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

Importance: We provide novel evidence of specific clinical and neuroimaging features that may help for the in vivo prediction of underlying pathology in patients with nonfluent/agrammatic primary progressive aphasia (nfvPPA) and progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) proved by autopsy.

Objective: To characterize the neurological, cognitive, and neuroimaging features of patients with nfvPPA-in whom either PSP or CBD was eventually confirmed at autopsy-at initial presentation and at 1-year follow-up.

Design, Setting, And Participants: A prospective longitudinal clinical-pathological study was conducted in a tertiary research clinic that specialized in cognitive disorders.

Inflectional morphology in primary progressive aphasia: an elicited production study.

Inflectional morphology lies at the intersection of phonology, syntax and the lexicon, three language domains that are differentially impacted in the three main variants of primary progressive aphasia (PPA). To characterize spared and impaired aspects of inflectional morphology in PPA, we elicited inflectional morphemes in 48 individuals with PPA and 13 healthy age-matched controls. We varied the factors of regularity, frequency, word class, and lexicality, and used voxel-based morphometry to identify brain regions where atrophy was predictive of deficits on particular conditions.

In vivo signatures of nonfluent/agrammatic primary progressive aphasia caused by FTLD pathology.

Objective: To identify early cognitive and neuroimaging features of sporadic nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) caused by frontotemporal lobar degeneration (FTLD) subtypes.

Methods: We prospectively collected clinical, neuroimaging, and neuropathologic data in 11 patients with sporadic nfvPPA with FTLD-tau (nfvPPA-tau, n = 9) or FTLD-transactive response DNA binding protein pathology of 43 kD type A (nfvPPA-TDP, n = 2). We analyzed patterns of cognitive and gray matter (GM) and white matter (WM) atrophy at presentation in the whole group and in each pathologic subtype separately.

Neuropsychological, behavioral, and anatomical evolution in right temporal variant frontotemporal dementia: a longitudinal and post-mortem single case analysis.

We describe a patient with semantic variant of frontotemporal dementia who received longitudinal clinical evaluations and structural MRI scans and subsequently came to autopsy. She presented with early behavior changes and semantic loss for foods and people and ultimately developed a pervasive semantic impairment affecting social-emotional as well as linguistic domains. Imaging revealed predominant atrophy of the right temporal lobe, with later involvement of the left, and pathology confirmed bilateral temporal involvement.

Elicitation of specific syntactic structures in primary progressive aphasia.

Many patients with primary progressive aphasia (PPA) are impaired in syntactic production. Because most previous studies of expressive syntax in PPA have relied on quantitative analysis of connected speech samples, which is a relatively unconstrained task, it is not well understood which specific syntactic structures are most challenging for these patients. We used an elicited syntactic production task to identify which syntactic structures pose difficulties for 31 patients with three variants of PPA: non-fluent/agrammatic, semantic and logopenic.

Syntactic processing depends on dorsal language tracts.

Frontal and temporal language areas involved in syntactic processing are connected by several dorsal and ventral tracts, but the functional roles of the different tracts are not well understood. To identify which white matter tract(s) are important for syntactic processing, we examined the relationship between white matter damage and syntactic deficits in patients with primary progressive aphasia, using multimodal neuroimaging and neurolinguistic assessment. Diffusion tensor imaging showed that microstructural damage to left hemisphere dorsal tracts--the superior longitudinal fasciculus including its arcuate component--was strongly associated with deficits in comprehension and production of syntax.

White matter damage in primary progressive aphasias: a diffusion tensor tractography study.

Primary progressive aphasia is a clinical syndrome that encompasses three major phenotypes: non-fluent/agrammatic, semantic and logopenic. These clinical entities have been associated with characteristic patterns of focal grey matter atrophy in left posterior frontoinsular, anterior temporal and left temporoparietal regions, respectively. Recently, network-level dysfunction has been hypothesized but research to date has focused largely on studying grey matter damage.

Neural correlates of syntactic processing in the nonfluent variant of primary progressive aphasia.

The left posterior inferior frontal cortex (IFC) is important for syntactic processing, and has been shown in many functional imaging studies to be differentially recruited for the processing of syntactically complex sentences relative to simpler ones. In the nonfluent variant of primary progressive aphasia (PPA), degeneration of the posterior IFC is associated with expressive and receptive agrammatism; however, the functional status of this region in nonfluent PPA is not well understood. Our objective was to determine whether the atrophic posterior IFC is differentially recruited for the processing of syntactically complex sentences in nonfluent PPA.

Multimodal cuing of autobiographical memory in semantic dementia.

Objective: Individuals with semantic dementia (SD) have impaired autobiographical memory (AM), but the extent of the impairment has been controversial. According to one report (Westmacott, Leach, Freedman, & Moscovitch, 2001), patient performance was better when visual cues were used instead of verbal cues; however, the visual cues used in that study (family photographs) provided more retrieval support than do the word cues that are typically used in AM studies. In the present study, we sought to disentangle the effects of retrieval support and cue modality.

Role of the precentral gyrus of the insula in complex articulation.

Previous research has suggested that the left anterior insula, specifically the superior precentral gyrus of the insula (SPGI), is a critical brain region for the coordination of complex articulatory movements. However, previous studies have not determined which articulatory factors are specifically dependent on this brain region. In the current study, 33 left hemisphere stroke patients with varying degrees of speech impairment were asked to perform multiple repetitions of single words that varied along three separate dimensions: number of syllables, degree of articulatory travel (i.

Connected speech production in three variants of primary progressive aphasia.

Primary progressive aphasia is a clinical syndrome defined by progressive deficits isolated to speech and/or language, and can be classified into non-fluent, semantic and logopenic variants based on motor speech, linguistic and cognitive features. The connected speech of patients with primary progressive aphasia has often been dichotomized simply as 'fluent' or 'non-fluent', however fluency is a multidimensional construct that encompasses features such as speech rate, phrase length, articulatory agility and syntactic structure, which are not always impacted in parallel. In this study, our first objective was to improve the characterization of connected speech production in each variant of primary progressive aphasia, by quantifying speech output along a number of motor speech and linguistic dimensions simultaneously.

Language networks in semantic dementia.

Cognitive deficits in semantic dementia have been attributed to anterior temporal lobe grey matter damage; however, key aspects of the syndrome could be due to altered anatomical connectivity between language pathways involving the temporal lobe. The aim of this study was to investigate the left language-related cerebral pathways in semantic dementia using diffusion tensor imaging-based tractography and to combine the findings with cortical anatomical and functional magnetic resonance imaging data obtained during a reading activation task. The left inferior longitudinal fasciculus, arcuate fasciculus and fronto-parietal superior longitudinal fasciculus were tracked in five semantic dementia patients and eight healthy controls.

Automated MRI-based classification of primary progressive aphasia variants.

Degeneration of language regions in the dominant hemisphere can result in primary progressive aphasia (PPA), a clinical syndrome characterized by progressive deficits in speech and/or language function. Recent studies have identified three variants of PPA: progressive non-fluent aphasia (PNFA), semantic dementia (SD) and logopenic progressive aphasia (LPA). Each variant is associated with characteristic linguistic features, distinct patterns of brain atrophy, and different likelihoods of particular underlying pathogenic processes, which makes correct differential diagnosis highly clinically relevant.

Learning diagnostic models using speech and language measures.

We describe results that show the effectiveness of machine learning in the automatic diagnosis of certain neurodegenerative diseases, several of which alter speech and language production. We analyzed audio from 9 control subjects and 30 patients diagnosed with one of three subtypes of Frontotemporal Lobar Degeneration. From this data, we extracted features of the audio signal and the words the patient used, which were obtained using our automated transcription technologies.

The neural basis of surface dyslexia in semantic dementia.

Semantic dementia (SD) is a neurodegenerative disease characterized by atrophy of anterior temporal regions and progressive loss of semantic memory. SD patients often present with surface dyslexia, a relatively selective impairment in reading low-frequency words with exceptional or atypical spelling-to-sound correspondences. Exception words are typically 'over-regularized' in SD and pronounced as they are spelled (e.

Abeta amyloid and glucose metabolism in three variants of primary progressive aphasia.

Objective: Alzheimer's disease (AD) is found at autopsy in up to one third of patients with primary progressive aphasia (PPA), but clinical features that predict AD pathology in PPA are not well defined. We studied the relationships between language presentation, Abeta amyloidosis, and glucose metabolism in three PPA variants using [11C]-Pittsburgh compound B ([11C]PIB) and [18F]-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG-PET).

Methods: Patients meeting PPA criteria (N = 15) were classified as logopenic aphasia (LPA), progressive nonfluent aphasia (PNFA), or semantic dementia (SD) based on language testing.

Performance in specific language tasks correlates with regional volume changes in progressive aphasia.

Background: Patterns of language impairment have long been used clinically to localize brain damage in stroke patients. The same approach might be useful in the differential diagnosis of progressive aphasia owing to neurodegenerative disease.

Objective: To investigate whether scores on 4 widely used language tasks correlate with regional gray matter loss in 51 patients with progressive language impairment owing to neurodegenerative disease.

Progressive nonfluent aphasia and its characteristic motor speech deficits.

Progressive nonfluent aphasia (PNFA) is a clinical syndrome characterized by motor speech impairment and agrammatism, with relative sparing of single word comprehension and semantic memory. PNFA has been associated with the characteristic pattern of left anterior insular and posterior frontal atrophy, including the motor and premotor regions and Broca's area. Postmortem histopathologic evidence has shown that PNFA is usually associated with tau pathology, although focal Alzheimer disease pathology and tau-negative, ubiquitin-TDP-43 inclusions also have been reported in association with this clinical syndrome.

Anatomical correlates of sentence comprehension and verbal working memory in neurodegenerative disease.

This study investigates whether sentence comprehension and nonsyntactic verbal working memory (vWM) are sustained by the same or by different neural systems. Scores in a sentence-picture matching task and in digits backward (DB) were correlated with magnetic resonance imaging voxelwise gray matter volumes using voxel-based morphometry in 58 patients with neurodegenerative diseases. Results showed that overall sentence comprehension scores, regardless of grammatical structure, correlated with gray matter volumes in the left temporoparietal region, whereas DB scores correlated with dorsolateral prefrontal and inferior parietal volumes.

An overview on Primary Progressive Aphasia and its variants.

We present a review of the literature on Primary Progressive Aphasia (PPA) together with the analysis of neuropschychological and neuroradiologic profiles of 42 PPA patients. Mesulam originally defined PPA as a progressive degenerative disorder characterized by isolated language impairment for at least two years. The most common variants of PPA are: 1) Progressive nonfluent aphasia (PNFA), 2) semantic dementia (SD), 3) logopenic progressive aphasia (LPA).

Clinical and anatomical correlates of apraxia of speech.

In a previous study (Dronkers, 1996), stroke patients identified as having apraxia of speech (AOS), an articulatory disorder, were found to have damage to the left superior precentral gyrus of the insula (SPGI). The present study sought (1) to characterize the performance of patients with AOS on a classic motor speech evaluation, and (2) to examine whether severity of AOS was influenced by the extent of the lesion. Videotaped speech evaluations of stroke patients with and without AOS were reviewed by two speech-language pathologists and independently scored.

Apraxia of speech: an overview.

Apraxia of speech (AOS) is a motor speech disorder that can occur in the absence of aphasia or dysarthria. AOS has been the subject of some controversy since the disorder was first named and described by Darley and his Mayo Clinic colleagues in the 1960s. A recent revival of interest in AOS is due in part to the fact that it is often the first symptom of neurodegenerative diseases, such as primary progressive aphasia and corticobasal degeneration.

Cognition and anatomy in three variants of primary progressive aphasia.

We performed a comprehensive cognitive, neuroimaging, and genetic study of 31 patients with primary progressive aphasia (PPA), a decline in language functions that remains isolated for at least 2 years. Detailed speech and language evaluation was used to identify three different clinical variants: nonfluent progressive aphasia (NFPA; n = 11), semantic dementia (SD; n = 10), and a third variant termed logopenic progressive aphasia (LPA; n = 10). Voxel-based morphometry (VBM) on MRIs showed that, when all 31 PPA patients were analyzed together, the left perisylvian region and the anterior temporal lobes were atrophied.