Jill S. Shapira

An investigation of moral judgement in frontotemporal dementia.

Objective:To investigate the basis of disturbed moral judgment in patients with frontotemporal dementia (FTD). Background:FTD is characterized by difficulty in modulating social behavior. Patients lack social propriety and may perform sociopathic acts. In addition, FTD patients often lack empathy for others. These findings suggest alterations in the nature of morality in patients with FTD. Method:We administered an inventory of moral knowledge and two moral dilemmas to 26 patients with the frontal variant of FTD, 26 patients with Alzheimer disease (AD), and 26 normal control subjects. The FTD patients met Consensus Criteria for FTD and had corroborative frontal abnormalities on functional neuroimaging. The FTD and AD patients were comparably impaired on dementia measures. Results:All these groups showed the retention of knowledge for moral behavior and the ability to make “impersonal” moral judgments. In contrast, the FTD patients were impaired in their ability to make immediate, emotionally based moral judgments compared with the patients with AD and the normal control subjects. Conclusions:These findings are consistent with an attenuation of the automatic emotional identification with others that is part of the innate moral sense. Such a disturbance may result from neurodegenerative disease affecting the ventromedial frontal cortex.

Preliminary findings : Behavioral worsening on donepezil in patients with frontotemporal dementia

OBJECTIVE The objective of this study was to evaluate donepezil, an acetylcholinesterase inhibitor, in the treatment of frontotemporal dementia (FTD). METHODS Twelve patients with FTD who received donepezil for six months were compared with 12 FTD controls on behavioral measures. RESULTS The groups did not differ on most variables at baseline or at six months; however, the donepezil group had greater worsening on the FTD Inventory. Four treated patients had increased disinhibited or compulsive acts, which abated with discontinuation of the medication. CONCLUSION There were no changes in global cognitive performance or dementia severity; however, a subgroup of patients with FTD can experience worsening of symptoms with donepezil.

Physostigmine ameliorates the delusions of Alzheimer's disease

Alzheimers disease (AD) patients frequently manifest delusions, and the cholinergic deficiency of AD may contribute to this aspect of the psychopathology of the disorder. In a double-blind, crossover study involving two patients, we compared the antidelusional efficacy of physostigmine, an acetylcholinesterase inhibitor, with haloperidol, a widely used neuroleptic agent. Physostigmine ameliorated the delusions and produced fewer side effects. These preliminary observations suggest that the cholinergic deficiency contributes to the occurrence of delusions in AD and cholinergic therapy may have a role in the treatment of the delusional symptoms.

Acquired Sociopathy and Frontotemporal Dementia

Background: It is not understood why some patients withfrontotemporal dementia (FTD) manifest sociopathic behavior. Objective: To examine the prevalence and characteristics of sociopathic behavior in FTD patients as compared to those with Alzheimer’s disease (AD). Methods and Participants: We surveyed a group of FTD patients and a group of AD patients for sociopathic behavior, evaluated the characteristics surrounding their acts, and compared the groups on neuropsychological tests and functional neuroimaging. Twenty-eight outpatients with FTD (15 men, 13 women; 61.9 ± 7.1 years; Mini-Mental State Examination score 23.6 ± 8.1) were compared with 28 patients with clinically probable AD (13 men, 15 women; 66.1 ± 9.2 years; Mini-Mental State Examination score 21.3 ± 5.3). Main outcome measures included: (a) the prevalence of sociopathic acts; (b) a structured interview; (c) neuropsychological tests including the Frontal Assessment Battery, and (d) clinically obtained positron emission tomography or single photon emission tomography scans. Results: Sixteen (57%) of the FTD patients had sociopathic behavior compared to two (7%) of the AD patients (χ2 = 13.84, p < 0.001). Sociopathic acts among FTD patients included unsolicited sexual acts, traffic violations, physical assaults, and other unacceptable behaviors. On interview, the FTD patients with sociopathic acts were aware of their behavior and knew that it was wrong but could not prevent themselves from acting impulsively. They claimed subsequent remorse, but they did not act on it or show concern for the consequences. Among FTD patients with sociopathy, neuropsychological assessment showed impaired motor inhibition, and functional neuroimaging showed right frontotemporal involvement. Conclusion: The results suggest that sociopathy in FTD results from a combination of diminished emotional concern for the consequences of their acts and disinhibition consequent to right frontotemporal dysfunction. In many jurisdictions, FTD patients with sociopathy would not pass legal criteria for ‘not guilty by reason of insanity’.

Variations in regional SPECT hypoperfusion and clinical features in frontotemporal dementia

Objective: To characterize the presenting clinical features for frontotemporal dementia (FTD) and contrast them with the degree of frontal and temporal hypoperfusion on SPECT imaging. Methods: The authors evaluated 74 patients who eventually met Consensus Criteria for the FTD form of frontotemporal lobar degeneration (excluding primary progressive aphasia and semantic dementia) on 2-year follow-up. On first presentation, these patients had undergone both an FTD Inventory for 12 features based on core and supportive Consensus Criteria and SPECT imaging. The initial clinical diagnostic features were contrasted with variations in regional SPECT hypoperfusion. Results: The patients with FTD had more hypoperfusion in the right frontal lobe than in other regions; the subgroup of 25 patients who met Consensus Criteria from the first presentation had the most right frontal hypoperfusion. Frontal lobe involvement was associated with significant apathy, whereas temporal lobe involvement was associated with hypomania-like behavior. Right frontal lobe hypoperfusion further predicted loss of insight, environmental dependency, and stereotyped behaviors. Other associations included left frontal hypoperfusion with a decline in personal hygiene and left temporal hypoperfusion with compulsions and mental rigidity. Conclusions: On first presentation, frontotemporal dementia (FTD) is disproportionately a right frontal disease evident on behavioral measures and on SPECT. Nonetheless, patients with FTD can initially present with further regional differences in clinical diagnostic features, such as apathy with bifrontal hypoperfusion and hypomania-like behaviors with anterior temporal involvement.

Functional neuroimaging and presenting psychiatric features in frontotemporal dementia

Background: Frontotemporal dementia (FTD) is a behavioural syndrome caused by degeneration of the frontal and anterior temporal lobes. Behavioural disturbances include psychiatric features. Whether patients with FTD present with psychiatric features varies with the initial neuroanatomical variability of FTD. Objective: To identify presenting psychiatric changes not part of diagnostic criteria of FTD and contrast them with the degree of hemispheric asymmetry and frontal and temporal hypoperfusion on single photon emission computed tomography (SPECT) imaging. Methods: 74 patients who met consensus criteria for FTD were evaluated at a two year follow up. All had brain SPECT on initial presentation. Results of an FTD psychiatric checklist were contrasted with ratings of regional hypoperfusion. Results: The regions of predominant hypoperfusion did not correlate with differences on FTD demographic variables but were associated with presenting psychiatric features. Dysthymia and anxiety were associated with right temporal hypoperfusion. “Moria” or frivolous behaviour also occurred with temporal lobe changes, especially on the right. The only significant frontal lobe feature was the presence of a peculiar physical bearing in association with right frontal hypoperfusion. Conclusions: Patients with FTD may present with psychiatric changes distinct from the behavioural diagnostic criteria for this disorder. Early temporal involvement is associated with frivolous behaviour and right temporal involvement is associated with emotional disturbances. In contrast, those with right frontal disease may present with alterations in non-verbal behaviour.

Psychotic Symptoms in Frontotemporal Dementia: Prevalence and Review

Background/Aims: Although most patients with frontotemporal dementia (FTD) present with neuropsychiatric symptoms, the frequency of psychotic symptoms is unclear. This study aims to determine the prevalence of psychotic symptoms in a large cohort of well-diagnosed and followed FTD patients compared to age-matched patients with Alzheimer’s disease (AD) and to further review the literature on psychosis in FTD. Methods: Delusions, hallucinations and paranoia were evaluated among 86 patients who met consensus criteria for FTD, had frontotemporal changes on functional neuroimaging and were followed for 2 years. They were compared to 23 patients with early-onset AD on a caregiver-administered psychiatric questionnaire. Results: Among the FTD patients, only 2 (2.3%) had delusions, 1 of whom had paranoid ideation; no FTD patient had hallucinations. This was significantly less than the AD patients, 4 (17.4%) of whom had delusions and paranoia. Other investigations fail to establish a significant association of psychosis with FTD. Conclusions: These findings, and a literature review, indicate that psychotic symptoms are rare in FTD, possibly due to limited temporal-limbic involvement in this disorder.

Stereotypical movements and frontotemporal dementia.

Stereotypical movements are characteristic of autism or mental retardation but can also occur in patients with dementia, particularly frontotemporal dementia (FTD). In this study, we administered the Abnormal Involuntary Movement Scale (AIMS) to 18 patients with FTD and to 18 patients with the most common form of dementia, Alzheimers disease (AD). The AIMS scores were gathered at the initial presentation of patients who had not received antipsychotic medications. Compared to the AD patients, the FTD patients had significantly more stereotypical movements, including frequent rubbing behaviors and some self‐injurious acts. All the FTD patients with stereotypical movements had compulsive‐like behaviors, suggesting a similar pathophysiologic cause, and most had a decrease in their stereotypical movements with the administration of sertraline, a serotonin selective reuptake inhibitor.

Altered emotional morality in frontotemporal dementia

Introduction. Frontotemporal dementia (FTD), a disorder characterised by abnormal social behaviour and potential sociopathy, provides a window to the neurobiology of moral behaviour. This study investigated the basis of altered moral judgements in patients with FTD. Methods. We administered an inventory of moral knowledge, five “reasoned” moral dilemmas, and five “emotional” moral dilemmas where subjects may cause direct harm to another through their own actions, to 21 patients with FTD compared to 21 comparably mildly impaired patients with Alzheimers disease (AD) and 21 normal controls. Among the FTD patients, the results were compared to findings on functional neuroimaging. Results. All groups showed retention of knowledge for moral behaviour and the ability to make reasoned moral judgements. In contrast to the other groups, the FTD patients were altered in their ability to make emotional moral judgements. Among the FTD patients, the altered moral judgements corresponded to right hemisphere frontotemporal involvement. Conclusions. In FTD patients, these findings suggest a decreased emotional responsiveness to others and a tendency to respond to moral dilemmas in a calculated fashion. Such a disturbance may result from ventromedial frontal dysfunction in FTD and supports the presence of a “morality” network in the brain, predominantly in the right hemisphere.

Fluent versus nonfluent primary progressive aphasia: A comparison of clinical and functional neuroimaging features

To better characterize fluent and nonfluent variants of primary progressive aphasia (PPA). Although investigators have recognized both fluent and nonfluent patients with PPA, the clinical and neuroimaging features of these variants have not been fully defined. We present clinical and neuropsychological data on 47 PPA patients comparing the fluent (n=21) and nonfluent (n=26) subjects. We further compared language features with PET/SPECT data available on 39 of these patients. Compared to the nonfluent PPA patients, those with fluent PPA had greater impairment of confrontational naming and loss of single word comprehension. They also exhibited semantic paraphasic errors and loss of single word comprehension. Patients with nonfluent PPA were more likely to be female, were more often dysarthric, and exhibited phonological speech errors in the absence of semantic errors. No significant differences were seen with regard to left hemisphere abnormalities, suggesting that both variants result from mechanisms that overlap frontal, temporal, and parietal regions. Of the language measures, only semantic paraphasias were strongly localized, in this case to the left temporal lobe. Fluent and nonfluent forms of PPA are clinically distinguishable by letter fluency, single word comprehension, object naming, and types of paraphasic errors. Nevertheless, there is a large amount of overlap between dysfunctional anatomic regions associated with these syndromes.