Features of Patients With Nonfluent/Agrammatic Primary Progressive Aphasia With Underlying Progressive Supranuclear Palsy Pathology or Corticobasal Degeneration

Santos‐Santos, Miguel A.; Mandelli, Maria Luisa; Binney, Richard J.; Ogar, Jennifer M.; Wilson, Stephen M.; Henry, Maya L.; Hubbard, Heidi; Meese, Minerva; Attygalle, Suneth; Rosenberg, Lynne; Pakvasa, Mikhail; Trojanowski, John Q.; Grinberg, Lea T.; Rosen, Howie; Boxer, Adam L.; Miller, Bruce L.; Seeley, William W.

doi:10.1001/jamaneurol.2016.0412

Cited by 134 publications

(106 citation statements)

References 42 publications

(55 reference statements)

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“…Clinical characteristics of AoS are thought to include the production of incorrect speech sounds and sequences of sounds that do not occur in the speaker’s native language, searching for the correct speech sound but not necessarily producing the intended target after several attempts, and oddly placed pauses in the speech stream. These characteristics are consistent with the observation that some patients with naPPA have an extrapyramidal disorder such as progressive supranuclear palsy or corticobasal degeneration that can result in poor control of the motor speech apparatus ( Josephs et al 2006, 2012; Santos-Santos et al 2016), although AoS can occur without any other observable motor disorder (Grossman 2012, Rohrer et al 2010a) and without evidence of a linguistic disorder such as agrammatism ( Josephs et al 2012). …”

Section: Nonfluent/agrammatic Primary Progressive Aphasiasupporting

confidence: 88%

“…Likewise, simplification of grammatical forms in semistructured speech samples have been related to GM atrophy in the inferior frontal and anterior–superior temporal regions of the left hemisphere (Gunawardena et al 2010, Rogalski et al 2011a, Wilson et al 2010b). Motor speech abnormalities in patients with movement disorders such as progressive supranuclear palsy are associated with atrophy of deep GM structures such as the striatum (Santos-Santos et al 2016). …”

Section: Nonfluent/agrammatic Primary Progressive Aphasiamentioning

confidence: 99%

“…This finding is consistent with observations of patients with autopsy-confirmed naPPA in whom imaging revealed WM disease in the superior longitudinal fasciculus, inferior frontal–occipital fasciculus, and uncinate fasciculus (Grossman et al 2013). Finally, WM atrophy is associated with dysarthria and motor speech abnormalities in frontal WM regions (Josephs et al 2012, Santos-Santos et al 2016). …”

Section: Nonfluent/agrammatic Primary Progressive Aphasiamentioning

confidence: 99%

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Linguistic Aspects of Primary Progressive Aphasia

Grossman

2018

Annu. Rev. Linguist.

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Primary progressive aphasia (PPA) refers to a disorder of declining language associated with neurodegenerative diseases such as frontotemporal degeneration and Alzheimer disease. Variants of PPA are important to recognize from a medical perspective because these syndromes are clinical markers suggesting specific underlying pathology. In this review, I discuss linguistic aspects of PPA syndromes that may prove informative for parsing our language mechanism and identifying the neural representation of fundamental elements of language. I focus on the representation of word meaning in a discussion of semantic variant PPA, grammatical comprehension and expression in a discussion of nonfluent/agrammatic variant PPA, the supporting role of short-term memory in a discussion of logopenic variant PPA, and components of language associated with discourse in a discussion of behavioral variant frontotemporal dementia. PPA provides a novel perspective that uniquely addresses facets of language and its disorders while complementing traditional aphasia syndromes that follow stroke.

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Section: Nonfluent/agrammatic Primary Progressive Aphasiasupporting

confidence: 88%

Section: Nonfluent/agrammatic Primary Progressive Aphasiamentioning

confidence: 99%

Section: Nonfluent/agrammatic Primary Progressive Aphasiamentioning

confidence: 99%

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Linguistic Aspects of Primary Progressive Aphasia

Grossman

2018

Annu. Rev. Linguist.

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“…28 The MDS PSP criteria recognize a clinical phenotype of PSP initially presenting with predominant speech and language disorder (PSP-SL) features of nfvPPA before developing other motor features of PSP. 19,20 A recent longitudinal study of 13 subjects with primary progressive AOS (PPAOS), which is similar to nfvPPA, found that five subjects developed a syndrome similar to PSP-RS about five years after onset, 19 and 22/25 nfvPPA in a larger series had tau pathology, most commonly 4R tau. 21 Similar to PSP-CBS, the new PSP criteria designate PSP-SL as possible PSP, but probable 4R tauopathy because determining which PSP-SL cases have PSP pathology based on clinical findings is impossible during life.…”

Section: Symptomatic Psp Phenotypesmentioning

confidence: 99%

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

Boxer

Golbe

et al. 2017

The Lancet Neurology

330

347

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Progressive supranuclear palsy (PSP), once simply considered a common cause of atypical parkinsonism is now recognized as a spectrum of motor and behavioral syndromes associated with a specific four repeat (4R) tau neuropathology at autopsy. There are currently no effective treatments for PSP, but because PSP is strongly linked biochemically and genetically to tau protein abnormalities, there is a growing interest in pursuing clinical trials of new tau-directed therapies for this disorder. Such new tau therapies are envisioned to have disease-modifying effects by reducing brain levels of toxic forms of tau or compensating for loss of tau function. To be most effective, these treatments will need to be initiated at early stages of disease. New research criteria that recognize early forms of PSP and operationalize diagnosis of the full spectrum of clinical phenotypes have recently been published. These criteria and new clinical trial designs have benefited from rapid advances in MRI, physiological and fluid biomarker development for PSP. As tau pathology is also central to Alzheimer’s disease and chronic traumatic encephalopathy, it is believed that a successful tau therapeutic for PSP would inform the treatment of other neurodegenerative diseases.

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“…12 Postmortem lateralization of pathology has been measured in limited PPA cases with FTLD-TDP, [13][14][15][16] whereas distribution of pathology in PPA with FTLD-Tau is understudied. 4,19 Here we use a digital approach to perform a fine-grained comparative study of postmortem FTLD-TDP and FTLD-Tau proteinopathies in PPA, and integrate antemortem clinical features and structural magnetic resonance imaging (MRI) with digital pathology. 4,19 Here we use a digital approach to perform a fine-grained comparative study of postmortem FTLD-TDP and FTLD-Tau proteinopathies in PPA, and integrate antemortem clinical features and structural magnetic resonance imaging (MRI) with digital pathology.…”

mentioning

confidence: 99%

Divergent patterns of TDP‐43 and tau pathologies in primary progressive aphasia

Giannini

Xie

McMillan

et al. 2019

Annals of Neurology

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Objective: To measure postmortem burden of frontotemporal lobar degeneration (FTLD) with TDP-43 (FTLD-TDP) or tau (FTLD-Tau) proteinopathy across hemispheres in primary progressive aphasia (PPA) using digital histopathology and to identify clinicopathological correlates of these distinct proteinopathies. Methods: In an autopsy cohort of PPA (FTLD-TDP = 13, FTLD-Tau = 14), we analyzed laterality and regional distribution of postmortem pathology, quantified using a validated digital histopathological approach, in available brain tissue from up to 8 cortical regions bilaterally. We related digital pathology to antemortem structural neuroimaging and specific clinical language features. Results: Postmortem cortical pathology was left-lateralized in both FTLD-TDP (beta = −0.15, standard error [SE] = 0.05, p = 0.007) and FTLD-Tau (beta = −0.09, SE = 0.04, p = 0.015), but the degree of lateralization decreased with greater overall dementia severity before death (beta = −8.18, SE = 3.22, p = 0.015). Among 5 core pathology regions sampled, we found greatest pathology in left orbitofrontal cortex (OFC) in FTLD-TDP, which was greater than in FTLD-Tau (F = 47.07, df = 1,17, p < 0.001), and in left midfrontal cortex (MFC) in FTLD-Tau, which was greater than in FTLD-TDP (F = 19.34, df = 1,16, p < 0.001). Postmortem pathology was inversely associated with antemortem magnetic resonance imaging cortical thickness (beta = −0.04, SE = 0.01, p = 0.007) in regions matching autopsy sampling. Irrespective of PPA syndromic variant, single-word comprehension impairment was associated with greater left OFC pathology (t = −3.72, df = 10.72, p = 0.004) and nonfluent speech with greater left MFC pathology (t = −3.62, df = 12.00, p = 0.004) among the 5 core pathology regions. Interpretation: In PPA, FTLD-TDP and FTLD-Tau have divergent anatomic distributions of left-lateralized postmortem pathology that relate to antemortem structural imaging and distinct language deficits. Although other brain regions may be implicated in neural networks supporting these complex language measures, our observations may eventually help to improve antemortem diagnosis of neuropathology in PPA.

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Features of Patients With Nonfluent/Agrammatic Primary Progressive Aphasia With Underlying Progressive Supranuclear Palsy Pathology or Corticobasal Degeneration

Cited by 134 publications

References 42 publications

Linguistic Aspects of Primary Progressive Aphasia

Linguistic Aspects of Primary Progressive Aphasia

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

Divergent patterns of TDP‐43 and tau pathologies in primary progressive aphasia

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