The graded multidimensional geometry of phenotypic variation and progression in neurodegenerative syndromes.

Clinical variants of Alzheimer's disease and frontotemporal lobar degeneration display a spectrum of cognitive-behavioural changes varying between individuals and over time. Understanding the landscape of these graded individual-/group-level longitudinal variations is critical for precise phenotyping; however, this remains challenging to model. Addressing this challenge, we leverage the National Alzheimer's Coordinating Center database to derive a unified geometric framework of graded longitudinal phenotypic variation in Alzheimer's disease and frontotemporal lobar degeneration. We included three time-point, cognitive-behavioural and clinical data from 390 typical, atypical and intermediate Alzheimer's disease and frontotemporal lobar degeneration variants (114 typical Alzheimer's disease; 107 behavioural variant frontotemporal dementia; 42 motor variants of frontotemporal lobar degeneration; and 103 primary progressive aphasia patients). On this data, we applied advanced data-science approaches to derive low-dimensional geometric spaces capturing core features underpinning clinical progression of Alzheimer's disease and frontotemporal lobar degeneration syndromes. To do so, we first used principal component analysis to derive six axes of graded longitudinal phenotypic variation capturing patient-specific movement along and across these axes. Then, we distilled these axes into a visualisable 2D manifold of longitudinal phenotypic variation using Uniform Manifold Approximation and Projection. Both geometries together enabled the assimilation and inter-relation of paradigmatic and mixed cases, capturing dynamic individual trajectories, and linking syndromic variability to neuropathology and key clinical end-points such as survival. Through these low-dimensional geometries, we show that (i) specific syndromes (Alzheimer's disease and primary progressive aphasia) converge over time into a de-differentiated pooled phenotype, while others (frontotemporal dementia variants) diverge to look different from this generic phenotype; (ii) phenotypic diversification is predicted by simultaneous progression along multiple axes, varying in a graded manner between individuals and syndromes; and (iii) movement along specific principal axes predicts survival at 36 months in a syndrome-specific manner and in individual pathological groupings. The resultant mapping of dynamics underlying cognitive-behavioural evolution potentially holds paradigm-changing implications to predicting phenotypic diversification and phenotype-neurobiological mapping in Alzheimer's disease and frontotemporal lobar degeneration.

Clinical dimensions along the non-fluent variant primary progressive aphasia spectrum.

It is debated whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) belong to the same clinical spectrum, traditionally termed non-fluent/agrammatic variant primary progressive aphasia (nfvPPA), or exist as two completely distinct syndromic entities with specific pathologic/prognostic correlates. We analysed speech, language and disease severity features in a comprehensive cohort of patients with progressive motor speech impairment and/or agrammatism to ascertain evidence of naturally occurring, clinically meaningful non-overlapping syndromic entities (e.g. PPAOS and PAA) in our data. We also assessed if data-driven latent clinical dimensions with aetiologic/prognostic value could be identified. We included 98 participants, 43 of whom had an autopsy-confirmed neuropathological diagnosis. Speech pathologists assessed motor speech features indicative of dysarthria and apraxia of speech (AOS). Quantitative expressive/receptive agrammatism measures were obtained and compared with healthy controls. Baseline and longitudinal disease severity was evaluated using the Clinical Dementia Rating Sum of Boxes (CDR-SB). We investigated the data's clustering tendency and cluster stability to form robust symptom clusters and employed principal component analysis to extract data-driven latent clinical dimensions (LCD). The longitudinal CDR-SB change was estimated using linear mixed-effects models. Of the participants included in this study, 93 conformed to previously reported clinical profiles (75 with AOS and agrammatism, 12 PPAOS and six PAA). The remaining five participants were characterized by non-fluent speech, executive dysfunction and dysarthria without apraxia of speech or frank agrammatism. No baseline clinical features differentiated between frontotemporal lobar degeneration neuropathological subgroups. The Hopkins statistic demonstrated a low cluster tendency in the entire sample (0.45 with values near 0.5 indicating random data). Cluster stability analyses showed that only two robust subgroups (differing in agrammatism, executive dysfunction and overall disease severity) could be identified. Three data-driven components accounted for 71% of the variance [(i) severity-agrammatism; (ii) prominent AOS; and (iii) prominent dysarthria]. None of these data-driven LCDs allowed an accurate prediction of neuropathology. The severity-agrammatism component was an independent predictor of a faster CDR-SB increase in all the participants. Higher dysarthria severity, reduced words per minute and expressive and receptive agrammatism severity at baseline independently predicted accelerated disease progression. Our findings indicate that PPAOS and PAA, rather than exist as completely distinct syndromic entities, constitute a clinical continuum. In our cohort, splitting the nfvPPA spectrum into separate clinical phenotypes did not improve clinical-pathological correlations, stressing the need for new biological markers and consensus regarding updated terminology and clinical classification.

Artificial intelligence classifies primary progressive aphasia from connected speech.

Neurodegenerative dementia syndromes, such as Primary Progressive Aphasias (PPA), have traditionally been diagnosed based in part on verbal and nonverbal cognitive profiles. Debate continues about whether PPA is best divided into three variants and also regarding the most distinctive linguistic features for classifying PPA variants. In this cross-sectional study, we first harnessed the capabilities of artificial intelligence (AI) and Natural Language Processing (NLP) to perform unsupervised classification of short, connected speech samples from 78 PPA patients. We then used NLP to identify linguistic features that best dissociate the three PPA variants. Large Language Models (LLMs) discerned three distinct PPA clusters, with 88.5% agreement with independent clinical diagnoses. Patterns of cortical atrophy of three data-driven clusters corresponded to the localization in the clinical diagnostic criteria. In the subsequent supervised classification, seventeen distinctive features emerged, including the observation that separating verbs into high and low-frequency types significantly improves classification accuracy. Using these linguistic features derived from the analysis of short, connected speech samples, we developed a classifier that achieved 97.9% accuracy in classifying the four groups (three PPA variants and healthy controls). The data-driven section of this study showcases the ability of LLMs to find natural partitioning in the speech of patients with PPA consistent with conventional variants. In addition, the work identifies a robust set of language features indicative of each PPA variant, emphasizing the significance of dividing verbs into high and low-frequency categories. Beyond improving diagnostic accuracy, these findings enhance our understanding of the neurobiology of language processing.

Neural mechanisms of sentence production: a volumetric study of primary progressive aphasia.

Studies on the neural bases of sentence production have yielded mixed results, partly due to differences in tasks and participant types. In this study, 101 individuals with primary progressive aphasia (PPA) were evaluated using a test that required spoken production following an auditory prime (Northwestern Assessment of Verbs and Sentences-Sentence Production Priming Test, NAVS-SPPT), and one that required building a sentence by ordering word cards (Northwestern Anagram Test, NAT). Voxel-Based Morphometry revealed that gray matter (GM) volume in left inferior/middle frontal gyri (L IFG/MFG) was associated with sentence production accuracy on both tasks, more so for complex sentences, whereas, GM volume in left posterior temporal regions was exclusively associated with NAVS-SPPT performance and predicted by performance on a Digit Span Forward (DSF) task. Verb retrieval deficits partly mediated the relationship between L IFG/MFG and performance on the NAVS-SPPT. These findings underscore the importance of L IFG/MFG for sentence production and suggest that this relationship is partly accounted for by verb retrieval deficits, but not phonological loop integrity. In contrast, it is possible that the posterior temporal cortex is associated with auditory short-term memory ability, to the extent that DSF performance is a valid measure of this in aphasia.

A syntax-lexicon trade-off in language production.

Spoken language production involves selecting and assembling words and syntactic structures to convey one's message. Here we probe this process by analyzing natural language productions of individuals with primary progressive aphasia (PPA) and healthy individuals. Based on prior neuropsychological observations, we hypothesize that patients who have difficulty producing complex syntax might choose semantically richer words to make their meaning clear, whereas patients with lexicosemantic deficits may choose more complex syntax. To evaluate this hypothesis, we first introduce a frequency-based method for characterizing the syntactic complexity of naturally produced utterances. We then show that lexical and syntactic complexity, as measured by their frequencies, are negatively correlated in a large (n = 79) PPA population. We then show that this syntax-lexicon trade-off is also present in the utterances of healthy speakers (n = 99) taking part in a picture description task, suggesting that it may be a general property of the process by which humans turn thoughts into speech.

Binary reversals: a diagnostic sign in primary progressive aphasia.

BACKGROUND: Binary reversals (exemplified by 'yes'/'no' confusions) have been described in patients with primary progressive aphasia (PPA) but their diagnostic value and phenotypic correlates have not been defined. METHODS: We conducted a retrospective cohort study analysing demographic, clinical, neuropsychological, linguistic and behavioural data from patients representing all major PPA syndromes (non-fluent/agrammatic variant, nfvPPA; logopenic variant, lvPPA; semantic variant, svPPA) and behavioural variant frontotemporal dementia (bvFTD). The prevalence of binary reversals and behavioural abnormalities, illness duration, parkinsonian features and neuropsychological test scores were compared between neurodegenerative syndromes, and the diagnostic predictive value of binary reversals was assessed using logistic regression. RESULTS: Data were obtained for 83 patients (21 nfvPPA, 13 lvPPA, 22 svPPA, 27 bvFTD). Binary reversals occurred in all patients with nfvPPA, but significantly less frequently and later in lvPPA (54%), svPPA (9%) and bvFTD (44%). Patients with bvFTD with binary reversals had significantly more severe language (but not general executive or behavioural) deficits than those without reversals. Controlling for potentially confounding variables, binary reversals strongly predicted a diagnosis of nfvPPA over other syndromes. CONCLUSIONS: Binary reversals are a sensitive (though not specific) neurolinguistic feature of nfvPPA, and should suggest this diagnosis if present as a prominent early symptom.

Dysphagia in primary progressive aphasia: Clinical predictors and neuroanatomical basis.

BACKGROUND AND PURPOSE: Dysphagia is an important feature of neurodegenerative diseases and potentially life-threatening in primary progressive aphasia (PPA) but remains poorly characterized in these syndromes. We hypothesized that dysphagia would be more prevalent in nonfluent/agrammatic variant (nfv)PPA than other PPA syndromes, predicted by accompanying motor features, and associated with atrophy affecting regions implicated in swallowing control. METHODS: In a retrospective case-control study at our tertiary referral centre, we recruited 56 patients with PPA (21 nfvPPA, 22 semantic variant [sv]PPA, 13 logopenic variant [lv]PPA). Using a pro forma based on caregiver surveys and clinical records, we documented dysphagia (present/absent) and associated, potentially predictive clinical, cognitive, and behavioural features. These were used to train a machine learning model. Patients' brain magnetic resonance imaging scans were assessed using voxel-based morphometry and region-of-interest analyses comparing differential atrophy profiles associated with dysphagia presence/absence. RESULTS: Dysphagia was significantly more prevalent in nfvPPA (43% vs. 5% svPPA and no lvPPA). The machine learning model revealed a hierarchy of features predicting dysphagia in the nfvPPA group, with excellent classification accuracy (90.5%, 95% confidence interval = 77.9-100); the strongest predictor was orofacial apraxia, followed by older age, parkinsonism, more severe behavioural disturbance, and more severe cognitive impairment. Significant grey matter atrophy correlates of dysphagia in nfvPPA were identified in left middle frontal, right superior frontal, and right supramarginal gyri and right caudate. CONCLUSIONS: Dysphagia is a common feature of nfvPPA, linked to underlying corticosubcortical network dysfunction. Clinicians should anticipate this symptom particularly in the context of other motor features and more severe disease.

Symptom-based staging for logopenic variant primary progressive aphasia.

BACKGROUND AND PURPOSE: Logopenic variant primary progressive aphasia (lvPPA) is a major variant presentation of Alzheimer's disease (AD) that signals the importance of communication dysfunction across AD phenotypes. A clinical staging system is lacking for the evolution of AD-associated communication difficulties that could guide diagnosis and care planning. Our aim was to create a symptom-based staging scheme for lvPPA, identifying functional milestones relevant to the broader AD spectrum. METHODS: An international lvPPA caregiver cohort was surveyed on symptom development under an 'exploratory' survey (34 UK caregivers). Feedback from this survey informed the development of a 'consolidation' survey (27 UK, 10 Australian caregivers) in which caregivers were presented with six provisional clinical stages and feedback was analysed using a mixed-methods approach. RESULTS: Six clinical stages were endorsed. Early symptoms included word-finding difficulty, with loss of message comprehension and speech intelligibility signalling later-stage progression. Additionally, problems with hearing in noise, memory and route-finding were prominent early non-verbal symptoms. 'Milestone' symptoms were identified that anticipate daily-life functional transitions and care needs. CONCLUSIONS: This work introduces a new symptom-based staging scheme for lvPPA, and highlights milestone symptoms that could inform future clinical scales for anticipating and managing communication dysfunction across the AD spectrum.

Comprehension of acoustically degraded speech in Alzheimer's disease and primary progressive aphasia.

Successful communication in daily life depends on accurate decoding of speech signals that are acoustically degraded by challenging listening conditions. This process presents the brain with a demanding computational task that is vulnerable to neurodegenerative pathologies. However, despite recent intense interest in the link between hearing impairment and dementia, comprehension of acoustically degraded speech in these diseases has been little studied. Here we addressed this issue in a cohort of 19 patients with typical Alzheimer's disease and 30 patients representing the three canonical syndromes of primary progressive aphasia (non-fluent/agrammatic variant primary progressive aphasia; semantic variant primary progressive aphasia; logopenic variant primary progressive aphasia), compared to 25 healthy age-matched controls. As a paradigm for the acoustically degraded speech signals of daily life, we used noise-vocoding: synthetic division of the speech signal into frequency channels constituted from amplitude-modulated white noise, such that fewer channels convey less spectrotemporal detail thereby reducing intelligibility. We investigated the impact of noise-vocoding on recognition of spoken three-digit numbers and used psychometric modelling to ascertain the threshold number of noise-vocoding channels required for 50% intelligibility by each participant. Associations of noise-vocoded speech intelligibility threshold with general demographic, clinical and neuropsychological characteristics and regional grey matter volume (defined by voxel-based morphometry of patients' brain images) were also assessed. Mean noise-vocoded speech intelligibility threshold was significantly higher in all patient groups than healthy controls, and significantly higher in Alzheimer's disease and logopenic variant primary progressive aphasia than semantic variant primary progressive aphasia (all P < 0.05). In a receiver operating characteristic analysis, vocoded intelligibility threshold discriminated Alzheimer's disease, non-fluent variant and logopenic variant primary progressive aphasia patients very well from healthy controls. Further, this central hearing measure correlated with overall disease severity but not with peripheral hearing or clear speech perception. Neuroanatomically, after correcting for multiple voxel-wise comparisons in predefined regions of interest, impaired noise-vocoded speech comprehension across syndromes was significantly associated (P < 0.05) with atrophy of left planum temporale, angular gyrus and anterior cingulate gyrus: a cortical network that has previously been widely implicated in processing degraded speech signals. Our findings suggest that the comprehension of acoustically altered speech captures an auditory brain process relevant to daily hearing and communication in major dementia syndromes, with novel diagnostic and therapeutic implications.

The right hemisphere's capacity for language: evidence from primary progressive aphasia.

The role of the right hemisphere (RH) in core language processes is still a matter of intense debate. Most of the relevant evidence has come from studies of gray matter, with relatively little research on RH white matter (WM) connectivity. Using Diffusion Tensor Imaging-based tractography, the current work examined the role of the two hemispheres in language processing in 33 individuals with Primary Progressive Aphasia (PPA), aiming to better characterize the contribution of the RH to language processing in the context of left hemisphere (LH) damage. The findings confirm the impact of PPA on the integrity of the WM language tracts in the LH. Additionally, an examination of the relationship between tract integrity and language behaviors provides robust evidence of the involvement of the WM language tracts of both hemispheres in language processing in PPA. Importantly, this study provides novel evidence of a unique contribution of the RH to language processing (i.e. a contribution independent from that of the language-dominant LH). Finally, we provide evidence that the RH contribution is specific to language processing rather than being domain general. These findings allow us to better characterize the role of RH in language processing, particularly in the context of LH damage.

The production of adjectives in narratives by individuals with primary progressive aphasia.

Adjectives (e.g., hungry) are an important part of language, but have been little studied in individuals with impaired language. Adjectives are used in two different ways in English: attributively, to modify a noun (the hungry dog); or predicatively, after a verb (the dog is hungry). Attributive adjectives have a more complex grammatical structure than predicative adjectives, and may therefore be particularly prone to disruption in individuals with grammatical impairments. We investigated adjective production in three subtypes of primary progressive aphasia (PPA: agrammatic, semantic, logopenic), as well as in agrammatic stroke aphasia and a group of healthy control participants. Participants produced narratives based on picture books, and we coded every adjective they produced for its syntactic structure. Compared to healthy controls, the two agrammatic groups, but not the other two patient groups, produced significantly fewer attributive adjectives per sentence. All four patient groups were similar to controls for their rate of predicative adjective production. In addition, we found a significant correlation in the agrammatic PPA participants between their rate of producing attributive adjective and impaired production of sentences with complex syntactic structure (subject cleft sentences like It was the boy that chased the girl); no such correlation was found for predicative adjectives. Irrespective of structure, we examined the lexical characteristics of the adjectives that were produced, including length, frequency, semantic diversity and neighborhood density. Overall, the lexical characteristics of the produced adjectives were largely consistent with the language profile of each group. In sum, the results suggest that attributive adjectives present a particular challenge for individuals with agrammatic language production, and add a new dimension to the description of agrammatism. Our results further suggest that attributive adjectives may be a fruitful target for improved treatment and recovery of agrammatic language.

Awareness and knowledge of dementia and its communication disorders amongst Brazilian speech and language therapists.

BACKGROUND: Speech and language therapists (SLTs) play an important role in assessing and rehabilitating communication disorders in people with dementia, but there is evidence to suggest that they do not receive appropriate training to provide management and support during their training. AIM: To investigate the level of awareness and knowledge that practising SLTs from Brazil have about dementia and their role in the care of dementia through an online survey. METHODS & PROCEDURES: An online survey tool was developed to collect information from practising Brazilian SLTs regarding their knowledge about dementia, awareness about their role in the care of people with dementia, and opinions on how SLTs may be better prepared to work in the dementia field. The survey was disseminated via social media, websites, and e-mail lists of researchers and stakeholders. OUTCOMES & RESULTS: A total of 227 SLTs completed the survey. Participants showed good knowledge of dementia in general, while their answers were less accurate on primary progressive aphasia. Regarding the awareness by SLTs of their role in the care of people with dementia, most agreed or strongly agreed that SLTs could help people in the diagnosis, treatment and prevention of dementia (> 80%). However, fewer participants agreed or strongly agreed that they felt confident in contributing to the treatment and diagnosis process of dementia (about 50%). To improve the training of SLTs in Brazil, most participants believed that it would be necessary to improve the teaching of dementia at the undergraduate speech and language therapy curriculum level and to develop recommendations or guidelines about speech and language therapy practice in dementia. CONCLUSIONS & IMPLICATIONS: The results of this survey point to a need for improvement in the knowledge and confidence of Brazilian SLTs about dementia. To reach this goal, targeted training courses and applied practice opportunities should be embedded within university curricula and training programmes. WHAT THIS PAPER ADDS: What is already known on the subject Many studies confirm the importance of speech and language therapy in the non-pharmacological treatment of people with dementia. However, other evidence suggests to a possible lack of training for Brazilian SLTs, especially in the curriculum of undergraduate courses. What this paper adds to existing knowledge This study reveals that Brazilian SLTs have substantial knowledge of dementia and recognize the significance of their role in treating people with dementia. However, a minority expressed confidence in their ability to assess and treat people with dementia. What are the potential or actual clinical implications of this work? The findings of this research demonstrate that Brazilian SLTs have good knowledge of dementia and endorse their professional role in dementia care; however, they lack confidence in their own skills and expertise in diagnostic assessment and treatment of dementia. Interventions aimed at boosting the SLT's confidence level could lead to improved patients outcomes and overall quality of care within clinical settings.

?It's all communication': Family members' perspectives on the communication needs for themselves and their relatives with primary progressive aphasia.

BACKGROUND: Communication disabilities, such as primary progressive aphasia (PPA), impact family members as well as the individuals with the condition. To provide adequate communication care to people with PPA (PwPPA) and their family members, it is crucial to understand the communication needs from the family members' perspectives. To date, research on the communication needs of people with primary progressive aphasia and their family members from the perspectives of family members has been limited. AIMS: The specific research objectives were to explore (a) the communication needs pertaining to PwPPA in the early, middle and late stages; and (b) the communication needs pertaining to family members of PwPPA in the early, middle and late stages, from the perspectives of family members. METHODS & PROCEDURES: This study employed a qualitative description approach, underpinned by the pragmatic paradigm. Data collection involved semi-structured qualitative interviews with eight family members (relatives of four individuals with the logopenic variant of PPA, of two individuals with the nonfluent variant of PPA, of one individual with the semantic variant of PPA and of one individual with mixed PPA). Qualitative content analysis was used to identify codes and categories in relation to the research objectives. OUTCOMES & RESULTS: Qualitative content analysis revealed eight categories of communication needs pertaining to the PwPPA: person-specific needs; diagnosis and disclosure; general communication difficulties; impact on communication in everyday life; impact on cognition; impact on psychosocial well-being; impact on person's dignity and autonomy; and future planning. Six categories were identified pertaining to the family members: information about and awareness of PPA; impact of communication difficulties on family/others; increased responsibilities for the family in everyday life; impact on psychosocial well-being; and future planning. CONCLUSIONS & IMPLICATIONS: This investigation has expanded our knowledge in the area by providing insights about communication needs which speech-language pathologists and other health professionals should be aware of and take into account when providing communication care to PwPPA and their families. WHAT THIS PAPER ADDS: What is already known on the subject Person- and family-centred communication care is optimally guided by the person's and family's needs and values. Research on communication care for people with primary progressive aphasia has underscored the inclusion of family members. Previous research has investigated the impact and experiences of living with primary progressive aphasia from the family member perspective. What this paper adds to existing knowledge To date, research focusing on identifying the communication needs of people with primary progressive aphasia and their family members from the perspective of family members is limited. This study adds the family members' perspectives on the communication needs pertaining to themselves and their relatives with primary progressive aphasia in the early, middle and late stages of primary progressive aphasia. What are the potential or clinical implications of this work? Several clinical implications have been raised. Family members experience communication needs for themselves and should be included as recipients of communication care. Clinicians supporting people with primary progressive aphasia should be cognizant of the impact of communication fatigue on everyday life and therapy tasks. Communication care for this population should include communication partner training, support for psychosocial well-being and support with communication around future planning.

Positive effects of speech and language therapy group interventions in primary progressive aphasia: A systematic review.

BACKGROUND: Primary progressive aphasia (PPA) is a neurodegenerative condition characterised by a prominent and progressive deterioration in language abilities, which significantly impacts quality of life and interpersonal relationships. Speech and language therapy plays a crucial role in offering interventions. Group intervention is one mode of delivery that could benefit communication functioning and overall wellbeing of people with PPA (pwPPA) and their care partners. Group interventions are also more efficient than one-to-one intervention and may facilitate peer support. AIMS: The aim of this review was to systematically evaluate the current evidence for the effectiveness of speech and language therapy groups for pwPPA and their care partners. Specifically, this paper considered three questions: 1.What evidence-based speech and language therapy groups for pwPPA and their care partners have been reported to date? 2.Are group communication interventions effective in improving quality of life and communication function for pwPPA and their care partners? 3.Are group communication interventions that are designed for people with communication difficulties of other aetiologies (such as stroke) effective for pwPPA? In addition, this review aimed to describe the structure and content of groups, including aims, disciplines involved, size and frequency of group meetings, and outcome measures. METHODS: MEDLINE, CINAHL and PsycINFO were used to retrieve articles of interest. A total of 10 studies published between 2009 and 2022 met the eligibility criteria and therefore were included in this study. Data were extracted from the articles regarding the structure and content of groups. MAIN CONTRIBUTION: Although evidence is currently limited, results suggest that speech and language therapy group intervention can improve specific linguistic processes, the use of communication strategies and psychosocial well-being. The importance of multidisciplinary input and care partners' involvement in groups was highlighted, along with the benefits of creative non-verbal activities as tools for self-expression. There is also initial evidence that telehealth group provision and one-off group sessions may be feasible and can benefit psychosocial well-being. Lastly, intentional recruitment and explicit education on different aphasia types are described as important when pwPPA participate in groups with mixed diagnoses. CONCLUSIONS: The literature on speech and language therapy group interventions for PPA shows promise of positive effects on communication function and psychosocial well-being of both pwPPA and their care partners. Speech and language therapists can consider these published interventions when designing and implementing similar groups, but more robust evidence is required to confirm the relative effectiveness of this approach. WHAT THIS PAPER ADDS: What is already known on this subject Speech pathology led group intervention shows some promise in benefitting communication functioning and overall well-being of pwPPA and their carers, but there has been no systematic evaluation of all the evidence regarding the efficacy of speech and language therapy led groups. Establishing feasibility, acceptability and efficacy of speech and language therapy group interventions for pwPPA and their carers may present a valuable addition for managing this progressive language disability. What this paper adds to existing knowledge Although evidence is currently limited, results from this systematic review suggest that speech and language therapy led group intervention can improve specific linguistic processes, the use of communication strategies and psychosocial well-being for pwPPA and their carers. The importance of multidisciplinary input and carers' involvement in groups was highlighted, along with the benefits of creative non-verbal activities as tools for self-expression. There is also initial evidence that telehealth group provision for carers may be feasible and can benefit psychosocial wellbeing. Lastly, intentional recruitment and explicit education on different aphasia types are described as important when pwPPA participate in groups with mixed diagnoses. What are the potential or actual clinical implications of this work? A synthesis of the evidence base for speech and language therapy led PPA groups, as well as a description of the group components and formats, will be valuable for clinical service planning, and will guide future examination of group options for pwPPA and their carers. Speech and language therapists can also consider the research findings from this systematic review when designing and implementing similar groups in their local context.

Comparing high definition transcranial direct current stimulation to left temporoparietal junction and left inferior frontal gyrus for logopenic primary progressive aphasia: A single-case study.

Logopenic variant primary progressive aphasia (lvPPA) is characterized by word-finding deficits and phonologic errors in fluent speech. Transcranial direct current stimulation (tDCS) targeting either left temporoparietal junction (TPJ) or left inferior frontal gyrus (IFG) show evidence of improving language function in lvPPA. The present case study evaluated the effects of two separate rounds of high definition tDCS (HD-tDCS) (4 mA; 30 sessions) on language and functional neuroimaging in a 57-year-old woman with lvPPA. Stimulation was centred on two different regions across rounds: (1) left TPJ, and (2) left (IFG). Results showed an improved proportion of content to floorholder words during a naturalistic speech task through both rounds as well as change in confrontation naming after TPJ (improvement) and IFG (worsened) stimulation. fMRI connectivity during task showed left lateralized positive correlations following round 1 and anti-correlations with components of the default mode network following round 2. Resting state segregation of a language-associated functional network increased following both rounds, and task-based segregation of the same network increased following IFG stimulation. These results suggest that stimulation to both regions using HD-tDCS may improve language function in lvPPA, while simultaneously eliciting widespread changes beyond the targeted area in neuronal activity and functional connectivity.

Smartphone use as an efficient tool to improve anomia in primary progressive aphasia.

Cognitive interventions are helpful in the non-pharmacological management of Primary progressive aphasia (PPA) and other neurodegenerative disorders of cognition, by helping patients to compensate for their cognitive deficits and improve their functional independence. In this study, we examined the effectiveness of cognitive rehabilitation based on the use of mobile device technology in PPA. The aim of this research study was to determine if BL, a patient with semantic variant PPA (svPPA) and severe anomia, was able to learn using specific smartphone functions and an application to reduce her word finding difficulties. She was trained during the intervention sessions on a list of target pictures to measure changes in picture naming performance. Errorless learning was applied during learning. BL quickly learned to use smartphone functions and the application over the course of the intervention. She significantly improved her anomia for trained pictures, and to a lesser extent for untrained semantically related pictures. Picture naming performance was maintained six months after the intervention, and she continued to use her smartphone regularly to communicate with family members and friends. This study confirms that smartphone use can be learned in PPA, which can help reduce the symptoms of anomia and improve communication skills.

More than a piece of cake: Noun classifier processing in primary progressive aphasia.

INTRODUCTION: Clinical understanding of primary progressive aphasia (PPA) has been primarily derived from Indo-European languages. Generalizing certain linguistic findings across languages is unfitting due to contrasting linguistic structures. While PPA patients showed noun classes impairments, Chinese languages lack noun classes. Instead, Chinese languages are classifier language, and how PPA patients manipulate classifiers is unknown. METHODS: We included 74 native Chinese speakers (22 controls, 52 PPA). For classifier production task, participants were asked to produce the classifiers of high-frequency items. In a classifier recognition task, participants were asked to choose the correct classifier. RESULTS: Both semantic variant (sv) PPA and logopenic variant (lv) PPA scored significantly lower in classifier production task. In classifier recognition task, lvPPA patients outperformed svPPA patients. The classifier production scores were correlated to cortical volume over left temporal and visual association cortices. DISCUSSION: This study highlights noun classifiers as linguistic markers to discriminate PPA syndromes in Chinese speakers. HIGHLIGHTS: Noun classifier processing varies in the different primary progressive aphasia (PPA) variants. Specifically, semantic variant PPA (svPPA) and logopenic variant PPA (lvPPA) patients showed significantly lower ability in producing specific classifiers. Compared to lvPPA, svPPA patients were less able to choose the accurate classifiers when presented with choices. In svPPA, classifier production score was positively correlated with gray matter volume over bilateral temporal and left visual association cortices in svPPA. Conversely, classifier production performance was correlated with volumetric changes over left ventral temporal and bilateral frontal regions in lvPPA. Comparable performance of mass and count classifier were noted in Chinese PPA patients, suggesting a common cognitive process between mass and count classifiers in Chinese languages.

Symptom-led staging for semantic and non-fluent/agrammatic variants of primary progressive aphasia.

INTRODUCTION: Here we set out to create a symptom-led staging system for the canonical semantic and non-fluent/agrammatic variants of primary progressive aphasia (PPA), which present unique diagnostic and management challenges not well captured by functional scales developed for Alzheimer's disease and other dementias. METHODS: An international PPA caregiver cohort was surveyed on symptom development under six provisional clinical stages and feedback was analyzed using a mixed-methods sequential explanatory design. RESULTS: Both PPA syndromes were characterized by initial communication dysfunction and non-verbal behavioral changes, with increasing syndromic convergence and functional dependency at later stages. Milestone symptoms were distilled to create a prototypical progression and severity scale of functional impairment: the PPA Progression Planning Aid ("PPA-Squared"). DISCUSSION: This work introduces a symptom-led staging scheme and functional scale for semantic and non-fluent/agrammatic variants of PPA. Our findings have implications for diagnostic and care pathway guidelines, trial design, and personalized prognosis and treatment for PPA. HIGHLIGHTS: We introduce new symptom-led perspectives on primary progressive aphasia (PPA). The focus is on non-fluent/agrammatic (nfvPPA) and semantic (svPPA) variants. Foregrounding of early and non-verbal features of PPA and clinical trajectories is featured. We introduce a symptom-led staging scheme for PPA. We propose a prototype for a functional impairment scale, the PPA Progression Planning Aid.

Distinct neurophysiology during nonword repetition in logopenic and non-fluent variants of primary progressive aphasia.

Overlapping clinical presentations in primary progressive aphasia (PPA) variants present challenges for diagnosis and understanding pathophysiology, particularly in the early stages of the disease when behavioral (speech) symptoms are not clearly evident. Divergent atrophy patterns (temporoparietal degeneration in logopenic variant lvPPA, frontal degeneration in nonfluent variant nfvPPA) can partially account for differential speech production errors in the two groups in the later stages of the disease. While the existing dogma states that neurodegeneration is the root cause of compromised behavior and cortical activity in PPA, the extent to which neurophysiological signatures of speech dysfunction manifest independent of their divergent atrophy patterns remain unknown. We test the hypothesis that nonword deficits in lvPPA and nfvPPA arise from distinct patterns of neural oscillations that are unrelated to atrophy. We use a novel structure-function imaging approach integrating magnetoencephalographic imaging of neural oscillations during a non-word repetition task with voxel-based morphometry-derived measures of gray matter volume to isolate neural oscillation abnormalities independent of atrophy. We find reduced beta band neural activity in left temporal regions associated with the late stages of auditory encoding unique to patients with lvPPA and reduced high-gamma neural activity over left frontal regions associated with the early stages of motor preparation in patients with nfvPPA. Neither of these patterns of reduced cortical oscillations was explained by cortical atrophy in our statistical model. These findings highlight the importance of structure-function imaging in revealing neurophysiological sequelae in early stages of dementia when neither structural atrophy nor behavioral deficits are clinically distinct.

Unravelling neurotransmitters impairment in primary progressive aphasias.

Primary progressive aphasias (PPAs) are a group of neurodegenerative diseases mainly characterized by language impairment, and with variably presence of dysexecutive syndrome, behavioural disturbances and parkinsonism. Detailed knowledge of neurotransmitters impairment and its association with clinical features hold the potential to develop new tailored therapeutic approaches. In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of magnetic resonance imaging (MRI)-based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmission. We included 103 PPA patients and 80 age-matched healthy controls (HC). We tested if the spatial patterns of grey matter volume (GMV) alterations in PPA patients (relative to HC) are correlated with specific neurotransmitter systems. As compared to HC, voxel-based brain changes in PPA were significantly associated with spatial distribution of serotonin, dopamine, and glutamatergic pathways (p < .05, False Discovery Rate corrected-corrected). Disease severity was negatively correlated with the strength of GMV colocalization of D1 receptors (p = .035) and serotonin transporter (p = .020). Moreover, we observed a significant negative correlation between positive behavioural symptoms, as measured with Frontal Behavioural Inventory, and GMV colocalization of D1 receptors (p = .007) and serotonin transporter (p < .001). This pilot study suggests that JuSpace is a helpful tool to indirectly assess neurotransmitter deficits in neurodegenerative dementias and may provide novel insight into disease mechanisms and associated clinical features.