The Experts below are selected from a list of 3024 Experts worldwide ranked by ideXlab platform
Joseph R Duffy - One of the best experts on this subject based on the ideXlab platform.
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a molecular pathology neurobiology biochemical genetic and neuroimaging study of progressive Apraxia of Speech
Nature Communications, 2021Co-Authors: Keith A Josephs, Edythe A Strand, Mary M. Machulda, Joseph R Duffy, Rene L Utianski, Hugo Botha, Heather M Clark, Peter R Martin, Nha Trang Thu PhamAbstract:Progressive Apraxia of Speech is a neurodegenerative syndrome affecting spoken communication. Molecular pathology, biochemistry, genetics, and longitudinal imaging were investigated in 32 autopsy-confirmed patients with progressive Apraxia of Speech who were followed over 10 years. Corticobasal degeneration and progressive supranuclear palsy (4R-tauopathies) were the most common underlying pathologies. Perceptually distinct Speech characteristics, combined with age-at-onset, predicted specific 4R-tauopathy; phonetic subtype and younger age predicted corticobasal degeneration, and prosodic subtype and older age predicted progressive supranuclear palsy. Phonetic and prosodic subtypes showed differing relationships within the cortico-striato-pallido-nigro-luysial network. Biochemical analysis revealed no distinct differences in aggregated 4R-tau while tau H1 haplotype frequency (69%) was lower compared to 1000+ autopsy-confirmed 4R-tauopathies. Corticobasal degeneration patients had faster rates of decline, greater cortical degeneration, and shorter illness duration than progressive supranuclear palsy. These findings help define the pathobiology of progressive Apraxia of Speech and may have consequences for development of 4R-tau targeting treatment.
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A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive Apraxia of Speech
'Springer Science and Business Media LLC', 2021Co-Authors: Keith A Josephs, Edythe A Strand, Mary M. Machulda, Joseph R Duffy, Rene L Utianski, Hugo Botha, Heather M Clark, Peter R Martin, Nha Trang Thu Pham, Julie StierwaltAbstract:Progressive Apraxia of Speech (PAOS) is a neurodegenerative syndrome of multiple etiologies which affects spoken communication. Here, the authors characterized the molecular pathology, biochemistry, genetics and longitudinal neuroimaging of 32 autopsy-confirmed patients with PAOS who were followed over 10 years
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ioflupane 123i dat scan spect identifies dopamine receptor dysfunction early in the disease course in progressive Apraxia of Speech
Journal of Neurology, 2020Co-Authors: Zeynep Idil Seckin, Jennifer L Whitwell, Mary M. Machulda, Joseph R Duffy, Rene L Utianski, Hugo Botha, Heather M Clark, Farwa Ali, Lennon Jordan, Hoon Ki MinAbstract:To describe 123I-FP-CIT (DAT scan) SPECT findings in progressive Apraxia of Speech (PAOS) patients and to compare those findings with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). PAOS is a neurodegenerative syndrome in which patients present with Apraxia of Speech, a motor Speech disorder affecting programming and planning of Speech. Patients with PAOS predictably develop Parkinsonism. DAT scan is a neuroimaging tool that assesses the integrity of presynaptic dopamine transporters in striatum and is usually abnormal in PSP and CBS. As part of an NIH-funded grant, we performed a DAT scan on 17 PAOS patients early in the disease course. DaTQUANT software was used to quantify uptake in the left and right caudate and anterior/posterior putamen, with striatum to background ratios (SBRs). The PAOS cohort was compared to 15 PSP and 8 CBS patients. Five PAOS patients (29%) showed abnormalities in at least one striatal region on DAT scan. When the five PAOS patients with abnormal DAT were compared to the PSP and CBS patients, the only difference observed was lower uptake in the posterior putamen in PSP (p = 0.03). There were no differences is putamen/caudate ratio or in symmetry of uptake, across all groups. There was also no difference in MDS-UPDRS-III scores between PAOS patients with and without abnormal DAT scans (p = 0.56). Abnormal DAT scan is observed early in the disease course in approximately 30% of PAOS patients, with striatal abnormalities similar to those in PSP and CBS.
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longitudinal flortaucipir 18f av 1451 pet imaging in primary progressive Apraxia of Speech
Cortex, 2020Co-Authors: Rene L Utianski, David S Knopman, Joseph R Duffy, Hugo Botha, Christopher G Schwarz, Heather M Clark, Peter R Martin, Ronald C Petersen, Alissa M Butts, Mary M. MachuldaAbstract:Abstract Primary progressive Apraxia of Speech (PPAOS) is a term used to describe a neurodegenerative condition in which Apraxia of Speech (AOS; a planning and/or programming deficit) occurs in the absence of aphasia (a language deficit). PPAOS is strongly associated with 4-repeat tau pathology. Elevated flortaucipir ([18F]AV-1451; FTP) uptake has been observed cross-sectionally in patients with PPAOS and those with aphasia. Here, we evaluated longitudinal changes in previously-identified regions of uptake and their relationship with clinical presentation. Thirteen patients who were diagnosed with PPAOS (5 female) at presentation underwent FTP PET imaging at two visits (mean 1 year interval). Median age was 72, with a median of 4 years disease duration at initial testing. Beta-amyloid status was assessed with Pittsburgh Compound B (PiB), where a global PiB ratio>1.48 was deemed amyloid positive (n = 4). FTP uptake was assessed as cortical to cerebellar crus ratios (SUVr) in cortical regions of interest. A single hierarchical linear model (HLM) compared PPAOS patients to 52 cognitively unimpaired controls of similar age and sex. Annualized SUVr change was the outcome, predicted by region, clinical status, and age. Person-specific effects accounted for intra-patient correlations and contralateral regions were included as repeated measures. Changes in clinical measures were assessed using Wilcoxon signed-rank tests; statistically significant changes in the Montreal Cognitive Assessment, MDS-UPDRS, motor section, and PSP Rating Scale were noted between visits. Changes in FTP SUVr were greater for patients than controls. The strongest changes in PPAOS patients were in the precentral gyrus, pallidum, and mid and superior frontal gyri, per the HLM. Qualitatively, larger changes were seen in patients who had developed aphasia by the time of their baseline scan (n = 5). While the biological mechanisms of FTP signal in non-AD tauopathies are unknown, this study demonstrates the utility of FTP in tracking disease progression in 4R tauopathies.
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progressive agrammatic aphasia without Apraxia of Speech as a distinct syndrome
Brain, 2019Co-Authors: Katerina A Tetzloff, Edythe A Strand, Mary M. Machulda, Joseph R Duffy, Rene L Utianski, Hugo Botha, Christopher G Schwarz, Heather M Clark, Peter R Martin, Matthew L SenjemAbstract:Agrammatic aphasia affects grammatical language production and can result from a neurodegenerative disease. Although it typically presents with concomitant Apraxia of Speech, this is not always the case. Little is known about the clinical course and imaging features of patients that present with agrammatism in the absence of Apraxia of Speech, which we will refer to as progressive agrammatic aphasia. We aimed to make a detailed description of the longitudinal clinical, linguistic, and neuroimaging features of a cohort of 11 patients with progressive agrammatic aphasia to provide a complete picture of this syndrome. All patients underwent detailed Speech and language, neurological and neuropsychological assessments, 3 T structural and diffusion tensor imaging MRI, 18F-fluorodeoxyglucose and Pittsburgh compound B PET. The 11 patients were matched by age and gender to 22 patients who had mixed Apraxia of Speech and agrammatism. The progressive agrammatic aphasia patients performed abnormally on tests of language, general cognition, executive function, and functional ability at baseline and declined in these measures over time. Only two patients eventually developed Apraxia of Speech, while parkinsonism was absent-to-mild throughout all visits for all patients. When compared to the patients with mixed Apraxia of Speech and agrammatism, the patients with progressive agrammatic aphasia performed better on tests of motor Speech and parkinsonism but more poorly, and declined faster over time, on tests of general aphasia severity, agrammatism, and naming. The patients with progressive agrammatic aphasia also showed different neuroimaging abnormalities, with greater atrophy, hypometabolism and white matter tract degeneration in the prefrontal and anterior temporal lobes compared to patients with mixed Apraxia of Speech and agrammatism. These differences were more pronounced as the disease progressed. These results demonstrate that progressive agrammatic aphasia has a different clinical disease course and different underlying neuroanatomical abnormalities than patients with the more common syndrome of mixed agrammatism and Apraxia of Speech. This supports the distinction of progressive agrammatic aphasia and has implications for the classification of patients with agrammatic aphasia.
Edythe A Strand - One of the best experts on this subject based on the ideXlab platform.
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a molecular pathology neurobiology biochemical genetic and neuroimaging study of progressive Apraxia of Speech
Nature Communications, 2021Co-Authors: Keith A Josephs, Edythe A Strand, Mary M. Machulda, Joseph R Duffy, Rene L Utianski, Hugo Botha, Heather M Clark, Peter R Martin, Nha Trang Thu PhamAbstract:Progressive Apraxia of Speech is a neurodegenerative syndrome affecting spoken communication. Molecular pathology, biochemistry, genetics, and longitudinal imaging were investigated in 32 autopsy-confirmed patients with progressive Apraxia of Speech who were followed over 10 years. Corticobasal degeneration and progressive supranuclear palsy (4R-tauopathies) were the most common underlying pathologies. Perceptually distinct Speech characteristics, combined with age-at-onset, predicted specific 4R-tauopathy; phonetic subtype and younger age predicted corticobasal degeneration, and prosodic subtype and older age predicted progressive supranuclear palsy. Phonetic and prosodic subtypes showed differing relationships within the cortico-striato-pallido-nigro-luysial network. Biochemical analysis revealed no distinct differences in aggregated 4R-tau while tau H1 haplotype frequency (69%) was lower compared to 1000+ autopsy-confirmed 4R-tauopathies. Corticobasal degeneration patients had faster rates of decline, greater cortical degeneration, and shorter illness duration than progressive supranuclear palsy. These findings help define the pathobiology of progressive Apraxia of Speech and may have consequences for development of 4R-tau targeting treatment.
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A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive Apraxia of Speech
'Springer Science and Business Media LLC', 2021Co-Authors: Keith A Josephs, Edythe A Strand, Mary M. Machulda, Joseph R Duffy, Rene L Utianski, Hugo Botha, Heather M Clark, Peter R Martin, Nha Trang Thu Pham, Julie StierwaltAbstract:Progressive Apraxia of Speech (PAOS) is a neurodegenerative syndrome of multiple etiologies which affects spoken communication. Here, the authors characterized the molecular pathology, biochemistry, genetics and longitudinal neuroimaging of 32 autopsy-confirmed patients with PAOS who were followed over 10 years
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progressive agrammatic aphasia without Apraxia of Speech as a distinct syndrome
Brain, 2019Co-Authors: Katerina A Tetzloff, Edythe A Strand, Mary M. Machulda, Joseph R Duffy, Rene L Utianski, Hugo Botha, Christopher G Schwarz, Heather M Clark, Peter R Martin, Matthew L SenjemAbstract:Agrammatic aphasia affects grammatical language production and can result from a neurodegenerative disease. Although it typically presents with concomitant Apraxia of Speech, this is not always the case. Little is known about the clinical course and imaging features of patients that present with agrammatism in the absence of Apraxia of Speech, which we will refer to as progressive agrammatic aphasia. We aimed to make a detailed description of the longitudinal clinical, linguistic, and neuroimaging features of a cohort of 11 patients with progressive agrammatic aphasia to provide a complete picture of this syndrome. All patients underwent detailed Speech and language, neurological and neuropsychological assessments, 3 T structural and diffusion tensor imaging MRI, 18F-fluorodeoxyglucose and Pittsburgh compound B PET. The 11 patients were matched by age and gender to 22 patients who had mixed Apraxia of Speech and agrammatism. The progressive agrammatic aphasia patients performed abnormally on tests of language, general cognition, executive function, and functional ability at baseline and declined in these measures over time. Only two patients eventually developed Apraxia of Speech, while parkinsonism was absent-to-mild throughout all visits for all patients. When compared to the patients with mixed Apraxia of Speech and agrammatism, the patients with progressive agrammatic aphasia performed better on tests of motor Speech and parkinsonism but more poorly, and declined faster over time, on tests of general aphasia severity, agrammatism, and naming. The patients with progressive agrammatic aphasia also showed different neuroimaging abnormalities, with greater atrophy, hypometabolism and white matter tract degeneration in the prefrontal and anterior temporal lobes compared to patients with mixed Apraxia of Speech and agrammatism. These differences were more pronounced as the disease progressed. These results demonstrate that progressive agrammatic aphasia has a different clinical disease course and different underlying neuroanatomical abnormalities than patients with the more common syndrome of mixed agrammatism and Apraxia of Speech. This supports the distinction of progressive agrammatic aphasia and has implications for the classification of patients with agrammatic aphasia.
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prosodic and phonetic subtypes of primary progressive Apraxia of Speech
Brain and Language, 2018Co-Authors: Rene L Utianski, Matthew L Senjem, Edythe A Strand, Mary M. Machulda, Joseph R Duffy, Hugo Botha, Christopher G Schwarz, Heather M Clark, Anthony J Spychalla, Clifford R JackAbstract:Primary progressive Apraxia of Speech (PPAOS) is a clinical syndrome in which Apraxia of Speech is the initial indication of neurodegenerative disease. Prior studies of PPAOS have identified hypometabolism, grey matter atrophy, and white matter tract degeneration in the frontal gyri, precentral cortex, and supplementary motor area (SMA). Recent clinical observations suggest two distinct subtypes of PPAOS may exist. Phonetic PPAOS is characterized predominantly by distorted sound substitutions. Prosodic PPAOS is characterized predominantly by slow, segmented Speech. Demographic, clinical, and neuroimaging data (MRI, DTI, and FDG-PET) were analyzed to validate these subtypes and explore anatomic correlates. The Phonetic subtype demonstrated bilateral involvement of the SMA, precentral gyrus, and cerebellar crus. The Prosodic subtype demonstrated more focal involvement in the SMA and right superior cerebellar peduncle. The findings provide converging evidence that differences in the reliably determined predominant clinical characteristics of AOS are associated with distinct imaging patterns, independent of severity.
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non right handed primary progressive Apraxia of Speech
Journal of the Neurological Sciences, 2018Co-Authors: Hugo Botha, Matthew L Senjem, David S Knopman, Jennifer L Whitwell, Edythe A Strand, Mary M. Machulda, Joseph R Duffy, Anthony J Spychalla, Nirubol Tosakulwong, Ronald C PetersenAbstract:In recent years a large and growing body of research has greatly advanced our understanding of primary progressive Apraxia of Speech. Handedness has emerged as one potential marker of selective vulnerability in degenerative diseases. This study evaluated the clinical and imaging findings in non-right handed compared to right handed participants in a prospective cohort diagnosed with primary progressive Apraxia of Speech. A total of 30 participants were included. Compared to the expected rate in the population, there was a higher prevalence of non-right handedness among those with primary progressive Apraxia of Speech (6/30, 20%). Small group numbers meant that these results did not reach statistical significance, although the effect sizes were moderate-to-large. There were no clinical differences between right handed and non-right handed participants. Bilateral hypometabolism was seen in primary progressive Apraxia of Speech compared to controls, with non-right handed participants showing more right hemispheric involvement. This is the first report of a higher rate of non-right handedness in participants with isolated Apraxia of Speech, which may point to an increased vulnerability for developing this disorder among non-right handed participants. This challenges prior hypotheses about a relative protective effect of non-right handedness for tau-related neurodegeneration. We discuss potential avenues for future research to investigate the relationship between handedness and motor disorders more generally.
Keith A Josephs - One of the best experts on this subject based on the ideXlab platform.
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a molecular pathology neurobiology biochemical genetic and neuroimaging study of progressive Apraxia of Speech
Nature Communications, 2021Co-Authors: Keith A Josephs, Edythe A Strand, Mary M. Machulda, Joseph R Duffy, Rene L Utianski, Hugo Botha, Heather M Clark, Peter R Martin, Nha Trang Thu PhamAbstract:Progressive Apraxia of Speech is a neurodegenerative syndrome affecting spoken communication. Molecular pathology, biochemistry, genetics, and longitudinal imaging were investigated in 32 autopsy-confirmed patients with progressive Apraxia of Speech who were followed over 10 years. Corticobasal degeneration and progressive supranuclear palsy (4R-tauopathies) were the most common underlying pathologies. Perceptually distinct Speech characteristics, combined with age-at-onset, predicted specific 4R-tauopathy; phonetic subtype and younger age predicted corticobasal degeneration, and prosodic subtype and older age predicted progressive supranuclear palsy. Phonetic and prosodic subtypes showed differing relationships within the cortico-striato-pallido-nigro-luysial network. Biochemical analysis revealed no distinct differences in aggregated 4R-tau while tau H1 haplotype frequency (69%) was lower compared to 1000+ autopsy-confirmed 4R-tauopathies. Corticobasal degeneration patients had faster rates of decline, greater cortical degeneration, and shorter illness duration than progressive supranuclear palsy. These findings help define the pathobiology of progressive Apraxia of Speech and may have consequences for development of 4R-tau targeting treatment.
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A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive Apraxia of Speech
'Springer Science and Business Media LLC', 2021Co-Authors: Keith A Josephs, Edythe A Strand, Mary M. Machulda, Joseph R Duffy, Rene L Utianski, Hugo Botha, Heather M Clark, Peter R Martin, Nha Trang Thu Pham, Julie StierwaltAbstract:Progressive Apraxia of Speech (PAOS) is a neurodegenerative syndrome of multiple etiologies which affects spoken communication. Here, the authors characterized the molecular pathology, biochemistry, genetics and longitudinal neuroimaging of 32 autopsy-confirmed patients with PAOS who were followed over 10 years
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primary progressive aphasias and Apraxia of Speech
Continuum: Lifelong Learning in Neurology, 2019Co-Authors: Hugo Botha, Keith A JosephsAbstract:Purpose of review This article reviews two of the primary progressive aphasias (PPAs), disorders characterized by the early and predominant impairment of language, and primary progressive Apraxia of Speech, a degenerative motor Speech disorder that is closely related to PPA. An outline of the history and controversy surrounding how these disorders are classified is provided before the article focuses on each disorder's clinical and imaging features. Recent findings Over the past decade, the classification of degenerative Speech and language disorders has been refined. Clinical, imaging, and pathologic evidence suggests that primary progressive Apraxia of Speech is a distinct degenerative disorder. Furthermore, multiple lines of evidence have highlighted issues with nonfluent/agrammatic variant PPA, which complicates the diagnosis, prognosis, and study of this disorder. Semantic variant PPA, while not without controversy, remains one of the most well-defined disorders, with good clinicopathologic correlation. Summary Accurate classification and diagnosis of these degenerative Speech and language disorders is crucial in clinical practice and ongoing research efforts. For nonfluent/agrammatic variant PPA, the authors suggest emphasizing agrammatism as the core inclusion criterion and taking care not to include patients with isolated or predominant Apraxia of Speech. Isolated Apraxia of Speech can be the manifestation of a degenerative disease and, based on the different prognosis, should be recognized as distinct from PPA. Finally, it is important to recognize that some patients with semantic dementia, despite sharing the same pathologic associations, may not meet criteria for PPA.
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clinical and imaging progression over 10 years in a patient with primary progressive Apraxia of Speech and autopsy confirmed corticobasal degeneration
Neurocase, 2018Co-Authors: Katerina A Tetzloff, Matthew L Senjem, Edythe A Strand, Mary M. Machulda, Joseph R Duffy, Sarah M Boland, Rene L Utianski, Hugo Botha, Christopher G Schwarz, Keith A JosephsAbstract:ABSTRACTPrimary progressive Apraxia of Speech (PPAOS) is a neurodegenerative disorder in which AOS is the sole presenting complaint. We report clinical and neuroimaging data spanning 10 years from ...
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temporal acoustic measures distinguish primary progressive Apraxia of Speech from primary progressive aphasia
Brain and Language, 2017Co-Authors: Joseph R Duffy, Edythe A Strand, Rene L Utianski, Keith A Josephs, Heather M Clark, Holly Hanley, Jennifer L WhitwellAbstract:The purpose of this study was to determine if acoustic measures of duration and syllable rate during word and sentence repetition, and a measure of within-word lexical stress, distinguish speakers with primary progressive Apraxia of Speech (PPAOS) from nonapraxic speakers with the agrammatic or logopenic variants of primary progressive aphasia (PPA), and control speakers. Results revealed that the PPAOS group had longer durations and reduced rate of syllable production for most words and sentences, and the measure of lexical stress. Sensitivity and specificity indices for the PPAOS versus the other groups were highest for longer multisyllabic words and sentences. For the PPAOS group, correlations between acoustic measures and perceptual ratings of AOS were moderately high to high. Several temporal measures used in this study may aid differential diagnosis and help quantify features of PPAOS that are distinct from those associated with PPA in which AOS is not present.
Mary M. Machulda - One of the best experts on this subject based on the ideXlab platform.
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a molecular pathology neurobiology biochemical genetic and neuroimaging study of progressive Apraxia of Speech
Nature Communications, 2021Co-Authors: Keith A Josephs, Edythe A Strand, Mary M. Machulda, Joseph R Duffy, Rene L Utianski, Hugo Botha, Heather M Clark, Peter R Martin, Nha Trang Thu PhamAbstract:Progressive Apraxia of Speech is a neurodegenerative syndrome affecting spoken communication. Molecular pathology, biochemistry, genetics, and longitudinal imaging were investigated in 32 autopsy-confirmed patients with progressive Apraxia of Speech who were followed over 10 years. Corticobasal degeneration and progressive supranuclear palsy (4R-tauopathies) were the most common underlying pathologies. Perceptually distinct Speech characteristics, combined with age-at-onset, predicted specific 4R-tauopathy; phonetic subtype and younger age predicted corticobasal degeneration, and prosodic subtype and older age predicted progressive supranuclear palsy. Phonetic and prosodic subtypes showed differing relationships within the cortico-striato-pallido-nigro-luysial network. Biochemical analysis revealed no distinct differences in aggregated 4R-tau while tau H1 haplotype frequency (69%) was lower compared to 1000+ autopsy-confirmed 4R-tauopathies. Corticobasal degeneration patients had faster rates of decline, greater cortical degeneration, and shorter illness duration than progressive supranuclear palsy. These findings help define the pathobiology of progressive Apraxia of Speech and may have consequences for development of 4R-tau targeting treatment.
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A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive Apraxia of Speech
'Springer Science and Business Media LLC', 2021Co-Authors: Keith A Josephs, Edythe A Strand, Mary M. Machulda, Joseph R Duffy, Rene L Utianski, Hugo Botha, Heather M Clark, Peter R Martin, Nha Trang Thu Pham, Julie StierwaltAbstract:Progressive Apraxia of Speech (PAOS) is a neurodegenerative syndrome of multiple etiologies which affects spoken communication. Here, the authors characterized the molecular pathology, biochemistry, genetics and longitudinal neuroimaging of 32 autopsy-confirmed patients with PAOS who were followed over 10 years
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ioflupane 123i dat scan spect identifies dopamine receptor dysfunction early in the disease course in progressive Apraxia of Speech
Journal of Neurology, 2020Co-Authors: Zeynep Idil Seckin, Jennifer L Whitwell, Mary M. Machulda, Joseph R Duffy, Rene L Utianski, Hugo Botha, Heather M Clark, Farwa Ali, Lennon Jordan, Hoon Ki MinAbstract:To describe 123I-FP-CIT (DAT scan) SPECT findings in progressive Apraxia of Speech (PAOS) patients and to compare those findings with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). PAOS is a neurodegenerative syndrome in which patients present with Apraxia of Speech, a motor Speech disorder affecting programming and planning of Speech. Patients with PAOS predictably develop Parkinsonism. DAT scan is a neuroimaging tool that assesses the integrity of presynaptic dopamine transporters in striatum and is usually abnormal in PSP and CBS. As part of an NIH-funded grant, we performed a DAT scan on 17 PAOS patients early in the disease course. DaTQUANT software was used to quantify uptake in the left and right caudate and anterior/posterior putamen, with striatum to background ratios (SBRs). The PAOS cohort was compared to 15 PSP and 8 CBS patients. Five PAOS patients (29%) showed abnormalities in at least one striatal region on DAT scan. When the five PAOS patients with abnormal DAT were compared to the PSP and CBS patients, the only difference observed was lower uptake in the posterior putamen in PSP (p = 0.03). There were no differences is putamen/caudate ratio or in symmetry of uptake, across all groups. There was also no difference in MDS-UPDRS-III scores between PAOS patients with and without abnormal DAT scans (p = 0.56). Abnormal DAT scan is observed early in the disease course in approximately 30% of PAOS patients, with striatal abnormalities similar to those in PSP and CBS.
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longitudinal flortaucipir 18f av 1451 pet imaging in primary progressive Apraxia of Speech
Cortex, 2020Co-Authors: Rene L Utianski, David S Knopman, Joseph R Duffy, Hugo Botha, Christopher G Schwarz, Heather M Clark, Peter R Martin, Ronald C Petersen, Alissa M Butts, Mary M. MachuldaAbstract:Abstract Primary progressive Apraxia of Speech (PPAOS) is a term used to describe a neurodegenerative condition in which Apraxia of Speech (AOS; a planning and/or programming deficit) occurs in the absence of aphasia (a language deficit). PPAOS is strongly associated with 4-repeat tau pathology. Elevated flortaucipir ([18F]AV-1451; FTP) uptake has been observed cross-sectionally in patients with PPAOS and those with aphasia. Here, we evaluated longitudinal changes in previously-identified regions of uptake and their relationship with clinical presentation. Thirteen patients who were diagnosed with PPAOS (5 female) at presentation underwent FTP PET imaging at two visits (mean 1 year interval). Median age was 72, with a median of 4 years disease duration at initial testing. Beta-amyloid status was assessed with Pittsburgh Compound B (PiB), where a global PiB ratio>1.48 was deemed amyloid positive (n = 4). FTP uptake was assessed as cortical to cerebellar crus ratios (SUVr) in cortical regions of interest. A single hierarchical linear model (HLM) compared PPAOS patients to 52 cognitively unimpaired controls of similar age and sex. Annualized SUVr change was the outcome, predicted by region, clinical status, and age. Person-specific effects accounted for intra-patient correlations and contralateral regions were included as repeated measures. Changes in clinical measures were assessed using Wilcoxon signed-rank tests; statistically significant changes in the Montreal Cognitive Assessment, MDS-UPDRS, motor section, and PSP Rating Scale were noted between visits. Changes in FTP SUVr were greater for patients than controls. The strongest changes in PPAOS patients were in the precentral gyrus, pallidum, and mid and superior frontal gyri, per the HLM. Qualitatively, larger changes were seen in patients who had developed aphasia by the time of their baseline scan (n = 5). While the biological mechanisms of FTP signal in non-AD tauopathies are unknown, this study demonstrates the utility of FTP in tracking disease progression in 4R tauopathies.
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progressive agrammatic aphasia without Apraxia of Speech as a distinct syndrome
Brain, 2019Co-Authors: Katerina A Tetzloff, Edythe A Strand, Mary M. Machulda, Joseph R Duffy, Rene L Utianski, Hugo Botha, Christopher G Schwarz, Heather M Clark, Peter R Martin, Matthew L SenjemAbstract:Agrammatic aphasia affects grammatical language production and can result from a neurodegenerative disease. Although it typically presents with concomitant Apraxia of Speech, this is not always the case. Little is known about the clinical course and imaging features of patients that present with agrammatism in the absence of Apraxia of Speech, which we will refer to as progressive agrammatic aphasia. We aimed to make a detailed description of the longitudinal clinical, linguistic, and neuroimaging features of a cohort of 11 patients with progressive agrammatic aphasia to provide a complete picture of this syndrome. All patients underwent detailed Speech and language, neurological and neuropsychological assessments, 3 T structural and diffusion tensor imaging MRI, 18F-fluorodeoxyglucose and Pittsburgh compound B PET. The 11 patients were matched by age and gender to 22 patients who had mixed Apraxia of Speech and agrammatism. The progressive agrammatic aphasia patients performed abnormally on tests of language, general cognition, executive function, and functional ability at baseline and declined in these measures over time. Only two patients eventually developed Apraxia of Speech, while parkinsonism was absent-to-mild throughout all visits for all patients. When compared to the patients with mixed Apraxia of Speech and agrammatism, the patients with progressive agrammatic aphasia performed better on tests of motor Speech and parkinsonism but more poorly, and declined faster over time, on tests of general aphasia severity, agrammatism, and naming. The patients with progressive agrammatic aphasia also showed different neuroimaging abnormalities, with greater atrophy, hypometabolism and white matter tract degeneration in the prefrontal and anterior temporal lobes compared to patients with mixed Apraxia of Speech and agrammatism. These differences were more pronounced as the disease progressed. These results demonstrate that progressive agrammatic aphasia has a different clinical disease course and different underlying neuroanatomical abnormalities than patients with the more common syndrome of mixed agrammatism and Apraxia of Speech. This supports the distinction of progressive agrammatic aphasia and has implications for the classification of patients with agrammatic aphasia.
Jennifer L Whitwell - One of the best experts on this subject based on the ideXlab platform.
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ioflupane 123i dat scan spect identifies dopamine receptor dysfunction early in the disease course in progressive Apraxia of Speech
Journal of Neurology, 2020Co-Authors: Zeynep Idil Seckin, Jennifer L Whitwell, Mary M. Machulda, Joseph R Duffy, Rene L Utianski, Hugo Botha, Heather M Clark, Farwa Ali, Lennon Jordan, Hoon Ki MinAbstract:To describe 123I-FP-CIT (DAT scan) SPECT findings in progressive Apraxia of Speech (PAOS) patients and to compare those findings with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). PAOS is a neurodegenerative syndrome in which patients present with Apraxia of Speech, a motor Speech disorder affecting programming and planning of Speech. Patients with PAOS predictably develop Parkinsonism. DAT scan is a neuroimaging tool that assesses the integrity of presynaptic dopamine transporters in striatum and is usually abnormal in PSP and CBS. As part of an NIH-funded grant, we performed a DAT scan on 17 PAOS patients early in the disease course. DaTQUANT software was used to quantify uptake in the left and right caudate and anterior/posterior putamen, with striatum to background ratios (SBRs). The PAOS cohort was compared to 15 PSP and 8 CBS patients. Five PAOS patients (29%) showed abnormalities in at least one striatal region on DAT scan. When the five PAOS patients with abnormal DAT were compared to the PSP and CBS patients, the only difference observed was lower uptake in the posterior putamen in PSP (p = 0.03). There were no differences is putamen/caudate ratio or in symmetry of uptake, across all groups. There was also no difference in MDS-UPDRS-III scores between PAOS patients with and without abnormal DAT scans (p = 0.56). Abnormal DAT scan is observed early in the disease course in approximately 30% of PAOS patients, with striatal abnormalities similar to those in PSP and CBS.
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non right handed primary progressive Apraxia of Speech
Journal of the Neurological Sciences, 2018Co-Authors: Hugo Botha, Matthew L Senjem, David S Knopman, Jennifer L Whitwell, Edythe A Strand, Mary M. Machulda, Joseph R Duffy, Anthony J Spychalla, Nirubol Tosakulwong, Ronald C PetersenAbstract:In recent years a large and growing body of research has greatly advanced our understanding of primary progressive Apraxia of Speech. Handedness has emerged as one potential marker of selective vulnerability in degenerative diseases. This study evaluated the clinical and imaging findings in non-right handed compared to right handed participants in a prospective cohort diagnosed with primary progressive Apraxia of Speech. A total of 30 participants were included. Compared to the expected rate in the population, there was a higher prevalence of non-right handedness among those with primary progressive Apraxia of Speech (6/30, 20%). Small group numbers meant that these results did not reach statistical significance, although the effect sizes were moderate-to-large. There were no clinical differences between right handed and non-right handed participants. Bilateral hypometabolism was seen in primary progressive Apraxia of Speech compared to controls, with non-right handed participants showing more right hemispheric involvement. This is the first report of a higher rate of non-right handedness in participants with isolated Apraxia of Speech, which may point to an increased vulnerability for developing this disorder among non-right handed participants. This challenges prior hypotheses about a relative protective effect of non-right handedness for tau-related neurodegeneration. We discuss potential avenues for future research to investigate the relationship between handedness and motor disorders more generally.
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tau pet imaging with 18f av 1451 in primary progressive Apraxia of Speech
Cortex, 2018Co-Authors: Rene L Utianski, Matthew L Senjem, Jennifer L Whitwell, Mary M. Machulda, Joseph R Duffy, Christopher G Schwarz, Heather M Clark, Nirubol Tosakulwong, Ronald C Petersen, Clifford R JackAbstract:Abstract Apraxia of Speech is a motor Speech disorder characterized by combinations of slow speaking rate, abnormal prosody, distorted sound substitutions, and trial-and-error articulatory movements. Apraxia of Speech is due to abnormal planning and/or programming of Speech production. It is referred to as primary progressive Apraxia of Speech (PPAOS) when it is the only symptom of a neurodegenerative condition. Past reports suggest an association of PPAOS with primary 4-repeat (4R) tau (e.g., progressive supranuclear palsy, corticobasal degeneration), rather than amyloid, pathology. The goal of the current study was to investigate the distribution of tau tracer uptake using [18F]AV-1451 positron emission tomography (PET) imaging in patients with PPAOS. Fourteen PPAOS patients underwent [18F]AV-1451 PET (tau-PET) imaging, [C11] Pittsburgh Compound B (PiB) PET and structural MRI and were matched 3:1 by age and sex to 42 cognitively normal controls. Tau-PET uptake was assessed at the region-of-interest (ROI) level and at the voxel-level. The PPAOS group (n = 14) showed increased tau-PET uptake in the precentral gyrus, supplementary motor area and Broca's area compared to controls. To examine whether tau deposition in Broca's area was related to the presence of aphasia, we examined a subgroup of the PPAOS patients who had predominant Apraxia of Speech, with concomitant aphasia (PPAOSa; n = 7). The PPAOSa patients showed tau-PET uptake in the same regions as the whole group. However, the remaining seven patients who did not have aphasia showed uptake only in superior premotor and precentral cortices, with no uptake observed in Broca's area. This cross-sectional study demonstrates that elevated tau tracer uptake is observed using [18F]AV-1451 in PPAOS. Further, it appears that [18F]AV-1451 is sensitive to the regional distribution of tau deposition in different stages of PPAOS, given the relationship between tau signal in Broca's area and the presence of aphasia.
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disrupted functional connectivity in primary progressive Apraxia of Speech
NeuroImage: Clinical, 2018Co-Authors: Hugo Botha, David S Knopman, Jennifer L Whitwell, Edythe A Strand, Mary M. Machulda, Joseph R Duffy, Rene L Utianski, Heather M Clark, Nirubol Tosakulwong, Ronald C PetersenAbstract:Apraxia of Speech is a motor Speech disorder thought to result from impaired planning or programming of articulatory movements. It can be the initial or only manifestation of a degenerative disease, termed primary progressive Apraxia of Speech (PPAOS). The aim of this study was to use task-free functional magnetic resonance imaging (fMRI) to assess large-scale brain network pathophysiology in PPAOS. Twenty-two PPAOS participants were identified from a prospective cohort of degenerative Speech and language disorders patients. All participants had a comprehensive, standardized evaluation including an evaluation by a Speech-language pathologist, examination by a behavioral neurologist and a multimodal imaging protocol which included a task-free fMRI sequence. PPAOS participants were age and sex matched to amyloid-negative, cognitively normal participants with a 1:2 ratio. We chose a set of hypothesis driven, predefined intrinsic connectivity networks (ICNs) from a large, out of sample independent component analysis and then used them to initialize a spatiotemporal dual regression to estimate participant level connectivity within these ICNs. Specifically, we evaluated connectivity within the Speech and language, face and hand sensorimotor, left working memory, salience, superior parietal, supramarginal, insular and deep gray ICNs in a multivariate manner. The spatial maps for each ICN were then compared between PPAOS and control participants. We used clinical measures of Apraxia of Speech severity to assess for clinical-connectivity correlations for regions found to differ between PPAOS and control participants. Compared to controls, PPAOS participants had reduced connectivity of the right supplementary motor area and left posterior temporal gyrus to the rest of the Speech and language ICN. The connectivity of the right supplementary motor area correlated negatively with an articulatory error score. PPAOS participants also had reduced connectivity of the left supplementary motor area to the face sensorimotor ICN, between the left lateral prefrontal cortex and the salience ICN and between the left temporal-occipital junction and the left working memory ICN. The latter connectivity correlated with the Apraxia of Speech severity rating scale, although the finding did not survive correction for multiple comparisons. Increased connectivity was noted in PPAOS participants between the dorsal posterior cingulate and the left working memory ICN. Our results support the importance of the supplementary motor area in the pathophysiology of PPAOS, which appears to be disconnected from Speech and language regions. Supplementary motor area connectivity may serve as a biomarker of degenerative Apraxia of Speech severity.
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temporal acoustic measures distinguish primary progressive Apraxia of Speech from primary progressive aphasia
Brain and Language, 2017Co-Authors: Joseph R Duffy, Edythe A Strand, Rene L Utianski, Keith A Josephs, Heather M Clark, Holly Hanley, Jennifer L WhitwellAbstract:The purpose of this study was to determine if acoustic measures of duration and syllable rate during word and sentence repetition, and a measure of within-word lexical stress, distinguish speakers with primary progressive Apraxia of Speech (PPAOS) from nonapraxic speakers with the agrammatic or logopenic variants of primary progressive aphasia (PPA), and control speakers. Results revealed that the PPAOS group had longer durations and reduced rate of syllable production for most words and sentences, and the measure of lexical stress. Sensitivity and specificity indices for the PPAOS versus the other groups were highest for longer multisyllabic words and sentences. For the PPAOS group, correlations between acoustic measures and perceptual ratings of AOS were moderately high to high. Several temporal measures used in this study may aid differential diagnosis and help quantify features of PPAOS that are distinct from those associated with PPA in which AOS is not present.