve throughout disease progression. These discrepancies and changes can complicate patient understanding, clinical care, and affect eligibility for clinical trials. We highlight the importance of diagnostic specificity, flexibility, and multidisciplinary collaboration in improving patient counseling, prognostication, treatment planning, and clinical research alignment, particularly in the context of the growing number of clinical trials and specialized, multidisciplinary clinics. Conclusions: This viewpoint explores how symptom-based, syndrome-based, and pathology-based diagnoses can work together to support patient care and research. Accurate and specific diagnosis of speech-language disorders has important implications for patient understanding of their condition, identity, prognostic accuracy, access to care, clinical trial enrollment, and treatment planning and efficacy. Misdiagnosis or vague labeling can result in inappropriate interventions, delayed support, and skewed research findings. We argue that multidisciplinary collaboration and flexibility in recognizing evolving symptom-based and syndrome-based labels over the disease course—and as the fields learn more—is essential to empower patients with accurate, actionable information. Embracing both the specificity and the complexity of progressive speech-language disorders can both enhance communication and facilitate research.

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.

Abstract Tau aggregation in early affected regions in the asymptomatic stage of Alzheimer’s disease marks a transitional phase between stable asymptomatic amyloid positivity and the clinically manifest stage. How this early region tau aggregation covertly affects brain function during this asymptomatic stage remains unclear. In this study, 83 participants underwent a 128 electrodes resting-state EEG, a dynamic 100 min tau PET scan (18F-MK6240), an amyloid PET scan, a structural T1 MRI scan and neuropsychological assessment. Tau PET data quality control led to a final sample of 66 subjects. Based on the clinical and cognitive status, amyloid and tau PET biomarkers, the group was composed of 37 cognitively unimpaired amyloid negative subjects, 14 cognitively unimpaired amyloid positive subjects and 15 patients with prodromal Alzheimer’s disease. We calculated the average undirected weighted Phase Lag Index in the alpha frequency band with eyes closed and used this as weights for the graph and analysed the global clustering coefficient and characteristic path length in sensor space. As a primary objective, we assessed how these global graph measures correlated with tau PET values, in an a priori defined early metaVOI, comprised of the entorhinal and perirhinal cortex, hippocampus, parahippocampus and fusiform cortex. As secondary analyses, we investigated which specific brain regions were mainly implicated, what the contribution was of amyloid, the effect of electrode density and the relation to cognitive performance. In the overall group and within the cognitively unimpaired amyloid positive subgroup, tau aggregation was associated with a decrease in global clustering coefficient and an increase in characteristic path length. These changes reflect the initial disintegration of the small-world brain network during the transitional phase, even before clinical symptoms are apparent. The correlations are most prominent in the perirhinal cortex, indicating that global deterioration of the network is already present early in the Alzheimer’s disease pathology. We obtained similar results with only taking 64 electrodes into account. To conclude, we found that in the asymptomatic stage of Alzheimer’s disease, tau PET load in medial temporal cortex is associated with global electrophysiological measures of network disintegration. The study demonstrates the potential value of high-density EEG in the era of biologically defined Alzheimer’s disease for characterizing brain function in the asymptomatic stage.

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

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.