Andrew R. Carr

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 Alzheimers 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.

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

ABSTRACT 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.

Neuropsychological and Neuroanatomical Correlates of the Social Norms Questionnaire in Frontotemporal Dementia Versus Alzheimer’s Disease

Traditional neuropsychological batteries may not distinguish early behavioral variant frontotemporal dementia (bvFTD) from Alzheimer’s disease (AD) without the inclusion of a social behavioral measure. We compared 33 participants, 15 bvFTD, and 18 matched patients with early-onset AD (eAD), on the Social Norms Questionnaire (SNQ), neuropsychological tests and 3-dimensional T1-weighted magnetic resonance imaging (MRI). The analyses included correlations of SNQ results (total score, overendorsement or “overadhere” errors, and violations or “break” errors) with neuropsychological results and tensor-based morphometry regions of interest. Patients with BvFTD had significantly lower SNQ total scores and higher overadhere errors than patients with eAD. On neuropsychological measures, the SNQ total scores correlated significantly with semantic knowledge and the overadhere subscores with executive dysfunction. On MRI analysis, the break subscores significantly correlated with lower volume of lateral anterior temporal lobes (aTL). The results also suggest that endorsement of social norm violations corresponds to the role of the right aTL in social semantic knowledge.

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

ABSTRACT 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.

Skin Conduction Levels Differentiate Frontotemporal Dementia From Alzheimer’s Disease

Patients with behavioral variant frontotemporal dementia (bvFTD) and Alzheimers 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.

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, Alzheimers 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.

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.

RESTING STATE FUNCTIONAL MAGNETIC RESONANCE IMAGING IN EARLY-ONSET ALZHEIMER’S DISEASE PHENOTYPES

Background:There is limited information on differences in resting state neural networks between early-onset Alzheimer’s disease (EOAD) phenotypic variants. This study distinguishes the non-amnestic phenotypes of EOAD from typical amnestic AD by mapping their weighted neuropsychological pattern onto resting state functional magnetic resonance imaging (rs-MRI) measures of functional connectivity. Methods: We examined functional magnetic resonance imaging (fMRI) connectivity in 14 patients with AD: 5 typical amnestic AD and 9 non-amnestic EOAD patients who were extensively diagnosed and characterized in terms of predominant presenting clinical symptoms. Resting state images were analyzed using Data Processing Assistant for Resting-State fMRI (DPARSFA) in Matlab and group averages and comparisons were made using SPM8. Between-group comparisons are shown at p<.005 uncorrected. The default mode network (DMN) resting state network (RSN) was created by correlating the time series from the posterior cingulate with the rest of the brain (Figure 1A). We interrogated right fronto-parietal connectivity using the right middle frontal gyrus as a seed region. Results:No betweengroup differences were observed in this small sample; however, the typical amnestic AD patients showed greater connectivity in frontal lobe relative to the non-amnestic EOAD patients in this RSN (Figure 1B). The region of the left inferior frontal gyrus showed reduced functional connectivity with bilateral temporal regions (Figure 1C). Typical amnestic AD also showed less connectivity between right hippocampus and bilateral hippocampi relative to non-amnestic EOAD patients (Fig 1D). Conclusions:Overall, this preliminary data suggests differential patterns of connectivity within RSNs in typical vs. non-amnestic presentations of Alzheimer’s disease. This pilot study suggests that the non-amnestic presentations tend to affect fronto-pareital networks more than those related to the hippocampi in typical AD. More work is ongoing to confirm and evaluate these preliminary findings.