Dataset Information

Whole-brain white matter disruption in semantic and nonfluent variants of primary progressive aphasia.

ABSTRACT: Semantic (svPPA) and nonfluent (nfPPA) variants of primary progressive aphasia are associated with distinct patterns of cortical atrophy and underlying pathology. Little is known, however, about their contrasting spread of white matter disruption and how this relates to grey matter (GM) loss. We undertook a structural MRI study to investigate this relationship. We used diffusion tensor imaging, tract-based spatial statistics, and voxel-based morphometry to examine fractional anisotropy (FA) and directional diffusivities in nine patients with svPPA and nine patients with nfPPA, and compared them to 16 matched controls after accounting for global GM atrophy. Significant differences in topography of white matter changes were found, with more ventral involvement in svPPA patients and more widespread frontal involvement in nfPPA individuals. However, each group had both ventral and dorsal tract changes, and both showed spread of diffusion abnormalities beyond sites of local atrophy. There was a clear dissociation in sensitivity of diffusion tensor imaging measures between groups. SvPPA patients showed widespread changes in FA and radial diffusivity, whereas changes in axial diffusivity were more restricted and proximal to sites of GM atrophy. NfPPA patients showed isolated changes in FA, but widespread axial and radial diffusivity changes. These findings reveal the extent of white matter disruption in these variants of PPA after accounting for GM loss. Further, they suggest that differences in the relative sensitivity of diffusion metrics may reflect differences in the nature of underlying white matter pathology in these two subtypes.

SUBMITTER: Schwindt GC

PROVIDER: S-EPMC6870114 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Whole-brain white matter disruption in semantic and nonfluent variants of primary progressive aphasia.

Schwindt Graeme C GC Graham Naida L NL Rochon Elizabeth E Tang-Wai David F DF Lobaugh Nancy J NJ Chow Tiffany W TW Black Sandra E SE

Human brain mapping 20111123 4

Semantic (svPPA) and nonfluent (nfPPA) variants of primary progressive aphasia are associated with distinct patterns of cortical atrophy and underlying pathology. Little is known, however, about their contrasting spread of white matter disruption and how this relates to grey matter (GM) loss. We undertook a structural MRI study to investigate this relationship. We used diffusion tensor imaging, tract-based spatial statistics, and voxel-based morphometry to examine fractional anisotropy (FA) and ...[more]

PMID: 22109837

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Project description:Primary progressive aphasia, a neurodegenerative syndrome, presents mainly with language impairment. Both semantic and logopenic variants are fluent variants of primary progressive aphasia. Before the research criteria of primary progressive aphasia were proposed, progressive fluent aphasias, such as progressive anomic aphasia, transcortical sensory aphasia and Wernicke's aphasia, were reported as classical progressive fluent aphasias seen in Alzheimer's disease. However, since the research criteria of primary progressive aphasia were established, classical fluent variants (other than semantic and logopenic variants) have been neglected and have not been included in the current classification of primary progressive aphasia. This study aimed to determine whether unclassified fluent variants (other than semantic and logopenic variants) can be manifestations of primary progressive aphasia. This study also reconfirmed the characteristics of classical progressive fluent aphasia, such as progressive anomic aphasia, progressive transcortical sensory aphasia and progressive Wernicke's aphasia as unclassified fluent variants of primary progressive aphasia, using comparison with the current model of primary progressive aphasia. Twelve consecutive patients with an unclassified fluent variant other than semantic or logopenic variant underwent language, neurological, neuropsychological and neuroimaging (MRI and single-photon emission computed tomography) testing. Based on comprehensive language tests, we redefined the diagnoses as primary progressive anomic aphasia (n = 8), primary progressive transcortical sensory aphasia (n = 3) and primary progressive Wernicke's aphasia (n = 1). Anomic aphasia was characterized by anomia but preserved repetition and comprehension; transcortical sensory aphasia by relatively preserved repetition but poor word comprehension; and Wernicke's aphasia by poor repetition and word comprehension. In patients with anomic aphasia, voxel-based morphometry of MRI data revealed cortical atrophy, which was most prominent in the temporoparietal lobes, with no obvious lateralization; in two-thirds of patients with transcortical sensory aphasia and in one patient with Wernicke's aphasia, it revealed atrophy, predominantly in the left temporoparietal lobe. Statistical analysis of single-photon emission computed tomography using three-dimensional stereotactic surface projections revealed patterns of left-sided hypoperfusion in the majority of patients. The temporal and parietal lobes were involved in all cases; the degree of hypoperfusion was higher in patients with transcortical sensory aphasia or Wernicke's aphasia than in patients with anomic aphasia. The present study demonstrated the clinical and imaging features of 12 patients with an unclassified fluent variant of primary progressive aphasia, which we redefined as primary progressive anomic aphasia, primary progressive transcortical sensory aphasia and primary progressive Wernicke's aphasia. Classical fluent variants other than semantic and logopenic variants can be found in primary progressive aphasia.

Project description:Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r(2) = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA.

Project description:BackgroundA subset of patients with the nonfluent variant of primary progressive aphasia (PPA) exhibit concomitant single-word comprehension problems, constituting a 'mixed variant' phenotype. This phenotype is rare and currently not fully characterized. The aim of this study was twofold: to assess the prevalence and nature of single-word comprehension problems in the nonfluent variant and to study multimodal imaging characteristics of atrophy, tau, and amyloid burden associated with this mixed phenotype.MethodsA consecutive memory-clinic recruited series of 20 PPA patients (12 nonfluent, five semantic, and three logopenic variants) were studied on neurolinguistic and neuropsychological domains relative to 64 cognitively intact healthy older control subjects. The neuroimaging battery included high-resolution volumetric magnetic resonance imaging processed with voxel-based morphometry, and positron emission tomography with the tau-tracer [18F]-THK5351 and amyloid-tracer [11C]-Pittsburgh Compound B.ResultsSeven out of 12 subjects who had been classified a priori with nonfluent variant PPA showed deficits on conventional single-word comprehension tasks along with speech apraxia and agrammatism, corresponding to a mixed variant phenotype. These mixed variant cases included three females and four males, with a mean age at onset of 65 years (range 44-77 years). Object knowledge and object recognition were additionally affected, although less severely compared with the semantic variant. The mixed variant was characterized by a distributed atrophy pattern in frontal and temporoparietal regions. A more focal pattern of elevated [18F]-THK5351 binding was present in the supplementary motor area, the left premotor cortex, midbrain, and basal ganglia. This pattern was closely similar to that seen in pure nonfluent variant PPA. At the individual patient level, elevated [18F]-THK5351 binding in the supplementary motor area and premotor cortex was present in six out of seven mixed variant cases and in five and four of these cases, respectively, in the thalamus and midbrain. Amyloid biomarker positivity was present in two out of seven mixed variant cases, compared with none of the five pure nonfluent cases.ConclusionsA substantial proportion of PPA patients with speech apraxia and agrammatism also have single-word comprehension deficits. At the neurobiological level, the mixed variant shows a high degree of similarity with the pure nonfluent variant of PPA.Trial registrationEudraCT, 2014-002976-10 . Registered on 13-01-2015.

Dataset Information

Whole-brain white matter disruption in semantic and nonfluent variants of primary progressive aphasia.

Publications

Whole-brain white matter disruption in semantic and nonfluent variants of primary progressive aphasia.

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