Primary Progressive Aphasia Group Research Articles

Everyday Memory Disturbance in Primary Progressive Aphasia

Introduction: Mounting evidence indicates distinct memory profiles among the primary progressive aphasia (PPA) variants. Neuropsychological tests reveal disproportionate memory impairments in the logopenic variant PPA (lv-PPA) relative to the non-fluent variant PPA (nfv-PPA) and semantic variant PPA (sv-PPA). The real-world experience of day-to-day memory disturbances in PPA, however, remains poorly understood. Methods: Everyday expressions of memory in 26 lv-PPA, 24 nfv-PPA, and 40 sv-PPA patients, and 70 healthy controls were examined using the Cambridge Behavioural Inventory-Revised (CBI-R) carer questionnaire. Kruskal-Wallis tests compared CBI-R Memory items (1–8) across groups. Receiver operating characteristic curves evaluated the most discriminative items to distinguish lv-PPA from nfv-PPA. Results: Compared to controls, lv-PPA and sv-PPA patients were reported to experience more day-to-day memory issues (item 1), increased repetition of questions (2), forgetting the names of familiar people and objects (4, 5), and poor concentration (6). lv-PPA patients were also reported to exhibit more occurrences of losing or misplacing items (3) and forgetting the day (7). All PPA groups experienced more confusion in unfamiliar environments (8) than controls. Direct comparisons among PPA groups revealed distinct profiles, with lv-PPA and sv-PPA patients exhibiting more frequent forgetting of names and objects (3, 4) than nfv-PPA, and sv-PPA demonstrating greater day-to-day memory impairment (1), repeated questions (2), and poor concentration (6) compared to nfv-PPA. Forgetting the names of familiar objects (5) was the most sensitive and specific item to distinguish lv-PPA from nfv-PPA. Conclusions: Our findings demonstrate distinct day-to-day memory profiles in PPA. Future research should explore the influence of language impairments on these profiles.

Dysfluency in primary progressive aphasia: Temporal speech parameters

ABSTRACT Analysing spontaneous speech in individuals experiencing fluency difficulties holds potential for diagnosing speech and language disorders, including Primary Progressive Aphasia (PPA). Dysfluency in the spontaneous speech of patients with PPA has mostly been described in terms of abnormal pausing behaviour, but the temporal features related to speech have drawn little attention. This study compares speech-related fluency parameters in the three main variants of PPA and in typical speech. Forty-three adults participated in this research, thirteen with the logopenic variant of PPA (lvPPA), ten with the non-fluent variant (nfvPPA), nine with the semantic variant (svPPA), and eleven who were healthy age-matched adults. Participants’ fluency was assessed through a picture description task from which 42 parameters were computed including syllable duration, speaking pace, the duration of speech chunks (i.e. interpausal units, IPU), and the number of linguistic units per IPU and per second. The results showed that each PPA variant exhibited abnormal speech characteristics reflecting various underlying factors, from motor speech deficits to higher-level issues. Out of the 42 parameters considered, 37 proved useful for characterising dysfluency in the three main PPA variants and 35 in distinguishing among them. Therefore, taking into account not only pausing behaviour but also temporal speech parameters can provide a fuller understanding of dysfluency in PPA. However, no single parameter by itself sufficed to distinguish one PPA group from the other two, further evidence that dysfluency is not dichotomous but rather multidimensional, and that complementary multiparametric analyses are needed.

Assessing informativeness in Spanish-speaking individuals with primary progressive aphasia

ABSTRACT Background Primary progressive aphasia (PPA) is a neurodegenerative disorder associated with atrophy of the frontotemporal region. It is primarily characterized by language impairments that become accentuated over time, often leading to isolation and social exclusion. There are three main subtypes, the semantic (svPPA), non-fluent (nfvPPA), and logopenic (lvPPA) variants, each presenting distinct language deficits, as captured by standard assessment batteries. However, such assessments often fail to adequately identify functional communication (dis)abilities in everyday life, which is crucial for effective diagnosis and treatment. One understudied aspect of communication is informativeness, the conveyance of an appropriate amount of information in an efficient fashion. Aim This study aimed to identify the unique features of each variant of PPA that distinguish it from healthy controls, and the dissimilarity across PPA groups, in terms of the effectiveness and efficiency with which Spanish-speaking individuals with PPA conveyed information. Methods and procedures Thirty-two Spanish-speaking patients with one of the three variants of PPA and 11 healthy individuals were audio-recorded performing a picture description task. The resulting recordings were transcribed, and the contents labelled according to whether they constituted relevant or off-topic content, each type of content being further divided into subcategories. In total, 51 parameters related to the (1) overall amount of speech and number of correct information units, (2) amount of relevant content, (3) completeness of the content, and (4) off-topic information were considered. Nonparametric analyses were conducted to assess the divergence from heathy controls of each PPA group, and the dissimilarity across PPA groups. Outcomes and results Results revealed disruptions in informativeness in all PPA variants compared to controls, with lvPPA characterized by inadequate content and a high concentration of off-topic elements, nfvPPA by inadequate content but efficient delivery, and svPPA by inadequate content delivered inefficiently. Conclusions This study revealed that all three variants of PPA are characterized by reduced informativeness, although each exhibits unique patterns in communicative efficiency and the presence of off-topic information. By assessing the total amount of relevant speech, efficiency in conveying content, and the presence of off-topic elements, this research enhances our understanding of the distinct communication impairments characterizing lvPPA, nfvPPA, and svPPA, and provides valuable insights that can be applied to developing tailored remedial strategies.

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

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. 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. 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. 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. 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 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.

Dyslexia phenotypes in Chinese‐speaking individuals with Primary Progressive Aphasia

AbstractBackgroundThere are more than 7,000 living languages worldwide with wide heterogeneities in their linguistic features. Varying dementia symptomatology has been noted across speakers of different languages. Chinese languages adopt logographic scripts that contrast greatly from Indo‐European languages with alphabetic writing systems. For instance, Chinese characters have weak grapheme‐phoneme correspondence, with only 19‐ 39% pronounced per their phonetic components. Chinese characters also have 20 different spatial configurations with varying visuospatial complexity and abundant heteronyms. Past literature has focused on the reading presentations of primary progressive aphasia (PPA) patients that adopt Indo‐European languages. This study outlined the reading presentations of Chinese‐speaking PPA patients.MethodThe CLAP (Chinese Language Assessment for PPA) battery is designed to characterize the neurolinguistics features of Chinese‐speaking PPA individuals. In CLAP character reading test, participants are tasked to read aloud 50 Chinese characters that vary in lexicality (pictographic, regular compound, and irregular compound characters), character frequency and concreteness. Voxel‐based morphometry(VBM) was performed to examine the neural basis of reading performance. Participants are also tasked with reading pairs of compound words with heteronyms (e.g., “bow tie” vs “bow down).ResultsA total of 15 Mandarin‐speaking controls and 38 PPA individuals [6 nonfluent variant (nfv) PPA, 9 semantic variant (sv) PPA and 23 logopenic variant (lv) PPA] completed CLAP reading task. In character reading test, svPPA scored significantly lower than controls and nfvPPA (pictographic: p = 0.026; regular compound: p = 0.007; irregular compound characters: p<0.001). Regardless of lexicality, the reading score significantly correlated with volumetric changes over left temporal pole. While over‐regularization errors/surface dyslexia was the most common reading error across control and PPA groups, it was not specific to svPPA (p = 0.109). Conversely, on heteronym word reading test, svPPA and lvPPA scored significantly lower in accuracy, with over‐regularization errors more frequently noted in svPPA group.ConclusionContrary to English svPPA patients that struggled specifically with irregular word reading and showed frequent surface dyslexia, Chinese PPA patients showed no variant‐specific differences across lexicality, and svPPA‐specific over‐regularization phenomenon were found at the lexical (i.e., heteronym‐reading) and not sub‐lexical reading. Diagnostic criteria for PPA syndrome vary with languages and should ideally be tailored linguistically.

56 Stereological Densities of Neuronal Tau Inclusions in Corticobasal Degeneration are Anatomically Distinct in PPA vs bvFTD

Objective:Primary progressive aphasia (PPA) is a dementia syndrome characterized early in its course by gradual dissolution of language and is associated with asymmetric atrophy in the language-dominant hemisphere (usually left). In contrast, behavioral variant frontotemporal dementia (bvFTD) is a dementia syndrome characterized by a progressive early decline in personality and comportment and is associated with relatively symmetric or rightward predominant bifrontal atrophy. This study analyzed the regional and hemispheric distributions of neuronal tau inclusions of the corticobasal degeneration variant of FTLD-tau pathology (FTLD-CBD) in individuals with PPA or bvFTD. The goal was to establish clinicopathologic concordance between FTLD-CBD and behavioral/comportmental vs aphasic dementia syndromes.Participants and Methods:Seven participants were clinically diagnosed with PPA and 6 were diagnosed with bvFTD. All had FTLD-CBD as the principal neuropathologic diagnosis at postmortem study. Sections from the following cortical regions were stained immunohistochemically with AT-8 to visualize neuronal tau inclusions: bilateral middle frontal gyrus (MFG), inferior parietal lobule (IPL), superior temporal gyrus (STG); and unilateral occipital cortex (OCC). Bilateral anterior temporal lobes (ATL) were analyzed in PPA cases only. Unbiased stereological analysis was performed to compare regional and hemispheric distributions between and within PPA vs. bvFTD groups.Results:Overall neocortical (MFG+STG+IPL) tau densities were significantly greater in the PPA group compared to the bvFTD group (p<0.05). Within the bvFTD group, the highest densities of tau inclusions were observed in the right MFG (mean=6,871.17; SD=3,220). In the PPA group, highest densities were observed in the left ATL (mean=9,901.81; SD=6,871). There was leftward hemispheric asymmetry of tau inclusions in IPL, STG and ATL which trended towards significance in the latter (p=0.083). Cortical distributions were symmetric or rightward predominant within the bvFTD group. Occipital cortex was devoid of inclusions.Conclusions:Preliminary stereological findings of FTLD-CBD tau inclusions suggest that the distributions of pathologic tau are different across two distinct clinical dementia phenotypes. The presence of left-sided neuronal tau inclusions in PPA is concordant with the aphasic phenotype whereas symmetric and frontal-predominant densities in bvFTD are consistent with comportmental dysfunction.

Linguistic Features in the Connected Speech for Primary Progressive Aphasia: Evidence from a Meta-analysis

Objectives: Primary progressive aphasia (PPA) is a neurodegenerative disease, where language disorder is a predominant symptom. Previous studies demonstrated that individuals with PPA shows different syntactic abilities when compared to other degenerative syndromes, suggesting that connected speech is the appropriate task for examining syntactic features. Therefore, the current study investigated the linguistic features of PPA in connected speech by conducting a systematic review.Methods: Thirteen studies were extracted from the three foreign databases (CINAHL EBSCO, PubMed, SCOPUS). Fluency, syntactic, and lexical features were converted to Hedges’ g to calculate the effect size of speech production among people with PPA and the control, and between linguistic features.Results: First, the PPA group showed a worse performance overall in the connected speech tasks compared to the control, having a moderate effect on only linguistic features. Second, the PPA group showed worse performance compared to the control in the fluency features, having PPA types as a moderator. Third, the control had better performance in the syntactic features, showing severity as a moderator. Lastly, performance between the PPA group and the control in lexical features had a moderate effect on PPA type.Conclusion: The current study demonstrated that the speech production of individuals with PPA in connected speech has a moderate effect on linguistic features. Moreover, the analysis of linguistic features of PPA in connected speech showed that each linguistic features has a different moderator. To be specific, fluency and lexical features were both discriminated by the PPA types, whereas syntactic features were differentiated by the severity, demonstrating that all people with all PPA types had difficulty in syntactic features.

Differential vulnerability of the dentate gyrus to tauopathies in dementias

The dentate gyrus (DG), a key hippocampal subregion in memory processing, generally resists phosphorylated tau accumulation in the amnestic dementia of the Alzheimer’s type due to Alzheimer’s disease (DAT-AD), but less is known about the susceptibility of the DG to other tauopathies. Here, we report stereologic densities of total DG neurons and tau inclusions in thirty-two brains of human participants with autopsy-confirmed tauopathies with distinct isoform profiles—3R Pick’s disease (PiD, N = 8), 4R corticobasal degeneration (CBD, N = 8), 4R progressive supranuclear palsy (PSP, N = 8), and 3/4R AD (N = 8). All participants were diagnosed during life with primary progressive aphasia (PPA), an aphasic clinical dementia syndrome characterized by progressive deterioration of language abilities with spared non-language cognitive abilities in early stages, except for five patients with DAT-AD as a comparison group. 51% of total participants were female. All specimens were stained immunohistochemically with AT8 to visualize tau pathology, and PPA cases were stained for Nissl substance to visualize neurons. Unbiased stereological analysis was performed in granule and hilar DG cells, and inclusion-to-neuron ratios were calculated. In the PPA group, PiD had highest mean total (granule + hilar) densities of DG tau pathology (p < 0.001), followed by CBD, AD, then PSP. PPA-AD cases showed more inclusions in hilar cells compared to granule cells, while the opposite was true in PiD and CBD. Inclusion-to-neuron ratios revealed, on average, 33% of all DG neurons in PiD cases contained a tau inclusion, compared to ~ 7% in CBD, 2% in AD, and 0.4% in PSP. There was no significant difference between DAT-AD and PPA-AD pathologic tau burden, suggesting that differences in DG burden are not specific to clinical phenotype. We conclude that the DG is differentially vulnerable to pathologic tau accumulation, raising intriguing questions about the structural integrity and functional significance of hippocampal circuits in neurodegenerative dementias.

'Like going into a chocolate shop, blindfolded': What do people with primary progressive aphasia want from speech and language therapy?

Primary progressive aphasia (PPA) describes a group of language-led dementias. PPAs are complex, diverse and difficult to diagnose, and therefore conventional models of aphasia and dementia treatment do not meet their needs. The research evidence on intervention for PPA is developing, but to date there are only a few case studies exploring the experiences of people with PPA (PwPPA) themselves. To explore the experiences and opinions of PwPPA and their communication partners (CPs) to understand how speech and language therapy (SLT) services can better meet their needs. A qualitative research approach was used whereby PwPPA and their friends or family members were recruited to participate in focus groups, via advertisements in the Rare Dementia Support PPA group newsletters. Consenting participants were allocated to attend one of four focus groups hosted on an online video conferencing platform. Participants were asked about their communication difficulties, and how SLT could address these needs. All meetings were transcribed, and data were examined using reflexive thematic analysis. Six PwPPA and 14 CPs representing all three PPA variants and mixed PPA participated in the focus groups. Four main themes were identified during the analysis of the focus group discussions: (1) CPs' burden, (2) adjusting to the diagnosis, (3) communication abilities and difficulties and (4) beyond language. A further 10 subthemes were identified. This study provides a greater understanding of the experiences and needs of PwPPA and their families in relation to SLT. This work underlines the importance of a person-centred approach that considers the broader needs of both the PwPPA and the people around them. This will enable service providers to deliver SLT that meets the needs of PwPPA and their families and will also inform future research in this field. What is already known on this subject We know that PwPPA can maintain or even make improvements in word retrieval and speech fluency with SLT exercises. There is also developing evidence of the benefits of interventions such as CP training, communication aid support and other functional interventions. What this paper adds to existing knowledge This study provides an understanding of the experiences and opinions of people living with PPA and their families in relation to SLT. Results demonstrate that PwPPA and their families have to navigate a complex journey, identifying strategies to support communication but also the influence of personality and other cognitive symptoms. SLT was useful, but not always available. What are the potential or actual clinical implications of this work? This study will enable service providers to better plan, justify funding for and delivery of SLT that will meet the needs of PwPPA and their families. Most importantly this work underlines the importance of a person-centred approach, incorporating the broader needs of the person with PPA and those around them.

Neuropsychiatric outcomes and caregiver distress in primary progressive aphasia.

In this study, we aimed to outline the neuropsychiatric consequences of primary progressive aphasia (PPA) and to understand how neuropsychiatric symptomatology affects distress in caregivers. The Neuropsychiatric Inventory (NPI) including the distress index (NPI-Distress) was used. Additional information about the caregiver burden was obtained using Zarit Burden Interview (ZBI). NPI, NPI-Distress, and ZBI data from 17 patients with a clinical diagnosis of PPA were compared with 10 stroke aphasia patients. Neuropsychiatric symptomatology was investigated based on three clusters; Mood, Frontal/Comportmental, and Psychotic/Disruptive. Additionally, the Activities of Daily Living Questionnaire (ADLQ) was used to outline the functional impairment. Twelve healthy controls were included to compare the neurocognitive test scores with PPA and stroke aphasia groups. A greater number of neuropsychiatric symptoms were observed in the PPA group compared to the stroke aphasia group. The number of symptoms in Mood, and Frontal/Comportmental clusters were greater than the number of symptoms in Psychotic/Disruptive clusters in the PPA group, whereas no significant relationship between the number of symptoms and symptom clusters was found in the stroke aphasia group. In the PPA group, a strong correlation was found between the NPI-Frequency×Severity scores and the NPI-Distress scores. Moreover, the NPI-Distress scores in the PPA group strongly correlated with the ZBI scores. Scores for anxiety, irritability/lability, and apathy had a stronger correlation with the NPI-Distress scores compared to the other NPI symptoms. The Communication subscale was the most impaired domain in the PPA group. Travel, and Employment and Recreation subscales showed greater functional impairment in the stroke aphasia group compared to the PPA group. Neuropsychiatric symptoms in PPA in our study were more frequent than previously reported. Furthermore, the distress index of the NPI was not only correlated with the severity of the neuropsychiatric symptoms but also reflected the overall burden on the caregivers in the PPA group.

The course of primary progressive aphasia diagnosis: a cross-sectional study

BackgroundThe primary progressive aphasia (PPA) diagnosis trajectory is debated, as several changes in diagnosis occur during PPA course, due to phenotype evolution from isolated language alterations to global cognitive impairment.The goal of the present study, based on a French cohort, was to describe the demographics and the evolution of subjects with (PPA) in comparison with Alzheimer’s disease (AD) on a period of 7 years.MethodsWe conducted a repeated cross-sectional study. The study population comprised individuals with PPA and AD diagnosis (N=167,191) from 2010 to 2016 in the French National data Bank (BNA). Demographic variables, MMSE scores, diagnosis status at each visit and prescribed treatments were considered.ResultsFrom 2010 to 2016, 5186 patients were initially diagnosed with PPA, 162,005 with AD. Compared to AD subjects, significant differences were found concerning age (younger at first diagnosis for PPA), gender (more balanced in PPA), education level (higher in PPA) and MMSE score (higher of 1 point in PPA).Percentage of pending diagnosis, delay between first consultation and first diagnosis and the number of different diagnoses before the diagnosis of interest were significantly higher in PPA group compared to AD group. Pharmacological and non-pharmacological treatments were significatively more recommended following PPA than AD diagnosis.ConclusionThis study improves the knowledge of PPA epidemiology and has the potential to help adopting appropriate public health service policies. It supports the hypothesis that PPA is diagnosed later than AD. The PPA diagnosis increases the prescription of non-pharmacological treatments, especially speech and language therapy (SLT) that is the main treatment available and most effective when at the initial stage.Trial registrationClinicalTrials.gov identifier NCT03687112

Differential linguistic features of verbal fluency in behavioral variant frontotemporal dementia and primary progressive aphasia

Frontotemporal dementia (FTD) is an early-onset neurodegenerative disorder with a heterogeneous clinical presentation. Verbal fluency is regularly used as a sensitive measure of language ability, semantic memory, and executive functioning, but qualitative changes in verbal fluency in FTD are currently overlooked. This retrospective study examined qualitative, linguistic features of verbal fluency in 137 patients with behavioral variant (bv)FTD (n = 50), or primary progressive aphasia (PPA) [25 non-fluent variant (nfvPPA), 27 semantic variant (svPPA), and 34 logopenic variant (lvPPA)] and 25 control participants. Between-group differences in clustering, switching, lexical frequency (LF), age of acquisition (AoA), neighborhood density (ND), and word length (WL) were examined in the category and letter fluency with analysis of variance adjusted for age, sex, and the total number of words. Associations with other cognitive functions were explored with linear regression analysis. The results showed that the verbal fluency performance of patients with svPPA could be distinguished from controls and other patient groups by fewer and smaller clusters, more switches, higher LF, and lower AoA (all p < 0.05). Patients with lvPPA specifically produced words with higher ND than the other patient groups (p < 0.05). Patients with bvFTD produced longer words than the PPA groups (p < 0.05). Clustering, switching, LF, AoA, and ND—but not WL—were differentially predicted by measures of language, memory, and executive functioning (range standardized regression coefficient 0.25–0.41). In addition to the total number of words, qualitative linguistic features differ between subtypes of FTD. These features provide additional information on lexical processing and semantic memory that may aid the differential diagnosis of FTD.

Dysgraphia Phenotypes in Native Chinese Speakers With Primary Progressive Aphasia.

Most primary progressive aphasia (PPA) literature is based on English language users. Linguistic features that vary from English, such as logographic writing systems, are underinvestigated. The current study characterized the dysgraphia phenotypes of patients with PPA who write in Chinese and investigated their diagnostic utility in classifying PPA variants. This study recruited 40 participants with PPA and 20 cognitively normal participants from San Francisco, Hong Kong, and Taiwan. We measured dictation accuracy using the Chinese Language Assessment for PPA (CLAP) 60-character orthographic dictation test and examined the occurrence of various writing errors across the study groups. We also performed voxel-based morphometry analysis to identify the gray matter regions correlated with dictation accuracy and prevalence of writing errors. All PPA groups produced significantly less accurate writing responses than the control group and no significant differences in dictation accuracy were noted among the PPA variants. With a cut score of 36 out of 60 in the CLAP orthographic dictation task, the test achieved sensitivity and specificity of 90% and 95% in identifying Chinese participants with PPA vs controls. In addition to a character frequency effect, dictation accuracy was affected by homophone density and the number of strokes in semantic variant PPA and logopenic variant PPA groups. Dictation accuracy was correlated with volumetric changes over left ventral temporal cortices, regions known to be critical for orthographic long-term memory. Individuals with semantic variant PPA frequently presented with phonologically plausible errors at lexical level, patients with logopenic variant PPA showed higher preponderance towards visual and stroke errors, and patients with nonfluent/agrammatic variant PPA commonly exhibited compound word and radical errors. The prevalence of phonologically plausible, visual, and compound word errors was negatively correlated with cortical volume over the bilateral temporal regions, left temporo-occipital area, and bilateral orbitofrontal gyri, respectively. The findings demonstrate the potential role of the orthographic dictation task as a screening tool and PPA classification indicator in Chinese language users. Each PPA variant had specific Chinese dysgraphia phenotypes that vary from those previously reported in English-speaking patients with PPA, highlighting the importance of language diversity in PPA.

Verbal and Nonverbal Memory in Neurodegenerative and Stroke Aphasia: Evidence From the Turkish Version of the Three Words Three Shapes Test.

Although language impairment is the most salient feature of cognitive impairment in both primary progressive aphasia (PPA) and stroke aphasia (SA), memory can also be impaired in both patient populations. To identify distinctive features of verbal and nonverbal memory processing in individuals with PPA and those with SA. We gave individuals with PPA (n = 14), those with SA (n = 8), and healthy controls (HC; n = 13) a comprehensive neuropsychological test battery and the Turkish version of the Three Words Three Shapes Test (3W3S-Turkish). The 3W3S-Turkish Test includes five subtests: Copy, Incidental Recall, Acquisition, Delayed Recall, and Recognition. High-resolution brain scans were performed in a subset of individuals with PPA and those with SA. Lesion distribution was limited to the dorsal language areas in the SA group, whereas peak atrophy areas in the PPA group extended beyond the language network, including the medial temporal lobe, precuneus, and posterior/medial portions of the cingulate cortex. Both the PPA and SA groups showed impairment in incidental recall, and the PPA group showed additional impairment in delayed recall. Greater impairment for verbal stimuli suggestive of material-specific memory impairment was evident in the PPA group's scores on the Incidental Recall and Delayed Recall subtests. Both aphasia groups retained the acquired information regardless of material type. Although both aphasia groups shared similarities in the involvement of the dorsal prefrontal working memory/attention network, the PPA group showed greater impairment in delayed recall compared with the SA group.

Cortical microstructure in primary progressive aphasia: a multicenter study

BackgroundCortical mean diffusivity is a novel imaging metric sensitive to early changes in neurodegenerative syndromes. Higher cortical mean diffusivity values reflect microstructural disorganization and have been proposed as a sensitive biomarker that might antedate macroscopic cortical changes. We aimed to test the hypothesis that cortical mean diffusivity is more sensitive than cortical thickness to detect cortical changes in primary progressive aphasia (PPA).MethodsIn this multicenter, case-control study, we recruited 120 patients with PPA (52 non-fluent, 31 semantic, and 32 logopenic variants; and 5 GRN-related PPA) as well as 89 controls from three centers. The 3-Tesla MRI protocol included structural and diffusion-weighted sequences. Disease severity was assessed with the Clinical Dementia Rating scale. Cortical thickness and cortical mean diffusivity were computed using a surface-based approach.ResultsThe comparison between each PPA variant and controls revealed cortical mean diffusivity increases and cortical thinning in overlapping regions, reflecting the canonical loci of neurodegeneration of each variant. Importantly, cortical mean diffusivity increases also expanded to other PPA-related areas and correlated with disease severity in all PPA groups. Cortical mean diffusivity was also increased in patients with very mild PPA when only minimal cortical thinning was observed and showed a good correlation with measures of disease severity.ConclusionsCortical mean diffusivity shows promise as a sensitive biomarker for the study of the neurodegeneration-related microstructural changes in PPA.

The Diagnostic Value of Language Screening in Primary Progressive Aphasia: Validation and Application of the Sydney Language Battery.

The three variants of primary progressive aphasia (PPA) differ in clinical presentation, underlying brain pathology, and clinical course, which stresses the need for early differentiation. However, brief cognitive tests that validly distinguish between all PPA variants are lacking. The Sydney Language Battery (SYDBAT) is a promising screening instrument that can be used as a first step in a comprehensive neuropsychological assessment to distinguish PPA subtypes, but evidence on its validity and reliability is to date limited. In the current study, the validation and diagnostic value of the SYDBAT are described for discriminating PPA subtypes as well as distinguishing PPA from mild cognitive impairment (MCI) or Alzheimer's dementia (AD). Forty-five patients with PPA (13 with semantic PPA, 20 with logopenic PPA, and 12 with nonfluent/agrammatic PPA), 25 MCI patients, 13 AD patients, and 50 cognitively unimpaired controls were included in this study. Both patients and controls completed the SYDBAT-NL (Dutch version). Performance on and predictive ability of the four subtests (i.e., Naming, Word Comprehension, Repetition, and Semantic Association) were assessed. In addition, construct validity and internal consistency were examined. Different SYDBAT performance patterns were found across PPA and non-PPA patient groups. While a discriminant function analysis based on SYDBAT subtest scores could predict PPA subtype with 78% accuracy, it was more difficult to disentangle PPA from non-PPA patients based on SYDBAT scores alone. For assisting in clinical interpretation, simple rules were set up and translated into a diagnostic decision tree for subtyping PPA, which was capable of diagnosing a large proportion of the cases. Satisfying validity and reliability measures were found. The SYDBAT is an easy-to-use and promising screen for assessing single-word language processes, which may contribute to the differential diagnostic process of PPA and the assessment of language impairment in MCI and AD. It can be easily implemented for initial screening of patients in a memory clinic.

Thematic Integration Impairments in Primary Progressive Aphasia: Evidence From Eye-Tracking.

Primary progressive aphasia (PPA) is a degenerative disease affecting language while leaving other cognitive facilities relatively unscathed. The agrammatic subtype of PPA (PPA-G) is characterized by agrammatic language production with impaired comprehension of noncanonical filler-gap syntactic structures, such as object-relatives [e.g., The sandwich that the girl ate (gap) was tasty], in which the filler (the sandwich) is displaced from the object position within the relative clause to a position preceding both the verb and the agent (the girl) and is replaced by a gap linked with the filler. One hypothesis suggests that the observed deficits of these structures reflect impaired thematic integration, including impaired prediction of the thematic role of the filler and impaired thematic integration at the gap, but spared structure building (i.e., creation of the gap). In the current study, we examined the on-line comprehension of object-relative and subject-relative clauses in healthy controls and individuals with agrammatic and logopenic PPA using eye-tracking. Eye-movement patterns in canonical subject-relative clause structures were essentially spared in both PPA groups. In contrast, eye-movement patterns in noncanonical object-relative clauses revealed delayed thematic prediction in both agrammatic and logopenic PPA, on-time structure building (i.e., gap-filling) in both groups, and abnormal thematic integration in agrammatic, but not logopenic, PPA. We argue that these results are consistent with the hypothesis that agrammatic comprehension deficits reflect impaired thematic integration.

Diagnostic Accuracy of Affective Social Tasks in the Clinical Classification Between the Behavioral Variant of Frontotemporal Dementia and Other Neurodegenerative Disease.

Severe socio-emotional impairments characterize the behavioral variant of frontotemporal dementia (bvFTD). However, literature reports social cognition disorders in other dementias. In this study, we investigated the accuracy of social cognition performances in the early and differential diagnosis of bvFTD. We included 131 subjects: 32 bvFTD, 26 Alzheimer's disease (AD), 16 primary progressive aphasia (PPA), 17 corticobasal syndrome (CBS), and 40 healthy control (HC). Each subject completed the Ekman 60 faces (Ek-60F) test assessing basic emotion recognition and the Story-based Empathy Task (SET) assessing attribution of intentions/emotions. A combined social measure (i.e., Emotion Recognition and Attribution (ERA) index) was calculated. One-way ANOVA has been used to compare performances among groups, while receiver operating characteristic (ROC) curve tested measures ability to distinguish subjects with and without bvFTD. Ek-60F and ERA index scores were significantly lower in bvFTD versus HC, AD, and PPA groups. ROC analyses significantly distinguished bvFTD from HC (AUC 0.82-0.92), with the Ek-60F test showing the highest performance, followed by the ERA index. These two social measures showed the best accuracy in detecting bvFTD from AD (AUC 0.78-0.74) and PPA (AUC 0.80-0.76). Investigated measures failed in detecting bvFTD from CBS. Accuracy analyses support the advantage of using social cognition tests for bvFTD diagnosis. Short social battery may reduce uncertainties and improve disease identification in clinical settings. We recommend a revision of current clinical criteria considering neuropsychological deficits in emotion recognition and processing tasks as key cognitive markers of this neurodegenerative syndrome.

Online sentence processing impairments in agrammatic and logopenic primary progressive aphasia: Evidence from ERP

Evidence from psycholinguistic research indicates that sentence processing is impaired in Primary Progressive Aphasia (PPA), and more so in individuals with agrammatic (PPA-G) than logopenic (PPA-L) subtypes. Studies have mostly focused on offline sentence production ability, reporting impaired production of verb morphology (e.g., tense, agreement) and verb-argument structure (VAS) in PPA-G, and mixed findings in PPA-L. However, little is known about real-time sentence comprehension in PPA. The present study is the first to compare real-time semantic, morphosyntactic and VAS processing in individuals with PPA (10 with PPA-G and 9 with PPA-L), and in two groups of healthy (22 young and 19 older) individuals, using event-related potentials (ERP). Participants were instructed to listen to sentences that were either well-formed (n = 150) or contained a violation of semantics (e.g., *Owen was mentoring pumpkins at the party, n = 50), morphosyntax (e.g., *The actors was singing in the theatre, n = 50) or VAS (*Ryan was devouring on the couch, n = 50), and were required to perform a sentence acceptability judgment task while EEG was recorded. Results indicated that in the semantic task both healthy and PPA groups showed an N400 response to semantic violations, which was delayed in PPA and older (vs. younger) groups. Morphosyntactic violations elicited a P600 in both groups of healthy individuals and in PPA-L, but not in PPA-G. A similar P600 response was also found only in healthy individuals for VAS violations; whereas, abnormal ERP responses were observed in both PPA groups, with PPA-G showing no evidence of VAS violation detection and PPA-L showing a delayed and abnormally-distributed positive component that was negatively associated with offline sentence comprehension scores. These findings support characterizations of sentence processing impairments in PPA-G, by providing online evidence that VAS and morphosyntactic processing are impaired, in the face of substantially preserved semantic processing. In addition, the results indicate that on-line processing of VAS information may also be impaired in PPA-L, despite their near-normal accuracy on standardized language tests of argument structure production.

Répéter s'il vous plait: Working memory intensive sentence repetition deficits as a sensitive neuropsychological marker of primary progressive aphasia

AbstractBackgroundSentence repetition deficits have been shown to be critical in diagnosing primary progressive aphasia (PPA), particularly the logopenic variant, distinguishing its symptoms from other Alzheimer’s disease related dementias [1‐3]. These impairments were found to be associated with working memory [4].MethodIn the current preliminary study, to further investigate how sentence repetition is mediated in memory in PPA and AD, we used a spoken sentence‐span task to examine groups of 6 French‐speaking PPA (including lvPPA and non‐fluent subtypes), 6 AD patients without aphasia, and 15 healthy ageing controls. The task required individuals to repeat meaningful French sentences with increasing number of content words ranging from three to nine. Each span of content words contained two items, and when the participants failed in repeating both items in one span, the task was terminated; when one item was incorrectly repeated half a point penalty was issued.ResultsBoth the patient groups performed more poorly than healthy controls in all measures (ts&gt;+/‐3.27). A set of mixed‐effects regression models showed that the PPA group had reduced sentence‐span (M PPA=5.08 vs. M AD=5.66; ß=0.58, SE=0.16, t=3.53, 95%CIs[0.25,0.91]), greater difficulty repeating content words (M PPA= 44.33 vs. M AD=50.00; ß=5.66, SE=2.19, t=2.57, 95%CIs[‐2.18,‐0.48]), and elevated number of substitution errors (M PPA= 6.16 vs. M AD=4.83; ß=‐1.33, SE=0.42, t=‐3.10, 95%CIs[1.32,10.01]) compared to the AD group (Figure 1). No group differences were found in repetition duration standardized by number of content words.ConclusionWe found that sentence repetition deficits in PPA have different characteristics than those in AD, submitting to earlier studies that associated PPA assessment with graphic markers [5]. We recommend clinicians to incorporate a sentence repetition task involving sentences with varying length and number of content words in their diagnostic assessment as this study suggests that working‐memory intensive sentence repetition decline appears to be a neuropsychological clinical marker distinguishing cognitive profiles of PPA from AD patients. [1]Hohlbaum, et al., Aphasiology, 2018. 32(12):1445‐1467. [2]Foxe, et al., Cortex, 2016. 83: p.39‐50. [3]Gorno‐Tempini, et al. Neurology, 2008. 71(16): p.1227‐1234. [4]Beales, et al., Brain and Language, 2019. 194: p.1‐11. [5]Gros, et al., Alzheimer’s&amp;Dementia, 2019. P1‐285(15): p.351‐352.