Neurocognitive basis of repetition deficits in primary progressive aphasia.
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ABSTRACT:
SUBMITTER: Lukic S
PROVIDER: S-EPMC6669076 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
Neurocognitive basis of repetition deficits in primary progressive aphasia.
Lukic Sladjana S Mandelli Maria Luisa ML Welch Ariane A Jordan Kesshi K Shwe Wendy W Neuhaus John J Miller Zachary Z Hubbard H Isabel HI Henry Maya M Miller Bruce L BL Dronkers Nina F NF Gorno-Tempini Maria Luisa ML
Brain and language 20190502
Previous studies indicate that repetition is affected in primary progressive aphasia (PPA), particularly in the logopenic variant, due to limited auditory-verbal short-term memory (avSTM). We tested repetition of phrases varied by length (short, long) and meaning (meaningful, non-meaningful) in 58 participants (22 logopenic, 19 nonfluent, and 17 semantic variants) and 21 healthy controls using a modified Bayles repetition test. We evaluated the relation between cortical thickness and repetition ...[more]
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Project description:Grammatical comprehension difficulty is an essential supporting feature of the non-fluent/agrammatic variant of primary progressive aphasia (naPPA), but well-controlled clinical measures of grammatical comprehension are unavailable.To develop a measure of grammatical comprehension and examine this comparatively in PPA variants and behavioural-variant frontotemporal degeneration (bvFTD) and to assess the neuroanatomic basis for these deficits with volumetric grey matter atrophy and whole-brain fractional anisotropy (FA) in white matter tracts.Case-control study.Academic medical centre.39 patients with variants of PPA (naPPA=12, lvPPA=15 and svPPA=12), 27 bvFTD patients without aphasia and 12 healthy controls.Grammatical comprehension accuracy.Patients with naPPA had selective difficulty understanding cleft sentence structures, while all PPA variants and patients with bvFTD were impaired with sentences containing a centre-embedded subordinate clause. Patients with bvFTD were also impaired understanding sentences involving short-term memory. Linear regressions related grammatical comprehension difficulty in naPPA to left anterior-superior temporal atrophy and reduced FA in corpus callosum and inferior frontal-occipital fasciculus. Difficulty with centre-embedded sentences in other PPA variants was related to other brain regions.These findings emphasise a distinct grammatical comprehension deficit in naPPA and associate this with interruption of a frontal-temporal neural network.
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Project description:Aphasia typically is associated with comparable difficulties in written and spoken modalities of language expression and comprehension. In contrast, auditory verbal agnosia is the disproportionate difficulty comprehending spoken compared to written language, also typically greater than difficulties with spoken and written language expression, in the absence of a primary sensory deficit. The terms pure word deafness and auditory verbal agnosia are often used synonymously. However, the broader term of auditory agnosia more accurately reflects difficulty processing both speech and non-speech sounds whereas individuals with auditory verbal agnosia (pure word deafness) have preserved processing of environmental sounds. Auditory agnosia is reported in the stroke literature, but rarely reported in progressive neurologic disorders. Here, we report a case of a woman who presented with what is best described as a prominent auditory deficit in the context of an initially unclassifiable, or mixed, primary progressive aphasia (PPA) with accompanying apraxia of speech. Her clinical presentation shared features with auditory agnosia, although sensory functioning was not formally assessed. We report clinical and neuroimaging data spanning 6 years and subsequent autopsy results. She presented at 65 years of age, 5 years post onset of symptoms that included insidious and progressive difficulties thinking of words, constructing sentences, pronouncing words, and understanding instructions. She had disproportionate difficulty with comprehension of spoken compared to written language. She eventually developed features of the nonfluent/agrammatic variant of PPA, as well as an apraxia of speech. Imaging with [18F]-fluorodeoxyglucose (FDG)-PET revealed progression of bilateral (left greater than right) hypometabolism involving the frontal, temporal (predominantly the lateral superior gyrus), and parietal lobes, that eventually included the supplementary motor area, anterior cingulate, and caudate. Autopsy revealed pathological lesions consistent with corticobasal degeneration.
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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.
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Project description:The primary progressive aphasias are a heterogeneous group of focal 'language-led' dementias that pose substantial challenges for diagnosis and management. Here we present a clinical approach to the progressive aphasias, based on our experience of these disorders and directed at non-specialists. We first outline a framework for assessing language, tailored to the common presentations of progressive aphasia. We then consider the defining features of the canonical progressive nonfluent, semantic and logopenic aphasic syndromes, including 'clinical pearls' that we have found diagnostically useful and neuroanatomical and other key associations of each syndrome. We review potential diagnostic pitfalls and problematic presentations not well captured by conventional classifications and propose a diagnostic 'roadmap'. After outlining principles of management, we conclude with a prospect for future progress in these diseases, emphasising generic information processing deficits and novel pathophysiological biomarkers.
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Project description:BACKGROUND:The efficacy of telerehabilitation-based treatment for anomia has been demonstrated in post-stroke aphasia, but the efficacy of this method of anomia treatment delivery has not been established within the context of degenerative illness. AIMS:The current study evaluated the feasibility and efficacy of a telerehabilitation-based approach to anomia treatment within the three subtypes of primary progressive aphasia (PPA). METHODS & PROCEDURES:Each of the three telerehabilitation participants represented a distinct subtype of PPA. Following a baseline evaluation of language and cognition, a phonological treatment and an orthographic treatment were administered to all participants over the course of six months. One month after the end of treatment, a post-treatment evaluation began. All treatment sessions and the majority of the evaluation sessions were administered via telerehabilitation. Treatment effects were examined within each subject, and treatment effects were also compared between each telerehabilitation participant and a group of in-person participants who had the same subtype of PPA. OUTCOMES & RESULTS:All three telerehabilitation participants exhibited positive treatment effects. CGR (nonfluent/agrammatic variant PPA) and WCH (logopenic variant PPA) showed maintenance of naming for prophylaxis items in both treatment conditions, while ACR (semantic variant PPA) demonstrated increased naming of remediation items in the phonological treatment condition. Compared to in-person participants with the same subtype of PPA, each of the telerehabilitation participants typically showed effects that were either within the expected range or larger than expected. CONCLUSIONS:Telerehabilitation-based anomia treatment is feasible and effective in all three subtypes of PPA.
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