Semantic Variant Primary Progressive Aphasia Research Articles

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

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. 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. 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. 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. 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 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.

Hemispheric asymmetries in hippocampal volume related to memory in left and right temporal variants of frontotemporal degeneration.

In addition to Alzheimer's disease (AD), the hippocampus is now known to be affected in variants of frontotemporal degeneration (FTD). In semantic variant primary progressive aphasia (svPPA), characterized by language impairments, hippocampal atrophy is greater in the left hemisphere. Nonverbal impairments (e.g., visual object recognition) are prominent in the right temporal variant of FTD (rtvFTD), and hippocampal atrophy may be greater in the right hemisphere. In this study we examined the hypothesis that leftward hippocampal asymmetry (predicted in svPPA) would be associated with selective verbal memory impairments (with relative preservation of visual memory), while rightward asymmetry (predicted in rtvFTD) would be associated with the opposite pattern (greater visual memory impairment). In contrast, we predicted that controls and individuals in the amnestic mild cognitive impairment stage of AD (aMCI), both of whom were expected to show symmetrical hippocampal volumes, would show roughly equivalent scores in verbal and visual memory. Participants completed delayed recall tests with words and geometric shapes, and hippocampal volumes were assessed with MRI. The aMCI sample showed symmetrical hippocampal atrophy, and similar degree of verbal and visual memory impairment. The svPPA sample showed greater left hippocampal atrophy and verbal memory impairment, while rtvFTD showed greater right hippocampal atrophy and visual memory impairment. Greater asymmetry in hippocampal volumes was associated with larger differences between verbal and visual memory in the FTD samples. Unlike AD, asymmetry is a core feature of brain-memory relationships in temporal variants of FTD.

Genetic Screening of Patients with Sporadic Alzheimer’s Disease and Frontotemporal Lobar Degeneration in the Chinese Population

Background: Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) account for the vast majority of neurodegenerative dementias. AD and FTLD have different clinical phenotypes with a genetic overlap between them and other dementias. Objective: This study aimed to identify the genetic spectrum of sporadic AD and FTLD in the Chinese population. Methods: A total of 74 sporadic AD and 29 sporadic FTLD participants were recruited. All participants underwent whole-exome sequencing (WES) and testing for a hexanucleotide expansion in C9orf72 was additionally performed for participants with negative WES results. Results: Four known pathogenic or likely pathogenic variants, including PSEN1 (p.G206D), MAPT (p.R5H), LRRK2 (p.W1434*), and CFAP43 (p.C934*), were identified in AD participants, and 1 novel pathogenic variant of ANXA11 (p.D40G) and two known likely pathogenic variants of MAPT (p.D177V) and TARDBP (p.I383V) were identified in FTLD participants. Twenty-four variants of uncertain significance as well as rare variants in risk genes for dementia, such as ABCA7, SORL1, TRPM7, NOS3, MPO, and DCTN1, were also found. Interestingly, several variants in participants with semantic variant primary progressive aphasia were detected. However, no participants with C9orf72 gene variants were found in the FTLD cohort. Conclusions: There was a high frequency of genetic variants in Chinese participants with sporadic AD and FTLD and a complex genetic overlap between these two types of dementia and other neurodegenerative diseases.

Clinical and neuroanatomical characterization of the semantic behavioral variant of frontotemporal dementia in a multicenter Italian cohort.

Semantic behavioral variant frontotemporal dementia (sbvFTD) is a neurodegenerative condition presenting with specific behavioral and semantic derangements and predominant atrophy of the right anterior temporal lobe (ATL). The objective was to evaluate clinical, neuropsychological, neuroimaging, and genetic features of an Italian sbvFTD cohort, defined according to recently proposed guidelines, compared to semantic variant primary progressive aphasia (svPPA) and behavioral variant FTD (bvFTD) patients. Fifteen sbvFTD, sixty-three bvFTD, and twenty-five svPPA patients and forty controls were enrolled. Patients underwent clinical, cognitive evaluations, and brain MRI. Symptoms of bvFTD patients between onset and first visit were retrospectively recorded and classified as early and late. Grey matter atrophy was investigated using voxel-based morphometry. sbvFTD experienced early criteria-specific symptoms: world, object and person-specific semantic loss (67%), complex compulsions and rigid thought (60%). Sequentially, more behavioral symptoms emerged (apathy/inertia, loss of empathy) along with non-criteria-specific symptoms (anxiety, suspiciousness). sbvFTD showed sparing of attentive/executive functions, especially compared to bvFTD and better language functions compared to svPPA. All sbvFTD patients failed at the famous face recognition test and more than 80% failed in understanding written metaphors and humor. At MRI, sbvFTD had predominant rightATL atrophy, almost specular to svPPA. Three sbvFTD patients presented pathogenic genetic variants. We replicated the application of sbvFTD diagnostic guidelines in an independent Italian cohort, demonstrating that the presence of person-specific semantic knowledge loss and mental rigidity, along with preserved executive functions and a predominant right ATL atrophy with sparing of frontal lobes, should prompt a diagnosis of sbvFTD.

Computer-Based Naming Treatment for Semantic Variant Primary Progressive Aphasia With History of Traumatic Brain Injury: A Single-Case Experimental Design.

The purpose of this study was to investigate the effectiveness of a self-administered naming treatment for one individual, B.N., presenting with semantic variant primary progressive aphasia (svPPA) and a history of traumatic brain injury (TBI). Naming treatment included components of Lexical Retrieval Cascade Treatment and was self-administered using an adaptive spaced retrieval software, Anki. Using a multiple-baseline, single-case experimental design, naming accuracy probes were taken during pretreatment, treatment, posttreatment, and follow-up (through 12 months) for 60 trained words and 10 untrained words. Item-level Bayesian generalized mixed-effects models were used to estimate (a) the treatment effect for trained words, (b) change in untrained words, and (c) maintenance of treatment effects from posttreatment to each subsequent follow-up. Statistical analyses revealed that a gain of 35 out of 60 trained words (35.3; 90% CI [30.6, 39.5]) was directly attributable to treatment. Following treatment, evidence of generalization to untrained words was not observed. During the follow-up period, there was gradual decline in naming accuracy of trained items. The positive treatment results reported here support the use of self-administered naming treatments for those with svPPA and a history of TBI. Although the utility of this treatment approach is constrained by patient factors including motivation, self-administered naming treatments represent a unique opportunity to expand access to speech-language intervention for people with svPPA, including those with concomitant diagnoses. https://doi.org/10.23641/asha.25119080.

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

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. 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. 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. This study highlights noun classifiers as linguistic markers to discriminate PPA syndromes in Chinese speakers. 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.

Hearing symptom profiles in Alzheimer’s disease and frontotemporal dementia

AbstractBackgroundHearing loss has emerged as a marker of cognitive decline and potential treatment target in dementia, however the symptom profiles that characterise hearing impairment in different dementia syndromes are poorly characterised. Beyond sound detection, these diseases impair aspects of auditory perception that are crucial for communication in daily life. Here we addressed changes in everyday hearing function in Alzheimer’s disease and frontotemporal dementia syndromes, using standardised auditory symptom questionnaires completed by patients’ caregivers.MethodPrimary caregivers for patients with Alzheimer’s disease (n = 20), logopenic variant primary progressive aphasia (n = 8), nonfluent variant primary progressive aphasia (n = 13), semantic variant primary progressive aphasia (n = 13) and behavioural variant frontotemporal dementia (n = 18) completed the Hearing Impairment Impact – Significant Other Profile, adapted Amsterdam Inventory for Auditory Disability and Khalfa Hyperacusis questionnaires. The Amsterdam Inventory for Auditory Disability was also completed by 15 healthy age‐matched individuals. No participant had a past history of significant otological disease.ResultScores on the Hearing Impairment Impact – Significant Other Profile and Khalfa Hyperacusis Questionnaire respectively demonstrated greater carer burden and increased sensitivity to sound in the behavioural variant frontotemporal dementia group compared with the Alzheimer’s disease group. On the Amsterdam Inventory for Auditory Disability, multi‐domain hearing difficulties were endorsed for the behavioural variant frontotemporal dementia and primary progressive aphasia groups relative to healthy controls, and total scores in the logopenic and semantic variant primary progressive aphasia groups were significantly worse than both the healthy control and Alzheimer’s disease groups. Syndromic groups showed differentiable hearing profiles across hearing domains.ConclusionMajor dementia syndromes have distinct profiles of everyday hearing difficulty, and patients with frontotemporal dementia and progressive aphasia syndromes may have particularly marked (albeit often unrecognised) changes in their hearing. These findings should motivate the development of bespoke auditory tests to assess central hearing function and personalised hearing management strategies in these diseases.

Differentiation of frontotemporal dementia subtypes using neuroimaging‐based multi‐type parallel feature embedding

AbstractBackgroundFrontotemporal dementia (FTD) represents a collection of neurocognitive syndromes with frontotemporal lobar degeneration (FTLD) neuropathology, and is associated with significant clinical, pathological, and genetic heterogeneity. We trained a deep neural network (DNN) classifier to differentiate behavioral‐variant FTD (bvFTD), semantic variant primary progressive aphasia (svPPA), and non‐fluent variant (nfvPPA) patients using MRI scans drawn from two multi‐site neuroimaging consortiums.MethodBvFTD (N = 173), nfvPPA (N = 63), and svPPA (N = 41) patients with T1‐MRI were extracted from the FTLD Neuroimaging Initiative (FTLDNI) and the ARTFL‐LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) databases. MRI data were preprocessed with FreeSurfer, with cortical thickness, cortical volume, and subcortical volumes extracted. Cortical measures were parcellated into 360 patches (i.e., ROIs) according to the HCP‐MMP1 atlas. Both the patch‐based cortical thickness and volume features were harmonized to control confounding effects of sex, age, total intracranial volume (TIV), cohort, and scanner. Multi‐type features were parallelly fed into a multi‐layer‐perceptron (MLP)‐based classifier. Weighted cross‐entropy loss function was used to account for unbalanced sample sizes across FTD subtypes. 10‐fold nested cross‐validation was used to evaluate the robustness of the classification model, with data split into 80/10/10 of training/validation/test data sets.ResultVisual evaluation z‐scores of cortical features among FTLDNI and ALLFTD groups revealed site‐specific differences significantly reduced by feature harmonization, especially for volume (Figure 1). The balanced accuracy of the ensembled DNN classifier of each FTD subtype on test sets across all ten folds reached 0.76 ± 0.09 for bvFTD, 0.79 ± 0.07 for nfvPPA, and 0.88 ± 0.07 for svPPA (Figure 2). Figure 3 shows confusion matrices for classification performance in the test set across ten cross‐validation folds.ConclusionWe developed a deep‐learning‐based framework to classify three FTD subtypes: bvFTD, nfvPPA, and svPPA. The combination of feature harmonization and parallel multi‐type feature embedding framework showed promising differentiation power. This work can be used to recognize at‐risk populations for early and precise diagnosis, to aid intervention planning. Future studies will compare classification based on different input features and use visualization methods to identify the most discriminative regions and explore their clinical relevance.

Progranulin gene mutation of frontotemporal dementia in China: A case report and literature review

AbstractBackgroundProgranulin (GRN) mutations of Frontotemporal dementia (FTD) were rarely reported in China. This study was to report one novel GRN mutation and summarize the genetic and clinical features of patients with GRN mutations in China.MethodComprehensive clinical, genetic, and neuroimaging examinations were conducted on a 58‐year‐old patient who was diagnosed with semantic variant primary progressive aphasia. A literature review was also conducted and the clinical and genetic features of patients with Progranulin mutations in China were summarized.ResultMarked lateral atrophy and hypometabolism on the left‐side frontal, temporal and parietal lobes of the patient were found on neuroimages, and amyloid and tau positron emission tomography ruled out pathological protein deposition. A novel heterozygous 45‐bp deletion (c.141414_1444delCCCTTCCCCGCCAGGCTGTGTGCTGCGAGGATCGCCAGCACTGCT) was identified through Whole Exon Sequencing of the patient’s genomic deoxyribonucleic acid. Nonsense‐mediated messenger ribonucleic acid decay was implicated in the degradation of the mutated messenger ribonucleic acid, and it was defined as pathogenic by American College of Medical Genetics and Genomics guidelines. In the literature review, we found Chinese reports of 13 patients with Progranulin mutations. A 1.2%–2.6% prevalence, an early disease onset and a female predominance were reported in Chinese patients with GRN mutations.ConclusionOur findings expand the mutational profile of Progranulin mutations in China and provide a basis for potential treatments for Progranulin.

In vivo Braak staing using 18F‐MK‐6240 PET in Alzheimer’s disease

AbstractBackgroundThis study aimed to identify the distribution of [18F]MK‐6240 PET retention and classified according to Braak staging in Alzheimer’s disease (AD). We also evaluated the relationship between [18F]MK‐6240 PET retention and cognitive functions and neurodegeneration.MethodWe enrolled 194 participants including 70 CU (cognitively unimpaired elderly participants older than 60 years old), 56 MCI, 60 probable AD, and 8 patients who had dementia other than AD (subcortical vascular dementia (n = 3), semantic variant primary progressive aphasia (n = 2), frontotemporal dementia (n = 2), corticobasal syndrome (n = 1)). All participants underwent 3T MRI, [18F]MK‐6240, and [18F]Flutemetamol (FLUTE) PET scans, APOE genotyping, and detailed neuropsychological tests. Braak staging was defined as the stages where regional SUVR of ROIs composing each Braak stage > = 1.3. We assessed the Braak staging in the subjects. Correlation analyses between global retention of MK‐6240 PET and neuropsychological test results or neurodegeneration were performed using linear regression.ResultThe proportion of amyloid positivity was 11.4% in CU, 45.5% in MCI, and 83.3% in probable AD. Among probable AD (n = 60), 12 patients were classified to other dementia after amyloid PET and tau PET confirmation. Main Braak stage was Braak 0 in CU, Braak III/IV in amyloid (+) MCI, Braak V/VI in AD dementia. In CU an patents with AD spectrum, global retention of MK‐6240 PET was significantly correlated with MMSE, CDR SOB, language, visuospatial function, memory and frontal/executive functions. In addition, global retention of MK‐6240 PET was correlated with the MRI markers for neurodegeneration, that is, mean cortical thickness and hippocampal volumes.Conclusion [ 18F]MK‐6240 PET successfully identified the Braak staging and associated with amyloid pathology and clinical phenotype in patients with AD. MK‐6240 PET also correlated with cognitive functions and neurodegeneration. MK6240 is a promising tau PET tracer with the potential to be sensitive surrogate markers of AD.

Functional neuroanatomy of music perception in frontotemporal dementia

AbstractBackgroundDespite considerable interest in music as an index of brain function and a therapeutic modality in dementia, the neural correlates of music processing in different dementias remain poorly defined. In the frontotemporal dementia spectrum, behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA) are often associated with striking changes in musical function and/or retained musical skills, suggesting frontotemporal dementia may be an instructive disease model in which to assess brain mechanisms of music processing in neurodegenerative pathologies. Here we addressed this issue using activation fMRI in patients with frontotemporal dementia.MethodNineteen patients (10 svPPA, nine bvFTD) and 26 healthy age‐matched controls underwent 3‐Tesla ‘sparse’ fMRI in which they listened passively to musical melodies. In a 2×2 factorial design, stimulus conditions were manipulated to probe two key dimensions of music processing: semantic memory (familiarity: familiar vs. novel melodies) and perceptual features (temporal structure: isochronous vs. anisochronous melodies). Post‐scan behavioral testing assessed participants’ ability to discriminate melodies under each of the two manipulated stimulus dimensions. Information about participant demographics and musical background was also collected.ResultThe healthy older control group showed separable profiles of activation in posterior superior temporal cortex for processing musical temporal structure, and in anterior temporal and inferior frontal cortices for processing musical familiarity. Compared with healthy older listeners, syndromic groups showed differential patterns of engagement of these distributed neural networks. In post‐scan behavioral testing, patients with bvFTD also exhibited significantly impaired musical familiarity judgments relative to healthy controls.ConclusionFrontotemporal dementia syndromes show distinct functional neuroanatomical signatures of music perception. Future work should explore fMRI of music processing as a probe of neural function in particular molecular pathologies and a candidate marker of therapeutic potential in dementia.

EEG correlates in the three variants of Primary Progressive Aphasia

AbstractBackgroundThe analysis of EEG cortical sources is promising for the investigation of neurodegenerative disorders. The aim of this study is to explore its value in the characterization of the three clinical presentations of primary progressive aphasia (PPA).MethodA resting‐state 19‐channel EEG was obtained in 48 patients diagnosed with PPA (21 nonfluent/agrammatic variant PPA [nfv‐PPA], 18 logopenic variant PPA [lv‐PPA], 9 semantic variant PPA [sv‐PPA]) and in 21 matched healthy controls. Using eLORETA, EEG current source density (CSD) values were estimated at voxel‐level and compared among groups of patients and controls.ResultPatients showed a low‐to‐moderate cognitive impairment. Lv‐PPA cases showed a higher delta density over the left frontal and temporal regions when compared to sv‐PPA subjects, and in left precuneus and posterior cingulate when compared to nfv‐PPA patients. They also displayed a higher delta density in left frontal, parietal and temporal regions than healthy subjects, and lower alpha1 density in left occipital regions compared with other patient groups. Lv‐PPA patients also showed reduced alpha2, beta1 and beta2 density over the left occipital regions when compared to healthy subjects. No significant differences were found in terms of CSD among sv‐PPA, nfv‐PPA and healthy subjects.ConclusionConsistently with our previous studies, findings in PPA patients suggest that Alzheimer’s disease (AD), but not fronto‐temporal degeneration (FTD), might induce a characteristic disruption of the cortical electrical activity, detectable by EEG. EEG might thus help in the differential diagnosis between AD‐related and FTD‐related PPA variants.

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.

A - 127 Unveiling Discrepancies in Identifying Depression in Dementia: a Comparative Analysis of Caregiver and Patient Self-Report Measures.

Standard assessment of depression in research and clinical care with persons with dementia (PWD) relies on caregiver report, and views of PWD are typically not incorporated due to concerns that they lack insight into their own neuropsychiatric status. This study explored the discrepancies between self-reported and caregiver-reported depression among PWD. Participants included 373 PWD who met criteria for Alzheimer's disease, behavioral variant frontotemporal dementia, semantic variant primary progressive aphasia, and progressive supranuclear palsy. Each PWD self-reported depressive symptoms using the Geriatric Depression Scale (GDS), including subscales of dysphoria, withdrawal, worry, worthlessness, and cognitive concern. Caregivers described the PWD using the Neuropsychiatric Inventory (NPI) depression and apathy subscales. Of the total sample, 112 (30%) patients were positive for depression on both their self-report (GDS total > =13) and their informant report (NPI depression = yes). However, 226 (60.5%) patients self-reported depression on the GDS, including dysphoria and hopelessness, but their caregivers reported no depression. Additionally, 110 (49%) patients who self-reported depression but whose informants reported no depression were described as apathetic by their informants, compared to 43 (19%) of these depressed patients whose informants did not report depression or apathy. These results suggest that overreliance on caregivers' reports of depression may seriously underrepresent rates of depression in PWD and mischaracterize patients' experience. Difficulty distinguishing depression from apathy accounted for only part of this PWD-caregiver discrepancy. Prioritizing PWD self-report of mood, and broadening caregiver education about depression, may improve care and quality of life for PWD.

A - 44 Social Cognition and its Neuroanatomic Correlates in Frontotemporal Dementia.

Frontotemporal dementia (FTD) often presents with impaired social cognition in both the behavioral and language variants. Establishing reliable measures and neural correlates of social cognition may aid in staging and monitoring FTD subtypes. Here, we examined group differences in social cognitive measures between FTD subtypes and cortical thickness correlates of social cognition across groups. Participants with behavioral variant FTD (n = 53; bvFTD), semantic variant primary progressive aphasia (n = 32; svPPA) and non-fluent variant PPA (n = 32; nfPPA) were enrolled in the Frontotemporal Lobar Degeneration Neuroimaging Initiative (NIFD). In first-visit data, we examined group differences in social cognition measures [Interpersonal Reactivity Index (IRI), Revised Social-Monitoring Scale (RSMS), and Behavioral Inhibition/Activation (BIS/BAS) Scales]. We used multivariate regression adjusted for age, total intracranial volume, and CDR global score to explore associations between social cognition and cortical thickness in pre-specified regions. Reduced perspective-taking and sensitivity to socio-emotional expressiveness was observed in early-stage bvFTD and svPPA groups compared to the nfPPA group. Across FTD cohorts, increased perspective-taking was associated with reduced cortical thickness of regions within the salience and default mode networks. Increased empathic concern was associated with increased left inferior parietal cortical thickness. Increased behavioral inhibition was associated with reduced right posterior cingulate cortical thickness. Increased behavioral activation was associated with reduced right pars triangularis cortical thickness. Social cognition is affected in early-stage bvFTD and svPPA to a greater extent than nfPPA. Neural correlates of social cognition are varied and warrant additional study as our findings contrast with previous literature that has typically linked lower perspective-taking with atrophy.

Multimodal Semantic Knowledge Assessment –Standard and Preliminary Data in Semantic Variant Primary Progressive Aphasia and Alzheimer’s Disease in Comparison with Vascular Aphasia

Les troubles lexico-sémantiques sont connus pour être l’une des manifestations majeures de l’aphasie, qu’elle soit d’origine vasculaire (comme l’aphasie sémantique -AS-) ou dégénérative (comme l’aphasie sémantique progressive primaire -APPvs- et la maladie d’Alzheimer -MA-). En pratique clinique, ces troubles sont principalement évalués par des tests verbaux, alors que, selon la littérature, le déficit doit être observé dans plusieurs modalités. Le but de cette étude était de créer une batterie française d’évaluation sémantique multimodale appelée EMCS (Évaluation Multimodale des Connaissances Sémantiques), qui étudie, en un temps plus court que les outils existants, l’efficacité de la mémoire sémantique à travers plusieurs tâches multimodales. Quatre-vingt-sept participants témoins français ont été recrutés. Ils ont subi les 10 tâches de la batterie EMCS, à savoir les modalités verbales et non verbales. Pour explorer la sensibilité de la batterie, trois patients AS, deux APPvs et deux MA au stade débutant de la maladie ont réalisé l’EMCS. Analyses et résultats : Les analyses statistiques ont permis d’établir des données normatives, avec des scores en percentiles, et ont mis en évidence, pour les témoins, un effet du niveau d’éducation pour la majorité des tests, un effet d’âge pour plusieurs tâches, mais pas d’effet de sexe. Pour chaque patient, les résultats se sont montrés discriminants par rapport au groupe témoin de référence pour plusieurs tâches, à savoir la dénomination d’images, les connaissances sémantiques sur les célébrités et l’épreuve gustative (p < 0,05). Discussion / Conclusion : La batterie EMCS peut contribuer à identifier, en un temps relativement court, des troubles sémantiques multimodaux chez des patients souffrant d’aphasie vasculaire et dégénérative. Ainsi, cet outil peut être une aide au diagnostic clinique et offre au clinicien la possibilité de déterminer, à un stade précoce, la nature de l’atteinte sémantique (accès ou centrale).

Increased Resolution of Structural MRI at 3T Improves Estimation of Regional Cortical Degeneration in Individual Dementia Patients Using Surface Thickness Maps.

Objective measurement of regional cortical atrophy in individual patients would be a highly desirable adjunct for diagnosis of degenerative dementias. We hypothesized that increasing the resolution of magnetic resonance scans would improve the sensitivity of cortical atrophy detection for individual patients. 46 participants including 8 semantic-variant primary progressive aphasia (svPPA), seven posterior cortical atrophy (PCA), and 31 cognitively unimpaired participants underwent clinical assessment and 3.0T brain scans. SvPPA and PCA were chosen because there is overwhelming prior knowledge of the expected atrophy pattern. Two sets of T1-weighted images with 0.8 mm3 (HighRes) and conventional 1.0 mm3 (ConvRes) resolution were acquired. The cortical ribbon was segmented using FreeSurfer software to obtain surface-based thickness maps. Inter-sequence performance was assessed in terms of cortical thickness and sub-cortical volume reproducibility, signal-to-noise and contrast-to-noise ratios. For clinical cases, diagnostic effect size (Cohen's d) and lesion distribution (z-score and t-value maps) were compared between HighRes and ConvRes scans. The HighRes scans produced higher image quality scores at 90 seconds extra scan time. The effect size of cortical thickness differences between patients and cognitively unimpaired participants was 15-20% larger for HighRes scans. HighRes scans showed more robust patterns of atrophy in expected regions in each and every individual patient. HighRes T1-weighted scans showed superior precision for identifying the severity of cortical atrophy in individual patients, offering a proof-of-concept for clinical translation. Studying svPPA and PCA, two syndromes with well-defined focal atrophy patterns, offers a method to clinically validate and contrast automated algorithms.

Auditory phonological identification impairment in primary progressive aphasia

ObjectiveTo examine the audiological characteristics and neuroanatomical regions associated with auditory phonological identification impairment in primary progressive aphasia (PPA). MethodsTwenty-seven patients with PPA [13 non-fluent/agrammatic variant PPA (nfvPPA), three logopenic variant PPA (lvPPA), seven semantic variant PPA (svPPA), and four mixed type PPA] were included in the study. Neuropsychological, language, audiological, and neuroradiological examinations were also performed. Auditory function examinations consisted of a pure-tone threshold test, a phonological identification task, and temporal auditory acuity tests, such as click counting or fusion. As an evaluation value of phonological identification ability, we calculated the discrepancy scores, which were the smaller discrepancy (left or right ear) in phonological identification ability scores between measured and expected values from the pure-tone threshold. In the neuroradiological examination, we evaluated the regional cerebral blood flow using 123I-iodoamphetamine single-photon emission computed tomography. ResultsEight of the 27 patients were allocated to the impaired phonological identification group, and four were considered to have significant impairment on further analysis. Two of these patients, one with lvPPA and one with mixed type of lvPPA and nfvPPA, showed apparent phonological identification deficits that could be observed in daily life. The discrepancy scores were not significantly related to the results of neuropsychological, language, or any other auditory examinations, except for the click counting score in the left ear. Voxel-based correlation analyses revealed that regional cerebral blood flow in the bilateral superior temporal gyrus and bilateral primary auditory cortex was significantly and positively correlated with phonological identification ability. ConclusionsOur results suggest that progressive dysfunction of the bilateral superior temporal gyrus and bilateral primary auditory cortex due to neurodegenerative diseases leads to phonological identification impairment in PPA syndrome.

A heterozygous splicing variant IVS9-7A > T in intron 9 of the MAPT gene in a patient with right-temporal variant frontotemporal dementia with atypical 4 repeat tauopathy

Right temporal variant frontotemporal dementia, also called right-predominant semantic dementia, often has an unclear position within the framework of the updated diagnostic criteria for behavioral variant frontotemporal dementia or primary progressive aphasia. Recent studies have suggested that this population may be clinically, neuropathologically, and genetically distinct from those with behavioral variant frontotemporal dementia or left-predominant typical semantic variant primary progressive aphasia. Here we describe a Japanese case of right temporal variant frontotemporal dementia with novel heterozygous MAPT mutation Adenine to Thymidine in intervening sequence (IVS) 9 at position -7 from 3ʹ splicing site of intron 9/exon 10 boundary (MAPT IVS9-7A > T). Postmortem neuropathological analysis revealed a predominant accumulation of 4 repeat tau, especially in the temporal lobe, amygdala, and substantia nigra, but lacked astrocytic plaques or tufted astrocytes. Immunoelectron microscopy of the tau filaments extracted from the brain revealed a ribbon-like structure. Moreover, a cellular MAPT splicing assay confirmed that this novel variant promoted the inclusion of exon 10, resulting in the predominant production of 4 repeat tau. These data strongly suggest that the MAPT IVS9-7 A > T variant found in our case is a novel mutation that stimulates the inclusion of exon 10 through alternative splicing of MAPT transcript and causes predominant 4 repeat tauopathy which clinically presents as right temporal variant frontotemporal dementia.

Cortical signature of depressive symptoms in frontotemporal dementia: A surface-based analysis.

Depressive symptoms are frequently reported in patients affected by frontotemporal dementia (FTD). At structural MRI, cortical features of depressed FTD patients have been poorly described. Our objective was to investigate correlations between cortical measures and depression severity in FTD patients. Data were obtained from the Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) database. We included 98 controls and 92 FTD patients, n = 38 behavioral variant FTD (bvFTD), n = 26 non-fluent variant Primary Progressive Aphasia (nfvPPA), and n = 28 semantic variant Primary Progressive Aphasia (svPPA). Patients underwent clinical and cognitive evaluations, as well as a 3D T1-weighted MRI on a 3 Tesla scanner (Siemens, Trio Tim system). Depression was evaluated by means of Geriatric Depression Scale (GDS). Surface-based analysis was performed on T1-weighted images to evaluate cortical thickness, a measure of gray matter integrity, and local gyrification index (lGI), a quantitative metric of cortical folding. Patients affected by svPPA were more depressed than controls at NPI and depression severity at GDS was higher in svPPA and bvFTD. Severity of depression correlated with a decrease in lGI in left precentral and superior frontal gyrus, supramarginal and postcentral gyrus and right precentral, supramarginal, superior parietal and superior frontal gyri. Furthermore, depression severity correlated positively with cortical thickness in the left medial orbitofrontal cortex. We found that lGI was associated with depressive symptoms over brain regions involved in the pathophysiology of major depressive disorder. This finding provides novel insights into the mechanisms underlying psychiatric symptoms in FTD.