Digital Speech Analysis in Progressive Supranuclear Palsy and Corticobasal Syndromes.
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ABSTRACT: Background
Progressive supranuclear palsy syndrome (PSPS) and corticobasal syndrome (CBS) as well as non-fluent/agrammatic primary progressive aphasia (naPPA) are often associated with misfolded 4-repeat tau pathology, but the diversity of the associated speech features is poorly understood.Objective
Investigate the full range of acoustic and lexical properties of speech to test the hypothesis that PSPS-CBS show a subset of speech impairments found in naPPA.Methods
Acoustic and lexical measures, extracted from natural, digitized semi-structured speech samples using novel, automated methods, were compared in PSPS-CBS (n = 87), naPPA (n = 25), and healthy controls (HC, n = 41). We related these measures to grammatical performance and speech fluency, core features of naPPA, to neuropsychological measures of naming, executive, memory and visuoconstructional functioning, and to cerebrospinal fluid (CSF) phosphorylated tau (pTau) levels in patients with available biofluid analytes.Results
Both naPPA and PSPS-CBS speech produced shorter speech segments, longer pauses, higher pause rates, reduced fundamental frequency (f0) pitch ranges, and slower speech rate compared to HC. naPPA speech was distinct from PSPS-CBS with shorter speech segments, more frequent pauses, slower speech rate, reduced verb production, and higher partial word production. In both groups, acoustic duration measures generally correlated with speech fluency, measured as words per minute, and grammatical performance. Speech measures did not correlate with standard neuropsychological measures. CSF pTau levels correlated with f0 range in PSPS-CBS and naPPA.Conclusion
Lexical and acoustic speech features of PSPS-CBS overlaps those of naPPA and are related to CSF pTau levels.
SUBMITTER: Parjane N
PROVIDER: S-EPMC8609610 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Mounting evidence suggests an association between cerebellar atrophy and cognitive impairment in the main frontotemporal dementia syndromes. In contrast, whether cerebellar atrophy is present in the motor syndromes associated with frontotemporal lobar degeneration (corticobasal syndrome and progressive supranuclear palsy) and the extent of its contribution to their cognitive profile remain poorly understood. The current study aimed to comprehensively chart profiles of cognitive impairment in relation to cerebellar atrophy in 49 dementia patients (corticobasal syndrome = 33; progressive supranuclear palsy = 16) compared to 33 age-, sex- and education-matched healthy controls. Relative to controls, corticobasal syndrome and progressive supranuclear palsy patients demonstrated characteristic cognitive impairment, spanning the majority of cognitive domains including attention and processing speed, language, working memory, and executive function with relative preservation of verbal and nonverbal memory. Voxel-based morphometry analysis revealed largely overlapping patterns of cerebellar atrophy in corticobasal syndrome and progressive supranuclear palsy relative to controls, primarily involving bilateral Crus II extending into adjacent lobules VIIb and VIIIa. After controlling for overall cerebral atrophy and disease duration, exploratory voxel-wise general linear model analysis revealed distinct cerebellar subregions differentially implicated across cognitive domains in each patient group. In corticobasal syndrome, reduction in grey matter intensity in the left Crus I was significantly correlated with executive dysfunction. In progressive supranuclear palsy, integrity of the vermis and adjacent right lobules I-IV was significantly associated with language performance. These results are consistent with the well-established role of Crus I in executive functions and provide further supporting evidence for vermal involvement in cognitive processing. The current study presents the first detailed exploration of the role of cerebellar atrophy in cognitive deficits in corticobasal syndrome and progressive supranuclear palsy, offering insights into the cerebellum's contribution to cognitive processing even in neurodegenerative syndromes characterized by motor impairment.
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Project description:ImportanceAtypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), may be difficult to distinguish in early stages and are often misdiagnosed as Parkinson disease (PD). The diagnostic criteria for PSP have been updated to encompass a range of clinical subtypes but have not been prospectively studied.ObjectiveTo define the distinguishing features of PSP and CBS subtypes and to assess their usefulness in facilitating early diagnosis and separation from PD.Design, setting, participantsThis cohort study recruited patients with APS and PD from movement disorder clinics across the United Kingdom from September 1, 2015, through December 1, 2018. Patients with APS were stratified into the following groups: those with Richardson syndrome (PSP-RS), PSP-subcortical (including PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (including PSP-frontal and PSP-CBS overlap subtypes), MSA-parkinsonism, MSA-cerebellar, CBS-Alzheimer disease (CBS-AD), and CBS-non-AD. Data were analyzed from February 1, through May 1, 2019.Main outcomes and measuresBaseline group comparisons used (1) clinical trajectory; (2) cognitive screening scales; (3) serum neurofilament light chain (NF-L) levels; (4) TRIM11, ApoE, and MAPT genotypes; and (5) volumetric magnetic resonance imaging measures.ResultsA total of 222 patients with APS (101 with PSP, 55 with MSA, 40 with CBS, and 26 indeterminate) were recruited (129 [58.1%] male; mean [SD] age at recruitment, 68.3 [8.7] years). Age-matched control participants (n = 76) and patients with PD (n = 1967) were included for comparison. Concordance between the antemortem clinical and pathologic diagnoses was achieved in 12 of 13 patients with PSP and CBS (92.3%) undergoing postmortem evaluation. Applying the Movement Disorder Society PSP diagnostic criteria almost doubled the number of patients diagnosed with PSP from 58 to 101. Forty-nine of 101 patients with reclassified PSP (48.5%) did not have the classic PSP-RS subtype. Patients in the PSP-subcortical group had a longer diagnostic latency and a more benign clinical trajectory than those in PSP-RS and PSP-cortical groups. The PSP-subcortical group was distinguished from PSP-cortical and PSP-RS groups by cortical volumetric magnetic resonance imaging measures (area under the curve [AUC], 0.84-0.89), cognitive profile (AUC, 0.80-0.83), serum NF-L level (AUC, 0.75-0.83), and TRIM11 rs564309 genotype. Midbrain atrophy was a common feature of all PSP groups. Eight of 17 patients with CBS (47.1%) undergoing cerebrospinal fluid analysis were identified as having the CBS-AD subtype. Patients in the CBS-AD group had a longer diagnostic latency, relatively benign clinical trajectory, greater cognitive impairment, and higher APOE-ε4 allele frequency than those in the CBS-non-AD group (AUC, 0.80-0.87; P < .05). Serum NF-L levels distinguished PD from all PSP and CBS cases combined (AUC, 0.80; P < .05).Conclusions and relevanceThese findings suggest that studies focusing on the PSP-RS subtype are likely to miss a large number of patients with underlying PSP tau pathology. Analysis of cerebrospinal fluid defined a distinct CBS-AD subtype. The PSP and CBS subtypes have distinct characteristics that may enhance their early diagnosis.
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Project description:Corticobasal degeneration (CBD), progressive supranuclear palsy (PSP) and a subset of frontotemporal dementia (FTD) are neurodegenerative disorders characterized by tau inclusions in neurons and glia (tauopathies). Although clinical, pathological and genetic evidence suggests overlapping pathobiology between CBD, PSP, and FTD, the relationship between these disorders is still not well understood. Using summary statistics (odds ratios and p values) from large genome-wide association studies (total n = 14,286 cases and controls) and recently established genetic methods, we investigated the genetic overlap between CBD and PSP and CBD and FTD. We found up to 800-fold enrichment of genetic risk in CBD across different levels of significance for PSP or FTD. In addition to NSF (tagging the MAPT H1 haplotype), we observed that SNPs in or near MOBP, CXCR4, EGFR, and GLDC showed significant genetic overlap between CBD and PSP, whereas only SNPs tagging the MAPT haplotype overlapped between CBD and FTD. The risk alleles of the shared SNPs were associated with expression changes in cis-genes. Evaluating transcriptome levels across adult human brains, we found a unique neuroanatomic gene expression signature for each of the five overlapping gene loci (omnibus ANOVA p < 2.0 × 10-16). Functionally, we found that these shared risk genes were associated with protein interaction and gene co-expression networks and showed enrichment for several neurodevelopmental pathways. Our findings suggest: (1) novel genetic overlap between CBD and PSP beyond the MAPT locus; (2) strong ties between CBD and FTD through the MAPT clade, and (3) unique combinations of overlapping genes that may, in part, influence selective regional or neuronal vulnerability observed in specific tauopathies.
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Project description:BackgroundMutations in the leucine-rich repeat kinase 2 gene (LRRK2) are the most common genetic cause of Parkinson's disease (PD). Unexpectedly, tau pathology has been reported in a subset of LRRK2 mutation carriers.MethodsTo estimate the frequency of pathogenic LRRK2 mutations and to evaluate the association of common LRRK2 variants with risk of primary tauopathies, we studied 1039 progressive supranuclear palsy (PSP) and 145 corticobasal degeneration patients from the Mayo Clinic Florida brain bank and 1790 controls ascertained at Mayo Clinic. Sanger sequencing of LRRK2 exons 30, 31, 35, and 41 was performed in all patients, and genotyping of all 17 known exonic variants with minor allele frequency >0.5% was performed in patients and controls.ResultsLRRK2 mutational screening identified 2 known pathogenic mutations (p.G2019S and p.R1441C), each in 1 PSP patient, the novel p.A1413T mutation in a PSP patient and the rare p.R1707K mutation in a corticobasal degeneration patient. Both p.A1413T and p.R1707K mutations were predicted damaging by at least 2 of 3 prediction programs and affect evolutionary conserved sites of LRRK2. Association analysis using common LRRK2 variants only showed nominal association of the p.L153L variant with PSP.ConclusionsOur study confirms the presence of pathogenic and potentially pathogenic LRRK2 mutations in pathologically confirmed primary tauopathies, albeit with low frequency. In contrast to PD, common LRRK2 variants do not appear to play a major role in determining PSP and corticobasal degeneration risk. © 2016 International Parkinson and Movement Disorder Society.
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Project description:Primary progressive apraxia of speech, a motor speech disorder of planning and programming, is a tauopathy that has overlapping histological features with progressive supranuclear palsy. We aimed to compare, for the first time, atrophy patterns, as well as white matter tract degeneration, between these two syndromes.Sixteen primary progressive apraxia of speech subjects were age- and gender-matched to 16 progressive supranuclear palsy subjects and 20 controls. All subjects were prospectively recruited, underwent neurological and speech evaluations and 3.0-Tesla magnetic resonance imaging. Grey and white matter atrophy was assessed using voxel-based morphometry and atlas-based parcellation, and white matter tract degeneration was assessed using diffusion tensor imaging.All progressive supranuclear palsy subjects had typical oculomotor/gait impairments, but none had speech apraxia. Both syndromes showed grey matter loss in supplementary motor area, white matter loss in posterior frontal lobes and degeneration of the body of the corpus callosum. Whilst lateral grey matter loss was focal, involving superior premotor cortex, in primary progressive apraxia of speech, loss was less focal extending into prefrontal cortex in progressive supranuclear palsy. Caudate volume loss and tract degeneration of superior cerebellar peduncles were also observed in progressive supranuclear palsy. Interestingly, area of the midbrain was reduced in both syndromes compared to controls, although this was greater in progressive supranuclear palsy.Although neuroanatomical differences were identified between these distinctive clinical syndromes, substantial overlap was also observed, including midbrain atrophy, suggesting these two syndromes may have common pathophysiological underpinnings.
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Project description:Purpose This study describes motor speech disorders and associated communication limitations in six variants of progressive supranuclear palsy (PSP). Method The presence, nature, and severity of dysarthria and apraxia of speech (AOS) were documented, along with scores on the Apraxia of Speech Rating Scale-Version 3 (ASRS-3) for 77 (40 male and 37 female) patients with PSP. Clinician-estimated and patient-estimated communication limitations were rated using the Motor Speech Disorders Severity Rating (MSDSR) Scale and the Communicative Effectiveness Survey (CES), respectively. Descriptive statistics were calculated for each of these dependent variables. One-tailed t tests were conducted to test mean differences in ASRS-3 and CES between participants with and without AOS and between participants with and without dysarthria. Spearman rank correlations were calculated between ASRS-3 scores and clinical judgments of AOS and dysarthria severity and between MSDSR and CES ratings. Results Nine participants (12%) had normal speech. Eighty-seven percent exhibited dysarthria; hypokinetic and mixed hypokinetic-spastic dysarthria were observed most frequently. AOS was observed in 19.5% of participants across all variants, but in only 10% exclusive of the PSP speech and language variant. Nearly half presented with AOS in which neither phonetic nor prosodic features clearly predominated. The mean ASRS-3 score for participants with AOS was significantly higher than for those without and correlated strongly with clinician judgment of AOS severity. Mean ASRS-3 was higher for participants with dysarthria than for those without but correlated weakly with dysarthria severity. Mean MSDSR and CES ratings were lower in participants with AOS compared to those without and moderately correlated with each other. Conclusions Motor speech disorders that negatively impact communicative effectiveness are common in PSP and occur in many variants. This is the first description of motor speech disorders across PSP variants, setting the stage for future research characterizing neuroanatomical correlates, progression of motor speech disorders, and benefits of targeted interventions. Supplemental Material https://doi.org/10.23641/asha.14111837.
| S-EPMC8702836 | biostudies-literature
Project description:BackgroundThe Movement Disorder Society clinical criteria for progressive supranuclear palsy (PSP) provide a framework for assessing the presence/severity of clinical symptoms and define a speech/language variant of PSP.ObjectivesTo evaluate the clinical criteria in a cohort of speech/language patients with longitudinal follow-up.MethodsA total of 52 patients presenting with progressive apraxia of speech and/or agrammatic aphasia were followed longitudinally for up to 6 visits with clinical assessments and magnetic resonance imaging. We assessed oculomotor, postural instability, and akinesia diagnostic levels and determined whether patients met criteria for possible PSP-speech/language or probable PSP at each visit. Kaplan-Meier curves assessed time-to-event probabilities according to age. Statistical parametric mapping and midbrain volume were assessed according to disease progression.ResultsFew PSP symptoms were observed early in the disease, with oculomotor abnormalities and falls first observed 2 years after onset. Falls were more common than vertical supranuclear gaze palsy. Bradykinesia and rigidity commonly developed but axial was rarely greater than appendicular rigidity. During follow-up, 54% met criteria for possible PSP-speech/language, 38% for probable PSP-Richardson's syndrome, and 38% for probable PSP-parkinsonism, most commonly 6 to 6.9 years after onset. The probability of developing PSP was greater when onset was at an age older than 70 years. Patients who progressed to probable PSP had more parkinsonism and oculomotor impairment at baseline and greater midbrain atrophy when compared with those who did not develop probable PSP.ConclusionsSymptoms typical of PSP commonly develop in patients presenting with a progressive speech/language disorder. Older age appears to be an important prognostic factor in these patients.
| S-EPMC6660227 | biostudies-literature
Project description:PurposeTo assess the clinical-metabolic correlates of language impairment in a large sample of patients clinically diagnosed as corticobasal syndrome (CBS) and progressive supranuclear palsy syndrome (PSPs).MethodsWe included 70 patients fulfilling current criteria for CBS (n = 33) or PSPs (n = 37). All subjects underwent clinical-neuropsychological and FDG-PET assessments at the time of diagnosis. The whole patient's cohort was grouped into three subgroups according to the language characteristics, i.e., (a) nfv-PPA; (b) subtle language impairments, LANG-; (c) no language deficits, NOL-. FDG-PET data were analysed using an optimized voxel-based SPM method at the single-subject and group levels in order to evaluate specific hypometabolic patterns and regional dysfunctional FDG-PET commonalities in subgroups.Results21 patients had a nfvPPA diagnosis (i.e., nfv-PPA/CBS = 12 and nfv-PPA/PSPs = 9), while 20 patients had a subtle language impairment LANG- (i.e., CBS = 12 and PSPs = 8), not fulfilling the criteria for a nfv-PPA diagnosis. The remaining sample (i.e., 9/33 CBS and 20/37 PSPs patients) did not show any language deficit. FDG-PET results in individuals with a nfv-PPA diagnosis were consistent with the typical nfv-PPA pattern of hypometabolism (i.e., left fronto-insular and superior medial frontal cortex involvement), both in CBS and PSPs. The LANG-CBS and LANG-PSPs subjects had different FDG-PET hypometabolic patterns involving, respectively, parietal and frontal regions. As expected, NOL-CBS and NOL-PSPs showed a predominant right hemisphere involvement, with selective functional metabolic signatures typical of the two syndromes.ConclusionsLanguage impairments, fulfilling the nfv-PPA criteria, are associated with both CBS and PSPs clinical presentations early in the disease course. Subtle language deficits may be present in an additional proportion of patients not fulfilling the nfv-PPA criteria. The topography of brain hypometabolism is a major dysfunctional signature of language deficits in CBS and PSPs clinical phenotypes.
| S-EPMC6978212 | biostudies-literature
Project description:IntroductionProgressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are progressive neurodegenerative syndromes characterised by Parkinsonism with additional features including cognitive dysfunction, falls, and oculomotor abnormalities. Understanding the epidemiology of these conditions is critical to planning for future service provision.MethodsWe conducted a systematic review of studies reporting incidence and prevalence of CBS and PSP. A search of the PubMed and EMBASE data bases was conducted from their date of inception to 13th July 2021. Meta-analysis of studies sharing similar methodologies was carried out to generate estimated pooled prevalence and incidence.ResultsWe found 32 studies meeting our criteria for inclusion. There were 20 studies with data on prevalence and 12 with incidence data of PSP. Prevalence of CBS was reported in eight studies while seven studies reported incidence. Reported estimates of prevalence for PSP ranged from 1.00 (0.9-1.1) to 18 (8-28) per 100,000 while prevalence rates for CBS ranged from 0.83 (0.1-3.0) to 25 (0-59). Incidence rates for PSP and CBS respectively ranged from 0.16 (0.07-0.39) to 2.6 per 100,000 person-years and 0.03 (0-0.18) to 0.8 (0.4-1.3) per 100,000 person-years. A random effects model meta-analysis of studies with similar methodologies yielded a pooled prevalence estimate for PSP of 6.92 (4.33-11.06, I2 = 89%, τ2 = 0.3907) and 3.91 (2.03-7.51, I2 = 72%, τ2 = 0.2573) per 100,000 for CBS.ConclusionStudies of the epidemiology of PSP and CBS report highly heterogeneous findings. There is a need for further studies using rigorous phenotyping and the most recent diagnostic criteria to understand the true burden of these conditions.
| S-EPMC10421779 | biostudies-literature