Time from injury and age interact in relationship with perceived quality of life outcomes following vocation-focused neuropsychological rehabilitation.

At the group level, community-based neuropsychological rehabilitation interventions with a vocational focus are generally effective among individuals with brain injuries. However, individual participants vary significantly in the extent of their improvement, prompting attempts to elucidate individual, injury-related, and environmental factors affecting prognosis. In this study, we examined the relationships between one such factor - "time from injury" (the time between injury and intervention) - and two outcome measures: employment status and perceived quality of life (PQoL), in 157 brain injury survivors, before and after a holistic neuropsychological vocational rehabilitation program. We also examined whether relationships between the variables were moderated by age at onset of treatment and injury severity. In the entire sample, both the proportion of employed participants and average PQoL increased following program participation. Neither, time from injury, severity, nor age at onset of treatment predicted the increase in employment proportion, and severity was not a significant predictor of PQoL. However, an interactive effect indicated that when treatment was started at a younger age, longer time from injury predicted higher levels of PQoL, but when treatment was started at older ages, longer time from injury predicted lower levels of PQoL. When interpreted alongside existing literature, these results suggest that delaying vocational components of rehabilitation can be beneficial for younger participants, while the effectiveness of vocational rehabilitation can be maximized by starting as early as possible among older participants. Most importantly, regardless of age, it appears that vocational rehabilitation can be effective even when initiated many years after injury.

Social Behavior Observer Checklist: Patterns of Spontaneous Behaviors Differentiate Patients With Neurodegenerative Disease From Healthy Older Adults.

Neurodegenerative disease syndromes often affect personality and interpersonal behavior in addition to cognition, but there are few structured observational measures of altered social demeanor validated for this population. We developed the Social Behavior Observer Checklist (SBOCL), a 3-min checklist tool, to facilitate identification of patterns of interpersonal behavior that are diagnostically relevant to different neurodegenerative syndromes. Research assistants without formal clinical training in dementia used the SBOCL to describe participants' behavior, including 125 healthy older adults and 357 patients diagnosed with one of five neurodegenerative disease syndromes: 135 behavioral variant frontotemporal dementia (bvFTD), 57 semantic variant primary progressive aphasia (svPPA), 51 non-fluent variant PPA (nfvPPA), 65 progressive supranuclear palsy (PSP), and 49 amyloid-positive Alzheimer's disease syndrome (AD), all of whom had concurrent 3D T1 MRI scans available for voxel-based morphometry analysis. SBOCL item interrater reliability ranged from moderate to very high, and score elevations showed syndrome-specific patterns. Subscale scores derived from a degree*frequency product of the items had excellent positive predictive value for identifying patients. Specifically, scores above 2 on the Disorganized subscale, and above 3 on the Reactive and Insensitive subscales, were not seen in any healthy controls but were found in many patients with bvFTD, svPPA, nfvPPA, PSP, and AD syndromes. Both the Disorganized and Reactive subscale scores showed significant linear relationships with frontal and temporal gray matter volume that generalized across syndromes. With these initial psychometric characteristics, the SBOCL may be a useful measure to help non-experts identify patients who are appropriate for additional specialized dementia evaluation, without adding time to patient encounters or requiring the presence of an informant.

Salience driven attention is pivotal to understanding others' intentions.

Interpreting others' beliefs, desires and intentions is known as "theory of mind" (ToM), and is often evaluated using simplified measurement tools, which may not correctly reflect the brain circuits that are required for real-life ToM functioning. We aimed to identify the brain structures necessary to correctly infer intentions from realistic scenarios by administering The Awareness of Social Inference Test, Enriched subtest to 47 patients with behavioural variant frontotemporal dementia, 24 patients with progressive supranuclear palsy syndrome, 31 patients with Alzheimer's syndrome, and 77 older healthy controls. Neuroimaging data was analyzed using voxel based morphometry, and participants' understanding of intentions was correlated with voxel-wise and region-of interest data. We found that structural integrity of the cinguloinsular cortex in the salience network (SN) was more pivotal for accurate ToM than previously described, emphasizing the importance of the SN for selectively recognizing and attending to social cues during ToM inferences.

Efficacy of Postacute Neuropsychological Rehabilitation for Patients with Acquired Brain Injuries is Maintained in the Long-Term.

OBJECTIVES: We examined the long-term maintenance of treatment outcomes in patients with acquired brain injuries who participated in community-based neuropsychological rehabilitation (NR) programs, in a prospective, within-subject, longitudinal, partial double-blind cohort study. METHODS: One hundred forty-three patients (39 females, mean age 33.5 years) who had experienced a brain injury (BI) (mean time since injury 3.95 years) were referred to a postacute community-based NR institute. Patients participated in one of the three programs aimed at improving their functional outcome: comprehensive-holistic neuropsychological rehabilitation, vocational-focused neuropsychological rehabilitation, and individual neuropsychological rehabilitation. Self-reported data regarding employment, community integration, perceived quality of life (PQoL), and mood were collected at program start and end, and annually for 3 years post program completion. Group placement was based on clinical considerations, such that the study did not aim to compare the programs, but rather to assess their long-term benefits. RESULTS: Employment status and stability, community integration, and PQoL improved significantly after program completion and continued to improve for the following 3 years. The proportion of individuals with mood disturbances did not change during or after the programs. CONCLUSIONS: A clear consensus regarding BI rehabilitation is that long-term maintenance of treatment outcomes is imperative to its efficacy. Our findings suggest that postacute NR programs provide participants with various tools, skills, and psychological perspectives that they continue to gain from and generalize to real life after program completion, reflecting transformational processes with stable long-term benefits.

Corticobasal syndrome with visual hallucinations and probable REM-sleep behavior disorder: an autopsied case report of a patient with CBD and LBD pathology.

Corticobasal syndrome and dementia with Lewy bodies are clinical presentations with unique and overlapping features but distinct pathological substrates. We report the case of an 80 year-old man who presented with apraxia, rigidity, slowness, right arm myoclonus, a 10-year history of probable REM-sleep behavior disorder, and later developed visual hallucinations. At autopsy, he had pathological features of corticobasal degeneration, and Lewy body disease confined to the brainstem. This report highlights the importance of considering co-existing pathologies when a clinical presentation defies categorization, and demonstrates that salient features of dementia with Lewy bodies may result from pathology limited to the brainstem.

Emotion detection deficits and changes in personality traits linked to loss of white matter integrity in primary progressive aphasia.

Non-cognitive features including personality changes are increasingly recognized in the three PPA variants (semantic-svPPA, non fluent-nfvPPA, and logopenic-lvPPA). However, differences in emotion processing among the PPA variants and its association with white matter tracts are unknown. We compared emotion detection across the three PPA variants and healthy controls (HC), and related them to white matter tract integrity and cortical degeneration. Personality traits in the PPA group were also examined in relation to white matter tracts. Thirty-three patients with svPPA, nfvPPA, lvPPA, and 32 HC underwent neuropsychological assessment, emotion evaluation task (EET), and MRI scan. Patients' study partners were interviewed on the Clinical Dementia Rating Scale (CDR) and completed an interpersonal traits assessment, the Interpersonal Adjective Scale (IAS). Diffusion tensor imaging of uncinate fasciculus (UF), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), and voxel-based morphometry to derive gray matter volumes for orbitofrontal cortex (OFC), anterior temporal lobe (ATL) regions were performed. In addition, gray matter volumes of white matter tract-associated regions were also calculated: inferior frontal gyrus (IFG), posterior temporal lobe (PTL), inferior parietal lobe (IPL) and occipital lobe (OL). ANCOVA was used to compare EET performance. Partial correlation and multivariate linear regression were conducted to examine association between EET and neuroanatomical regions affected in PPA. All three variants of PPA performed significantly worse than HC on EET, and the svPPA group was least accurate at recognizing emotions. Performance on EET was related to the right UF, SLF, and ILF integrity. Regression analysis revealed EET performance primarily relates to the right UF integrity. The IAS subdomain, cold-hearted, was also associated with right UF integrity. Disease-specific emotion recognition and personality changes occur in the three PPA variants and are likely associated with disease-specific neuroanatomical changes. Loss of white matter integrity contributes as significantly as focal atrophy in behavioral changes in PPA.

A neural network underlying intentional emotional facial expression in neurodegenerative disease.

Intentional facial expression of emotion is critical to healthy social interactions. Patients with neurodegenerative disease, particularly those with right temporal or prefrontal atrophy, show dramatic socioemotional impairment. This was an exploratory study examining the neural and behavioral correlates of intentional facial expression of emotion in neurodegenerative disease patients and healthy controls. One hundred and thirty three participants (45 Alzheimer's disease, 16 behavioral variant frontotemporal dementia, 8 non-fluent primary progressive aphasia, 10 progressive supranuclear palsy, 11 right-temporal frontotemporal dementia, 9 semantic variant primary progressive aphasia patients and 34 healthy controls) were video recorded while imitating static images of emotional faces and producing emotional expressions based on verbal command; the accuracy of their expression was rated by blinded raters. Participants also underwent face-to-face socioemotional testing and informants described participants' typical socioemotional behavior. Patients' performance on emotion expression tasks was correlated with gray matter volume using voxel-based morphometry (VBM) across the entire sample. We found that intentional emotional imitation scores were related to fundamental socioemotional deficits; patients with known socioemotional deficits performed worse than controls on intentional emotion imitation; and intentional emotional expression predicted caregiver ratings of empathy and interpersonal warmth. Whole brain VBMs revealed a rightward cortical atrophy pattern homologous to the left lateralized speech production network was associated with intentional emotional imitation deficits. Results point to a possible neural mechanisms underlying complex socioemotional communication deficits in neurodegenerative disease patients.

Distinct Subtypes of Behavioral Variant Frontotemporal Dementia Based on Patterns of Network Degeneration.

IMPORTANCE: Clearer delineation of the phenotypic heterogeneity within behavioral variant frontotemporal dementia (bvFTD) will help uncover underlying biological mechanisms and improve clinicians' ability to predict disease course and to design targeted management strategies. OBJECTIVE: To identify subtypes of bvFTD syndrome based on distinctive patterns of atrophy defined by selective vulnerability of specific functional networks targeted in bvFTD using statistical classification approaches. DESIGN, SETTING AND PARTICIPANTS: In this retrospective observational study, 90 patients meeting the Frontotemporal Dementia Consortium consensus criteria for bvFTD underwent evaluation at the Memory and Aging Center of the Department of Neurology at University of California, San Francisco. Patients underwent a multidisciplinary clinical evaluation, including clinical demographics, genetic testing, symptom evaluation, neurologic examination, neuropsychological bedside testing, and socioemotional assessments. All patients underwent structural magnetic resonance imaging at their earliest evaluation at the memory clinic. From each patient's structural imaging scans, the mean volumes of 18 regions of interest (ROI) constituting the functional networks specifically vulnerable in bvFTD, including the salience network (SN), with key nodes in the frontoinsula and pregenual anterior cingulate, and the semantic appraisal network (SAN), anchored in the anterior temporal lobe and subgenual cingulate, were estimated. Principal component and cluster analyses of ROI volumes were used to identify patient clusters with anatomically distinct atrophy patterns. Data were collected from from June 19, 2002, to January 13, 2015. MAIN OUTCOMES AND MEASURES: Evaluation of brain morphology and other clinical features, including presenting symptoms, neurologic examination signs, neuropsychological performance, rate of dementia progression, and socioemotional function, in each patient cluster. RESULTS: Ninety patients (54 men [60%]; 36 women [40%]; mean [SD] age at evaluation, 55.1 [9.7] years) were included in the analysis. Four subgroups of patients with bvFTD with distinct anatomic patterns of network degeneration were identified, including 2 salience network-predominant subgroups (frontal/temporal [SN-FT] and frontal [SN-F]), a semantic appraisal network-predominant group (SAN), and a subcortical-predominant group. Subgroups demonstrated distinct patterns of cognitive, socioemotional, and motor symptoms, as well as genetic compositions and estimated rates of disease progression. CONCLUSIONS AND RELEVANCE: Divergent patterns of vulnerability in specific functional network components make an important contribution to the clinical heterogeneity of bvFTD. The data-driven anatomic classification identifies biologically meaningful anatomic phenotypes and provides a replicable approach to disambiguate the bvFTD syndrome.

Cognition and neuropsychiatry in behavioral variant frontotemporal dementia by disease stage.

OBJECTIVE: To characterize the cognitive and neuropsychiatric symptoms of patients with behavioral variant frontotemporal dementia (bvFTD) over the natural course of the disease. METHODS: We examined the initial and subsequent neuropsychological test performance and neuropsychiatric symptoms in a large cohort of patients with bvFTD (n = 204) across progressive stages of disease as measured by the Clinical Dementia Rating (CDR). We also compared cognitive and neuropsychiatric impairments of patients with bvFTD to those of an age-matched cohort with Alzheimer disease (AD) dementia (n = 674). RESULTS: At the earliest stage (CDR = 0.5), patients with bvFTD had profound neuropsychiatric disturbances, insensitivity to errors, slower response times, and poor naming, with intact attention span, memory, and facial affect naming. Tests continuing to show progressive, statistically significant stepwise declines after the CDR = 1 stage included free recall, visuoconstruction, set-shifting, error insensitivity, semantic fluency, design fluency, emotion naming, calculations, confrontation naming, syntax comprehension, and verbal agility. At CDR = 0.5, patients with bvFTD significantly outperformed patients with AD in episodic memory and were faster in set-shifting, while scoring quantitatively worse in lexical fluency, emotion naming, and error sensitivity. The overall rate of disease progression in bvFTD was more rapid than in AD. CONCLUSION: There are distinct patterns of cognitive deficits differentiating the earlier and later disease stages in bvFTD, with the pattern of cognitive decline revealing in greater detail the natural history of the disease. These cognitive symptoms are readily apparent clinical markers of dysfunction in the principal brain networks known to undergo molecular and anatomical changes in bvFTD, thus are important indicators of the evolving pathology in individual patients.

Neural substrates of spontaneous narrative production in focal neurodegenerative disease.

Conversational storytelling integrates diverse cognitive and socio-emotional abilities that critically differ across neurodegenerative disease groups. Storytelling patterns may have diagnostic relevance and predict anatomic changes. The present study employed mixed methods discourse and quantitative analyses to delineate patterns of storytelling across focal neurodegenerative disease groups, and to clarify the neuroanatomical contributions to common storytelling characteristics. Transcripts of spontaneous social interactions of 46 participants (15 behavioral variant frontotemporal dementia (bvFTD), 7 semantic variant primary progressive aphasia (svPPA), 12 Alzheimer's disease (AD), and 12 healthy older normal controls (NC)) were analyzed for storytelling frequency and characteristics, and videos of the interactions were rated for patients' level of social attentiveness. Compared to controls, svPPAs told more stories and autobiographical stories, and perseverated on aspects of self during the interaction, whereas ADs told fewer autobiographical stories than NCs. svPPAs and bvFTDs were rated as less attentive to social cues. Aspects of storytelling were related to diverse cognitive and socio-emotional functions, and voxel-based anatomic analysis of structural magnetic resonance imaging revealed that temporal organization, narrative evaluations patterns, and social attentiveness correlated with atrophy corresponding to known intrinsic connectivity networks, including the default mode, limbic, salience, and stable task control networks. Differences in spontaneous storytelling among neurodegenerative groups elucidated diverse cognitive, socio-emotional, and neural contributions to narrative production, with implications for diagnostic screening and therapeutic intervention.

Neural basis of motivational approach and withdrawal behaviors in neurodegenerative disease.

INTRODUCTION: The Behavioral Inhibition System (BIS) and the Behavioral Activation System (BAS) have been theorized as neural systems that regulate approach/withdrawal behaviors. Behavioral activation/inhibition balance may change in neurodegenerative disease based on underlying alterations in systems supporting motivation and approach/withdrawal behaviors, which may in turn be reflected in neuropsychiatric symptoms. METHOD: A total of 187 participants (31 patients diagnosed with behavioral variant of FTD [bvFTD], 13 semantic variant of primary progressive aphasia [svPPA], 14 right temporal variant FTD [rtFTD], 54 Alzheimer's disease [AD], and 75 older healthy controls [NCs]) were included in this study. Changes in behavioral inhibition/activation were measured using the BIS/BAS scale. We analyzed the correlation between regional atrophy pattern and BIS/BAS score, using voxel-based morphometry (VBM). RESULTS: ADs had significantly higher BIS scores than bvFTDs and NCs. bvFTDs activation-reward response (BAS-RR) was significantly lower than ADs and NCs, though their activation-drive (BAS-D) was significantly higher than in ADs. Both AD and rtFTD patients had abnormally low activation fun-seeking (BAS-FS) scores. BIS score correlated positively with right anterior cingulate and middle frontal gyrus volume, as well as volume in the right precentral gyrus and left insula/operculum. CONCLUSIONS: AD, bvFTD, and rtFTD patients show divergent patterns of change in approach/withdrawal reactivity. High BIS scores correlated with preservation of right-predominant structures involved in task control and self-protective avoidance of potentially negative reinforcers. Damage to these regions in bvFTD may create a punishment insensitivity that underlies patients' lack of self-consciousness in social contexts.

Impaired Recognition and Regulation of Disgust Is Associated with Distinct but Partially Overlapping Patterns of Decreased Gray Matter Volume in the Ventroanterior Insula.

BACKGROUND: The ventroanterior insula is implicated in the experience, expression, and recognition of disgust; however, whether this brain region is required for recognizing disgust or regulating disgusting behaviors remains unknown. METHODS: We examined the brain correlates of the presence of disgusting behavior and impaired recognition of disgust using voxel-based morphometry in a sample of 305 patients with heterogeneous patterns of neurodegeneration. Permutation-based analyses were used to determine regions of decreased gray matter volume at a significance level p <= .05 corrected for family-wise error across the whole brain and within the insula. RESULTS: Patients with behavioral variant frontotemporal dementia and semantic variant primary progressive aphasia were most likely to exhibit disgusting behaviors and were, on average, the most impaired at recognizing disgust in others. Imaging analysis revealed that patients who exhibited disgusting behaviors had significantly less gray matter volume bilaterally in the ventral anterior insula. A region of interest analysis restricted to behavioral variant frontotemporal dementia and semantic variant primary progressive aphasia patients alone confirmed this result. Moreover, impaired recognition of disgust was associated with decreased gray matter volume in the bilateral ventroanterior and ventral middle regions of the insula. There was an area of overlap in the bilateral anterior insula where decreased gray matter volume was associated with both the presence of disgusting behavior and impairments in recognizing disgust. CONCLUSIONS: These findings suggest that regulating disgusting behaviors and recognizing disgust in others involve two partially overlapping neural systems within the insula. Moreover, the ventral anterior insula is required for both processes.

Self-awareness in neurodegenerative disease relies on neural structures mediating reward-driven attention.

Accurate self-awareness is essential for adapting one's tasks and goals to one's actual abilities. Patients with neurodegenerative diseases, particularly those with right frontal involvement, often present with poor self-awareness of their functional limitations that may exacerbate their already jeopardized decision-making and behaviour. We studied the structural neuroanatomical basis for impaired self-awareness among patients with neurodegenerative disease and healthy older adults. One hundred and twenty-four participants (78 patients with neurodegenerative diseases including Alzheimer's disease, behavioural variant frontotemporal dementia, right-temporal frontotemporal dementia, semantic variant and non-fluent variant primary progressive aphasia, and 46 healthy controls) described themselves on the Patient Competency Rating Scale, rating observable functioning across four domains (daily living activities, cognitive, emotional control, interpersonal). All participants underwent structural magnetic resonance imaging. Informants also described subjects' functioning on the same scale. Self-awareness was measured by comparing self and informant ratings. Group differences in discrepancy scores were analysed using general linear models, controlling for age, sex and disease severity. Compared with controls, patients with behavioural variant frontotemporal dementia overestimated their functioning in all domains, patients with Alzheimer's disease overestimated cognitive and emotional functioning, patients with right-temporal frontotemporal dementia overestimated interpersonal functioning, and patients with non-fluent aphasia overestimated emotional and interpersonal functioning. Patients with semantic variant aphasia did not overestimate functioning on any domain. To examine the neuroanatomic correlates of impaired self-awareness, discrepancy scores were correlated with brain volume using voxel-based morphometry. To identify the unique neural correlates of overlooking versus exaggerating deficits, overestimation and underestimation scores were analysed separately, controlling for age, sex, total intracranial volume and extent of actual functional decline. Atrophy related to overestimating one's functioning included bilateral, right greater than left frontal and subcortical regions, including dorsal superior and middle frontal gyri, lateral and medial orbitofrontal gyri, right anterior insula, putamen, thalamus, and caudate, and midbrain and pons. Thus, our patients' tendency to under-represent their functional decline was related to degeneration of domain-general dorsal frontal regions involved in attention, as well as orbitofrontal and subcortical regions likely involved in assigning a reward value to self-related processing and maintaining accurate self-knowledge. The anatomic correlates of underestimation (right rostral anterior cingulate cortex, uncorrected significance level) were distinct from overestimation and had a substantially smaller effect size. This suggests that underestimation or 'tarnishing' may be influenced by non-structural neurobiological and sociocultural factors, and should not be considered to be on a continuum with overestimation or 'polishing' of functional capacity, which appears to be more directly mediated by neural circuit dysfunction.

Neural substrates of socioemotional self-awareness in neurodegenerative disease.

BACKGROUND: Neuroimaging studies examining neural substrates of impaired self-awareness in patients with neurodegenerative diseases have shown divergent results depending on the modality (cognitive, emotional, behavioral) of awareness. Evidence is accumulating to suggest that self-awareness arises from a combination of modality-specific and large-scale supramodal neural networks. METHODS: We investigated the structural substrates of patients' tendency to overestimate or underestimate their own capacity to demonstrate empathic concern for others. Subjects' level of empathic concern was measured using the Interpersonal Reactivity Index, and subject-informant discrepancy scores were used to predict regional atrophy pattern, using voxel-based morphometry analysis. Of the 102 subjects, 83 were patients with neurodegenerative diseases such as behavioral variant frontotemporal dementia (bvFTD) or semantic variant primary progressive aphasia (svPPA); the other 19 were healthy older adults. RESULTS: bvFTD and svPPA patients typically overestimated their level of empathic concern compared to controls, and overestimating one's empathic concern predicted damage to predominantly right-hemispheric anterior infero-lateral temporal regions, whereas underestimating one's empathic concern showed no neuroanatomical basis. CONCLUSIONS: These findings suggest that overestimation and underestimation of one's capacity for empathic concern cannot be interpreted as varying degrees of the same phenomenon, but may arise from different pathophysiological processes. Damage to anterior infero-lateral temporal regions has been associated with semantic self-knowledge, emotion processing, and social perspective taking; neuropsychological functions partly associated with empathic concern itself. These findings support the hypothesis that-at least in the socioemotional domain-neural substrates of self-awareness are partly modality-specific.

Anterior temporal lobe degeneration produces widespread network-driven dysfunction.

The neural organization of semantic memory remains much debated. A 'distributed-only' view contends that semantic knowledge is represented within spatially distant, modality-selective primary and association cortices. Observations in semantic variant primary progressive aphasia have inspired an alternative model featuring the anterior temporal lobe as an amodal hub that supports semantic knowledge by linking distributed modality-selective regions. Direct evidence has been lacking, however, to support intrinsic functional interactions between an anterior temporal lobe hub and upstream sensory regions in humans. Here, we examined the neural networks supporting semantic knowledge by performing a multimodal brain imaging study in healthy subjects and patients with semantic variant primary progressive aphasia. In healthy subjects, the anterior temporal lobe showed intrinsic connectivity to an array of modality-selective primary and association cortices. Patients showed focal anterior temporal lobe degeneration but also reduced physiological integrity throughout distributed modality-selective regions connected with the anterior temporal lobe in healthy controls. Physiological deficits outside the anterior temporal lobe correlated with scores on semantic tasks and with anterior temporal subregion atrophy, following domain-specific and connectivity-based predictions. The findings provide a neurophysiological basis for the theory that semantic processing is orchestrated through interactions between a critical anterior temporal lobe hub and modality-selective processing nodes.

Comprehension of insincere communication in neurodegenerative disease: lies, sarcasm, and theory of mind.

Comprehension of insincere communication is an important aspect of social cognition requiring visual perspective taking, emotion reading, and understanding others' thoughts, opinions, and intentions. Someone who is lying intends to hide their insincerity from the listener, while a sarcastic speaker wants the listener to recognize they are speaking insincerely. We investigated whether face-to-face testing of comprehending insincere communication would effectively discriminate among neurodegenerative disease patients with different patterns of real-life social deficits. We examined ability to comprehend lies and sarcasm from a third-person perspective, using contextual cues, in 102 patients with one of four neurodegenerative diseases (behavioral variant frontotemporal dementia [bvFTD], Alzheimer's disease [AD], progressive supranuclear palsy [PSP], and vascular cognitive impairment) and 77 healthy older adults (normal controls--NCs). Participants answered questions about videos depicting social interactions involving deceptive, sarcastic, or sincere speech using The Awareness of Social Inference Test. All subjects equally understood sincere remarks, but bvFTD patients displayed impaired comprehension of lies and sarcasm compared with NCs. In other groups, impairment was not disease-specific but was proportionate to general cognitive impairment. Analysis of the task components revealed that only bvFTD patients were impaired on perspective taking and emotion reading elements and that both bvFTD and PSP patients had impaired ability to represent others' opinions and intentions (i.e., theory of mind). Test performance correlated with informants' ratings of subjects' empathy, perspective taking and neuropsychiatric symptoms in everyday life. Comprehending insincere communication is complex and requires multiple cognitive and emotional processes vulnerable across neurodegenerative diseases. However, bvFTD patients show uniquely focal and severe impairments at every level of theory of mind and emotion reading, leading to an inability to identify obvious examples of deception and sarcasm. This is consistent with studies suggesting this disease targets a specific neural network necessary for perceiving social salience and predicting negative social outcomes.

Personality and social cognition in neurodegenerative disease.

PURPOSE OF REVIEW: Neurodegenerative diseases often cause focal damage to brain structures mediating social cognition and personality, resulting in altered interpersonal communication and behavior. We review recent research describing this phenomenon in various aspects of social cognition. RECENT FINDINGS: Corresponding to their pervasive socioemotional deficits, patients with frontotemporal dementia perform poorly on laboratory-based tasks including recognizing emotions, attending to salient information that guides social behavior, representing social knowledge, comprehending others' mental states, and maintaining insight to their own difficulties. Together with poor executive and regulation mechanisms, these social cognition deficits ultimately impact behavior. Patients with logopenic and nonfluent primary progressive aphasia have some deficits recognizing emotional prosody, whereas those with the semantic variant show more widespread deficits in social comprehension. Although Alzheimer's disease patients perform poorly on some social cognition tasks, this typically reflects general cognitive impairment, and their real-life social functioning is less affected than in diseases targeting frontotemporal structures. Studies in motor diseases such as Parkinson's suggest some degradation of emotion recognition and social comprehension, which should be investigated further. SUMMARY: We summarize recent findings concerning perception and evaluation of socioemotional information, social knowledge storage and access, advanced information processing mechanisms, and behavioral response selection and regulation across various neurodegenerative diseases.