Neuropsychiatric Effects on Decision-Making in Early Alzheimer Disease.

BACKGROUND: Neuropsychiatric symptoms can impact decision-making in patients with Alzheimer disease (AD). METHODS: Using a simple decision-making task, a variant of the ultimatum game (UG) modified to control feelings of unfairness, this study investigated rejection responses among responders to unfair offers. The UG was administered to 11 patients with AD, 10 comparably demented patients with behavioral variant frontotemporal dementia (bvFTD), and 9 healthy controls (HC). The results were further compared with differences on the caregiver Neuropsychiatric Inventory (NPI). RESULTS: Overall, patients with AD significantly rejected more total offers than did the patients with bvFTD and the HC (P < .01). On the NPI, the only domain that was significantly worse among the patients with AD compared to the other groups was dysphoria/depression. CONCLUSIONS: These results suggest that early AD can be distinguished based on increased rejections of offers in decision-making, possibly consequent to a heightened sense of unfairness from dysphoria/depression.

Impaired Empathy Versus General Hypoemotionality in Frontotemporal Dementia.

OBJECTIVE: Impaired empathy is a diagnostic feature of behavioral variant frontotemporal dementia (bvFTD), but it is not clear whether it is caused by a primary impairment in empathy or by general emotional blunting. METHODS: Patients with bvFTD who met criteria for loss of empathy (N=10) and patients with Alzheimer's disease (N=15) were assessed with a measure for empathy (Socioemotional Dysfunction Scale [SDS]) and a measure for general emotion (Scale for Emotional Blunting [SEB]). All patients underwent neuroimaging. Both patient groups and a healthy control group (N=18) were evaluated by using autonomic responses (skin conductance responses [SCR]) to pictures from the Internal Affective Picture System (IAPS) (presence or absence of empathy stimuli and high versus low emotion). RESULTS: All participants reported understanding the content and others' perspectives on the empathy pictures; however, only patients with bvFTD showed impaired empathic behavior on the SDS, which persisted after adjusting for measures from the emotion scale (SEB). Patients with bvFTD had significantly lower SCR for all the IAPS stimuli, including for empathy pictures, which also persisted after adjusting for emotional content. On MRI analysis, SCR across groups significantly correlated with the volume of the dorsal anterior cingulate gyrus (dACC). CONCLUSIONS: These results indicate that patients with bvFTD have decreased empathic behavior with or without emotional blunting, and they exhibit decreased psychophysiological responses to empathy stimuli, independent of general emotion. These preliminary findings suggest a specific impairment in emotional empathy, possibly related to impairment of the emotional appraisal role of the dACC.

Skin Conduction Levels Differentiate Frontotemporal Dementia From Alzheimer's Disease.

Patients with behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) differ in basic emotional tone. Skin conduction levels (SCLs), a measure of sympathetic tone, may be a sensitive test for discriminating these two dementias early in their course. Previous research has shown differences in resting SCLs between patients with bvFTD and AD, but no study has evaluated the discriminability of SCLs during different environmental conditions. The authors compared bvFTD patients (N=8), AD patients (N=10), and healthy control subjects (N=9) on SCL measures pertaining to real-life vignettes or scenarios differing in valence and emotional intensity. The SCLs among the bvFTD patients were decreased across all conditions, whereas the SCLs among the AD patients were increased compared with control participants. On analysis, the SCLs in response to emotional stimuli differentiated bvFTD from AD with an area under the receiver operator characteristic curve of 95.3%. At a cutoff ≤0.77 µS, emotional vignettes distinguished bvFTD from AD with a sensitivity of 86% and a specificity of 96%. These preliminary results indicate the potential utility of SCLs for differentiating bvFTD from AD early in their course, regardless of environmental condition.

Psychotic-Like Speech in Frontotemporal Dementia.

Behavioral variant frontotemporal dementia (bvFTD) may result in psychotic-like speech without other psychotic features. The authors identified a bvFTD subgroup with pressure of speech, tangentiality, derailment, clanging/rhyming, and punning associated with the right anterior temporal atrophy and sparing of the left frontal lobe.

Emotional quotient in frontotemporal dementia vs. Alzheimer's disease: the role of socioemotional agnosia.

INTRODUCTION: Socioemotional dysfunction distinguishes behavioural variant frontotemporal dementia (bvFTD) from other dementias. Patients with bvFTD not only have early social impairment and emotional blunting, but they also have agnosia of their socioemotional dysfunction. METHODS: To investigate the relationship between agnosia and dysfunction, we assessed self-knowledge of socioemotional dysfunction with an emotional quotient (EQ) scale administered to 12 patients with bvFTD and a comparison group of 12 age-matched patients with Alzheimer's disease (AD), and compared these self-ratings to caregiver ratings of social dysfunction and emotional blunting. RESULTS: The bvFTD patients self-rated as having higher EQs than the AD patients, particularly higher self-ratings of their Social Skills, an EQ subscale which correlated with increased emotional blunting. On within-groups analysis, the bvFTD patients' high self-ratings of their EQ Appraisal of Emotions correlated with increased socioemotional dysfunction, whereas all of the AD patients' self-ratings correlated appropriately with their degree of dysfunction. CONCLUSIONS: Large socioemotional agnosia scores (EQ minus function) distinguishes bvFTD from AD. Additionally, in bvFTD, agnosia specifically for their ability to appreciate others' emotions correlates with the degree of socioemotional dysfunction, suggesting a role for socioemotional agnosia in increasing socioemotional dysfunction.

Person-Based Versus Generalized Impulsivity Disinhibition in Frontotemporal Dementia and Alzheimer Disease.

BACKGROUND: While much disinhibition in dementia results from generalized impulsivity, in behavioral variant frontotemporal dementia (bvFTD) disinhibition may also result from impaired social cognition. OBJECTIVE: To deconstruct disinhibition and its neural correlates in bvFTD vs. early-onset Alzheimer's disease (eAD). METHODS: Caregivers of 16 bvFTD and 21 matched-eAD patients completed the Frontal Systems Behavior Scale disinhibition items. The disinhibition items were further categorized into (1) "person-based" subscale which predominantly associated with violating social propriety and personal boundary and (2) "generalized-impulsivity" subscale which included nonspecific impulsive acts. Subscale scores were correlated with grey matter volumes from tensor-based morphometry on magnetic resonance images. RESULTS: In comparison to the eAD patients, the bvFTD patients developed greater person-based disinhibition ( P < 0.001) but comparable generalized impulsivity. Severity of person-based disinhibition significantly correlated with the left anterior superior temporal sulcus (STS), and generalized-impulsivity correlated with the right orbitofrontal cortex (OFC) and the left anterior temporal lobe (aTL). CONCLUSIONS: Person-based disinhibition was predominant in bvFTD and correlated with the left STS. In both dementia, violations of social propriety and personal boundaries involved fronto-parieto-temporal network of Theory of Mind, whereas nonspecific disinhibition involved the OFC and aTL.

Frontotemporal asymmetry in socioemotional behavior: A pilot study in frontotemporal dementia.

Clinical studies report abnormal socioemotional behavior in patients with right frontotemporal disease, but neuroimaging studies of socioemotional behavior usually show bilateral activations in normal subjects. This discrepancy suggests that impaired interhemispheric collaboration for socioemotional functions results from asymmetric frontotemporal disease. Behavioral variant frontotemporal dementia (bvFTD) can clarify the contribution of direction-independent frontotemporal asymmetry. In a two-part study, we evaluated bvFTD patients using socioemotional scales and magnetic and resonance imaging measures. Part A compared 18 patients on scales of social dysfunction and emotional intelligence with degree of asymmetry in frontal lobe volumes and analyzed differences between lower and higher asymmetry groups. Part B compared 24 patients on scales of social observation and emotional blunting with degree of asymmetry in frontotemporal cortical thickness using multiple linear regression. Both results showed that left or right hemispheric-specific contributions did not account for all socioemotional differences and that frontal lobe and frontotemporal differences in atrophy between the hemispheres accounted for significant variance in abnormalities in social and emotional behavior. These preliminary results indicate that the degree of frontal lobe and frontotemporal asymmetric involvement, regardless of direction or laterality, significantly contribute to socioemotional dysfunction and support the hypothesis that interhemispheric collaboration is important for complex socioemotional behavior.

Affective Empathy in Behavioral Variant Frontotemporal Dementia: A Meta-Analysis.

Background: Empathy deficits are a widely recognized symptom in the behavioral variant frontotemporal dementia (bvFTD), and although several reviews have examined cognitive empathy deficits, there are no meta-analytic studies on affective empathy deficits. Objective: Identify salience of affective empathy in bvFTD. Method: A thorough review of affective empathy found 139 possible studies, but only 10 studies included measures of affective empathy and met standardized criteria. Results: BvFTD patients demonstrated a modest impairment compared to controls across all tasks (d = 0.98). Empathic concern as measured by the interpersonal reactivity index was particularly effected (d = 1.12). Conclusions: This study provides evidence for an increased commitment to observing affective empathy in bvFTD and capturing its role in the disorder.

Screening for Emotional Expression in Frontotemporal Dementia: A Pilot Study.

OBJECTIVE: Although emotional blunting is a core feature of behavioral variant frontotemporal dementia (bvFTD), there are no practical clinical measures of emotional expression for the early diagnosis of bvFTD. METHOD: Three age-matched groups (bvFTD, Alzheimer's disease (AD), and healthy controls (HC)) of eight participants each were presented with real-life vignettes varying in emotional intensity (high versus low) with either negative or positive outcomes. This study evaluated verbal (self-reports of distress) and visual (presence or absence of facial affect) measures of emotional expression during the vignettes. RESULTS: The bvFTD patients did not differ from the AD and HC groups in reported distress or in the amount of facial affect during vignettes with high emotional intensity or type of outcome. However, the bvFTD patients reported significantly less distress and had correspondingly few facial affective expressions when compared on vignettes of low intensity. CONCLUSIONS: Patients with bvFTD require a high intensity of emotional stimulus and are significantly hyporesponsive to low-intensity stimuli. Simple screening or observations of verbal and facial responsiveness to mildly arousing stimuli may aid in differentiating bvFTD from normal subjects and patients with other dementias. Future studies can investigate whether delivering information with high emotional intensity can facilitate communication with patients with bvFTD.

Behavioral and autonomic reactivity to moral dilemmas in frontotemporal dementia versus Alzheimer's disease.

The personal/impersonal distinction of moral decision-making postulates intuitive emotional responses from medial frontal activity and rational evaluation from lateral frontal activity. This model can be analyzed in behavioral variant frontotemporal dementia (bvFTD), a disorder characterized by impaired emotional intuitions, ventromedial prefrontal cortex (vmPFC) involvement, and relative sparing of lateral frontal regions. Moral dilemmas were presented to 10 bvFTD, 11 Alzheimer's disease (AD), and 9 healthy control (HC) participants while recording skin conductance responses, a measure of emotional arousal. We evaluated their personal versus impersonal conflict, subjective discomfort, and adherence to social norms. Replicating prior work, bvFTD participants were more willing to harm in the personal, but not the impersonal, dilemma compared to AD and HC groups. BvFTD participants had lower arousal and less of an increase in conflict on the personal versus the impersonal dilemma, in contrast to increased arousal and conflict for the AD and HC groups. Furthermore, bvFTD participants verbalized less discomfort, a correlate of low adherence to social norms. These findings support impaired emotional reactions to moral dilemmas in bvFTD and vmPFC lesions and the personal/impersonal model. It suggests a reversion to utilitarian-like considerations when emotional intuition is impaired in the brain.

The attribution of animacy and agency in frontotemporal dementia versus Alzheimer's disease.

Impaired attribution of animacy (state of living or being sentient) and of agency (capability of intrinsically-driven action) may underlie social behavior disturbances in behavioral variant frontotemporal dementia (bvFTD). We presented the Heider and Simmel film of moving geometric shapes to 11 bvFTD patients, 11 Alzheimer's disease (AD) patients, and 12 healthy controls (HCs) and rated their recorded verbal responses for animacy attribution and agency attribution. All participants had skin conductance (SC) continuously recorded while viewing the film, and all dementia participants underwent magnetic resonance imaging (MRI) for regions of interest. The bvFTD patients, but not the AD patients, were impaired in animacy attribution, compared to the HCs. In contrast, both bvFTD and AD groups were impaired in agency attribution, compared to the HCs, and only the HCs had increasing SC responsiveness during viewing of the film. On MRI analysis of cortical thicknesses, animacy scores significantly correlated across groups with the right pars orbitalis and opercularis; agency scores with the left inferior and superior parietal cortices and the supramarginal gyrus; and both scores with the left cingulate isthmus involved in visuospatial context. These findings suggest that bvFTD is specifically associated with impaired animacy attribution from right inferior frontal atrophy. In contrast, both dementias may have impaired agency attribution from left parietal cortical atrophy and absent SC increases during the film, a sympathetic indicator of attribution of a social "story" to the moving shapes. These findings clarify disease-related changes in social attribution and corroborate the neuroanatomical origins of animacy and agency.

An investigation of care-based vs. rule-based morality in frontotemporal dementia, Alzheimer's disease, and healthy controls.

Behavioral changes in dementia, especially behavioral variant frontotemporal dementia (bvFTD), may result in alterations in moral reasoning. Investigators have not clarified whether these alterations reflect differential impairment of care-based vs. rule-based moral behavior. This study investigated 18 bvFTD patients, 22 early onset Alzheimer's disease (eAD) patients, and 20 healthy age-matched controls on care-based and rule-based items from the Moral Behavioral Inventory and the Social Norms Questionnaire, neuropsychological measures, and magnetic resonance imaging (MRI) regions of interest. There were significant group differences with the bvFTD patients rating care-based morality transgressions less severely than the eAD group and rule-based moral behavioral transgressions more severely than controls. Across groups, higher care-based morality ratings correlated with phonemic fluency on neuropsychological tests, whereas higher rule-based morality ratings correlated with increased difficulty set-shifting and learning new rules to tasks. On neuroimaging, severe care-based reasoning correlated with cortical volume in right anterior temporal lobe, and rule-based reasoning correlated with decreased cortical volume in the right orbitofrontal cortex. Together, these findings suggest that frontotemporal disease decreases care-based morality and facilitates rule-based morality possibly from disturbed contextual abstraction and set-shifting. Future research can examine whether frontal lobe disorders and bvFTD result in a shift from empathic morality to the strong adherence to conventional rules.