scholarly journals The natural history of primary progressive aphasia: beyond aphasia

2021 ◽  
Author(s):  
Hulya Ulugut ◽  
Simone Stek ◽  
Lianne E. E. Wagemans ◽  
Roos J. Jutten ◽  
Maria Antoinette Keulen ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Primary Progressive Aphasia ◽  
Cognitive Test ◽  
Motor Deficits ◽  
Behavioral Disturbances ◽  
Progressive Aphasia ◽  
Clinical Criteria ◽  
Primary Progressive ◽  
Clinical Onset ◽  
History Of

Abstract Introduction Primary progressive aphasia (PPA) is divided into three prototypical subtypes that are all characterized by their single core symptom of aphasia. Although later in their course, other cognitive, behavioral, and motor domains may become involved, little is known about the progression profile of each subtype relative to the other subtypes. Methods In this longitudinal retrospective cohort study, based on the recent biomarker-supported diagnostic criteria, 24 subjects diagnosed with semantic variant (svPPA), 22 with non-fluent variant (nfvPPA), and 18 with logopenic variant (lvPPA) were collected and followed up for 1–6 years. Symptom distribution, cognitive test and neuropsychiatric inventory scores, and progression into another syndrome were assessed. Results Over time, lvPPA progressed with broader language problems (PPA-extended) and nfvPPA progressed to mutism, whereas semantic impairment remained the major problem in svPPA. Apart from linguistic problems, svPPA developed pronounced behavioral disturbances, whereas lvPPA exhibited a greater cognitive decline. By contrast, in nfvPPA motor deficits were more common. Furthermore, within 5 years (IQR = 2.5) after clinical onset, 65.6% of the patients additionally fulfilled the clinical criteria for another neurodegenerative syndrome (PPA-plus). Fourteen out of 24 (58%) svPPA patients additionally met the diagnostic criteria of behavioral variant frontotemporal dementia (5.1 years, IQR = 1.1), whereas the clinical features of 15/18 (83%) lvPPA patients were consistent with Alzheimer disease dementia (4.5 years IQR = 3.4). Furthermore, 12/22 (54%) of the subjects with the nfvPPA progressed to meet the diagnostic criteria of corticobasal syndrome, progressive supranuclear palsy, or motor neuron disease (5.1 years IQR = 3.4). Discussion Despite aphasia being the initial and unique hallmark of the syndrome, our longitudinal results showed that PPA is not a language limited disorder and progression differs widely for each subtype, both with respect to the nature of symptoms and disease duration.

scholarly journals Primary progressive aphasia: Classification of variants in 100 consecutive Brazilian cases

2013 ◽  
Vol 7 (1) ◽  
pp. 110-121 ◽  
Author(s):  
Mirna Lie Hosogi Senaha ◽  
Paulo Caramelli ◽  
Sonia M.D. Brucki ◽  
Jerusa Smid ◽  
Leonel T. Takada ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Language Impairment ◽  
Demographic Data ◽  
Primary Progressive Aphasia ◽  
Clinical Syndrome ◽  
Progressive Aphasia ◽  
Primary Progressive ◽  
Diagnosis And Classification ◽  
Consensus Classification

ABSTRACT Primary progressive aphasia (PPA) is a neurodegenerative clinical syndrome characterized primarily by progressive language impairment. Recently, consensus diagnostic criteria were published for the diagnosis and classification of variants of PPA. The currently recognized variants are nonfluent/agrammatic (PPA-G), logopenic (PPA-L) and semantic (PPA-S). Objective: To analyze the demographic data and the clinical classification of 100 PPA cases. Methods: Data from 100 PPA patients who were consecutively evaluated between 1999 and 2012 were analyzed. The patients underwent neurological, cognitive and language evaluation. The cases were classified according to the proposed variants, using predominantly the guidelines proposed in the consensus diagnostic criteria from 2011. Results: The sample consisted of 57 women and 43 men, aged at onset 67.2±8.1 years (range of between 53 and 83 years). Thirty-five patients presented PPA-S, 29 PPA-G and 16 PPA-L. It was not possible to classify 20% of the cases into any one of the proposed variants. Conclusion: It was possible to classify 80% of the sample into one of the three PPA variants proposed. Perhaps the consensus classification requires some adjustments to accommodate cases that do not fit into any of the variants and to avoid overlap where cases fit more than one variant. Nonetheless, the established current guidelines are a useful tool to address the classification and diagnosis of PPA and are also of great value in standardizing terminologies to improve consistency across studies from different research centers.

277 Disentangling corticobasal syndrome from corticobasal degeneration

2018 ◽  
Vol 89 (10) ◽  
pp. A40.4-A41
Author(s):  
Lamb Ruth ◽  
Rohrer Jonathan ◽  
Lubbe Steven ◽  
Weil Rimona ◽  
Lashley Tammaryn ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Family History ◽  
Primary Progressive Aphasia ◽  
Corticobasal Syndrome ◽  
Loss Of Function ◽  
Progressive Aphasia ◽  
Primary Progressive ◽  
Atypical Parkinsonian Syndrome ◽  
History Of ◽  
Lateral Sclerosis

Mutations in the TANK-binding kinase (TBK1) gene have been shown to cause frontotemporal dementia (FTLD) and amyotrophic lateral sclerosis (ALS). The phenotype is highly variable and has been associated with behavioural variant FTD, primary progressive aphasia and pure amyotrophic lateral sclerosis. We describe the clinical, anatomical and pathological features of a patient with onset of a corticobasal syndrome (CBS)/primary progressive aphasia overlap aged 59. The patient presented with progressive speech difficulties and later developed an asymmetric akinetic-rigid syndrome. Neuroimaging showed asymmetrical frontal atrophy, predominantly affecting the right side. There was a strong family history of neurodegenerative disease with 4/7 siblings developing either dementia or ALS in their 50’s-60’s. Following death at age 71, post mortem examination revealed FTLD TDP-43 type A pathology. Genetic screening did not reveal a mutation in the progranulin, microtubule-associated protein tau or C9orf72 genes. However exome sequencing revealed a novel E703X mutation in the TBK1 gene. Although segregation data was not available, this loss of function mutation is highly likely to be pathogenic. In conclusion, we show that TBK1 can be a cause of an atypical parkinsonian syndrome and screening for TBK1 should be considered in CBS patients with a family history of dementia, ALS or CBS.

P1-048 Natural history of primary progressive aphasia

2004 ◽  
Vol 25 ◽  
pp. S108
Author(s):  
Emilie Le Rhun ◽  
Brigitte Debachy ◽  
Laurence Laurier-Grimonprez ◽  
Xavier Leclerc ◽  
Marc Steinling ◽  
...  
Keyword(s):  
Natural History ◽  
Primary Progressive Aphasia ◽  
Progressive Aphasia ◽  
Primary Progressive ◽  
History Of

scholarly journals Non-primary progressive language impairment in neurodegenerative conditions: protocol for a scoping review

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Sharon A. Savage ◽  
Aida Suárez-González ◽  
Alice Cassani ◽  
Ragaviveka Gopalan ◽  
Joshua Stott
Keyword(s):  
Scoping Review ◽  
Language Impairment ◽  
Primary Progressive Aphasia ◽  
Systematic Investigation ◽  
Motor Deficits ◽  
Progressive Aphasia ◽  
Primary Progressive ◽  
Cognitive Behaviour ◽  
Language Difficulties ◽  
The Impact

Abstract Background Progressive language difficulties arise in many neurodegenerative conditions, causing significant impact upon patients and families. This occurs most obviously in primary progressive aphasia (PPA) but can also occur within other forms of progressive disease. In these cases, language decline may be significant, but as they are not the presenting or dominant symptom, may be overlooked in favour of more prominent cognitive, behaviour or motor deficits. To date, there has been no systematic investigation into non-primary progressive aphasia. This scoping review aims to describe the currently reported language impairments found in non-language-led dementias and identify their clinical relevance, defined as the impact on everyday living. It also seeks to identify the reported interventions for language impairment in this patient group to-date. Method We will conduct a scoping review of published studies that have assessed and/or treated aphasia in people diagnosed with a neurodegenerative condition other than primary progressive aphasia. The systematic search will include the electronic databases PubMed, MEDLINE, OVID-EMBASE, PsycINFO, and speechBITE, using search terms for specific non-language-led dementia subtypes. Findings will be mapped and described according to the type of language difficulties identified and rehabilitation approaches employed. Intervention studies will be evaluated for their methodological rigour using validated scales. Discussion This scoping review will provide an overview of the types of aphasia found in neurodegenerative conditions where language dysfunction is not the primary focus. Current treatment approaches (and gaps in the provision of treatment) will be identified.

scholarly journals Differences in Sex Distribution Between Genetic and Sporadic Frontotemporal Dementia

2021 ◽  
pp. 1-9
Author(s):  
Sterre C.M. de Boer ◽  
Lina Riedl ◽  
Sven J. van der Lee ◽  
Markus Otto ◽  
Sarah Anderl-Straub ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Primary Progressive Aphasia ◽  
The Other ◽  
Genetic Mutations ◽  
Sex Distribution ◽  
Progressive Aphasia ◽  
Clinical Criteria ◽  
Primary Progressive ◽  
Sporadic Cases ◽  
Semantic Variant

Background: Reported sex distributions differ between frontotemporal dementia (FTD) cohorts. Possible explanations are the evolving clinical criteria of FTD and its subtypes and the discovery of FTD causal genetic mutations that has resulted in varying demographics. Objective: Our aim was to determine the sex distribution of sporadic and genetic FTD cases and its subtypes in an international cohort. Methods: We included 910 patients with behavioral variant frontotemporal dementia (bvFTD; n = 654), non-fluent variant primary progressive aphasia (nfvPPA; n = 99), semantic variant primary progressive aphasia (svPPA; n = 117), and right temporal variant frontotemporal dementia (rtvFTD; n = 40). We compared sex distribution between genetic and sporadic FTD using χ2-tests. Results: The genetic FTD group consisted of 51.2% males, which did not differ from sporadic FTD (57.8% male, p = 0.08). In the sporadic bvFTD subgroup, males were predominant in contrast to genetic bvFTD (61.6% versus 52.9% males, p = 0.04). In the other clinical FTD subgroups, genetic cases were underrepresented and within the sporadic cases sex distribution was somewhat equal. Conclusion: The higher male prevalence in sporadic bvFTD may provide important clues for its differential pathogenesis and warrants further research.

scholarly journals Survival in the Three Common Variants of Primary Progressive Aphasia: A Retrospective Study in a Tertiary Memory Clinic

2021 ◽  
Vol 11 (9) ◽  
pp. 1113
Author(s):  
Maud Tastevin ◽  
Monica Lavoie ◽  
Justine de la Sablonnière ◽  
Julie Carrier-Auclair ◽  
Robert Jr. Laforce
Keyword(s):  
Symptom Onset ◽  
Causes Of Death ◽  
Primary Progressive Aphasia ◽  
Progressive Aphasia ◽  
Primary Progressive ◽  
Common Causes ◽  
Life Issues ◽  
History Of ◽  
Advanced Stages ◽  
End Of Life Issues

Knowledge on the natural history of the three main variants of primary progressive aphasia (PPA) is lacking, particularly regarding mortality. Moreover, advanced stages and end of life issues are rarely discussed with caregivers and families at diagnosis, which can cause more psychological distress. We analyzed data from 83 deceased patients with a diagnosis of PPA. We studied survival in patients with a diagnosis of logopenic variant (lvPPA), semantic variant (svPPA), or non-fluent variant (nfvPPA) and examined causes of death. From medical records, we retrospectively collected data for each patient at several time points spanning five years before the first visit to death. When possible, interviews were performed with proxies of patients to complete missing data. Results showed that survival from symptom onset and diagnosis was significantly longer in svPPA than in lvPPA (p = 0.002) and nfvPPA (p < 0.001). No relevant confounders were associated with survival. Mean survival from symptom onset was 7.6 years for lvPPA, 7.1 years for nfvPPA, and 12 years for svPPA. The most common causes of death were natural cardio-pulmonary arrest and pneumonia. Aspiration pneumonia represented 23% of deaths in nfvPPA. In conclusion, this pilot study found significant differences in survival between the three variants of PPA with svPPA showing the longest and nfvPPA showing more neurologically-related causes of death.

scholarly journals Familial language network vulnerability in primary progressive aphasia

Neurology ◽  
2020 ◽  
Vol 95 (7) ◽  
pp. e847-e855 ◽  
Author(s):  
Sandra Weintraub ◽  
Benjamin Rader ◽  
Christina Coventry ◽  
Jaiashre Sridhar ◽  
Jessica Wood ◽  
...  
Keyword(s):  
Primary Progressive Aphasia ◽  
Structural Mri ◽  
Cognitive Test ◽  
Network Vulnerability ◽  
Total Brain Volume ◽  
Temporal Area ◽  
Course Of Illness ◽  
Progressive Aphasia ◽  
Primary Progressive ◽  
Language Network

ObjectiveTo investigate evidence of the potential role of early cortical vulnerability in the development of primary progressive aphasia (PPA).MethodA woman with a diagnosis of PPA and her 9 adult siblings, 7 with developmental language disabilities, underwent neuropsychological testing, structural MRI, and resting-state fMRI. Whole-exome sequencing was conducted for genes associated with dyslexia or with neurodegenerative dementia.ResultsThe siblings demonstrated lower verbal than nonverbal cognitive test scores in a developmental dyslexia pattern. On structural MRI, although the siblings did not differ from controls in total brain volume, the left hemisphere language area volume was significantly smaller than the right. Furthermore, cortical connectivity between the left superior temporal area, previously identified as the region of peak atrophy in the proband early in the course of illness, and adjacent language network components, including the planum temporale, was decreased in the siblings. No distinctive genetic signatures were identified.ConclusionThis report further supports the hypothesis that at least some cases of PPA may be based on a familial language network vulnerability that interferes with the acquisition of language in some members and that makes the language network a locus of least resistance to the effects of an independently late-arising neurodegenerative disease in others. This association offers a conceptual model to explain why identical neurodegenerative diseases may selectively target the language network in some individuals while targeting networks that regulate memory or behavior in others. The genetic basis for this vulnerability remains to be determined.

Natural history of primary progressive aphasia

Neurology ◽  
2005 ◽  
Vol 65 (6) ◽  
pp. 887-891 ◽  
Author(s):  
E. Le Rhun ◽  
F. Richard ◽  
F. Pasquier
Keyword(s):  
Natural History ◽  
Primary Progressive Aphasia ◽  
Progressive Aphasia ◽  
Primary Progressive ◽  
History Of

scholarly journals Redefining the multidimensional clinical phenotypes of frontotemporal lobar degeneration syndromes

2019 ◽  
Author(s):  
Alexander G. Murley ◽  
Ian Coyle-Gilchrist ◽  
Matthew Rouse ◽  
P Simon Jones ◽  
Win Li ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Clinical Features ◽  
Frontotemporal Lobar Degeneration ◽  
Clinical Phenotype ◽  
Principal Component ◽  
Primary Progressive Aphasia ◽  
Diagnostic Features ◽  
Cross Sectional ◽  
Progressive Aphasia ◽  
Primary Progressive

AbstractThe syndromes caused by frontotemporal lobar degeneration (FTLD) have highly heterogenous and overlapping clinical features. There has been great progress in the refinement of clinical diagnostic criteria in the last decade, but we propose that a better understanding of aetiology, pathophysiology and symptomatic treatments can arise from a transdiagnostic approach to clinical phenotype and brain morphometry. In a cross-sectional epidemiological study, we examined 310 patients with a syndrome likely to be caused by frontotemporal lobar degeneration, including behavioural variant frontotemporal dementia (bvFTD), the non-fluent (nfvPPA), semantic (svPPA) variants of primary progressive aphasia, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). We also included patients with logopenic primary progressive aphasia (lvPPA) and those who met criteria for PPA but not one of the three subtypes. To date, forty-nine patients have a neuropathological diagnosis. A principal component analysis identified symptom dimensions that broadly recapitulated the core features of the main clinical syndromes. However, the subject-specific scores on these dimensions showed considerable overlap across the diagnostic groups. Sixty-two percent of participants had phenotypic features that met the diagnostic criteria for more than one syndrome. Behavioural disturbance was prevalent in all groups. Forty-four percent of patients with CBS had PSP-like features and thirty percent of patients with PSP had CBS-like features. Many patients with PSP and CBS had language impairments consistent with nfvPPA while patients with bvFTD often had semantic impairments. Using multivariate source-based morphometry on a subset of patients (n=133), we identified patterns of co-varying brain atrophy that were represented across the diagnostic groups. Canonical correlation analysis of clinical and imaging components found three key brain-behaviour relationships that revealed a continuous spectrum across the cohort rather than discrete diagnostic entities. In the forty-six patients with longitudinal follow up (mean 3.6 years) syndromic overlap increased with time. Together, these results show that syndromes associated with FTLD do not form discrete mutually exclusive categories from their clinical features or structural brain changes, but instead exist in a multidimensional spectrum. Patients often manifest diagnostic features of multiple disorders and deficits in behaviour, movement and language domains are not confined to specific diagnostic groups. It is important to recognise individual differences in clinical phenotype, both for clinical management and to understand pathogenic mechanisms. We suggest that the adoption of a transdiagnostic approach to the spectrum of FTLD syndromes provides a useful framework with which to understand disease progression, heterogeneity and treatment.

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