Impairments in the Face-Processing Network in Developmental Prosopagnosia and Semantic Dementia.

BACKGROUND: Developmental prosopagnosia (DP) and semantic dementia (SD) may be the two most common neurologic disorders of face processing, but their main clinical and pathophysiologic differences have not been established. To identify those features, we compared patients with DP and SD. METHODS: Five patients with DP, five with right temporal-predominant SD, and ten normal controls underwent cognitive, visual perceptual, and face-processing tasks. RESULTS: Although the patients with SD were more cognitively impaired than those with DP, the two groups did not differ statistically on the visual perceptual tests. On the face-processing tasks, the DP group had difficulty with configural analysis and they reported relying on serial, feature-by-feature analysis or awareness of salient features to recognize faces. By contrast, the SD group had problems with person knowledge and made semantically related errors. The SD group had better face familiarity scores, suggesting a potentially useful clinical test for distinguishing SD from DP. CONCLUSIONS: These two disorders of face processing represent clinically distinguishable disturbances along a right hemisphere face-processing network: DP, characterized by early configural agnosia for faces, and SD, characterized primarily by a multimodal person knowledge disorder. We discuss these preliminary findings in the context of the current literature on the face-processing network; recent studies suggest an additional right anterior temporal, unimodal face familiarity-memory deficit consistent with an "associative prosopagnosia."

Skin conductance levels may reflect emotional blunting in behavioral variant frontotemporal dementia.

Emotional blunting is a core diagnostic feature of behavioral variant frontotemporal dementia (bvFTD). The authors evaluated skin conductance as a measure of emotional blunting among 10 patients with bvFTD compared with 10 with Alzheimer's disease and 14 healthy control subjects. Despite responses to an auditory startle stimulus, skin conductance levels (SCLs) were lower in the patients with bvFTD compared with the other groups. The low SCLs significantly correlated with ratings of emotional blunting. The authors conclude that low SCLs in bvFTD indicate a low resting sympathetic state and low emotional arousal. The measurement of SCLs may be a useful noninvasive diagnostic test for bvFTD.

Kissing or "osculation" in frontotemporal dementia.

The authors investigated the neuropsychiatry of kissing in frontotemporal dementia. Among 15 patients, two had compulsive social kissing, bitemporal involvement, and Klüver-Bucy symptoms, and four pursued kissing with sexually disinhibited behavior. Future research should clarify the neuropsychiatric significance of kissing behavior.

Observational themes of social behavioral disturbances in frontotemporal dementia.

ABSTRACT Background: Caregivers report early disturbances in social behavior among patients with behavioral variant frontotemporal dementia (bvFTD); however, there are few direct observational studies of these social behavioral disturbances. This study aimed to identify social behavioral themes in bvFTD by direct observation in naturalistic interactions. The identification of these themes can help caregivers and clinicians manage the social behavioral disturbances of this disease. Methods: Researchers observed 13 bvFTD patients in their homes and community-based settings and recorded field notes on their interpersonal interactions. A qualitative analysis of their social behavior was then conducted using ATLAS.ti application and a constant comparison method. Results: Qualitative analysis revealed the following themes: (1) diminished relational interest and initiation, indicating failure to seek social interactions; (2) lack of social synchrony/intersubjectivity, indicating an inability to establish and maintain interpersonal relationships; and (3) poor awareness and adherence to social boundaries and norms. These themes corresponded with changes from caregiver reports and behavioral scales. Conclusion: This analysis indicates that real-world observation validates the diagnostic criteria for bvFTD and increases understanding of social behavioral disturbances in this disorder. The results of this and future observational studies can highlight key areas for clinical assessment, caregiver education, and targeted interventions that enhance the management of social behavioral disturbances in bvFTD.

Observation of social behavior in frontotemporal dementia.

BACKGROUND: The most characteristic manifestations of behavioral variant frontotemporal dementia (bvFTD) are abnormalities in social behavior. However, distinguishing bvFTD based on social behavior can be difficult in structured clinical settings. METHODS: Using a Social Observation Inventory, 10 patients with bvFTD and 10 patients with Alzheimer's disease (AD) were compared to their caregiver interlocutors on 1-hour mealtime, in-home videotaped segments. RESULTS: Compared to caregivers and patients with AD, patients with bvFTD were significantly disturbed in social behavior. In contrast, patients with AD were indistinguishable from their caregivers. The lack of "you" comments and decreased tact and manners distinguished 92.6% of the patients with bvFTD from patients with AD and caregivers. The Social Observation Inventory scores correlated with scores on frontal-executive tests and socioemotional scales. CONCLUSIONS: The systematic observation of social behavior during routine activities may be one of the best ways to distinguish patients with bvFTD from normal individuals and from patients with other dementias.

Hypersexual behavior in frontotemporal dementia: a comparison with early-onset Alzheimer's disease.

The basis of hypersexual behavior among patients with dementia is not entirely clear. Hypersexual behavior may be a particular feature of behavioral variant frontotemporal dementia (bvFTD), which affects ventromedial frontal and adjacent anterior temporal regions specialized in interpersonal behavior. Recent efforts to define hypersexual disorder indicate an increasing awareness of heightened sexual activity as a source of personal distress and functional impairment, and clarification of hypersexuality in bvFTD could contribute to understanding the neurobiology of this behavior. This study reviewed 47 patients with bvFTD compared to 58 patients with Alzheimer's disease (AD) for the presence of heightened sexual activity to the point of distress to caregivers and others. Hypersexual behavior occurred in 6 (13 %) bvFTD patients compared to none of the AD patients. Caregivers judged all six bvFTD patients with hypersexual behavior as having a dramatic increase in sexual frequency from premorbid levels. All had general disinhibition, poor impulse control, and actively sought sexual stimulation. They had widened sexual interests and experienced sexual arousal from previously unexciting stimuli. One patient, with early and predominant right anterior temporal involvement, was easily aroused by slight stimuli, such as touching her palms. Although previously considered to be predominantly disinhibited sexual behavior as part of generalized disinhibition, these patients with dementia illustrate varying degrees of increased sexual desire. We conclude that bvFTD is uniquely associated with hypersexuality; it is more than just cognitive impairment with frontal disinhibition but also involves alterations in sexual drive, possibly from right anterior temporal- limbic involvement in this disease.

Clinicopathologic differences among patients with behavioral variant frontotemporal dementia.

OBJECTIVE: To characterize the presenting symptoms and signs of patients clinically diagnosed with behavioral variant frontotemporal dementia (bvFTD) and who had different neuropathologic findings on autopsy. METHODS: This study reviewed all patients entered as clinical bvFTD in the National Alzheimer's Coordinating Center's database and who had both clinical and neuropathologic data from 2005 to 2011. Among the 107 patients identified, 95 had unambiguous pathologic findings, including 74 with frontotemporal lobar degeneration (bvFTD-FTLD) and 21 with Alzheimer disease (bvFTD-AD). The patients with bvFTD-FTLD were further subdivided into τ-positive (n = 23) or τ-negative (n = 51) histopathology subgroups. Presenting clinical signs and symptoms were compared between these neuropathologic groups. RESULTS: The patients with bvFTD-FTLD were significantly more likely than patients with bvFTD-AD to have initially predominant personality changes and poor judgment/decision-making. In contrast, patients with bvFTD-AD were more likely than patients with bvFTD-FTLD to have memory difficulty and delusions/hallucinations and agitation. Within the bvFTD-FTLD group, the τ-positive subgroup had more patients with initial behavioral problems and personality change than the τ-negative subgroup, who, in turn, had more patients with initial cognitive impairment and speech problems. CONCLUSION: During life, patients with AD pathology may be misdiagnosed with bvFTD if they have an early age at onset and prominent neuropsychiatric features despite having greater memory difficulties and more intact personality and executive functions than patients with bvFTD-FTLD. Among those with FTLD pathology, patients with τ-positive bvFTD were likely to present with behavior/personality changes. These findings offer clues for antemortem recognition of neuropathologic subtypes of bvFTD.

Nonamnestic presentations of early-onset Alzheimer's disease.

Early-onset Alzheimer's disease (EOAD) beginning before the age of 65 may differ from late-onset AD (LOAD) in clinical course and frequency of nonamnestic presentations. In a 10-year retrospective review, 125 patients with EOAD, diagnosed clinically and verified by functional neuroimaging, were compared with 56 patients with LOAD and further classified depending on predominant cognitive difficulty on presentation. Eighty (64%) of the patients with EOAD had a nonamnestic presentation, compared with only 7 (12.5%) of the patients with LOAD. Compared with LOAD, the patients with EOAD had a shorter duration with lower Mini-Mental State Examination scores. The neuroimaging reports among the patients with EOAD showed more hippocampal atrophy with an amnestic presentation, more left parietal changes with impaired language presentations, and more right parietal and occipital changes with impaired visuospatial presentations. These findings indicate that EOAD differs from LOAD in a more aggressive course and in having predominantly nonamnestic presentations that vary in neuropathological location.

Loss of emotional insight in behavioral variant frontotemporal dementia or "frontal anosodiaphoria".

Loss of insight is a prominent clinical manifestation of behavioral variant frontotemporal dementia (bvFTD), but its characteristics are poorly understood. Twelve bvFTD patients were compared with 12 Alzheimer's disease (AD) patients on a structured insight interview of cognitive insight (awareness of having a disorder) and emotional insight (concern over having a disorder). Compared to the AD patients, the bvFTD patients were less aware and less concerned about their disorder, and they had less appreciation of its effects on themselves and on others. After corrective feedback ("updating"), the bvFTD patients were just as aware of their disorder as the AD patients but remained unconcerned and unappreciative of its effects. These findings suggest that lack of insight in bvFTD is not due to "anosognosia," or impaired cognitive and executive awareness of disease, but to "frontal anosodiaphoria," or lack of emotional concern over having bvFTD and its impact on themselves and others.

The spectrum of sociopathy in dementia.

Although well-known from head trauma and acute strokes, sociopathic behavior from dementia is less known and understood. This study reviewed 33 dementia patients who had been in trouble with the law. They were divided into two groups: 22 who committed impulsive sociopathic acts and 11 who committed non-impulsive acts. The impulsive patients demonstrated nonviolent acts, such as disinhibited sexual behavior or pathological stealing, and had disproportionate frontal-caudate atrophy on neuroimaging. The majority of non-impulsive patients demonstrated agitation-paranoia, sometimes with reactive aggression, delusional beliefs, or aphasic paranoia, and had advanced memory and other cognitive impairment. The impulsive patients tended to have frontally predominant illnesses such as frontotemporal dementia or Huntington's disease, whereas the non-impulsive group tended to have Alzheimer's disease or prominent aphasia. Sociopathy has different causes in dementia. Two common mechanisms are disinhibition, with frontally predominant disease, and agitation-paranoia, with greater cognitive impairment. These forms of sociopathy differ significantly from the antisocial/psychopathic personality.

Pedophilic behavior from brain disease.

INTRODUCTION: Child molestation or other pedophilic behavior may result as a consequence of a brain disorder. AIM: To characterize the mechanisms of pedophilic behavior associated with neurological diseases. METHODS: We report eight patients with pedophilic behavior as a manifestation of their brain disorder and review the literature. MAIN OUTCOME MEASURES: The sexual, neuropsychiatric, and neurological aspects of a series of patients. RESULTS: All eight developed sexual behavior toward prepubescent children in mid- to late-life coincident with the development of a neurological disorder. Five had limited insight, anxiety, or concern for their behavior and tended to have frontal lobe executive deficits. Most of this group had frontally predominant disorders. Two others retained insight and concern in the context of marked hypersexuality. This second group had treated Parkinson's disease and resembled reports of pedophilic behavior from subcortical lesions. The further presence of right temporal lobe-amygdala involvement may have predisposed to specific sexual preoccupation in some patients. CONCLUSIONS: Brain disorders may release a predisposition to sexual attraction for children through disinhibition with frontal disease, sexual preoccupation with right temporal disease, or hypersexuality with subcortical disease in non-motor basal ganglia, hypothalamus, or septal nuclei. Differentiating these mechanisms of pedophilic behavior from brain disease could facilitate targeted interventions.

Interhemispheric differences in knowledge of animals among patients with semantic dementia.

OBJECTIVE: To investigate interhemispheric differences on naming and fluency tasks for living versus nonliving things among patients with semantic dementia (SD). BACKGROUND: In SD, left-temporal involvement impairs language and word comprehension, and right-temporal involvement impairs facial recognition. There may be other interhemispheric differences, particularly in the animate-inanimate dichotomy. METHOD: On the basis of magnetic resonance imaging (MRI) ratings of anterior temporal atrophy, 36 patients who met criteria for SD were divided into 21 with left-predominant and 11 with right-predominant involvement (4 others were too symmetric for analysis). The left and right-predominant groups were compared on naming, fluency, and facial recognition tests. RESULTS: Consistent with greater language impairment, the left-predominant patients had worse naming, especially inanimate and letter fluency, than the right-predominant patients. In contrast, difference in scores suggested selective impairment of animal naming, animal name fluency, and semantic knowledge for animate items among the right-predominant patients. Proportionally more right than left-predominant patients misnamed animal items and faces. CONCLUSIONS: These findings support interhemispheric differences in animal knowledge. Whereas left-predominant SD equally affects animate and inanimate words from language involvement, right-predominant SD, with greater sparing of language, continues to impair other semantic aspects of animals. The right anterior temporal region seems to make a unique contribution to knowledge of living things.

"Fantastic thinking" in pathologically proven Pick disease.

BACKGROUND: Reports of false beliefs may be a unique feature of behavioral variant frontotemporal dementia (bvFTD) but the nature of these experiences is unclear. OBJECTIVE: To report a case of pathologically verified Pick disease in a patient presenting with prominent and recurrent fantasies. METHODS: We describe the clinical, neuroradiologic, and neuropathologic findings of a 53-year-old woman presenting with fantasies and meeting Clinical Consensus Criteria for bvFTD. RESULTS: Early in her course, she reported interactions with different actors, having torrid affairs with them, and other related fantasies. When confronted with her false beliefs, she admitted that these relationships were imaginary. Autopsy revealed Pick disease with tau-immunoreactive Pick bodies in the frontal and temporal cortices, and in the hippocampi. CONCLUSIONS: Fantastic thinking, or vividly experienced imagination, may be a manifestation of bvFTD that is distinct from delusions and confabulations and could be the source of previously reported delusions and confabulations in bvFTD.

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 Alzheimer's 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.

"Denkfaulheit" in frontotemporal dementia: a preliminary analysis.

The initial recognition of frontotemporal dementia is often difficult. Frontotemporal dementia presents with subtle personality changes in the absence of a definitive biomarker. The authors report an analysis of cognitive shallowness, or "Denkfaulheit," in patients with frontotemporal dementia early in its course.

The spectrum of recurrent thoughts and behaviors in frontotemporal dementia.

This article describes the spectrum of recurrent thoughts and behaviors that can result from frontotemporal dementia (FTD) and its variants. Although repetitive behaviors can result from a range of brain disorders, FTD is the most common neurologic cause of new-onset recurrent thoughts and behaviors in middle or late life. Patients with FTD can manifest typical or bizarre compulsions, hoarding, verbal and motor stereotypies and complex tics; self-injurious acts, perseverations; and fixed, obsessional thoughts. The frequency and variability of these repetitive behaviors suggest a common disturbance of orbitofrontal-basal ganglia circuits involved in response inhibition. The amelioration of these recurrent events with the administration of serotonin selective reuptake inhibitors further suggests a serotonergic deficit.

Changes in dietary or eating behavior in frontotemporal dementia versus Alzheimer's disease.

BACKGROUND: Changes in dietary or eating behavior are common in dementia and may help distinguish between different dementing illnesses. OBJECTIVE: To evaluate and characterize differences in dietary and eating behavior among patients with early frontotemporal dementia (FTD) versus Alzheimer's disease (AD). METHODS: This study administered the Food-Related Problems Questionnaire (FRPQ) to caregivers of 16 patients with FTD and 16 comparable patients with AD. The FRPQ was evaluated at initial presentation when patients presented for a diagnostic evaluation. RESULTS: Compared with the AD patients, the FTD patients had significantly more changes on the FRPQ. Subscale analysis indicated that the FTD patients showed impairment of observed satiety, improper taking of food, and inappropriate responses when food was not available. CONCLUSIONS: The use of food-related questionnaires, such as the FRPQ, can help distinguish FTD patients, early in their course, from those with AD and can further characterize the altered dietary and eating behavior.

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.

Accuracy of the clinical evaluation for frontotemporal dementia.

BACKGROUND: Without a definitive clinical test, the early diagnosis of frontotemporal dementia (FTD) can be difficult. OBJECTIVE: To evaluate the accuracy of the clinical evaluation for FTD. DESIGN: Retrospective assessment of consensus criteria for FTD, neuropsychological measures, magnetic resonance images, and single-photon emission computed tomography/positron emission tomography (SPECT/PET) scans at baseline compared with a standard of subsequent clinical diagnosis after follow-up and reevaluation to year 2. SETTING: University hospital. PATIENTS: A total of 134 patients referred for clinical evaluation of suspected FTD. These patients had 1 or more core or supportive features of FTD in the absence of another etiology on initial assessment. MAIN OUTCOME MEASURES: Sensitivities, specificities, and predictive values of consensus criteria for FTD, magnetic resonance images, and SPECT/PET scans at initial assessment. RESULTS: The sensitivities and specificities for the diagnosis of FTD were 36.5% and 100.0% for consensus criteria, 63.5% and 70.4% for magnetic resonance images, and 90.5% and 74.6% for SPECT/PET scans, respectively. With a previous prevalence of nearly 50% for FTD, the positive predictive value was greatest for consensus criteria (100.0%), and the negative predictive value was greatest for SPECT/PET (89.8%). The initial neuropsychological results did not distinguish FTD, but the pattern of progression (worse naming and executive functions and preserved constructional ability) helped establish the diagnosis at year 2. CONCLUSIONS: Consensus criteria for FTD and neuropsychological measures lacked sensitivity for FTD; however, neuroimaging, particularly functional brain studies, greatly increased the sensitivity of detecting FTD. The clinical diagnosis of FTD needs to combine neuropsychiatric features with SPECT or PET findings while following the changes on neuropsychological tests.