Real World Financial Mismanagement in Alzheimer's Disease, Frontotemporal Dementia, and Primary Progressive Aphasia.

Background: Whereas clinical experience in dementia indicates high risk for financial mismanagement, there has been little formal study of real world financial errors in dementia. Objective: We aimed to compare caregiver-reported financial mistakes among people with Alzheimer's disease, behavioral variant frontotemporal dementia (bvFTD), and primary progressive aphasia (PPA). Methods: Caregivers reported whether participants with dementia had made financial mistakes within the last year; and if so, categorized these as resulting from: (a) being too trusting or gullible, (b) being wasteful or careless with money, or (c) trouble with memory. In a pre-registered analysis https://archive.org/details/osf-registrations-vupj7-v1), we examined the hypotheses that (1) financial mistakes due to impaired socioemotional function and diminished sensitivity to negative outcomes are more prevalent in bvFTD than in Alzheimer's disease, and (2) financial mistakes due to memory are more prevalent in Alzheimer's disease than in bvFTD. Exploratory analyses addressed vulnerability in PPA and brain-behavior relationships using voxel-based morphometry. Results: Concordant with our first hypothesis, bvFTD was more strongly associated than Alzheimer's disease with mistakes due to being too trusting/gullible or wasteful/careless; contrary to our second hypothesis, both groups were similarly likely to make mistakes due to memory. No differences were found between Alzheimer's disease and PPA. Exploratory analyses indicated associations between financial errors and atrophy in right prefrontal and insular cortex. Conclusions: Our findings cohere with documented socioemotional and valuation impairments in bvFTD, and with research indicating comparable memory impairment between bvFTD and Alzheimer's disease.

Clinical and cortical trajectories in non-fluent primary progressive aphasia and Alzheimer's disease: A role for emotion processing.

OBJECTIVES: To examine the clinical trajectories and neural correlates of cognitive and emotion processing changes in the non-fluent/agrammatic (nfvPPA) and the logopenic (lvPPA) variants of primary progressive aphasia (PPA). DESIGN: Observational case-control longitudinal cohort study. SETTING: Research clinic of frontotemporal dementia. PARTICIPANTS: This study recruited 29 non-semantic PPA patients (15 nfvPPA and 14 lvPPA) and compared them with 15 Alzheimer's disease (AD) patients and 14 healthy controls. MEASUREMENTS: Participants completed an annual assessment (median = 2 years; range = 1-5 years) of general cognition, emotion processing and structural MRI. Linear mixed effects models investigated clinical and imaging trajectories between groups. RESULTS: Over time, lvPPA showed the greatest cognitive deterioration. In contrast, nfvPPA showed significant decline in emotion recognition, whereas AD showed preserved emotion recognition, even with disease progression. Importantly, lvPPA also developed emotion processing impairments, with disease progression. Both nfvPPA and lvPPA showed continuing cortical atrophy in hallmark language-processing regions associated with these syndromes, together with progressive involvement of the right hemisphere regions, mirroring left hemisphere atrophy patterns at presentation. Decline in emotion processing was associated with bilateral frontal atrophy in nfvPPA and right temporal atrophy in lvPPA. CONCLUSIONS: Our results show divergent clinical courses in nfvPPA and lvPPA, with rapid cognitive and neural deterioration in lvPPA and emotion processing decline in both groups and support the concurrent assessment of cognition and emotion processing in the clinic to inform diagnosis and monitoring in the non-semantic variants of PPA.

Assessing processing speed and its neural correlates in the three variants of primary progressive aphasia with a non-verbal tablet-based task.

Prior research has revealed distinctive patterns of impaired language abilities across the three variants of Primary Progressive Aphasia (PPA): nonfluent/agrammatic (nfvPPA), logopenic (lvPPA) and semantic (svPPA). However, little is known about whether, and to what extent, non-verbal cognitive abilities, such as processing speed, are impacted in PPA patients. This is because neuropsychological tests typically contain linguistic stimuli and require spoken output, being therefore sensitive to verbal deficits in aphasic patients. The aim of this study is to investigate potential differences in processing speed between PPA patients and healthy controls, and among the three PPA variants, using a brief non-verbal tablet-based task (Match) modeled after the WAIS-III digit symbol coding test, and to determine its neural correlates. Here, we compared performance on the Match task between PPA patients (n = 61) and healthy controls (n = 59) and across the three PPA variants. We correlated performance on Match with voxelwise gray and white matter volumes. We found that lvPPA and nfvPPA patients performed significantly worse on Match than healthy controls and svPPA patients. Worse performance on Match across PPA patients was associated with reduced gray matter volume in specific parts of the left middle frontal gyrus, superior parietal lobule, and precuneus, and reduced white matter volume in the left parietal lobe. To conclude, our behavioral findings reveal that processing speed is differentially impacted across the three PPA variants and provide support for the potential clinical utility of a tabled-based task (Match) to assess non-verbal cognition. In addition, our neuroimaging findings confirm the importance of a set of fronto-parietal regions that previous research has associated with processing speed and executive control. Finally, our behavioral and neuroimaging findings combined indicate that differences in processing speed are largely explained by the unequal distribution of atrophy in these fronto-parietal regions across the three PPA variants.

Expressive Prosody in Patients With Focal Anterior Temporal Neurodegeneration.

BACKGROUND AND OBJECTIVES: Progressive focal anterior temporal lobe (ATL) neurodegeneration has been historically called semantic dementia. More recently, semantic variant primary progressive aphasia (svPPA) and semantic behavioral variant frontotemporal dementia (sbvFTD) have been linked with predominant left and right ATL neurodegeneration, respectively. Nonetheless, clinical tools for an accurate diagnosis of sbvFTD are still lacking. Expressive prosody refers to the modulation of pitch, loudness, tempo, and quality of voice used to convey emotional and linguistic information and has been linked to bilateral but right-predominant frontotemporal functioning. Changes in expressive prosody can be detected with semiautomated methods and could represent a useful diagnostic marker of socioemotional functioning in sbvFTD. METHODS: Participants underwent a comprehensive neuropsychological and language evaluation and a 3T MRI at the University of California San Francisco. Each participant provided a verbal description of the picnic scene from the Western Aphasia Battery. The fundamental frequency (f0) range, an acoustic measure of pitch variability, was extracted for each participant. We compared the f0 range between groups and investigated associations with an informant-rated measure of empathy, a facial emotion labeling task, and gray matter (GM) volumes using voxel-based morphometry. RESULTS: Twenty-eight patients with svPPA, 18 with sbvFTD, and 18 healthy controls (HCs) were included. f0 range was significantly different across groups: patients with sbvFTD showed reduced f0 range in comparison with both patients with svPPA (mean difference of -1.4 ± 2.4 semitones; 95% CI -2.4 to -0.4]; p < 0.005) and HCs (mean difference of -1.9 ± 3.0 semitones; 95% CI -3.0 to -0.7]; p < 0.001). A higher f0 range was correlated with a greater informant-rated empathy (r = 0.355; p ≤ 0.05), but not facial emotion labeling. Finally, the lower f0 range was correlated with lower GM volume in the right superior temporal gyrus, encompassing anterior and posterior portions (p < 0.05 FWE cluster corrected). DISCUSSION: Expressive prosody may be a useful clinical marker of sbvFTD. Reduced empathy is a core symptom in sbvFTD; the present results extend this to prosody, a core component of social interaction, at the intersection of speech and emotion. They also inform the long-standing debate on the lateralization of expressive prosody in the brain, highlighting the critical role of the right superior temporal lobe.

Comparing two picture naming tasks in primary progressive aphasia: Insights from behavioural and neural results.

Picture naming tests are widely used to evaluate language impairments in neurodegenerative diseases, especially in Primary Progressive Aphasia (PPA). The available tests differ for many factors affecting the performance, e.g. format of stimuli and their psycholinguistic properties. We aim to identify the most appropriate naming test to be used on PPA according to the clinical and research demands. We investigated the behavioural characteristics, i.e. proportion of correct responses and error type, and their neural correlates in two Italian naming tests, CaGi naming (CaGi) and naming subtest of the Screening for Aphasia in NeuroDegeneration battery (SAND), administered to 52 PPA patients who underwent an FDG-PET scan. We analysed the effectiveness of the tests in distinguishing PPA versus controls and among PPA variants, considering the psycholinguistic variables affecting performance. We explored the brain metabolic correlates of behavioural performance in the tests. SAND, differently from CaGi, has time limits for the response and its items are less frequent and acquired later. SAND and CaGi differed in terms of number of correct responses and error profile, suggesting a higher difficulty to name SAND items compared to CaGi. Semantic errors predominated in CaGi, while anomic and semantic errors were equally frequent in SAND. Both tests distinguished PPA from controls, but SAND outperformed CaGi in discriminating among PPA variants. FDG-PET imaging revealed a shared metabolic involvement of temporal areas associated with lexico-semantic processing, encompassing anterior fusiform, temporal pole, and extending to posterior fusiform in sv-PPA. Concluding, a picture naming test with response time limit and items which are less frequent and acquired later in life, as SAND, may be effective at highlighting subtle distinctions between PPA variants, improving the diagnosis. Conversely, a naming test without time limit for the response, as CaGi, may be useful for a better characterization of the nature of the naming impairment at the behavioural level, eliciting more naming errors than anomia, possibly helping in the development of rehabilitation protocols.

The eyes speak when the mouth cannot: Using eye movements to interpret omissions in primary progressive aphasia.

Though it may seem simple, object naming is a complex multistage process that can be impaired by lesions at various sites of the language network. Individuals with neurodegenerative disorders of language, known as primary progressive aphasias (PPA), have difficulty with naming objects, and instead frequently say "I don't know" or fail to give a vocal response at all, known as an omission. Whereas other types of naming errors (paraphasias) give clues as to which aspects of the language network have been compromised, the mechanisms underlying omissions remain largely unknown. In this study, we used a novel eye tracking approach to probe the cognitive mechanisms of omissions in the logopenic and semantic variants of PPA (PPA-L and PPA-S). For each participant, we identified pictures of common objects (e.g., animals, tools) that they could name aloud correctly, as well as pictures that elicited an omission. In a separate word-to-picture matching task, those pictures appeared as targets embedded among an array with 15 foils. Participants were given a verbal cue and tasked with pointing to the target, while eye movements were monitored. On trials with correctly-named targets, controls and both PPA groups ceased visual search soon after foveating the target. On omission trials, however, the PPA-S group failed to stop searching, and went on to view many foils "post-target". As further indication of impaired word knowledge, gaze of the PPA-S group was subject to excessive "taxonomic capture", such that they spent less time viewing the target and more time viewing related foils on omission trials. In contrast, viewing behavior of the PPA-L group was similar to controls on both correctly-named and omission trials. These results indicate that the mechanisms of omission in PPA differ by variant. In PPA-S, anterior temporal lobe degeneration causes taxonomic blurring, such that words from the same category can no longer be reliably distinguished. In PPA-L, word knowledge remains relatively intact, and omissions instead appear to be caused by downstream factors (e.g., lexical access, phonological encoding). These findings demonstrate that when words fail, eye movements can be particularly informative.

Utility of a Spanish version of Three Words-Three Shapes Test to detect memory impairment in primary progressive aphasia.

INTRODUCTION: Three Words-Three Shapes (3W3S) is a bedside test that assesses verbal and non-verbal memory and has proven useful in staging memory decline in amnestic disorders and primary progressive aphasia. Given its simple structure, the 3W3S can be easily adapted to other languages maintaining the original shapes and only modifying the words. We aim to validate a Spanish version of the 3W3S test and establish whether memory loss patterns present in amnesic disorders associated with Alzheimer's etiology and PPA were correctly characterized. METHOD: The translation and adaptation of the 3W3S were performed according to standardized guidelines and applied to a cohort of patients with Dementia of Alzheimer's type (DAT = 20), mild cognitive impairment (aMCI= 20), primary progressive aphasia (PPA = 20), and healthy controls (HC = 20). RESULTS: In verbal memory performance, PPA patients' score was lower than that of MCI and HC and similar to DAT's in the effortless encoding (p < 0.001), delayed recall (p < 0.001), and recognition (p < 0.012). For non-verbal performance, PPA patients performed better than DAT and similar to HC and MCI subjects (p < 0.001). CONCLUSIONS: Results show good applicability of 3W3S to determine memory function in PPA patients, independently from language ability. Visual and verbal components of memory are dissociated in PPA.

Executive functions in primary progressive aphasia: A meta-analysis.

Executive functions (EFs) refer to a set of cognitive processes, specifically shifting, inhibition, updating of working memory, and are involved in the cognitive control of behavior. Conflicting results have been reported regarding impairments of EFs in Primary Progressive Aphasia (PPA). We performed a multi-level meta-analysis to confirm whether deficits of EFs exist in this population, focusing on a common EFs composite, and the components shifting, inhibition and updating separately. We included 141 studies that report on 294 EFs tasks. The overall mean weighted effect size was large (d = -1,28), indicating poorer EFs in PPA as compared to age-matched cognitively healthy controls. Differences between effect sizes of the EFs components were not significant, indicating all components are affected similarly. Overall, moderator analysis revealed that PPA variant and disease duration were significant moderators of performance, while task modality and years of education were not. The non-fluent/agrammatic PPA and the logopenic PPA variants were similarly affected, but the semantic variant was affected to a lesser extent. We discuss implications for clinical and research settings, and future research.

Characterization of the logopenic variant of Primary Progressive Aphasia: A systematic review and meta-analysis.

The linguistic and anatomical variability of the logopenic variant of Primary Progressive Aphasia (lv-PPA) as defined by current diagnostic criteria has been the topic of an intense debate. The present review and meta-analysis aims at characterizing the profile of lv-PPA, by a comprehensive analysis of the available literature on the neuropsychological, neuroimaging, electrophysiological, pathological, and genetic features of lv-PPA. We conducted a systematic bibliographic search, leading to the inclusion of 207 papers. Of them, 12 were used for the Anatomical Likelihood Estimation meta-analysis on grey matter revealed by magnetic resonance imaging data. The results suggest that the current guidelines outline a relatively consistent syndrome, characterized by a core set of linguistic and, to a lesser extent, non-linguistic deficits, mirroring the involvement of left temporal and parietal regions typically affected by Alzheimer Disease pathology. Variations of the lv-PPA profile are discussed in terms of heterogeneity of the neuropsychological instruments and the diagnostic criteria adopted.

The affective, behavioural, and cognitive reactions to a diagnosis of Primary Progressive Aphasia: A qualitative descriptive study.

OBJECTIVES: Receiving a diagnosis of neurodegenerative disorder is life changing. Primary progressive aphasia is one such disease. Understanding how receiving this diagnosis impacts on individuals may help plan support services. However, limited qualitative research from the perspectives of people with Primary Progressive Aphasia are available for suitable care planning. Current literature primarily focuses on experiences of family members. The present study aims to fill this gap by examining the affective, behavioural, and cognitive experiences of people with Primary Progressive Aphasia. METHODS: Semi-structured interviews were conducted with six participants with PPA. A qualitative descriptive approach was used to describe responses from participants on: (i) what they experienced prior to receiving their diagnosis; (ii) their experience of receiving the diagnosis; and (iii) how they were living with their PPA. Verbatim transcripts were analysed using thematic analysis to identify main themes. RESULTS: Analysis revealed a superordinate theme of Multifaceted Grief with subthemes described in sequence of research questions posed, representing the three phases of Pre-Diagnosis, Time of Diagnosis, and Post-Diagnosis. Themes collectively revealed participants' ongoing experience of loss in dealing with the evolving challenges of Primary Progressive Aphasia. Experiences of loss emerged with descriptions of feelings, thoughts, and limitations in relation to changes imposed by the illness, impacting daily activities and life roles central to participants' pre-diagnosis sense of self. CONCLUSION: Participants' affective, behavioural and cognitive reactions to their Primary Progressive Aphasia diagnosis marks the onset of Multifaceted Grief borne of loss of communication and cognition. Participants expressed a need for information regarding a possible Primary Progressive Aphasia trajectory and support to enable a successful transition as their disease progressed. Collaborative engagement between speech pathologists and people with Primary Progressive Aphasia incorporates addressing all levels of the International Classification of Functioning and Health by considering neurological, psychological, and psychosocial experiences of the person with the diagnosis.

Writing errors in primary progressive aphasia.

Peripheral errors in writing, that is errors produced download the spelling, have been occasionally described in primary progressive aphasia (PPA), but the possibility that these errors might be a marker of parkinsonism associated to some subtypes of PPA has not been explored. We investigated whether errors of peripheral nature characterize the writing disorder in PPA when associated with parkinsonian signs (PSs). Subgroups of PPA without PSs and with PSs were studied. The proportion of the central and peripheral errors in writing words and pseudowords was calculated in each group. In writing words, central errors significantly exceeded peripheral errors in subgroups without PSs. The higher the number of peripheral errors, the higher the probability of presenting PSs. No relation emerged between any error and the Unified Parkinson's Disease Rating Scale, but both types of errors correlated with measures of cognitive ability. Peripheral errors emerge when PSs are associated with PPA and may be linked to a decay of the cognitive control on movement, possibly involving the right hemisphere. Peripheral errors have clinical relevance in PPA, to the extent that they may assume the significance of a marker of specific subtypes and can help to outline the specific clinical picture of individual patients.

Primary Progressive Aphasia Presenting With Neuropsychiatric Symptoms.

We describe a case of primary progressive aphasia (PPA) with an underlying neurodegenerative motor disorder (possible ALS or PSP), presenting with symptoms of irritability and frustration, that were misdiagnosed and treated as a primary psychiatric disorder, i.e. depression. PPA is a rare neurodegenerative disorder characterized by insidious onset and gradual progression of speech and language impairment. We emphasize that PPA can initially masquerade as or be accompanied by neuropsychiatric symptoms potentially leading to misdiagnosis. Most prevalent neuropsychiatric symptoms reported in the PPA literature are agitation, depression, anxiety, apathy, irritability, abnormal appetite and disinhibition. To ensure early diagnosis of PPA, if a patient presents with new psychiatric symptoms accompanied by new onset speech and/or language impairment, referral to a specialist (i.e., neurologist and/or speech-language pathologist) is recommended.

The natural history of primary progressive aphasia: beyond aphasia.

INTRODUCTION: Primary progressive aphasia (PPA) is divided into three prototypical subtypes that are all characterized by their single core symptom of aphasia. Although later in their course, other cognitive, behavioral, and motor domains may become involved, little is known about the progression profile of each subtype relative to the other subtypes. METHODS: In this longitudinal retrospective cohort study, based on the recent biomarker-supported diagnostic criteria, 24 subjects diagnosed with semantic variant (svPPA), 22 with non-fluent variant (nfvPPA), and 18 with logopenic variant (lvPPA) were collected and followed up for 1-6 years. Symptom distribution, cognitive test and neuropsychiatric inventory scores, and progression into another syndrome were assessed. RESULTS: Over time, lvPPA progressed with broader language problems (PPA-extended) and nfvPPA progressed to mutism, whereas semantic impairment remained the major problem in svPPA. Apart from linguistic problems, svPPA developed pronounced behavioral disturbances, whereas lvPPA exhibited a greater cognitive decline. By contrast, in nfvPPA motor deficits were more common. Furthermore, within 5 years (IQR = 2.5) after clinical onset, 65.6% of the patients additionally fulfilled the clinical criteria for another neurodegenerative syndrome (PPA-plus). Fourteen out of 24 (58%) svPPA patients additionally met the diagnostic criteria of behavioral variant frontotemporal dementia (5.1 years, IQR = 1.1), whereas the clinical features of 15/18 (83%) lvPPA patients were consistent with Alzheimer disease dementia (4.5 years IQR = 3.4). Furthermore, 12/22 (54%) of the subjects with the nfvPPA progressed to meet the diagnostic criteria of corticobasal syndrome, progressive supranuclear palsy, or motor neuron disease (5.1 years IQR = 3.4). DISCUSSION: Despite aphasia being the initial and unique hallmark of the syndrome, our longitudinal results showed that PPA is not a language limited disorder and progression differs widely for each subtype, both with respect to the nature of symptoms and disease duration.

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

PURPOSE: 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). METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Language training for oral and written naming impairment in primary progressive aphasia: a review.

BACKGROUND: Primary progressive aphasia (PPA) is a neurodegenerative disorder characterized by a gradual, insidious and progressive loss of language abilities, with naming difficulties being an early and persistent impairment common to all three variants. In the absence of effective pharmacological treatments and given the progressive nature of the disorder, in the past few decades, many studies have investigated the effectiveness of language training to minimize the functional impact of word-finding difficulties in daily life. MAIN BODY: We review language treatments most commonly used in clinical practice among patients with different variants of PPA, with a focus on the enhancement of spoken and written naming abilities. Generalization of gains to the ability to name untrained stimuli or to other language abilities and the maintenance of these results over time are also discussed. Forty-eight studies were included in this literature review, identifying four main types of language treatment: a) lexical retrieval treatment, b) phonological and/or orthographic treatment, c) semantic treatment, and d) a multimodality approach treatment. Overall, language training is able to induce immediate improvements of naming abilities in all variants of PPA. Moreover, despite the large variability among results, generalization and long-term effects can be recorded after the training. The reviewed studies also suggest that one factor that determines the choice of a particular approach is the compromised components of the lexical/semantic processing system. CONCLUSION: The majority of studies have demonstrated improvements of naming abilities following language treatments. Given the progressive nature of PPA, it is essential to apply language treatment in the early stages of the disease.

Clinical, Imaging, and Pathologic Characteristics of Patients With Right vs Left Hemisphere-Predominant Logopenic Progressive Aphasia.

OBJECTIVE: To assess and compare demographic, clinical, neuroimaging, and pathologic characteristics of a cohort of patients with right hemisphere-predominant vs left hemisphere-predominant logopenic progressive aphasia (LPA). METHODS: This is a case-control study of patients with LPA who were prospectively followed at Mayo Clinic and underwent [18F]-fluorodeoxyglucose (FDG) PET scan. Patients were classified as rLPA if right temporal lobe metabolism was ≥1 SD lower than left temporal lobe metabolism. Patients with rLPA were frequency-matched 3:1 to typical left-predominant LPA based on degree of asymmetry and severity of temporal lobe metabolism. Patients were compared on clinical, imaging (MRI, FDG-PET, ß-amyloid, and tau-PET), and pathologic characteristics. RESULTS: Of 103 prospectively recruited patients with LPA, 8 (4 female) were classified as rLPA (7.8%); all patients with rLPA were right-handed. Patients with rLPA had milder aphasia based on the Western Aphasia Battery-Aphasia Quotient (p = 0.04) and less frequent phonologic errors (p = 0.015). Patients with rLPA had shorter survival compared to typical LPA: hazard ratio 4.0 (1.2-12.9), p = 0.02. There were no other differences in demographics, handedness, genetics, or neurologic or neuropsychological tests. Compared to the 24 frequency-matched patients with typical LPA, patients with rLPA showed greater frontotemporal hypometabolism of the nondominant hemisphere on FDG-PET and less atrophy in amygdala and hippocampus of the dominant hemisphere. Autopsy evaluation revealed a similar distribution of pathologic findings in both groups, with Alzheimer disease pathologic changes being the most frequent pathology. CONCLUSIONS: rLPA is associated with less severe aphasia but has shorter survival from reported symptom onset than typical LPA, possibly related to greater involvement of the nondominant hemisphere.

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

BACKGROUND: Severe socio-emotional impairments characterize the behavioral variant of frontotemporal dementia (bvFTD). However, literature reports social cognition disorders in other dementias. OBJECTIVE: In this study, we investigated the accuracy of social cognition performances in the early and differential diagnosis of bvFTD. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

A double dissociation between plural and possessive "s": Evidence from the Morphosyntactic Generation test.

People with aphasia demonstrate impaired production of bound inflectional morphemes, such as noun plurals and possession. They often show greater difficulty in marking possession versus plurality. Using a new tool for eliciting language, the Morphosyntactic Generation test, we assessed people with primary progressive aphasia and those in the acute and chronic phase following left hemisphere stroke. Clinical profiles were associated with different strengths and weaknesses in language production. Performance of the plural was stronger than possessive in group analyses. However, some individuals demonstrated the inverse pattern of performance. These participants provide counter-evidence to the theory that difficulty with marking possessives is purely the result of their greater cognitive-linguistic complexity and support a functional double dissociation between possessives and plurals. The deficits resulted from morphosyntactic impairment. Future work is needed to understand why plural and possessive markers were differently sensitive to neurological disorders of language.

Smaller Volume in Left-Lateralized Brain Structures Correlates with Greater Experience of Negative Non-target Emotions in Neurodegenerative Diseases.

Subjective emotional experience that is congruent with a given situation (i.e., target emotions) is critical for human survival (e.g., feeling disgusted in response to contaminated food motivates withdrawal behaviors). Neurodegenerative diseases including frontotemporal dementia and Alzheimer's disease affect brain regions critical for cognitive and emotional functioning, resulting in increased experience of emotions incongruent with the situation (i.e., non-target emotions, such as feeling happy when seeing someone grieving). We examined neuroanatomical correlates of subjective experience of non-target emotions in 147 patients with neurodegenerative diseases and 26 healthy individuals. Participants watched three films intended to elicit particular target emotions and rated their experience of negative and positive target and non-target emotions after watching each film. We found that smaller volume in left hemisphere regions (e.g., caudate, putamen, and dorsal anterior insula) was associated with greater experience of negative non-target emotions. Follow-up analyses confirmed that these effects were left-lateralized. No correlates emerged for positive non-target emotions. These findings suggest that volume loss in left-hemisphere regions produces a more diffuse, incongruent experience of non-target emotions. These findings provide a potential neuroanatomical basis for understanding how subjective emotional experience is constructed in the brain and how this can be disrupted in neurodegenerative disease.

When affect overlaps with concept: emotion recognition in semantic variant of primary progressive aphasia.

The most recent theories of emotions have postulated that their expression and recognition depend on acquired conceptual knowledge. In other words, the conceptual knowledge derived from prior experiences guide our ability to make sense of such emotions. However, clear evidence is still lacking to contradict more traditional theories, considering emotions as innate, distinct and universal physiological states. In addition, whether valence processing (i.e. recognition of the pleasant/unpleasant character of emotions) also relies on semantic knowledge is yet to be determined. To investigate the contribution of semantic knowledge to facial emotion recognition and valence processing, we conducted a behavioural and neuroimaging study in 20 controls and 16 patients with the semantic variant of primary progressive aphasia, a neurodegenerative disease that is prototypical of semantic memory impairment, and in which an emotion recognition deficit has already been described. We assessed participants' knowledge of emotion concepts and recognition of 10 basic (e.g. anger) or self-conscious (e.g. embarrassment) facial emotional expressions presented both statically (images) and dynamically (videos). All participants also underwent a brain MRI. Group comparisons revealed deficits in both emotion concept knowledge and emotion recognition in patients, independently of type of emotion and presentation. These measures were significantly correlated with each other in patients and with semantic fluency in patients and controls. Neuroimaging analyses showed that both emotion recognition and emotion conceptual knowledge were correlated with reduced grey matter density in similar areas within frontal ventral, temporal, insular and striatal regions, together with white fibre degeneration in tracts connecting frontal regions with each other as well as with temporal regions. We then performed a qualitative analysis of responses made during the facial emotion recognition task, by delineating valence errors (when one emotion was mistaken for another of a different valence), from other errors made during the emotion recognition test. We found that patients made more valence errors. The number of valence errors correlated with emotion conceptual knowledge as well as with reduced grey matter volume in brain regions already retrieved to correlate with this score. Specificity analyses allowed us to conclude that this cognitive relationship and anatomical overlap were not mediated by a general effect of disease severity. Our findings suggest that semantic knowledge guides the recognition of emotions and is also involved in valence processing. Our study supports a constructionist view of emotion recognition and valence processing, and could help to refine current theories on the interweaving of semantic knowledge and emotion processing.