Progressive Fluent Aphasia Research Articles

Aphasic mild cognitive impairment in prodromal dementia with Lewy bodies.

This study aimed to determine the characteristics of aphasic mild cognitive impairment (aphasic MCI), which is characterized by a progressive and relatively prominent language impairment compared with other cognitive impairments, in the prodromal phase of dementia with Lewy bodies (DLB). Of the 26 consecutive patients with aphasic MCI who had been prospectively recruited at our hospital, 8 patients were diagnosed with prodromal DLB and underwent language, neurological, neuropsychological, and neuroimaging (N-isopropyl-p-[123I] iodoamphetamine single-photon emission computed tomography; IMP-SPECT) testing. Three of these patients also underwent cholinesterase inhibitor therapy with donepezil. In our aphasic MCI cohort, the clinical diagnosis of probable prodromal DLB accounted for more than 30% of cases; therefore, the presence of language impairment in prodromal DLB was not very uncommon. Five patients were diagnosed with progressive anomic aphasia and three with logopenic progressive aphasia. Anomic aphasia was characterized by apparent anomia but relatively preserved repetition and comprehension ability and logopenic progressive aphasia by anomia, phonemic paraphasia, and impaired repetition. IMP-SPECT revealed hypoperfusion of the temporal and parietal lobes in the left hemisphere in all but one patient. All patients who underwent cholinesterase inhibitor therapy with donepezil showed improvement in general cognitive function, including language function. The clinical and imaging features of aphasic MCI in prodromal DLB are similar to those observed in Alzheimer's disease. Progressive fluent aphasia, such as progressive anomic aphasia and logopenic progressive aphasia, is one of the clinical presentations in prodromal state of DLB. Our findings provide further insight into the clinical spectrum of prodromal DLB and may contribute to the development of medication for progressive aphasia caused by cholinergic insufficiency.

Unclassified fluent variants of primary progressive aphasia: distinction from semantic and logopenic variants.

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.

Classification and clinicoradiologic features of primary progressive aphasia (PPA) and apraxia of speech

The consensus criteria for the diagnosis and classification of primary progressive aphasia (PPA) have served as an important tool in studying this group of disorders. However, a large proportion of patients remain unclassifiable whilst others simultaneously meet criteria for multiple subtypes. We prospectively evaluated a large cohort of patients with degenerative aphasia and/or apraxia of speech using multidisciplinary clinical assessments and multimodal imaging. Blinded diagnoses were made using operational definitions with important differences compared to the consensus criteria. Of the 130 included patients, 40 were diagnosed with progressive apraxia of speech (PAOS), 12 with progressive agrammatic aphasia, 9 with semantic dementia, 52 with logopenic progressive aphasia, and 4 with progressive fluent aphasia, while 13 were unclassified. The PAOS and progressive fluent aphasia groups were least impaired. Performance on repetition and sentence comprehension was especially poor in the logopenic group. The semantic and progressive fluent aphasia groups had prominent anomia, but only semantic subjects had loss of word meaning and object knowledge. Distinct patterns of grey matter loss and white matter changes were found in all groups compared to controls. PAOS subjects had bilateral frontal grey matter loss, including the premotor and supplementary motor areas, and bilateral frontal white matter involvement. The agrammatic group had more widespread, predominantly left sided grey matter loss and white matter abnormalities. Semantic subjects had bitemporal grey matter loss and white matter changes, including the uncinate and inferior occipitofrontal fasciculi, whereas progressive fluent subjects only had left sided temporal involvement. Logopenic subjects had diffuse and bilateral grey matter loss and diffusion tensor abnormalities, maximal in the posterior temporal region. A diagnosis of logopenic aphasia was strongly associated with being amyloid positive (46/52 positive). Our findings support consideration of an alternative way of identifying and categorizing subtypes of degenerative speech and language disorders.

Aphasia with left occipitotemporal hypometabolism: A novel presentation of posterior cortical atrophy?

Alzheimer’s disease is a common neurodegenerative disease often characterized by initial episodic memory loss. Atypical focal cortical presentations have been described, including the logopenic variant of primary progressive aphasia (lvPPA) which presents with language impairment, and posterior cortical atrophy (PCA) which presents with prominent visuospatial deficits. Both lvPPA and PCA are characterized by specific patterns of hypometabolism: left temporoparietal in lvPPA and bilateral parietoccipital in PCA. However, not every patient fits neatly into these categories. We retrospectively identified two patients with progressive aphasia and visuospatial deficits from a speech and language based disorders study. The patients were further characterized by MRI, fluorodeoxyglucose F18 and Pittsburgh Compound B (PiB) positron emission tomography. Two women, aged 62 and 69, presented with a history of a few years of progressive aphasia characterized by fluent output with normal grammar and syntax, anomia without loss of word meaning, and relatively spared repetition. They demonstrated striking deficits in visuospatial function for which they were lacking insight. Prominent hypometabolism was noted in the left occipitotemporal region and diffuse retention of PiB was noted. Posterior cortical atrophy may present focally with left occipitotemporal metabolism characterized clinically with a progressive fluent aphasia and prominent ventral visuospatial deficits with loss of insight.

Aphasia with left occipitotemporal hypometabolism: A novel presentation of posterior cortical atrophy?

Alzheimer's disease is a common neurodegenerative disease often characterized by initial episodic memory loss. Atypical focal cortical presentations have been described, including the logopenic variant of primary progressive aphasia (lvPPA) which presents with language impairment, and posterior cortical atrophy (PCA) which presents with prominent visuospatial deficits. Both lvPPA and PCA are characterized by specific patterns of hypometabolism: left temporoparietal in lvPPA and bilateral parietoccipital in PCA. However, not every patient fits neatly into these categories. We retrospectively identified two patients with progressive aphasia and visuospatial deficits from a speech and language based disorders study. The patients were further characterized by MRI, fluorodeoxyglucose F18 and Pittsburgh Compound B (PiB) positron emission tomography. Two women, aged 62 and 69, presented with a history of a few years of progressive aphasia characterized by fluent output with normal grammar and syntax, anomia without loss of word meaning, and relatively spared repetition. They demonstrated striking deficits in visuospatial function for which they were lacking insight. Prominent hypometabolism was noted in the left occipitotemporal region and diffuse retention of PiB was noted. Posterior cortical atrophy may present focally with left occipitotemporal metabolism characterized clinically with a progressive fluent aphasia and prominent ventral visuospatial deficits with loss of insight.

Novel Evidence of Phenotypical Variability in the Hexanucleotide Repeat Expansion in Chromosome 9

C9ORF72 repeat expansion is currently considered as a major genetic cause of amyotrophic lateral sclerosis (ALS) and, in particular, of combined frontotemporal dementia-motor neuron disorder (FTD-MND) pedigrees. Studies of large series of patients have indicated that various phenotypic presentations may be observed even in the same family. Here, we describe four patients carrying a C9ORF72 mutation with heterogeneous clinical presentation sharing a rapid disease course. Cases #1 and #2 presented with predominant semantic deficits, accompanied in one patient by clinical signs of ALS. Case #3 showed a phenotype compatible with a diagnosis of behavioral variant of FTD. Case #4 presented with memory impairments, apathy, and social withdrawal, and had negative cerebrospinal fluid markers for Alzheimer's disease. Two patients showed a positive familiar history of MND and dementia (at least one first-degree family member affected). The two other patients were apparently sporadic cases. Our data provide further evidence for the heterogeneity of phenotypes associated with the C9ORF72 mutation and indicate its association with a fluent progressive aphasia phenotype. The present findings confirm the importance of screening for the hexanucleotide repeat expansion in chromosome 9 in the case not only of familial, but also of sporadic FTD, and in the presence of atypical cognitive disorders.

Comorbid Multiple Sclerosis and TDP-43 Proteinopathy in a Gulf War Sea Captain

Comorbid Multiple Sclerosis and TDP-43 Proteinopathy in a Gulf War Sea Captain

POD07 Tinnitus and hyperacusis in semantic dementia

IntroductionSemantic dementia (SemD) is a canonical subtype of frontotemporal lobar degeneration characterised by progressive fluent aphasia in the context of focal asymmetric (predominantly left-sided) anterior temporal atrophy. Nonverbal auditory symptoms...

002 Clinical varieties of memory disorders

: This talk will give an overview regarding clinical memory disorders. These encompass far more than just the dementias. Amnesic disorders can be transient or persisting. They can have a...

Fluorodeoxyglucose F18 Positron Emission Tomography in Progressive Apraxia of Speech and Primary Progressive Aphasia Variants

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.

Demencia frontotemporal: Experiencia clínica

Front temporal dementias (FTD) are neurodegenerative disorders characterized by alterations in behavior, affection and language, with relative sparing of episodic memory. There are three major forms of FTD: the frontal or behavioral form, progressive non-fluent aphasia and semantic dementia (that may begin as a fluent progressive aphasia).To report a retrospective clinical experience of patients with frontotemporal dementia.Review of 3,700 records of neuropsychological assessments of patients with behavioral disturbances, studied between 1981 and 2008. Of these, 63 patients (59% females) complied with the criteria for frontotemporal dementia.There were 47 cases with the frontal variant, four with non-fluent progressive aphasia and six with fluent progressive aphasias (2 evolved to semantic dementia). The mean age of onset was 60+/-11 years. There were no familiar cases of FTD.It is clinically difficult to diagnose FTD, since evaluation of attitude or language is required. In addition to structural images, functional images were helpful in some cases, but the definitive diagnosis is anatomical.

Frontotemporal dementia: Review of 63 cases

Front temporal dementias (FTD) are neurodegenerative disorders characterized by alterations in behavior, affection and language, with relative sparing of episodic memory. There are three major forms of FTD: the frontal or behavioral form, progressive non-fluent aphasia and semantic dementia (that may begin as a fluent progressive aphasia). To report a retrospective clinical experience of patients with frontotemporal dementia. Review of 3,700 records of neuropsychological assessments of patients with behavioral disturbances, studied between 1981 and 2008. Of these, 63 patients (59% females) complied with the criteria for frontotemporal dementia. There were 47 cases with the frontal variant, four with non-fluent progressive aphasia and six with fluent progressive aphasias (2 evolved to semantic dementia). The mean age of onset was 60+/-11 years. There were no familiar cases of FTD. It is clinically difficult to diagnose FTD, since evaluation of attitude or language is required. In addition to structural images, functional images were helpful in some cases, but the definitive diagnosis is anatomical.

Very Early Semantic Dementia With Progressive Temporal Lobe Atrophy

Semantic dementia is a syndrome within the spectrum of frontotemporal lobar degenerations characterized by fluent progressive aphasia (particularly anomia) and loss of word meaning. To report a unique case of very early semantic dementia with a slowly progressive course, allowing insights into the early natural history of this disorder. Case report. A tertiary care center. A 62-year-old woman who presented with "memory loss" complaints. Clinical course, neuropsychological data, and magnetic resonance imaging results. The patient was first evaluated when the results of standard neuropsychological measures were normal but subtle left anterior temporal lobe atrophy was present. During the follow-up period of 8 years, she developed profound anomia and loss of word meaning associated with progressive left anterior temporal lobe atrophy, consistent with semantic dementia. In more recent years, anterograde memory impairment and mild prosopagnosia evolved in association with left hippocampal atrophy and subtle atrophy in the homologous gyri of the right anterior temporal lobe. She remains functionally independent despite her current deficits. Early identification of patients who will develop semantic dementia is difficult and might be missed with standard clinical, neuropsychological, and structural neuroimaging evaluations. Recognition of this relatively rare syndrome is important for early diagnosis and prognostication and particularly for therapeutic interventions in the future.

P2-077: Comparison of manual and automated determination of hippocampal volumes in MCI and older adults with cognitive complaints

of language and semantic memory testing. Results: As a group, patients with progressive fluent aphasia demonstrated prominent left-greater-thanright temporopolar thinning, while patients with progressive non-fluent aphasia demonstrated thinning in left-greater-than-right inferior frontoinsular cortex. Yet there were notable individual differences in anatomic abnormalities that corresponded with differences in language, cognition, and behavior. Within the group of patients with fluent aphasia, the patient with the most prominent semantic impairment had the greatest degree of thinning of the left temporopolar cortex (31%) as compared to a group of controls; this patient also had prominent abnormalities of affective and social behavior, which may relate to prominent right temporopolar thinning (29%). Within the group of patients with non-fluent aphasia, the patient with non-fluent progressive aphasia and apraxia of speech had thinning not only in left inferior frontal gyrus (19%) but also in ventral precentral gyrus (26%) and supplementary motor area (24%). Conclusions: Quantitative cortical thickness analysis of MRI data shows promise in applications to individual subjects with progressive aphasia for localizing regional cortical thinning that may underlie specific language and behavioral abnormalities. Further investigation will determine whether this approach will be helpful in more detailed subtyping of these patients, in differential diagnosis, or as an imaging biomarker for monitoring the effects of potential future therapies. Supported by NIA R01-AG29411, K23-AG22509, NCRR P41RR14075, U24-RR021382, and the MIND Institute.

Démence sémantique : réflexions d’un groupe de travail pour des critères de diagnostic en français et la constitution d’une cohorte de patients

Semantic dementia (SD) is a syndrome of progressive loss of semantic knowledge for objects and people. International criteria propose that SD be included in the frontotemporal lobar degeneration syndromes, with progressive non-fluent aphasia and frontotemporal dementia (FTD). However, several related syndromes have been defined that clinically and conceptually share both similarities and differences with SD: fluent progressive aphasia, progressive prosopagnosia, temporal variant of FTD. In order to establish a French consensus for the diagnosis and modalities of evaluation and follow-up of SD, a working group, composed of neurologists, neuropsychologists and speech-therapists, was established by the Groupe de réflexion sur les évaluations cognitives (GRECO). New criteria were elaborated, based on clinical, neuropsychological, and imaging data. They define typical and atypical forms of SD. A diagnosis of typical SD relies on an isolated and progressive loss of semantic knowledge, attested by a deficit of word comprehension and a deficit of objects and/or people identification, with imaging showing temporal atrophy and/or hypometabolism. SD is atypical if the deficit of semantic knowledge is present only within a single modality (verbal versus visual), or if non-semantic deficits (mild and not present at onset) and/or neurological signs, are associated with the semantic loss.

Progressive aphasia secondary to Alzheimer disease vs FTLD pathology.

The pathology causing progressive aphasia is typically a variant of frontotemporal lobar degeneration, especially with ubiquitin-positive inclusions (FTLD-U). Less commonly the underlying pathology is Alzheimer disease (AD). To compare clinicopathologic and MRI features of subjects with progressive aphasia and AD pathology to subjects with aphasia and FTLD-U pathology and subjects with typical AD. We identified 5 subjects with aphasia and AD pathology and 5 with aphasia and FTLD-U pathology with an MRI from a total of 216 aphasia subjects. Ten subjects with typical AD clinical features and AD pathology were also identified. All subjects with AD pathology underwent pathologic reanalysis with TDP-43 immunohistochemistry. Voxel-based morphometry (VBM) was used to assess patterns of gray matter atrophy in the aphasia cases with AD pathology, aphasia cases with FTLD-U, and typical AD cases with AD pathology, compared with a normal control group. All aphasic subjects had fluent speech output. However, those with AD pathology had better processing speed than those with FTLD-U pathology. Immunohistochemistry with TDP-43 antibodies was negative. VBM revealed gray matter atrophy predominantly in the temporoparietal cortices, with notable sparing of the hippocampus in the aphasia with AD subjects. In comparison, the aphasic subjects with FTLD-U showed sparing of the parietal lobe. Typical AD subjects showed temporoparietal and hippocampal atrophy. A temporoparietal pattern of atrophy on MRI in patients with progressive fluent aphasia and relatively preserved processing speed is suggestive of underlying Alzheimer disease pathology rather than frontotemporal lobar degeneration with ubiquitin-only immunoreactive changes.

Age of acquisition effects on action naming in progressive fluent aphasia

Age of acquisition effects on action naming in progressive fluent aphasia

Access to knowledge from pictures but not words in a patient with progressive fluent aphasia

We present data from a patient with a progressive fluent aphasia, BA, who exhibited a severe verbal impairment but a relatively preserved access to knowledge from pictures. She exhibited surface dyslexia and dysgraphia and was impaired in the production of the past tense of irregular verbs and the plural form of irregular nouns. She exhibited a mild-moderate impairment in auditory and visual lexical decision tasks that, we argue, was explicable on the basis of a semantic deficit. Knowledge of numbers and body parts was largely preserved even when on tasks involving verbal stimuli. On the basis of this and other evidence, we argue for a distributed, multi-modality system for semantic memory in which information is stored in different brain regions and in different representational formats.

Clinicopathologic Case Report: Progressive Aphasia in a 77-Year-Old Man

Clinicopathologic Case Report: Progressive Aphasia in a 77-Year-Old Man

Access to knowledge from pictures but not words in a patient with progressive fluent aphasia

Access to knowledge from pictures but not words in a patient with progressive fluent aphasia