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.     

Longitudinal study of single‐word comprehension in semantic dementia: A comparison with primary progressive aphasia and Alzheimer's disease

Background: Although semantic dementia (SD) is characterised by a multimodal loss of semantic knowledge, it has been demonstrated that lexical‐semantic representations are not equally disrupted in SD and that some categories may be recognised better than others. Little is known, however, about the pattern of the category‐specific comprehension deficits in SD and whether it differs from that of other forms of progressive aphasias.

Aims: This exploratory study aimed to investigate the evolution of category‐specific deficits of single‐word comprehension in progressive aphasias.

Methods & Procedures: A total of 19 patients with a clinical diagnosis of SD, 25 patients with primary progressive aphasia with agrammatic and relatively nonfluent speech (PPA), and 25 patients with Alzheimer's disease (AD) with aphasia were studied longitudinally with the Western Aphasia Battery (WAB). The Auditory Word Recognition subtest of the WAB was utilised to assess comprehension of words derived from different semantic categories.

Outcomes & Results: The analysis revealed that, over time, category‐specific deficits of single‐word comprehension were seen in all three groups of patients. Participants with SD as well as those with PPA and AD were impaired on both pointing to fingers and the right–left orientation task. However, patients with SD were the only group that showed defective recognition of their own body parts. Interestingly, individuals with SD had no difficulties identifying colours, letters, and numbers, even during the follow‐up testing. In addition, in all three groups the extent of category‐specific deficits was associated with the severity of aphasia.

Conclusions: These results indicate that category‐specific deficits of single‐word comprehension are frequently seen not only in patients with SD but also in individuals with PPA or AD, and that the extent of these deficits is associated with the severity of aphasia. However, the pattern of these deficits is often different in these three forms of neurodegenerative conditions and more dissociations between semantic categories are observed as each of these diseases progresses.     

Understanding and living with primary progressive aphasia: Current progress and challenges for the future

Background: Primary progressive aphasia (PPA) is a progressive language disorder in which aphasia is the first and most prominent symptom of degenerative brain disease. PPA has received increasing attention in the scientific literature over the past 30 years, but there remains a relative lack of awareness and understanding of it in the wider clinical community. As editors of the volume, Clinical Perspectives on Primary Progressive Aphasia, we invited the contributing authors to provide an up-to-date survey of research on a range of topics that are relevant to clinical practice in PPA.

Aims: The aim of this article is to address some key questions that may arise when an individual receives a diagnosis of PPA and to direct readers to additional sources of information in this volume and elsewhere that will allow them to gain further knowledge about topics of interest.

Main Contribution: We address the following questions: (1) What is PPA? (2) How is PPA diagnosed? (3) What happens to a person’s language when they have PPA? (4) How will the disease progress over time? (5) How does PPA impact a person’s life and the life of their family and friends? (6) What treatments and support are available? (7) What other services should we be providing?

Conclusions: Considerable progress has been made in our understanding of PPA and the relationship between the symptomatology, progression, pathology, and genetics of PPA. However, there are many challenges remaining, particularly in terms of ensuring that people with PPA and their families and friends receive optimal information and support at diagnosis and appropriate interventions and/or management strategies throughout their journey with PPA.     

Relearning lost vocabulary in nonfluent progressive aphasia with MossTalk Words®

Background: The literature on aphasia has been growing rapidly, with reports of different therapeutic approaches for a post‐stroke anomia. While individuals with post‐stroke anomia frequently recover to some extent, the other end of the aphasia recovery continuum is occupied by those who experience relentless language dissolution as a result of progressive disorders such as primary progressive aphasia. One of the most recent additions to the field of aphasia rehabilitation is therapy whereby either part of or the entire therapy is administered via computer‐based programmes. There have been few treatment studies investigating the rehabilitation of language abilities in people with primary progressive aphasia (PPA).

Aims: The objectives of this investigation were to examine the ability of PPA individuals to relearn lost words and to determine the extent of benefits derived from MossTalk Words®, a computer‐based treatment for anomia.

Methods and Procedures: Using a multiple baseline across behaviours design, we explored treatment‐specific effects, maintenance, and generalisation of improvements derived from this therapy programme. Two participants with nonfluent PPA were treated, each on three lists of words for which low and stable baselines were first established. Sessions occurred two to three times a week. Treatment involved the presentation of a picture on the computer screen, with the participants being required to name it. Success in treatment was measured by probing list naming every second session. Once a participant attained 80% accuracy over two consecutive probes, or participated in 12 sessions (whichever occurred first), treatment of a list was terminated and the next list was started. Each participant was tested on all items immediately after therapy, and again 1 month later.

Outcomes and Results: Both participants improved their naming skills with the MossTalk Words®. P1 required only four sessions to reach the proposed criterion of 80% (up to 100%) correct on each list. The effects of treatment were maintained immediately and, to a lesser degree, 4 weeks later. P2 required all 12 sessions for each of the three lists. Results were variable immediately after testing, but seemingly maintained 4 weeks later.

Conclusions: The results demonstrate that both participants with primary progressive aphasia benefited (although to a different extent) from a computer‐based treatment for anomia. These results are encouraging and suggest that such a treatment may be a viable therapy approach for patients who suffer from PPA in the absence of a generalised cognitive impairment.     

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.     

SECT and MAST: new tests to assess grammatical abilities in primary progressive aphasia

Background: The presence/absence of agrammatism is critical for the classification of the different subtypes of primary progressive aphasia (PPA). Its quantitative evaluation is, however, a challenge in clinical practice because there are few brief, reliable, and easy-to-administer tests. Linguistic analysis of connected speech is the gold standard but is impractical outside the research setting.

Aims: To tackle the need for brief grammatical tests, we developed the SEntence Comprehension Test (with auditory and visual versions, SECT A and V) and the Make A Sentence Test (MAST).

Methods & Procedures: The tests were given to 92 participants (41 PPA patients, 21 Alzheimer’s disease patients, and 30 controls) from the Cambridge Longitudinal Study of PPA. Classification of the different subtypes of PPA was made purely on clinical assessment to avoid circularity from using the tests for diagnostic purposes. In addition, speech samples were recorded during a face-to-face semi-structured interview and all participants completed a standard neuropsychological battery as well as the three new tests.

Outcomes & Results: All patients were impaired relative to controls on the SECT A and V. After controlling for semantic impairment, only the mixed variant of PPA (mPPA) and the non-fluent variant of PPA were impaired on the MAST. When controlling for working memory in SECT A, the mPPA only remained impaired. Regression analyses demonstrated that performance on the SECT A and V, and the MAST, was strongly related to measures of the patients’ spontaneous speech, particularly the number of grammatical errors and the percentage of abandoned and elliptical sentences. Performance on the SECT A was also significantly predicted by speech rate.

Conclusion: The SECT and the MAST are brief tests capable of reflecting grammatical difficulty in spontaneous speech.     

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.     

The benefits and protective effects of behavioural treatment for dysgraphia in a case of primary progressive aphasia

Background: Spoken and written language difficulties are the predominant symptoms in the progressive neurodegenerative disease referred to as primary progressive aphasia (PPA). There has been very little research on the effectiveness of intervention on spoken language impairments in this context and none directed specifically at progressive written language impairment.

Aims: To examine the effectiveness of behavioural intervention for dysgraphia in a case of primary progressive aphasia.

Methods & Procedures: We carried out a longitudinal single‐case study that allowed us to examine the effectiveness of a non‐intensive spell‐study‐spell intervention procedure. We did so by comparing performance on four sets of words: trained, repeated, homework, and control words at five evaluations: baseline, during intervention, after the intervention, and at 6‐ and 12‐month follow‐up.

Outcomes & Results: We find that: (1) at the end of the intervention, Trained words show a small but statistically significant improvement relative to baseline and an advantage in accuracy over Control, Homework, and Repeated word sets. (2) All word sets exhibited a decline in accuracy from the end of treatment to the 6‐month follow‐up evaluation, consistent with the degenerative nature of the illness. Nonetheless, accuracy on Trained words continued to be superior to that of Control words and not statistically different from pre‐intervention baseline levels. (3) Repeated testing and practice at home yielded modest numerical advantages relative to Control words; but these differences were, for many comparisons, not statistically significant. (4) At 12 months post‐intervention, all words sets had significantly declined relative to pre‐intervention baselines and performance on the four sets was comparable.

Conclusions: This investigation documents—for the first time—that behavioural intervention can provide both immediate and short‐term benefits for dysgraphia in the context of primary progressive aphasia.     

The patterns of progression in primary progressive aphasia—Implications for assessment and management

Background: Primary progressive aphasia (PPA) is a progressive language disorder with preserved cognitive function for at least 2 years from onset. The main variants currently distinguished are: non-fluent/agrammatic (nfvPPA), semantic (svPPA), and logopenic (lvPPA). Patients with initial language presentation may subsequently develop other symptoms, such as behavioural dysfunction or apraxia. The clinical pattern of PPA depends on the location of atrophy, the underlying pathology, and the stage of the disease.

Aims: This review aims at characterising longitudinal changes in clinical presentations of different PPA variants and at presenting implications of these changes for the assessment, diagnosis, and management.

Main contribution: The three PPA variants differ not only in terms of language impairment, but also with regard to cognitive and behavioural profile. Apraxia and rigidity frequently occur in the course of nfvPPA. Patients with lvPPA seem to follow the pattern of aphasic Alzheimer’s disease, where language impairment is accompanied by episodic memory deficit. Individuals diagnosed with svPPA often develop behavioural dysfunction similar to that observed in behavioural variant of frontotemporal dementia.

Conclusions: Implications for patient care are dependent on PPA variant and on the stage of the disease. In svPPA, emphasis should be on the management of semantic and behavioural problems in daily life. Caregivers of nfvPPA patients should be informed about the possible emergence of apraxia and other movement disorders. In contrast, families of individuals with lvPPA should be made aware of and trained to cope with an episodic memory decline and possible progression to other varieties of PPA.     

Cognition and anatomy in three variants of primary progressive aphasia

We performed a comprehensive cognitive, neuroimaging, and genetic study of 31 patients with primary progressive aphasia (PPA), a decline in language functions that remains isolated for at least 2 years. Detailed speech and language evaluation was used to identify three different clinical variants: nonfluent progressive aphasia (NFPA; n = 11), semantic dementia (SD; n = 10), and a third variant termed logopenic progressive aphasia (LPA; n = 10). Voxel-based morphometry (VBM) on MRIs showed that, when all 31 PPA patients were analyzed together, the left perisylvian region and the anterior temporal lobes were atrophied. However, when each clinical variant was considered separately, distinctive patterns emerged: (1) NFPA, characterized by apraxia of speech and deficits in processing complex syntax, was associated with left inferior frontal and insular atrophy; (2) SD, characterized by fluent speech and semantic memory deficits, was associated with anterior temporal damage; and (3) LPA, characterized by slow speech and impaired syntactic comprehension and naming, showed atrophy in the left posterior temporal cortex and inferior parietal lobule. Apolipoprotein E epsilon4 haplotype frequency was 20% in NFPA, 0% in SD, and 67% in LPA. Cognitive, genetic, and anatomical features indicate that different PPA clinical variants may correspond to different underlying pathological processes.     

Biomarkers in the primary progressive aphasias

Background: Primary progressive aphasia (PPA) is a progressive disorder of language that is increasingly recognised as an important presentation of a specific spectrum of neurodegenerative conditions.

Aims: In an era of etiologically specific treatments for neurodegenerative conditions, it is crucial to establish the histopathologic basis for PPA. In this review, I discuss biomarkers for identifying the pathology underlying PPA.

Main Contribution: Clinical syndromes suggest a probabilistic association between a specific PPA variant and an underlying pathology, but there are also many exceptions. A considerable body of work with biomarkers is now emerging as an important addition to clinical diagnosis. I review genetic, neuroimaging and biofluid studies that can help determine the pathologic basis for PPA.

Conclusions: Together with careful clinical examination, there is great promise that supplemental biomarker assessments will lead to accurate diagnosis of the pathology associated with PPA during life and serve as the basis for clinical trials in this spectrum of disease.     

原发性进行性失语的临床、影像及语言特征

目的 探讨原发性进行性失语（PPA）的临床、影像及语言特征.方法 PPA患者7例,其中语义性痴呆（SD）6例,进行性非流利性失语（PNFA）1例,收集患者的人口学资料、病史,进行头MRI检查,采用汉语失语成套测验进行语言评估.结果 患者平均发病年龄56岁,均缓慢起病,以语言表达、命名障碍为首发症状.MRI示左侧颞极萎缩为主,病程长的患者左侧额叶和顶叶、右侧颞叶也明显萎缩.语言评估发现所有患者的自发语言、复述、命名、听理解、阅读和书写均不同程度损害.SD患者言语流利,复述、朗读能力下降相对较轻,命名、复杂语句的理解能力损害突出.PNFA言语顿挫吃力,患者列名能力明显下降,但命名相对保存完好.结论 PPA多为老年前期发病,语言障碍为最早、最突出的症状.MRI特征性的改变为额叶和颞极萎缩,左侧为著.其中SD表现为命名性失语和经皮质感觉性失语,PNFA表现为经皮质运动性失语的特征.     

Phonetic and phonological aspects of speech in Alzheimer’s disease

ABSTRACT

Background: Alzheimer’s disease (AD) can involve changes in communication and can lead to mutism in severe cases. Oral communication may be impaired by phonetic-motor disorders, such as apraxia of speech (AOS), or by language disorders, such as aphasia. Therefore, the identification of manifestations of AOS and phonemic paraphasias in patients with AD is critical to understanding the communication changes and determining the therapeutic planning.

Aims: To identify the distribution of phonetic–phonological manifestations in older patients with AD and healthy older subjects and assess whether these manifestations indicate the origin of the changes, including a predominantly phonetic-motor origin, a predominantly phonological–linguistic origin, or both.

Methods & Procedures: This cross-sectional study evaluated 90 patients with AD and 30 healthy older volunteers. All of the participants underwent the same repetition task for phonetic and phonological assessments using the current classification of phonetic–phonological manifestations; this classification distinguishes characteristics that are mostly related to AOS from other signs that are mostly related to aphasia. Negative binomial regression analysis was conducted to compare the amount of each manifestation presented by the two groups.

Outcomes & Results: The patients with AD showed significantly more signs of aphasia (self-correction, and vowel and consonant substitutions), AOS (prolonged intervals and extended vowel duration), and AOS or aphasia (distortion, omission, attempts at the syllable level, distorted substitutions, and additions) than the healthy older volunteers.

Conclusions: Older adults with AD presented phonetic and phonological changes of aphasia and AOS and, consequently, limitations in symbolic–linguistic planning and motor planning.     

Phonological encoding in apraxia of speech and aphasia

Background: Apraxia of speech (AOS) is considered a speech motor planning/programming disorder. While it is possible that co-occurring phonological impairments exist, the speech motor planning/programming deficit often makes it difficult to assess the phonological encoding stage directly. Studies using online methods have suggested that activation of phonological information may be protracted in AOS.

Aims: The present study was designed to investigate the integrity of the phonological encoding stage in AOS and aphasia. We tested two specific hypotheses, the Frame Hypothesis and the Segment Hypothesis. According to the Frame Hypothesis, speakers with AOS have an impairment in retrieving metrical frames (e.g., number of syllables); according to the Segment Hypothesis, speakers with AOS have an impairment in retrieving segments (e.g., consonants).

Methods & Procedures: Four individuals with AOS and varying degrees of aphasia, two speakers with aphasia, and 13 age-matched control speakers completed an online priming task in which participants name pictures in sets that do or do not share number of syllables (e.g., balcony-coconut-signature vs. balcony-carrot-sock), the initial consonant (e.g., carpenter-castle-cage vs. carpenter-beaver-sun), or both (e.g., boomerang-butterfly-bicycle vs. boomerang-sausage-cat). Error rates and reaction times were measured.

Outcomes & Results: Data for controls replicated previous literature. Reaction time data supported the Segment Hypothesis for speakers with AOS and for one speaker with aphasia without AOS, with no differences in pattern from controls for the other speaker with aphasia without AOS.

Conclusions: These results suggest that speakers with AOS may also have difficulties at the phonological encoding stage. Theoretical and clinical implications of these findings are discussed.     

The genetics of primary progressive aphasia

Background: Primary progressive aphasia (PPA) is a disorder in which language impairment is the initial and predominant symptom. Three main phenotypes are described, the nonfluent variant (nfvPPA), the semantic variant (svPPA) and the logopenic variant (lvPPA). Although PPA is most commonly a sporadic disorder, recent studies have shown an association of PPA with mutations in a number of genes.

Aims: To understand the extent to which PPA may be inherited, which genetic mutations may cause it, and whether the phenotypes of genetic PPA differ from sporadic PPA.

Main Contribution: In around 20–30% of patients with PPA, a family history is present although nfvPPA is more heritable than svPPA and lvPPA which are both usually sporadic disorders. Mutations in the progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72), genes are the major causes of genetic PPA.

Conclusions: Key pointers that may suggest testing for a GRN mutation in PPA are a family history of one of the disorders within the frontotemporal dementia spectrum, a nfvPPA phenotype, particularly if presenting with a prominent anomia and asymmetrical fronto-temporo-parietal atrophy. In someone with nfvPPA and a family history, GRN should be tested initially but a search for hexanucleotide repeat expansions in the C9orf72 gene should be performed if negative, particularly if there are features of motor neurone disease, or a family history of someone with motor neurone disease. Mutations in other genes are only very rare causes of PPA but if GRN and C9orf72 are both negative, testing for mutations in the microtubule-associated protein tau (MAPT), valosin-containing protein (VCP) and presenilin 1 (PSEN1) should be considered.     

Treating a semantic word production deficit in aphasia with verbal and gesture methods

Background: Classical aphasiology, based on the study of stroke sequelae, fuses speech fluency and grammatical ability. Nonfluent (Broca's) aphasia often is accompanied by agrammatism; whereas in the fluent aphasias grammatical deficits are not typical. The assumption that a similar relationship exists in primary progressive aphasia (PPA) has led to the dichotomisation of this syndrome into fluent and nonfluent subtypes.

Aims: This study compared elements of fluency and grammatical production in the narrative speech of individuals with PPA to determine if they can be dissociated from one another.

Methods &; Procedures: Speech samples from 37 individuals with PPA, clinically assigned to agrammatic (N?=?11), logopaenic (N?=?20), and semantic (N?=?6) subtypes, and 13 cognitively healthy control participants telling the “Cinderella Story” were analysed for fluency—i.e., words per minute (WPM) and mean length of utterance in words (MLU-W)—and grammaticality, i.e., the proportion of grammatically correct sentences, open-to-closed-class word ratio, noun-to-verb ratio, and correct production of verb inflection, noun morphology, and verb argument structure. Between-group differences were analysed for each variable. Correlational analyses examined the relation between WPM and each grammatical variable, and an off-line measure of sentence production.

Outcomes &; Results: Agrammatic and logopaenic groups both had lower scores on the fluency measures and produced significantly fewer grammatical sentences than did semantic and control groups. However, only the agrammatic group evinced significantly impaired production of verb inflection and verb argument structure. In addition some semantic participants showed abnormal open-to-closed and noun-to-verb ratios in narrative speech. When the sample was divided on the basis of fluency, all the agrammatic participants fell in the nonfluent category. The logopaenic participants varied in fluency but those with low fluency showed variable performance on measures of grammaticality. Correlational analyses and scatter plots comparing fluency and each grammatical variable revealed dissociations within PPA participants, with some nonfluent participants showing normal grammatical skill.

Conclusions: Grammatical production is a complex construct comprising correct usage of several language components, each of which can be selectively affected by disease. This study demonstrates that individuals with PPA show dissociations between fluency and grammatical production in narrative speech. Grammatical ability, and its relationship to fluency, varies from individual to individual, and from one variant of PPA to another, and can even be found in individuals with semantic PPA in whom a fluent aphasia is usually thought to accompany preserved ability to produce grammatical utterances.     

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.