Primary progressive aphasia: a clinical approach.
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ABSTRACT:
SUBMITTER: Marshall CR
PROVIDER: S-EPMC5990560 | biostudies-literature | 2018 Jun
REPOSITORIES: biostudies-literature
Publications
Primary progressive aphasia: a clinical approach.
Marshall Charles R CR Hardy Chris J D CJD Volkmer Anna A Russell Lucy L LL Bond Rebecca L RL Fletcher Phillip D PD Clark Camilla N CN Mummery Catherine J CJ Schott Jonathan M JM Rossor Martin N MN Fox Nick C NC Crutch Sebastian J SJ Rohrer Jonathan D JD Warren Jason D JD
Journal of neurology 20180201 6
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 a ...[more]
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Project description:Primary Progressive Aphasia (PPA) is a syndrome due to different neurodegenerative disorders selectively disrupting language functions. PPA specialist care is underdeveloped. There are very few specialists (neurologists, psychiatrists, neuropsychologists, and speech therapists) and few hospital- or community-based services dedicated to the diagnosis and continuing care of people with PPA. Currently, healthcare systems struggle to provide adequate coverage of care that is too often fragmented, uncoordinated, and unresponsive to the needs of people with PPA and their families. Recently, attention has been gained by non-invasive brain stimulation techniques that allow a personalized treatment approach, such as transcranial Direct Current Stimulation (tDCS). The MAINSTREAM trial looks forward to introducing and evaluating therapeutic innovations such as tDCS coupled with language therapy in rehabilitation settings. A Multimodal Approach for Clinical Diagnosis and Treatment of Primary Progressive Aphasia, MAINSTREAM (ID: 3430931) was registered in the clinicaltrials.gov database (identifier: NCT05730023) on 15 February 2023.
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Project description:Many patients who meet core/root criteria for Primary Progressive Aphasia (PPA) are not classifiable as a recognized variant and are often excluded from neuroimaging studies. Here, we detail neurological, neuropsychological, speech and language assessments, and anatomic and molecular neuroimaging (MRI, PiB-PET, and FDG-PET) for fifteen (8 female) clinically unclassifiable PPA patients. Median age of onset was 64?years old with median 3?years disease duration at exam. Three patients were amyloid positive on PiB-PET. 14/15 patients had abnormal FDG-PETs with left predominant hypometabolism, affecting frontal, temporal, parietal, and even occipital lobes. Patients had mild to severe clinical presentations. Visualization of the FDG-PETs principal component analysis revealed patterns of hypometabolism similar to those seen in the PPA variants and suggests the brain regions affected in unclassifiable PPA patients are no different from those who are more easily classifiable. These findings may inform future modifications to the diagnostic criteria to improve diagnostic classification.
| S-EPMC6726500 | biostudies-literature
Project description:Background and purposeDysphagia is an important feature of neurodegenerative diseases and potentially life-threatening in primary progressive aphasia (PPA) but remains poorly characterized in these syndromes. We hypothesized that dysphagia would be more prevalent in nonfluent/agrammatic variant (nfv)PPA than other PPA syndromes, predicted by accompanying motor features, and associated with atrophy affecting regions implicated in swallowing control.MethodsIn a retrospective case-control study at our tertiary referral centre, we recruited 56 patients with PPA (21 nfvPPA, 22 semantic variant [sv]PPA, 13 logopenic variant [lv]PPA). Using a pro forma based on caregiver surveys and clinical records, we documented dysphagia (present/absent) and associated, potentially predictive clinical, cognitive, and behavioural features. These were used to train a machine learning model. Patients' brain magnetic resonance imaging scans were assessed using voxel-based morphometry and region-of-interest analyses comparing differential atrophy profiles associated with dysphagia presence/absence.ResultsDysphagia was significantly more prevalent in nfvPPA (43% vs. 5% svPPA and no lvPPA). The machine learning model revealed a hierarchy of features predicting dysphagia in the nfvPPA group, with excellent classification accuracy (90.5%, 95% confidence interval = 77.9-100); the strongest predictor was orofacial apraxia, followed by older age, parkinsonism, more severe behavioural disturbance, and more severe cognitive impairment. Significant grey matter atrophy correlates of dysphagia in nfvPPA were identified in left middle frontal, right superior frontal, and right supramarginal gyri and right caudate.ConclusionsDysphagia is a common feature of nfvPPA, linked to underlying corticosubcortical network dysfunction. Clinicians should anticipate this symptom particularly in the context of other motor features and more severe disease.
| S-EPMC11295169 | biostudies-literature
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Project description:Logopenic primary progressive aphasia (lvPPA) is a progressive language disorder characterized by anomia, difficulty repeating complex sentences, and phonological errors. The majority, although not all, lvPPA patients have underlying Alzheimer's disease. We aimed to determine whether clinical or neuroimaging features differ according to the deposition of A? on Pittsburgh-compound B PET in lvPPA. Clinical features, patterns of atrophy on MRI, hypometabolism on FDG-PET, and white matter tract degeneration were compared between six PiB-negative and 20 PiB-positive lvPPA patients. PiB-negative patients showed more asymmetric left-sided patterns of atrophy, hypometabolism and white matter tract degeneration, with greater left anteromedial temporal and medial prefrontal involvement, than PiB-positive patients. PiB-positive patients showed greater involvement of right temporoparietal and frontal lobes. There was very little evidence for clinical differences between the groups. Strikingly asymmetric neuroimaging findings with relatively preserved right hemisphere may provide clues that AD pathology is absent in lvPPA.
| S-EPMC4380294 | biostudies-literature
Project description:It is debated whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) belong to the same clinical spectrum, traditionally termed non-fluent/agrammatic variant primary progressive aphasia (nfvPPA), or exist as two completely distinct syndromic entities with specific pathologic/prognostic correlates. We analysed speech, language and disease severity features in a comprehensive cohort of patients with progressive motor speech impairment and/or agrammatism to ascertain evidence of naturally occurring, clinically meaningful non-overlapping syndromic entities (e.g. PPAOS and PAA) in our data. We also assessed if data-driven latent clinical dimensions with aetiologic/prognostic value could be identified. We included 98 participants, 43 of whom had an autopsy-confirmed neuropathological diagnosis. Speech pathologists assessed motor speech features indicative of dysarthria and apraxia of speech (AOS). Quantitative expressive/receptive agrammatism measures were obtained and compared with healthy controls. Baseline and longitudinal disease severity was evaluated using the Clinical Dementia Rating Sum of Boxes (CDR-SB). We investigated the data's clustering tendency and cluster stability to form robust symptom clusters and employed principal component analysis to extract data-driven latent clinical dimensions (LCD). The longitudinal CDR-SB change was estimated using linear mixed-effects models. Of the participants included in this study, 93 conformed to previously reported clinical profiles (75 with AOS and agrammatism, 12 PPAOS and six PAA). The remaining five participants were characterized by non-fluent speech, executive dysfunction and dysarthria without apraxia of speech or frank agrammatism. No baseline clinical features differentiated between frontotemporal lobar degeneration neuropathological subgroups. The Hopkins statistic demonstrated a low cluster tendency in the entire sample (0.45 with values near 0.5 indicating random data). Cluster stability analyses showed that only two robust subgroups (differing in agrammatism, executive dysfunction and overall disease severity) could be identified. Three data-driven components accounted for 71% of the variance [(i) severity-agrammatism; (ii) prominent AOS; and (iii) prominent dysarthria]. None of these data-driven LCDs allowed an accurate prediction of neuropathology. The severity-agrammatism component was an independent predictor of a faster CDR-SB increase in all the participants. Higher dysarthria severity, reduced words per minute and expressive and receptive agrammatism severity at baseline independently predicted accelerated disease progression. Our findings indicate that PPAOS and PAA, rather than exist as completely distinct syndromic entities, constitute a clinical continuum. In our cohort, splitting the nfvPPA spectrum into separate clinical phenotypes did not improve clinical-pathological correlations, stressing the need for new biological markers and consensus regarding updated terminology and clinical classification.
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Project description:ObjectiveTo determine whether logopenic features of phonologic loop dysfunction reflect Alzheimer disease (AD) neuropathology in primary progressive aphasia (PPA).MethodsWe performed a retrospective case-control study of 34 patients with PPA with available autopsy tissue. We compared baseline and longitudinal clinical features in patients with primary AD neuropathology to those with primary non-AD pathologies. We analyzed regional neuroanatomic disease burden in pathology-defined groups using postmortem neuropathologic data.ResultsA total of 19/34 patients had primary AD pathology and 15/34 had non-AD pathology (13 frontotemporal lobar degeneration, 2 Lewy body disease). A total of 16/19 (84%) patients with AD had a logopenic spectrum phenotype; 5 met published criteria for the logopenic variant (lvPPA), 8 had additional grammatical or semantic deficits (lvPPA+), and 3 had relatively preserved sentence repetition (lvPPA-). Sentence repetition was impaired in 68% of patients with PPA with AD pathology; forward digit span (DF) was impaired in 90%, substantially higher than in non-AD PPA (33%, p < 0.01). Lexical retrieval difficulty was common in all patients with PPA and did not discriminate between groups. Compared to non-AD, PPA with AD pathology had elevated microscopic neurodegenerative pathology in the superior/midtemporal gyrus, angular gyrus, and midfrontal cortex (p < 0.01). Low DF scores correlated with high microscopic pathologic burden in superior/midtemporal and angular gyri (p ≤ 0.03).ConclusionsPhonologic loop dysfunction is a central feature of AD-associated PPA and specifically correlates with temporoparietal neurodegeneration. Quantitative measures of phonologic loop function, combined with modified clinical lvPPA criteria, may help discriminate AD-associated PPA.
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Project description:BackgroundTraumatic brain injury (TBI) and repetitive head impacts (RHI) have been linked to increased risk for multiple types of neurodegenerative disease, higher dementia risk, and earlier age of dementia symptom onset, suggesting transdiagnostic implications for later-life brain health. Frontotemporal dementia (FTD) and primary progressive aphasia (PPA) represent a spectrum of clinical phenotypes that are neuropathologically diverse. FTD/PPA diagnoses bring unique challenges due to complex cognitive and behavioral symptoms that disproportionately present as an early-onset dementia (before age 65). We performed a detailed characterization of lifetime head trauma exposure in individuals with FTD and PPA compared to healthy controls to examine frequency of lifetime TBI and RHI and associated clinical implications.MethodsWe studied 132 FTD/PPA (age 68.9 ± 8.1, 65% male) and 132 sex-matched healthy controls (HC; age 73.4 ± 7.6). We compared rates of prior TBI and RHI (contact/collision sports) between FTD/PPA and HC (chi-square, logistic regression, analysis of variance). Within FTD/PPA, we evaluated associations with age of symptom onset (analysis of variance). Within behavioral variant FTD, we evaluated associations with cognitive function and neuropsychiatric symptoms (linear regression controlling for age, sex, and years of education).ResultsYears of participation were greater in FTD/PPA than HC for any contact/collision sport (8.5 ± 6.7yrs vs. 5.3 ± 4.5yrs, p = .008) and for American football (6.2yrs ± 4.3yrs vs. 3.1 ± 2.4yrs; p = .003). Within FTD/PPA, there were dose-dependent associations with earlier age of symptom onset for TBI (0 TBI: 62.1 ± 8.1, 1 TBI: 59.9 ± 6.9, 2 + TBI: 57.3 ± 8.4; p = .03) and years of American football (0yrs: 62.2 ± 8.7, 1-4yrs: 59.7 ± 7.0, 5 + yrs: 55.9 ± 6.3; p = .009). Within bvFTD, those who played American football had worse memory (z-score: -2.4 ± 1.2 vs. -1.4 ± 1.6, p = .02, d = 1.1).ConclusionsLifetime head trauma may represent a preventable environmental risk factor for FTD/PPA. Dose-dependent exposure to TBI or RHI influences FTD/PPA symptom onset and memory function in bvFTD. Clinico-pathological studies are needed to better understand the neuropathological correlates linking RHI or TBI to FTD/PPA onset and symptoms.
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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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Project description:The aim is to explore the evolution of the logopenic variant of primary progressive aphasia as a distinct clinical entity and to outline recent advances that have clarified its clinical characteristics, neural underpinnings, and potential genetic and pathological bases. This is particularly relevant as researchers attempt to identify clinico-pathological relationships in subtypes of primary progressive aphasia in hopes of utilizing language phenotype as a marker of underlying disease.Recent work has served to refine and expand upon the clinical phenotype of the logopenic variant. Logopenic patients show a unique pattern of spared and impaired language processes that reliably distinguish this syndrome from other variants of progressive aphasia. Specifically, they exhibit deficits in naming and repetition in the context of spared semantic, syntactic, and motor speech abilities. Further, there is a growing body of evidence indicating a possible link between the logopenic phenotype and specific pathological and genetic correlates.Findings indicate that the logopenic variant is a distinct subtype of progressive aphasia that may hold value as a predictor of underlying pathology. Additional research, however, is warranted in order to further clarify the cognitive-linguistic profile and to confirm its relation to certain pathological and genetic processes.
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