Shweta Antani

Trying to tell a tale Discourse impairments in progressive aphasia and frontotemporal dementia

Objective: To assess discourse in patients with frontotemporal dementia (FTD). Methods: The authors asked patients with progressive nonfluent aphasia (PNFA), patients with semantic dementia (SemD), and nonaphasic patients with a disorder of social comportment and executive functioning (SOC/EXEC) to narrate the story of a wordless childrens picture book. Results: The authors found significant discourse impairments in all three groups of patients. Moreover, there were qualitatively important differences between the groups. Patients with PNFA had the sparsest output, producing narratives with the fewest words per minute. Patients with SemD had difficulty retrieving words needed to tell their narratives. Though not aphasic, patients with SOC/EXEC had profound difficulty organizing their narratives, and they could not effectively express the point of the story. This deficit correlated with poor performance on a measure of executive resources requiring an organized mental search. In addition, a correlation of narrative organization with cortical atrophy in patients with SOC/EXEC was significant in right frontal and anterior temporal brain regions. Conclusions: Impaired day-to-day communication in nonaphasic frontotemporal dementia patients with a disorder of social comportment and executive functioning is due in part to a striking deficit in discourse organization associated with right frontotemporal disease. Difficulty with discourse in progressive aphasia is due largely to the language impairments of these patients.

Patterns of neuropsychological impairment in frontotemporal dementia

Objective: To differentiate frontotemporal dementia (FTD) subtypes from each other and from probable Alzheimer disease (AD) using neuropsychological tests. Methods: Patients with FTD and AD (n = 109) were studied with a comprehensive neuropsychological protocol at first contact. Data were subjected to a principal components analysis (PCA) to extract core neuropsychological features. A five-factor solution accounted for 72.89% of the variance and yielded factors related to declarative memory, working memory/visuoconstruction, processing speed/mental flexibility, lexical retrieval, and semantic memory. Results: Between- and within-group analyses revealed that patients with AD obtain their lowest scores on tests of declarative memory while semantic dementia (SemD) patients are particularly disadvantaged on tests of semantic memory. On tests of processing speed/mental flexibility time to completion was faster for social comportment/dysexecutive (SOC/EXEC) patients, but these patients made more errors on some tests. Patients with corticobasal degeneration (CBD) and progressive nonfluent aphasia (PNFA) were impaired on tests of working memory. Logistic regression analyses using factor scores successfully assigned FTD subgroups and AD patients into their respective diagnostic categories. Conclusion: Patients with differing frontotemporal dementia phenotypes can be distinguished from each other and from Alzheimer disease using neuropsychological tests.

Metacognitive deficits in frontotemporal dementia

Objectives: To investigate whether metacognitive impairments in self-awareness and self-monitoring occur in patients with frontotemporal dementia (FTD), particularly among those with prominent social and dysexecutive impairments. Methods: Patients diagnosed with FTD were divided by clinical subtype (social–dysexecutive (n = 12) aphasic (n = 15), and constituent subgroups of progressive non-fluent aphasia and semantic dementia) and compared with subjects with probable Alzheimer’s disease (AD, n = 11) and age-matched healthy controls (n = 11). All subjects completed comprehensive behavioural ratings scales, which were compared with caregiver ratings. Subjects also rated their test performances in verbal associative fluency, word list learning, and memory task with comparisons made between actual and judged performance levels. Results: The FTD sample as a whole showed significantly less behavioural self-awareness and self-knowledge than the AD and healthy control samples. FTD patients with prominent social and dysexecutive impairments demonstrated the most extensive loss of self-awareness and self-knowledge, significantly overrating themselves in multiple social, emotional, and cognitive domains, and failing to acknowledge that any behavioural change had occurred in most areas. The remaining clinical samples showed select and minimal discrepancies. All clinical groups were significantly unaware of their apathy levels. Most FTD patients judged episodic cognitive test performance adequately, with partial difficulties observed in the socially impaired and progressive non-fluent aphasia subgroups. Conclusions: FTD patients, particularly those with prominent social and dysexecutive impairments, exhibit profound metacognitive anosognosia that may represent a loss of self-awareness, self-monitoring, and self-knowledge, likely related to significant prefrontal pathophysiology. Other FTD clinical groups and AD patients showed less pervasive and more select metacognitive deficiencies.

Oops! Resolving social dilemmas in frontotemporal dementia

Objectives: Our social cognition model posits that social knowledge and executive resources guide interpersonal decision making. We investigated this model by examining the resolution of standardised social dilemmas in patients with a social and executive disorder (SOC/EXEC) caused by frontotemporal dementia (FTD). Methods: Patients with SOC/EXEC (n = 12) and those with progressive aphasia (APH, n = 14) completed measures requiring resolution of social dilemmas (Guilford’s Cartoon Predictions Test), social cognition (theory of mind false belief vignettes and a behavioural rating measure of empathy) and executive measures of cognitive flexibility (Visual Verbal Test). Regression analysis related judgments of social dilemmas to cortical volume using voxel based morphometry of high resolution structural MRI. Results: Patients with SOC/EXEC were impaired in judgments of social dilemmas as well as theory of mind, self-awareness of empathy and cognitive flexibility. Patients with APH were much less impaired in the social and cognitive measures. There were strong correlations among social dilemma, theory of mind and mental flexibility measures in patients with SOC/EXEC, and stepwise regression showed that mental flexibility was most predictive of social dilemma judgments. Social dilemma impairments in the SOC/EXEC sample correlated with cortical atrophy in the orbital frontal, superior temporal, visual association and posterior cingulate regions of the right hemisphere. Conclusions: Deficits in patients with SOC/EXEC in resolving social dilemmas are related to depleted executive resources and social knowledge that appear to arise from disease that interrupts a right frontal–temporal neural network crucial for mediating social cognition.

Apathy in frontotemporal dementia: Behavioral and neuroimaging correlates

We investigated the occurrence of goal-directed motivational change in the form of apathy in patients with frontotemporal dementia (FTD), particularly those with behavioral variant social and executive deficits (bvFTD). Standardized behavioral inventory was employed to survey and compare apathy ratings from patients and caregivers. In cases of bvFTD, apathy ratings were further related to measures of social cognition, executive function, and atrophy on brain MRI. Results indicated that caregivers rated bvFTD patients as having significantly elevated apathy scores though patient self-ratings were normal. Caregiver and self-ratings of FTD samples with progressive nonfluent aphasia and semantic dementia did not differ from healthy controls and their informants. In the bvFTD sample, caregiver apathy scores were not correlated with general cognitive screening or depression scores, but were significantly correlated with social cognition and executive function measures. Voxel-based morphometry revealed that apathy ratings in bvFTD were related to prominent atrophy in the right caudate (including the ventral striatum), the right temporo-parietal junction, right posterior inferior and middle temporal gyri, and left frontal operculum- anterior insula region. Findings suggest that bvFTD is associated with a significant breakdown in goal-directed motivated behavior involving disruption of cortical-basal ganglia circuits that is also related to social and executive function deficits.

The role of ventral medial prefrontal cortex in social decisions: Converging evidence from fMRI and frontotemporal lobar degeneration

The ventral medial prefrontal cortex (vmPFC) has been implicated in social and affectively influenced decision-making. Disease in this region may have clinical consequences for social judgments in patients with frontotemporal lobar degeneration (FTLD). To test this hypothesis, regional cortical activation was monitored with fMRI while healthy adults judged the acceptability of brief social scenarios such as cutting into a movie ticket line or going through a red light at 2 AM. The scenarios described: (i) a socially neutral condition, (ii) a variant of each scenario containing a negatively valenced feature, and (iii) a variant containing a positively valenced feature. Results revealed that healthy adults activated vmPFC during judgments of negatively valenced scenarios relative to positive scenarios and neutral scenarios. In a comparative behavioral study, the same social decision-making paradigm was administered to patients with a social disorder due to FTLD. Patients differed significantly from healthy controls, specifically showing less sensitivity to negatively valenced features. Comparative anatomical analysis revealed considerable overlap of vmPFC activation in healthy adults and vmPFC cortical atrophy in FTLD patients. These converging results support the role of vmPFC in social decision-making where potentially negative consequences must be considered.

Lexical acquisition in progressive aphasia and frontotemporal dementia

We investigated the characteristics of language difficulty in frontotemporal dementia (FTD) by exposing these patients to a new verb in a naturalistic manner and then assessing acquisition of the grammatical, semantic, and thematic matrix information associated with the new word. We found that FTD patients have difficulty relative to healthy seniors in their acquisition of the new verb, but that progressive nonfluent aphasia (PNFA), semantic dementia (SD), and social/dysexecutive variant (SOC/EXEC) subgroups of FTD demonstrate relatively distinct impairment profiles. Specifically, PNFA patients showed relative difficulty assigning the new verb to its correct grammatical form class, reflecting compromised processing of the associated grammatical information. SD patients were impaired at associating the new word with its pictorial representation, suggesting impaired processing of the new verbs semantic attributes. SOC/EXEC patients showed their greatest difficulty judging violations of the new words associated thematic roles, implying that limited executive resources underlie in part the difficulty in integrating grammatical and semantic information into a coherent thematic matrix. Similar impairment profiles were seen during a follow-up session one week after the initial evaluation. These deficits in lexical acquisition reflect the breakdown of a language-processing system that consists of highly interactive but partially dissociable grammatical, semantic, and resource-based components, leading to relatively distinct language-processing deficits in each subgroup of patients with FTD.