Gesture profiles distinguish primary progressive aphasia variants: a preliminary study

To determine patterns of hypometabolism on fluorodeoxyglucose F18 positron emission tomography (FDG-PET) in patients with progressive apraxia of speech (PAS) and primary progressive aphasia (PPA) variants and to use these patterns to further refine current classification. We identified all patients who had FDG-PET and PAS or PPA who were evaluated by an expert speech-language pathologist. Patterns of hypometabolism were independently classified by 2 raters blinded to clinical data. Three speech-language pathologists reclassified all patients into 1 of 7 operationally defined categories of PAS and PPA blinded to FDG-PET data. Tertiary care medical center. Twenty-four patients with PAS or PPA and FDG-PET. Fluorodeoxyglucose F18 PET hypometabolic pattern. Of the 24 patients in the study, 9 had nonfluent speech output; 14, fluent speech; and 1 was unclassifiable. Twenty-one patients showed FDG hypometabolism; the remaining 3 did not. Among the patients showing hypometabolism, 8 had a prerolandic pattern of which 7 had nonfluent speech including progressive nonfluent aphasia (n = 3), PAS (n = 1), and mixed nonfluent aphasia/apraxia of speech (n = 3); the other patient had PPA unclassifiable. The remaining 13 had a postrolandic pattern, all with fluent speech (P < .001), including logopenic progressive aphasia (n = 6), progressive fluent aphasia (n = 6), and semantic dementia (n = 1). Patterns of hypometabolism differed between the nonfluent variants and between the fluent variants, including progressive fluent aphasia. Patterns of FDG-PET hypometabolism support the clinical categorizations of fluency, the distinction of apraxia of speech from progressive nonfluent aphasia, and the designation of a progressive fluent aphasia category.

Differentiating between primary progressive aphasia (PPA) variants based on the profile of language deficits can be difficult in a proportion of patients. Further, little is presently know about the pattern of longitudinal changes in behavior in PPA variants. To determine the presence of behavioral changes in the main variants of PPA: semantic (sv-PPA), nonfluent/agrammatic (nfv-PPA), and logopenic (lv-PPA), and establish the course of these changes over time. We measured behavioral changes in 73 prospectively recruited PPA (30 sv-PPA, 22 nfv-PPA, and 21 lv-PPA), as well as 33 behavioral variant frontotemporal dementia (bv-FTD) and 31 Alzheimer's disease (AD) patients, at baseline and after 1 year, using the Cambridge Behavioural Inventory Revised. All included patients had mild dementia severity at baseline. Both at baseline and follow-up, sv-PPA exhibited significantly more behavioral disturbances of the type characteristic of bv-FTD compared with other PPA variants. 74% of sv-PPA patients with mild dementia severity exhibited at least one behavior disturbance at baseline, which increased to 84% during follow-up. Behavioral symptoms did not differ between nfv-PPA and lv-PPA groups at baseline. At follow-up, however, empathy loss was significantly more pronounced in nfv-PPA. The prevalence and course of behavioral symptoms in lv-PPA was similar to that found in AD. sv-PPA show more prominent FTD-like behavioral disturbances compared with other PPA variants which typically emerge already early in the disease course. Empathy loss may be an important factor that helps differentiating nfv-PPA from lv-PPA. Our results may allow improved prediction of likely progression in behavioral symptoms across the PPA variants.

Predicting primary progressive aphasias with support vector machine approaches in structural MRI data

BackgroundAlzheimer’s disease is a neurodegenerative disease involving the deposition of pathologic amyloid-β and tau protein in the cerebral cortex. Alzheimer’s disease is commonly characterized by progressive impairment of recent memory. Primary progressive aphasia is also often observed in patients with Alzheimer’s disease. Moreover, language-associated symptoms, such as primary progressive aphasia, are diverse and varied in Alzheimer’s disease. However, nonfluent/agrammatic variant primary progressive aphasia is not generally considered a symptom of Alzheimer’s disease. To date, there has been no longitudinal study of primary progressive aphasia in Japanese-speaking patients or in patients speaking other languages with pathologically diagnosed Alzheimer’s disease. Here we present a longitudinal study of primary progressive aphasia in a Japanese patient pathologically diagnosed with Alzheimer’s disease.Case presentationA 75-year-old Japanese man, whose wife reported that his memory was impaired, also suffered from suspected aphasia. He was pathologically diagnosed with Alzheimer’s disease using 11C-Pittsburgh compound-B positron emission tomography and 18F-THK5351 positron emission tomography. Based on clinical observation and the results of the Japanese standard language test of aphasia, he was also diagnosed with nonfluent/agrammatic variant primary progressive aphasia. During the subsequent 2 years, his cognitive impairment, aphasia, and behavioral and psychological symptoms of dementia progressed. Furthermore, progression of pathologic amyloid-β and tau protein deposition was revealed through 11C-Pittsburgh compound-B positron emission tomography and 18F-THK5351 positron emission tomography. Although the results of [123I] iodoamphetamine single-photon emission computed tomography suggested corticobasal degeneration, this was not observed on the [123I] FP-CIT single-photon emission computed tomography (SPECT) (DaTscan). A previous study had reported that Alzheimer’s disease with a nonfluent/agrammatic variant primary progressive aphasia was accompanied by corticobasal degeneration; however, this was not true in our case.ConclusionsThis is possibly the first longitudinal study of nonfluent/agrammatic variant primary progressive aphasia in a Japanese-speaking patient with pathologically diagnosed Alzheimer’s disease, but without corticobasal degeneration.

BackgroundPicture naming tests are widely used to evaluate language impairments, especially in Primary Progressive Aphasia (PPA). The available instruments differ for type of stimuli and their psycholinguistic properties, known to affect the performance. We aim to identify the most appropriate naming test to be used on PPA, based on clinical and research demands.MethodWe investigated the behavioural characteristics (proportion of correct responses, error type) and the neural correlates of CaGi (Catricalà et al., 2013) and SAND (Catricalà et al., 2017) naming tests, administered to 84 healthy controls and 52 PPA (15 semantic, svPPA; 20 logopenic, lv‐PPA; 7 non fluent, nfv‐PPA; 10 mixed PPA), the latter also undergoing an FDG‐PET scan. We analyzed the ability of the tests in distinguishing PPA versus controls and between PPA variants, considering the psycholinguistic variables affecting the performance. We explored the brain metabolic correlates of the behavioural performance.ResultSAND, differently from CaGi, had response time limit and less frequent and later acquired items. A greater difficulty to name SAND items compared to CaGi ones was found. While semantic errors predominated in CaGi, both anomic and semantic errors were equally frequent in SAND. Both tests distinguished PPA from controls, but SAND outperformed CaGi in discriminating among PPA variants. FDG‐PET imaging revealed a shared metabolic involvement of the temporal areas, including the anterior fusiform gyrus, the temporal pole, and extending to the posterior fusiform gyrus in sv‐PPA, associated with lexico‐semantic processing.ConclusionA naming test with response time limits and more difficult items (as SAND) better highlights subtle distinctions between PPA variants, improving the diagnosis. Conversely, a naming test devoid of response time limits (as CaGi), may be more suited for an in‐depth characterization of the impairment and for guiding rehabilitation.

PurposeTo assess the binding of the PET tracer [18F]THK5351 in patients with different primary progressive aphasia (PPA) variants and its correlation with clinical deficits. The majority of patients with nonfluent variant (NFV) and logopenic variant (LV) PPA have underlying tauopathy of the frontotemporal lobar or Alzheimer disease type, respectively, while patients with the semantic variant (SV) have predominantly transactive response DNA binding protein 43-kDa pathology.MethodsThe study included 20 PPA patients consecutively recruited through a memory clinic (12 NFV, 5 SV, 3 LV), and 20 healthy controls. All participants received an extensive neurolinguistic assessment, magnetic resonance imaging and amyloid biomarker tests. [18F]THK5351 binding patterns were assessed on standardized uptake value ratio (SUVR) images with the cerebellar grey matter as the reference using statistical parametric mapping. Whole-brain voxel-wise regression analysis was performed to evaluate the association between [18F]THK5351 SUVR images and neurolinguistic scores. Analyses were performed with and without partial volume correction.ResultsPatients with NFV showed increased binding in the supplementary motor area, left premotor cortex, thalamus, basal ganglia and midbrain compared with controls and patients with SV. Patients with SV had increased binding in the temporal lobes bilaterally and in the right ventromedial frontal cortex compared with controls and patients with NFV. The whole-brain voxel-wise regression analysis revealed a correlation between agrammatism and motor speech impairment, and [18F]THK5351 binding in the left supplementary motor area and left postcentral gyrus. Analysis of [18F]THK5351 scans without partial volume correction revealed similar results.Conclusion[18F]THK5351 imaging shows a topography closely matching the anatomical distribution of predicted underlying pathology characteristic of NFV and SV PPA. [18F]THK5351 binding correlates with the severity of clinical impairment.

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Event Abstract Back to Event Relationship between word properties of fluency tasks at baseline and treatment outcomes in Primary Progressive Aphasia Adrià Rofes1, 2*, Vânia De Aguiar3, Bronte Ficek3, Kimberly T. Webster3, Haley Wendt3, Brenda Rapp2 and Kyrana Tsapkini3 1 Global Brain Health Institute, Trinity College, Ireland 2 Johns Hopkins University, Cognitive Science, United States 3 Johns Hopkins University, Neurology, United States Background: Fluency tasks are frequently used to investigate how language components break down in neurological populations (Marczinski & Kertesz, 2006; Rofes et al., 2017). In one minute, participants say as many words as possible starting with a specific letter or from a semantic category. Recent work examines the mean word properties of the words that are produced, including imageability, length, and others. This work has shown promising results in using these properties to identify variants of Primary Progressive Aphasia (PPA, Rofes et al., 2018; Vita et al., 2014), raising the question of whether properties of words retrieved during fluency tasks and obtained before naming/spelling therapy may relate to treatment outcomes. This information could open a window to using fluency tasks as a rapid method to recognize which individuals are more likely to benefit from therapy. Methods: Twenty-nine English-native speakers with PPA and a mild to moderate language impairment underwent 3 weeks of naming/spelling therapy, where they received either anodal tDCS stimulation over the left IFG or sham (randomized) – the left IFG has been repeatedly implicated in fluency tasks (Costafreda et al., 2006). Before therapy, participants were assessed with three letter fluency tasks (F, A, S) and three category fluency tasks (animals, vegetables, fruits). To evaluate the relationship between pre-treatment fluency data and responsiveness to therapy, we carried linear models using Change in spelling accuracy (post minus pre letter accuracy scores for treated or untreated words) as the dependent variable; main effects for Word Property (mean values for frequency, imageability, familiarity, age-of-acquisition, semantic association, length, orthographic or phonological neighborhood, concreteness) and Stimulation Type (tDCS/sham); and an interaction Stimulation Type (tDCS/sham) and Word Property. We evaluated separate models for each Word Property as produced in letter or category fluency. Also, we evaluated separate models for treated and untreated words, allowing for assessment of generalization effects. Results: For treated words, people with lower mean concreteness and lower mean imageability scores in letter fluency who received tDCS, changed more than those who received sham. For untreated words, people with lower mean concreteness and lower mean imageability scores in category fluency who received tDCS, changed more than those who received sham. Conclusions: The properties of words produced in fluency tasks at baseline were associated with treatment (language therapy +/- tDCS) outcomes. The same word properties (i.e., concreteness, imageability), in different fluency tasks, were associated with change for treated and untreated words, possibly reflecting different learning mechanisms. Finally, letter fluency and category fluency may be used independently to identify which individuals may benefit the most from specific types of therapy. Figure 1 References Costafreda, S. G., Fu, C. H., Lee, L., Everitt, B., Brammer, M. J., & David, A. S. (2006). A systematic review and quantitative appraisal of fMRI studies of verbal fluency: role of the left inferior frontal gyrus. Human brain mapping, 27, 799-810. Marczinski, C. A., & Kertesz, A. (2006). Category and letter fluency in semantic dementia, primary progressive aphasia, and Alzheimer’s disease. Brain and language, 97, 258-265. Rofes, A., De Aguiar, V., Ficek, B., Webster, K., Wendt, H., Rapp, B., & Tsapkini, K. (2018). Word properties of fluency tasks in three variants of Primary Progressive Aphasia. Alzheimer's Association Satellite Symposium, Apr. 17-18, Buenos Aires, Argentina. Rofes, A., Mandonnet, E., Godden, J., Baron, M. H., Colle, H., Darlix, A., …, Wager, M. (2017). Survey on current practices within the European Low Grade Glioma Network: language and cognitive assessment part. Acta Neurochirurgica, 159, 1167-1178. Vita, M. G., Marra, C., Spinelli, P., Caprara, A., Scaricamazza, E., Castelli, D., ... & Quaranta, D. (2014). Typicality of words produced on a semantic fluency task in amnesic mild cognitive impairment: linguistic analysis and risk of conversion to dementia. Journal of Alzheimer's Disease, 42, 1171-1178. Keywords: Imageability, concreteness, fluency, treatment outcome, PPA Conference: Academy of Aphasia 56th Annual Meeting, Montreal, Canada, 21 Oct - 23 Oct, 2018. Presentation Type: oral presentation Topic: Eligible for a student award Citation: Rofes A, De Aguiar V, Ficek B, Webster KT, Wendt H, Rapp B and Tsapkini K (2019). Relationship between word properties of fluency tasks at baseline and treatment outcomes in Primary Progressive Aphasia. Conference Abstract: Academy of Aphasia 56th Annual Meeting. doi: 10.3389/conf.fnhum.2018.228.00006 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Apr 2018; Published Online: 22 Jan 2019. * Correspondence: Dr. Adrià Rofes, Global Brain Health Institute, Trinity College, Dublin, Ireland, a.rofes@rug.nl Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Adrià Rofes Vânia De Aguiar Bronte Ficek Kimberly T Webster Haley Wendt Brenda Rapp Kyrana Tsapkini Google Adrià Rofes Vânia De Aguiar Bronte Ficek Kimberly T Webster Haley Wendt Brenda Rapp Kyrana Tsapkini Google Scholar Adrià Rofes Vânia De Aguiar Bronte Ficek Kimberly T Webster Haley Wendt Brenda Rapp Kyrana Tsapkini PubMed Adrià Rofes Vânia De Aguiar Bronte Ficek Kimberly T Webster Haley Wendt Brenda Rapp Kyrana Tsapkini Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

The semantic variant of primary progressive aphasia (PPA) is characterized by the combination of word comprehension deficits, fluent aphasia and a particularly severe anomia. In this study, two novel tasks were used to explore the factors contributing to the anomia. The single most common factor was a blurring of distinctions among members of a semantic category, leading to errors of overgeneralization in word-object matching tasks as well as in word definitions and object descriptions. This factor was more pronounced for natural kinds than artifacts. In patients with the more severe anomias, conceptual maps were more extensively disrupted so that inter-category distinctions were as impaired as intra-category distinctions. Many objects that could not be named aloud could be matched to the correct word in patients with mild but not severe anomia, reflecting a gradual intensification of the semantic factor as the naming disorder becomes more severe. Accurate object descriptions were more frequent than accurate word definitions and all patients experienced prominent word comprehension deficits that interfered with everyday activities but no consequential impairment of object usage or face recognition. Magnetic resonance imaging revealed three characteristics: greater atrophy of the left hemisphere; atrophy of anterior components of the perisylvian language network in the superior and middle temporal gyri; and atrophy of anterior components of the face and object recognition network in the inferior and medial temporal lobes. The left sided asymmetry and perisylvian extension of the atrophy explains the more profound impairment of word than object usage and provides the anatomical basis for distinguishing the semantic variant of primary progressive aphasia from the partially overlapping group of patients that fulfil the widely accepted diagnostic criteria for semantic dementia.

BackgroundThe analysis of EEG cortical sources is promising for the investigation of neurodegenerative disorders. The aim of this study is to explore its value in the characterization of the three clinical presentations of primary progressive aphasia (PPA).MethodA resting‐state 19‐channel EEG was obtained in 48 patients diagnosed with PPA (21 nonfluent/agrammatic variant PPA [nfv‐PPA], 18 logopenic variant PPA [lv‐PPA], 9 semantic variant PPA [sv‐PPA]) and in 21 matched healthy controls. Using eLORETA, EEG current source density (CSD) values were estimated at voxel‐level and compared among groups of patients and controls.ResultPatients showed a low‐to‐moderate cognitive impairment. Lv‐PPA cases showed a higher delta density over the left frontal and temporal regions when compared to sv‐PPA subjects, and in left precuneus and posterior cingulate when compared to nfv‐PPA patients. They also displayed a higher delta density in left frontal, parietal and temporal regions than healthy subjects, and lower alpha1 density in left occipital regions compared with other patient groups. Lv‐PPA patients also showed reduced alpha2, beta1 and beta2 density over the left occipital regions when compared to healthy subjects. No significant differences were found in terms of CSD among sv‐PPA, nfv‐PPA and healthy subjects.ConclusionConsistently with our previous studies, findings in PPA patients suggest that Alzheimer’s disease (AD), but not fronto‐temporal degeneration (FTD), might induce a characteristic disruption of the cortical electrical activity, detectable by EEG. EEG might thus help in the differential diagnosis between AD‐related and FTD‐related PPA variants.

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. 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. 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.

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 6 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 under both treatment conditions, while ACR (semantic variant PPA) demonstrated increased naming of remediation items under 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.

ABSTRACTBackground: Individuals with primary progressive aphasia (PPA) and their caregivers want to know what to expect so that they can plan support appropriately. The ability to predict decline in naming and semantic knowledge, and advise individuals with PPA and their caregivers regarding future planning, would be invaluable clinically.Aims: The aims of this study were to investigate patterns of decline in naming and semantic knowledge in each of the clinical variants of PPA (logopenic variant PPA, lvPPA; nonfluent agrammatic PPA, nfaPPA; and semantic variant PPA, svPPA) and to examine the effects of other variables on rate of decline. We hypothesized that speech-language rehabilitation, higher education, and higher baseline test scores would be associated with slower decline, and older age with faster decline.Methods and Procedures: A total of 94 participants with PPA underwent language testing, including 36 participants with lvPPA, 31 participants with nfaPPA, and 27 participants with svPPA. All participant groups were similar in age and education. We focused on decline on three tests: the short form of the Boston Naming Test (BNT), the Hopkins Assessment of Naming Actions (HANA), and the short form of the Pyramids and Palm Trees Test (PPTT).Outcome and Results: Across language tests, the most precipitous rates of decline (loss of points per month) occurred in nfaPPA, followed by svPPA, then lvPPA. Female sex, longer symptom duration, higher baseline test score, and speech-language rehabilitation were associated with slower decline.Conclusions: PPA variants were distinguishable by rapidity of decline, with nfaPPA having the most precipitous decline. As hypothesized, higher baseline test scores and speech-language rehabilitation were associated with slower decline. Surprisingly, age and education were not important prognostically for individuals in this study. Further study of prognostically-relevant variables in PPA is indicated in this population.

Background/Aim: To investigate in variants of primary progressive aphasia (PPA) the association between current clinical and neuroimaging criteria and biochemical/genetic markers at the individual level. Methods: Thirty-two PPA patients were classified as non-fluent/agrammatic (nfvPPA), semantic (svPPA), or logopenic variant (lvPPA) or as unclassifiable (uPPA). In all patients, we evaluated the neuroimaging criteria (magnetic resonance imaging and/or single photon emission computed tomography/positron emission tomography) of each variant and studied serum progranulin levels, APOE genotype and Alzheimer’s disease (AD)-cerebrospinal fluid (CSF) biomarkers. Cases with a first-degree family history of early-onset dementia were genetically tested. Results: Ten of 15 (66%) nfvPPA, 5/5 (100%) svPPA and 7/7 (100%) lvPPA patients showed at least one positive neuroimaging-supported diagnostic criterion. All lvPPA and 3/5 (60%) uPPA patients presented AD-CSF biomarkers, which were absent in nfvPPA and svPPA cases. Four (27%) nfvPPA patients had dementia-causing mutations: 2 carried a GRN mutation and 2 the C9ORF72 hexanucleotide expansion. Conclusions: There was an excellent association between clinical criteria and neuroimaging-supported biomarkers in svPPA and lvPPA, as well as with AD-CSF biochemical markers in the lvPPA. Neuroimaging, biochemical and genetic findings in nfvPPA were heterogeneous. Incorporating biochemical/genetic markers into the PPA clinical diagnosis would allow clinicians to improve their predictions of PPA neuropathology, especially in nfvPPA and uPPA cases.

Primary progressive aphasia is a neurodegenerative condition characterised by a progressive and isolated disorder of expressive language, associated with atrophy of the left posterior frontoinsular region (nonfluent/agrammatic variant) or with atrophy of the left temporoparietal junction area (logopenic variant). This literature review reports studies about language therapies for these two variants of primary progressive aphasia. More precisely, the review presents the behavioral interventions and the augmentative/alternative communication tools reported in the literature to improve language performances or to compensate for language difficulties. Most of these studies reported that interventions are efficient. However, inconsistent results are found regarding maintenance of improvement and generalization to untreated language abilities. Other studies are still required to establish the clinical relevance of interventions for language and communication disorders in primary progressive aphasia. In these studies, the use of more ecological interventions focusing on the specific needs of people living with this disease should be specifically addressed.