Automated Detection of Speech Timing Alterations in Autopsy-Confirmed Nonfluent/Agrammatic Variant Primary Progressive Aphasia

García, Adolfo M.; Welch, Ariane E.; Mandelli, Maria Luisa; Henry, Maya L.; Lukic, Sladjana; Torres‐Prioris, María José; Deleon, Jessica; Ratnasiri, Buddhika; Puls, Diego L. Lorca; Miller, Bruce L.; Seeley, William W.; Vogel, Adam P.; Gorno‐Tempini, Maria Luisa

doi:10.1212/wnl.0000000000200750

Cited by 18 publications

(12 citation statements)

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“…Beyond these discrepancies, our results revealed that, independently of the metric or elicitation task, the semantic group could not be differentiated from the healthy participants. This was compatible with García and colleagues’ findings [ 57 ], according to which the silent pause mean duration and duration variability (i.e., standard deviation of duration) significantly increased in non-fluent patients compared to healthy speakers and semantic patients, while no differences were detected between the latter two groups. However, it should be noted that this study measured silent pauses using a reading task and not in connected speech.…”

Section: Discussionsupporting

confidence: 93%

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Silent Pauses and Speech Indices as Biomarkers for Primary Progressive Aphasia

et al. 2022

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Background and Objectives: Recent studies highlight the importance of investigating biomarkers for diagnosing and classifying patients with primary progressive aphasia (PPA). Even though there is ongoing research on pathophysiological indices in this field, the use of behavioral variables, and especially speech-derived factors, has drawn little attention in the relevant literature. The present study aims to investigate the possible utility of speech-derived indices, particularly silent pauses, as biomarkers for primary progressive aphasia (PPA). Materials and Methods: We recruited 22 PPA patients and 17 healthy controls, from whom we obtained speech samples based on two elicitation tasks, i.e., cookie theft picture description (CTP) and the patients’ personal narration of the disease onset and course. Results: Four main indices were derived from these speech samples: speech rate, articulation rate, pause frequency, and pause duration. In order to investigate whether these indices could be used to discriminate between the four groups of participants (healthy individuals and the three patient subgroups corresponding to the three variants of PPA), we conducted three sets of analyses: a series of ANOVAs, two principal component analyses (PCAs), and two hierarchical cluster analyses (HCAs). The ANOVAs revealed significant differences between the four subgroups for all four variables, with the CTP results being more robust. The subsequent PCAs and HCAs were in accordance with the initial statistical comparisons, revealing that the speech-derived indices for CTP provided a clearer classification and were especially useful for distinguishing the non-fluent variant from healthy participants as well as from the two other PPA taxonomic categories. Conclusions: In sum, we argue that speech-derived indices, and especially silent pauses, could be used as complementary biomarkers to efficiently discriminate between PPA and healthy speakers, as well as between the three variants of the disease.

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Section: Discussionsupporting

confidence: 93%

“…Speech samples were recorded and transcribed based on guidelines for discourse transcription in Greek [ 57 ]. The first 100 words uttered were isolated, and the silent pauses and speech duration were annotated, following a specific pipeline, previously implemented in speech samples of patients with post-stroke aphasia [ 35 ].…”

Section: Methodsmentioning

confidence: 99%

Silent Pauses and Speech Indices as Biomarkers for Primary Progressive Aphasia

et al. 2022

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“…This is in keeping with our previous observations that prosodic AOS is associated with PSP pathology while phonetic AOS is associated with CBD pathology 6 . A previous study found that abnormal speech timing, a type of dysprosody, is associated with CBD pathology in patients with nfvPPA 45 . Those findings may appear contradictory; however, it is difficult to compare both studies since the referenced paper did not specify the breakdown of dysarthria and AOS subtype.…”

Section: Discussionsupporting

confidence: 86%

“…6 A previous study found that abnormal speech timing, a type of dysprosody, is associated with CBD pathology in patients with nfvPPA. 45 Those findings may appear contradictory; however, it is difficult to compare both studies since the referenced paper did not specify the breakdown of dysarthria and AOS subtype. In addition, our study excluded patients with aphasia and greater aphasia severity may have influenced the differences in results (e.g., linguistic interference inflating at least the pause duration measure).…”

Section: Ta B L Ementioning

confidence: 99%

Clinicopathological associations of hemispheric dominance in primary progressive apraxia of speech

Robinson

Duffy

Clark

et al. 2023

Euro J of Neurology

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Objective Primary progressive apraxia of speech (PPAOS) is associated with imaging abnormalities in the lateral premotor cortex (LPC) and supplementary motor area (SMA). It is not known whether greater involvement of these regions in either hemisphere is associated with demographics, presenting, and/or longitudinal features. Methods In 51 prospectively recruited PPAOS patients who completed [18F]‐fluorodeoxyglucose (FDG) positron emission tomography (PET), we classified patients as left‐dominant, right‐dominant, or symmetric, based on visual assessment of the LPC and SMA on FDG‐PET. SPM and statistical analyses of regional metabolic values were performed. Diagnosis of PPAOS was made if apraxia of speech was present and aphasia absent. Thirteen patients completed ioflupane‐123I (dopamine transporter [DAT]) scans. We compared cross‐sectional and longitudinal clinicopathological, genetic, and neuroimaging characteristics across the three groups, with area under the receiver‐operating curve (AUROC) determined as a measure of effect size. Results In all, 49% of the PPAOS patients were classified as left‐dominant, 31% as right‐dominant, and 20% as symmetric, which was supported by results from the SPM and regional analyses. There were no differences in baseline characteristics. Longitudinally, right‐dominant PPAOS showed faster rates of progression of ideomotor apraxia (AUROC 0.79), behavioral disturbances (AUROC 0.84), including disinhibition symptoms (AUROC 0.82) and negative behaviors (AUROC 0.82), and parkinsonism (AUROC 0.75) compared to left‐dominant PPAOS. Symmetric PPAOS showed faster rates of dysarthria progression compared to left‐dominant (AUROC 0.89) and right‐dominant PPAOS (AUROC 0.79). Five patients showed abnormal DAT uptake. Braak neurofibrillary tangle stage differed across groups (p = 0.01). Conclusions Patients with PPAOS and a right‐dominant pattern of hypometabolism on FDG‐PET have the fastest rates of decline of behavioral and motor features.

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“…Thus, robust and reproducible quantitative, objective measures of AOS and other motor speech impairments are needed to advance the classification of the nfvPPA-S. For example, in a recent study from our group, we showed that automated speech timing measures (i.e., articulation rate) might provide valuable information to characterize the nfvPPA-S and its neuropathological bases. 56 Thanks to its objectivity and scalability, automated speech analysis could offer important diagnostic support to standard speech assessments. However, further studies are needed to determine these new measurements' full diagnostic and prognostic potential.…”

Section: Discussionmentioning

confidence: 99%

Clinical dimensions along the progressive nonfluent variant primary progressive aphasia spectrum

Illán-Gala

Lorca-Puls

Ezzes

et al. 2023

Preprint

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It is debated whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) belong to the same clinical spectrum traditionally termed nonfluent/agrammatic variant primary progressive aphasia (nfvPPA) or exist as two completely distinct syndromic entities with specific pathologic/prognostic correlates. We analyzed speech, language, and disease severity features in a comprehensive cohort of patients with a progressive motor speech impairment and/or agrammatism to ascertain any evidence of the existence of naturally occurring, non-overlapping syndromic entities (e.g., PPAOS and PAA) in our data. We also assessed if data-driven latent clinical dimensions with etiologic/prognostic value could be identified. We included 98 participants with progressive motor speech impairment and/or agrammatism, with 43 having an autopsy-confirmed neuropathological diagnosis. Speech pathologists assessed motor speech features indicative of dysarthria and apraxia of speech (AOS). Quantitative expressive/receptive agrammatism measures were obtained and compared with healthy controls. Baseline and longitudinal disease severity was evaluated using the Clinical Dementia Rating sum-of-boxes (CDR-SB). We investigated the data's clustering tendency to form robust symptom clusters and employed principal component analysis to extract data-driven latent clinical dimensions (LCD). The longitudinal CDR-SB change was estimated utilizing linear mixed-effects models. Of the participants included in this study, 91 conformed to previously reported clinical profiles (69 with AOS and agrammatism, 18 PPAOS, and 4 PAA). The remaining seven participants were characterized by nonfluent speech and dysarthria without apraxia of speech or agrammatism. No baseline clinical features differentiated between FTLD neuropathological subgroups. Critically, the Hopkins statistic dismissed the presence of non-overlapping syndromic clusters in the entire sample (.45 with values near 0.5 indicating random data). Three data-driven components accounted for 71% of the variance ([i] severity-agrammatism, [ii] prominent AOS, and [iii] prominent dysarthria). The component typified by prominent dysarthria was more specific to patients with Progressive Supranuclear Palsy (4/5 [80%] participants with autopsy in this group had PSP), while the severity-agrammatism component predicted a faster CDR-SB increase. Higher dysarthria severity, reduced words per minute, and expressive and receptive agrammatism severity at baseline independently predicted accelerated disease progression (as measured by the CDR-SB score). Our findings indicate that PPAOS and PAA, rather than exist as completely distinct syndromic entities, constitute a clinical continuum strongly predictive of underlying Frontotemporal Lobar Degeneration (FTLD, 66% 4R tauopathy, 16% Pick's disease, 9.3% FTLD TDP type A, and 12% other pathologies). While highlighting the graded distinctions (rather than sharp boundaries) that characterize the nfvPPA spectrum may be useful for establishing early clinical rehabilitation strategies, novel clinical and biological markers are needed to improve clinical-pathological correlations.

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Automated Detection of Speech Timing Alterations in Autopsy-Confirmed Nonfluent/Agrammatic Variant Primary Progressive Aphasia

Cited by 18 publications

References 50 publications

Silent Pauses and Speech Indices as Biomarkers for Primary Progressive Aphasia

Silent Pauses and Speech Indices as Biomarkers for Primary Progressive Aphasia

Clinicopathological associations of hemispheric dominance in primary progressive apraxia of speech

Clinical dimensions along the progressive nonfluent variant primary progressive aphasia spectrum

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