Word retrieval therapies in primary progressive aphasia

Background: Primary progressive aphasia (PPA) with its three variants is a progressive neurodegenerative dementia in which language impairment is the first and most dominant symptom. Traditionally, speech-language pathologists who deliver therapy to adults with acquired neurogenic language disorders shy away from treatment of progressive aphasia as there is no promise of lasting effects and only limited data regarding treatment efficacy.

Aims: This paper comprises the most current review of the literature focused on treatment of naming impairments in PPA, and aims to encourage and assist clinicians in selecting intervention approaches for individuals with PPA. It highlights current trends and challenges in delivering successful therapy for naming deficits in PPA.

Main Contribution: We reviewed papers that reported different forms of naming therapy for patients with PPA, which included interventions that, although not always aimed directly at anomic deficits, brought about improvement in naming. Immediate gains, maintenance, and generalisation effects are summarised, along with a variety of approaches and methodologies that can be applied to the PPA population. We also provide a list of factors that were found to contribute to the success of therapy and to the maintenance and/or generalisation of treatment gains.

Conclusions: Current literature delivers encouraging evidence for clinicians wanting to provide naming therapy to patients with PPA. Although PPA is a progressive disorder, both the immediate treatment effects and, in many cases, maintenance results show that improvements are possible. The issues of generalisation of naming gains beyond the clinician’s office still require more studies to determine the best conditions, designs, and patient suitability.     

Differential diagnosis of primary progressive aphasia variants using the international criteria

Background: Based upon the profile linguistic and speech deficits, the current International Criteria for diagnosis and classification of primary progressive aphasia (PPA) suggest the distinction of semantic, nonfluent/agrammatic and logopenic variants, each of which is commonly associated with specific pathology and distribution of brain atrophy. Although the vast majority of cases fit in this tripartite schema, some cases remain unclassifiable because of the presence of overlapping deficits, or conversely, because of the presence of isolated deficits.

Aims: In this review, we describe relevant clinical features that characterise each variant and discuss emerging issues derived from the application of the International Criteria.

Main Contribution: Based on a hierarchical approach that comprises the evaluation of single-word comprehension, motor speech disorder, agrammatism and sentence repetition, we propose a heuristic solution aimed to reduce the number of cases with ambiguous identification and thereby optimise the application of the current International Criteria.

Conclusions: Despite the clinical heterogeneity of cases with PPA, the current International Criteria, together with the proposed heuristic solution, provide a valid framework into which the vast majority of cases can be classified. The development of robust clinical markers aimed to distinguish cases with motor speech disorders from those with logopenic variant remains clinically challenging.     

Patterns of decline in naming and semantic knowledge in primary progressive aphasia

Background: 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.     

Long-term follow-up in primary progressive aphasia: Clinical course and health care utilisation

Background: Primary progressive aphasia (PPA) is a rare disorder. Data on health care utilisation and care-relevant symptoms are scarce.

Aims: The study aimed at finding out how patients with PPA are cared for, the extent of professional support utilised by family caregivers, and which care-relevant clinical symptoms and signs occur with advanced disease.

Method & Procedures: Forty-three family caregivers of patients with PPA were interviewed with a standardised questionnaire.

Outcomes & Results: A majority of caregivers cared for the patients at home without any support. More than 40% of the patients were treated with cholinesterase inhibitors or memantine. Only 9% of the patients received speech therapy. In advanced PPA, the majority of patients were unable to communicate and almost all needed 24-hr care. Other neurological symptoms appeared, and a considerable number of patients suffered from moderate or severe somatic illnesses.

Conclusion: Future studies are necessary to investigate the reasons why the PPA caregivers hardly utilise informal and formal support, what their specific needs are, and which kind of support and interventions prove to be useful.     

Distinguishing logopenic from semantic & nonfluent variant primary progressive aphasia: Patterns of linguistic and behavioral correlations

While language characteristics of logopenic variant primary progressive aphasia (lvPPA) are well-defined, behavioral characteristics are less understood. We investigated correlations between language and behavioral scores across three variants of primary progressive aphasia (PPA) and found language performance and behavioral disturbances are correlated in lvPPA, but not other PPA subtypes. Results suggest that unlike other PPA variants, patients diagnosed with lvPPA do not develop negative behaviors until language deficits are severe. This is consistent with the underlying neuropathology of lvPPA, Alzheimer's Disease. Such findings are crucial to clinical prognosis, especially when considering the progressive nature of this disease.     

Functional disability in primary progressive aphasia

Background: In primary progressive aphasia (PPA), assessment of language predominates over assessment of functional impairment in activities of daily living (ADLs) in clinical and research environments. Most of the knowledge on functional disability in PPA relies largely on anecdotal experience and limited numbers of studies published to date.

Aims: (1) To describe the different patterns of ADL functional disability in the main PPA variants: semantic variant, nonfluent aphasia, and the more recently defined logopenic variant; (2) to draw relations between functional disability, cognitive, and behavioural symptoms in the PPAs; (3) to examine the impact of functional disability on carer burden, and (4) to provide specific strategies to address the described problems.

Main Contribution: Profiles of disease progression are described from a functional perspective, as well as the relationship (or lack thereof) between functional disability and cognitive and behavioural symptoms. Dementia-management strategies for carers and professionals in overcoming day-to-day difficulties are provided, and the impact of functional deficits on those around the patient, including their spouses and children, are discussed.

Conclusions: Patterns of ADL functional disability and their progression vary between PPA subtypes. Understanding these different profiles of impairment is critical to the development of tailored interventions. There is a range of therapeutic strategies which can be trialled to promote improved ADL functioning, which in turn may also help in reducing levels of carer burden in PPA.     

Primary progressive aphasia and Pick complex

Ten autopsied patients from a prospectively followed, clinically defined, neuropsychologically and radiologically documented cohort with primary progressive aphasia were histologically characterized. All were variants of frontotemporal degeneration (Pick complex): Pick body dementia, n=3, corticobasals degeneration (CBD), n=4, and tau and synuclein negative ubiquitinated inclusions of the motor neuron disease type, n=3. All shared superficial cortical spongiosis, neuronal loss, and gliosis. Although most patients had fluent anomic aphasia at onset, all progressed to a nonfluent or mute state. Comprehension, episodic memory, and activities of daily living were initially preserved. Three cases with Pick body dementia had verbal apraxia and stuttering at onset. Two of the patients with CBD pathology were older than the average primary progressive aphasia (PPA). All patients developed secondary syndromes either of frontotemporal dementia (FTD) and/or extrapyramidal-apraxic manifestations (CBD). By the time autopsy was obtained, the pathology appeared outside the language areas. Progressive aphasias secondary to Alzheimer's disease (AD) were excluded on the basis of early loss of memory and comprehension.Rather than the previously emphasized histological heterogeneity, clinically probable PPA has a predictive value of a group of related pathologies, collectively named frontotemporal degeneration, or Pick complex. This series of autopsied cases provides evidence for the clinical and pathological overlap of PPA with FTD and CBD, and contributes to the diagnostic and neuropsychological definition of PPA.     

Therapy for naming deficits in two variants of primary progressive aphasia

Background: Primary progressive aphasia (PPA) refers to a progressive and selective decline in language due to neurodegenerative disease. There are three variants of PPA, progressive nonfluent aphasia (PNFA), semantic dementia (SD), and logopaenic progressive aphasia (LPA). All variants include impaired object naming, but distinct underlying deficits might interfere with naming. Therefore, individuals with different types of PPA may respond differently to naming therapy.

Aims: To identify differences in patterns of success and generalisation in response to the same treatment in patient with LPA and a patient with SD. Furthermore, we wished to identify whether the treatment effect was item specific (trained words) or generalised to untrained words in trained or untrained categories.

Methods & Procedures: Participants included an individual with LPA and one with SD. An assessment of lexical processing was administered before and after a naming treatment to assess underlying deficits and generalisation effects. Therapy consisted of a cueing hierarchy treatment. Treatment items consisted of pictured objects in the categories of fruits/vegetables and clothing.

Outcomes & Results: Two different patterns of performance were observed. The LPA participant improved in naming of treated items and untreated items in both treated and untreated categories. The participant with SD improved in naming treated items only, but showed less deterioration in untreated items in treated than untreated categories.

Conclusions: Individuals with PPA can show improved naming (at least temporarily) with therapy, but generalisation to untrained items may depend on the underlying cause of the naming deficit, which may differ across subtypes.     

Trouble and repair during conversations of people with primary progressive aphasia

Background: Primary progressive aphasia (PPA) affects a range of language domains that impact on communication. Little is known about the nature of conversation breakdown in PPA. The identification of trouble in conversation, its repair and the success of repairs has been used effectively to examine conversation breakdown in neurogenic language disorders such as dementia of the Alzheimer type (DAT) and acute onset aphasia. This study investigated trouble and repair in the conversations of people with PPA.

Aims: The first aim of this study is to describe the contributions of individuals with PPA and their conversation partner to conversation. The second aim is to describe the trouble that occurs in dyadic conversations between three individuals with PPA and their communication partner. The third aim is to describe the repair behaviours used by the individuals with PPA and their communication partners.

Methods & Procedures: Dyadic conversations about everyday activities between three individuals with PPA and their partners and three control dyads were video recorded and transcribed. Number of words, number of turns and length of turns were measured and trouble-indicating behaviours (TIBs) and repair behaviours were categorised.

Outcomes & Results: Individuals with PPA had reduced mean length of turn but maintained their share of turn-taking. They demonstrated a variety of TIBs that differed from the noninteractive repairs, which do not require a response from the partner in the conversation and which have been observed in studies of conversation in DAT. Their partners bore the greater burden of highlighting trouble and need for repair using collaborative, interactive, TIBs. Three different conversational profiles were observed in the three PPA dyads, reflecting different patterns of language and cognitive impairment.

Conclusions: Individuals with PPA were active participants in conversation effectively indicating and responding to trouble. Understanding trouble and repair in the conversations of individuals with PPA has the potential to enhance assessment and inform clinical practice.     

Corticobasal degeneration with primary progressive aphasia and accentuated cortical lesion in superior temporal gyrus: case report and review

A 57-year-old woman showed progressive sensory aphasia as an initial symptom, and then developed total aphasia within 6 years and, finally, severe dementia. Neuropathologically, the cerebral cortex was most severely affected in the superior and transverse temporal gyri, and subsequently in the inferior frontal gyrus, especially in the pars opercularis. The degeneration in the subcortical grey matter was most severe in the substantia nigra, and it was moderate to mild in the ventral part of thalamus, globus pallidus and striatum. Cytopathologically, in addition to achromatic ballooned neurons, massive tau-positive types of cytosekeletal abnormalities were observed both in neurons and glia, mainly in the degenerating region. This cytoskeletal pathology coincided with that reported in corticobasal degeneration (CBD). On Bodian staining, only a few neurofibrillary tangles were found in the entorhinal pre-alpha layer and substantia nigra. Pick’s bodies and senile plaques could not be found. This case is thought to represent a type of CBD, but with its cortical lesion focus located in the speech area instead of the frontoparietal region. A survey of 28 pathologically evaluated cases of CBD revealed two similar cases, both of which began with progressive aphasia and presented cortical degeneration in the superior temporal gyrus. An overview of CBD cases clarified the features in another group of cases, in which the cerebral accentuated focus was shifted forward from the central region, clinically resembling Pick’s disease. The clinical manifestations in CBD seem to be the expression of these diverse cortical lesions. Primary progressive aphasia may include cases of CBD with involvement of the language center. Received: 5 February 1996 / Revised, accepted: 13 May 1996     

Patterns of hemispheric compromise in primary progressive apraxia of speech: From clinical profiling to differential diagnosis

In this issue of European Journal of Neurology, Robinson et al. present a novel study on primary progressive apraxia of speech. The authors describe different clinicopathological profiles in patients with left-dominant, right-dominant, and bilateral atrophy of the supplementary motor area and lateral premotor cortex. This commentary discusses the importance of this evidence for understanding individual differences among these patients, distinguishing them from those with nonfluent variant primary progressive aphasia, and analyzing the relations between motor speech deficits and underlying pathology.     

Agrammatic primary progressive aphasia in two dextral patients with right hemispheric involvement

Agrammatic primary progressive aphasia (PPA-G) has been known to be associated with focal brain atrophy involving the left posterior frontal and anterior insular regions. However, aphasia can also rarely result from right hemispheric lesions in right-handed patients, so-called crossed aphasia in dextrals (CAD). We report two right-handed patients with PPA-G whose 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) showed hypometabolism predominantly in the right hemisphere, implicating “crossed PPA-G.”     

Longitudinal imaging and deterioration in word comprehension in primary progressive aphasia: Potential clinical significance

Background: Three variants of primary progressive aphasia (PPA), distinguished by language performance and supportive patterns of atrophy on imaging, have different clinical courses and the prognoses for specific functions. For example, semantic variant PPA alone is distinguished by impaired word comprehension. However, sometimes individuals with high education show normal performance on word-comprehension tests early on, making classification difficult. Furthermore, as the condition progresses, individuals with other variants develop word-comprehension deficits and other behavioural symptoms, making distinctions between variants less clear. Longitudinal brain imaging allows identification of specific areas of atrophy in individual patients, which identifies the location of disease in each patient.

Aims: We hypothesised that the areas of atrophy in individual PPA participants would be closely correlated with the decline in word comprehension over time. We propose that areas where tissue volume is correlated with word comprehension are areas that: (1) are essential for word comprehension, (2) compensate for word comprehension in some individuals with semantic variant PPA early in the course, and (3) show atrophy in individuals with logopenic and nonfluent variant PPA only late in the course.

Methods and Procedures: Fifteen participants with PPA (five logopenic variant PPA; eight semantic variant PPA; two nonfluent/agrammatic variant PPA; mean age 67.8), underwent high resolution magnetic resonance imaging and cognitive tests at least 9 months apart. The correlations between change in regional volumes and change in auditory word-comprehension scores were investigated using Spearman test.

Outcomes & Results: While scores on auditory word comprehension at Time 1 were correlated with volume loss in right and left temporal pole and left inferior temporal cortex (areas of atrophy associated with semantic variant PPA), deterioration in auditory word comprehension from Time 1 to Time 2 was associated with individual atrophy in left middle temporal cortex, left angular gyrus, and right inferior and middle temporal cortex.

Conclusions: Progressive atrophy in focal areas surrounding left temporal pole and left inferior temporal cortex, and right homologous area is closely related to progressive decline in auditory word comprehension. These correlations likely reflect areas that compensate for subtle deficits early in the course of semantic variant PPA, as well as areas that are critical for auditory word comprehension that eventually atrophy in individuals with other variants of PPA. Individual patterns of atrophy also help us understand and predict the clinical course of individuals, such as associated behavioural or motor deficits.     

Motor speech disorders associated with primary progressive aphasia

Background: Primary progressive aphasia (PPA) and conditions that overlap with it can be accompanied by motor speech disorders. Recognition and understanding of motor speech disorders can contribute to a fuller clinical understanding of PPA and its management as well as its localisation and underlying pathology.

Aims: To review the types of motor speech disorders that may occur with PPA, its primary variants, and its overlap syndromes (progressive supranuclear palsy syndrome, corticobasal syndrome, motor neuron disease), as well as with primary progressive apraxia of speech.

Main Contribution: The review should assist clinicians’ and researchers’ understanding of the relationship between motor speech disorders and PPA and its major variants. It also highlights the importance of recognising neurodegenerative apraxia of speech as a condition that can occur with little or no evidence of aphasia.

Conclusion: Motor speech disorders can occur with PPA. Their recognition can contribute to clinical diagnosis and management of PPA and to understanding and predicting the localisation and pathology associated with PPA variants and conditions that can overlap with them.     

Electroencephalography in primary progressive aphasia and apraxia of speech

ABSTRACT

Background: Past research has demonstrated that electroencephalography (EEG) is sensitive to what we now know as Primary Progressive Aphasia (PPA); however, the EEG profiles of patients with Primary Progressive Apraxia of Speech (PPAOS) and PPA, in the context of current consensus criteria, have not been studied.

Aims: The primary goal of this study was to explore the EEG profiles of patients of the nonfluent/agrammatic variant of PPA (agPPA) and PPAOS.

Methods and Procedures: Three patients with agPPA and five patients with PPAOS (two with aphasia) completed a head MRI scan and clinical EEG recording. Clinical radiologists and electrophysiologists reviewed respective imaging, blinded to clinical diagnosis.

Outcomes and Results: Patients with PPAOS who did not have aphasia had normal EEGs, while those with aphasia demonstrated theta slowing. Patients with agPPA also showed theta slowing, with one exception. MRI scans showed non-specific, age-related changes across clinical presentations.

Conclusions: This preliminary study suggests theta slowing is consistent with neurodegenerative aphasia, but not isolated apraxia of speech. EEG is a low-cost mechanism to identify possible biomarkers for use when clinical severity limits behavioral examinations or expert examiners are unavailable.     

Verbal creativity in semantic variant primary progressive aphasia

Emergence of visual and musical creativity in the setting of neurologic disease has been reported in patients with semantic variant primary progressive aphasia (svPPA), also called semantic dementia (SD). It is hypothesized that loss of left anterior frontotemporal function facilitates activity of the right posterior hemispheric structures, leading to de novo creativity observed in visual artistic representation. We describe creativity in the verbal domain, for the first time, in three patients with svPPA. Clinical presentations are carefully described in three svPPA patients exhibiting verbal creativity, including neuropsychology, neurologic exam, and structural magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) was performed to quantify brain atrophy patterns in these patients against age-matched healthy controls. All three patients displayed new-onset creative writing behavior and produced extensive original work during the course of disease. Patient A developed interest in wordplay and generated a large volume of poetry. Patient B became fascinated with rhyming and punning. Patient C wrote and published a lifestyle guidebook. An overlap of their structural MR scans showed uniform sparing in the lateral portions of the language-dominant temporal lobe (superior and middle gyri) and atrophy in the medial temporal cortex (amygdala, limbic cortex). New-onset creativity in svPPA may represent a paradoxical functional facilitation. A similar drive for production is found in visually artistic and verbally creative patients. Mirroring the imaging findings in visually artistic patients, verbal preoccupation and creativity may be associated with medial atrophy in the language-dominant temporal lobe, but sparing of lateral dominant temporal and non-dominant posterior cortices.     

Progressive supranuclear palsy syndrome presenting as progressive nonfluent aphasia: A neuropsychological and neuroimaging analysis

There is currently considerable interest in the clinical spectrum of progressive nonfluent aphasia (PNFA) and progressive supranuclear palsy (PSP) and the intersection of these two entities. Here, we undertook a detailed prospective clinical, neuropsychological, and neuroimaging analysis of 14 consecutive patients presenting with PNFA to identify cases meeting clinical criteria for PSP. These patients had further detailed assessment of extrapyramidal and oculomotor functions. All patients had high‐resolution MR brain volumetry and a cortical thickness analysis was undertaken on the brain images. Four patients presenting with PNFA subsequently developed features of a PSP syndrome, including a typical oculomotor palsy. The neuropsychological profile in these cases was similar to other patients with PNFA, however, with more marked reduction in propositional speech, fewer speech errors, less marked impairment of literacy skills but more severe associated deficits of episodic memory and praxis. These PSP‐PNFA cases had less prominent midbrain atrophy but more marked prefrontal atrophy than a comparison group of five patients with pathologically confirmed PSP without PNFA and more prominent midbrain atrophy but less marked perisylvian atrophy than other PNFA cases. In summary, although the PSP‐PNFA syndrome overlaps with PNFA without PSP, certain neuropsychological and neuroanatomical differences may help predict the development of a PSP syndrome. © 2010 Movement Disorder Society     

Atypical clinical features associated with mixed pathology in a case of non-fluent variant primary progressive aphasia

A 66-year-old woman presented with agrammatism and apraxia of speech, meeting criteria for non-fluent/agrammatic variant primary progressive aphasia (nfvPPA). However, three years later, she developed frontal/executive, short-term phonological memory, visuospatial, and visual memory deficits suggesting involvement of multiple brain networks. Multimodal neuroimaging showed damage of both fronto-striatal and posterior brain regions. She was found to have multiple pathological processes: corticobasal degeneration (CBD), Alzheimer’s disease (AD), and TAR DNA-binding protein (TDP)-43 type A. We hypothesize that cognitive and neuroimaging findings consistent with damage to multiple brain networks, each associated with vulnerability to certain molecular disease subtypes, could indicate mixed pathology.