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 dis-inhibited 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.

Objective

To assess whether the production of profanity during letter fluency testing distinguishes frontotemporal dementia (FTD) and Alzheimer's disease (AD) patients.

Background

Alterations in language and social behavior typify FTD spectrum disorders. Nonetheless, in can be difficult to distinguish pathologically-defined frontotemporal lobar degeneration (FTLD) from AD clinically. Assessing verbal fluency by having patients generate as many words as they can beginning with specific letters in a given period of time can yield diverse information of diagnostic utility.

Method

Words produced during FAS letter fluency testing were reviewed and instances of the use of "f*ck", "*ss", and "sh*t" and other words felt to be inappropriate were sought. The frequency of these words was compared between clinically diagnosed FTD and AD patients using chi-square tests.

Results

We found that 6/32 (18.8%) patients with FTD generated the word "f*ck" during the "F" trial as opposed to none of 38 patients with AD (p = 0.007). Patients who said "f*ck" had diagnoses of either behavioral variant FTD (3/15), progressive non-fluent aphasia (2/8), or semantic dementia (1/3).

Conclusions

Though the specific neuropathology in these cases is uncertain, generation of "f*ck" during letter fluency testing appears to have utility in differentiating FTD from AD.

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.

Brain disorders can lead to criminal violations. Patients with frontotemporal dementia (FTD) are particularly prone to sociopathic behavior while retaining knowledge of their acts and of moral and conventional rules. This report describes four FTD patients who committed criminal violations in the presence of clear consciousness and sufficiently intact cognition. They understood the nature of their acts and the potential consequences, but did not feel sufficiently concerned to be deterred. FTD involves a unique pathologic combination affecting the ventromedial prefrontal cortex, with altered moral feelings, right anterior temporal loss of emotional empathy, and orbitofrontal changes with disinhibited, compulsive behavior. These case histories and the literature indicate that those with right temporal FTD retain the capacity to tell right from wrong but have the slow and insidious loss of the capacity for moral rationality. Patients with early FTD present a challenge to the criminal justice system to consider alterations in moral cognition before ascribing criminal responsibility.

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.

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.

Background

Semantic dementia is a neurodegenerative disorder characterized by the loss of meaning of words or concepts. semantic dementia can offer potential insights into the mechanisms of content-specific delusions.

Objective

The authors present a rare case of semantic dementia with Cotard syndrome, a delusion characterized by nihilism or self-negation.

Method

The semantic deficits and other features of semantic dementia were evaluated in relation to the patient's Cotard syndrome.

Results

Mrs. A developed the delusional belief that she was wasting and dying. This occurred after she lost knowledge for her somatic discomforts and sensations and for the organs that were the source of these sensations. Her nihilistic beliefs appeared to emerge from her misunderstanding of her somatic sensations.

Conclusion

This unique patient suggests that a mechanism for Cotard syndrome is difficulty interpreting the nature and source of internal pains and sensations. We propose that loss of semantic knowledge about one's own body may lead to the delusion of nihilism or death.

Based on the recent literature and collective experience, an international consortium developed revised guidelines for the diagnosis of behavioural variant frontotemporal dementia. The validation process retrospectively reviewed clinical records and compared the sensitivity of proposed and earlier criteria in a multi-site sample of patients with pathologically verified frontotemporal lobar degeneration. According to the revised criteria, ‘possible’ behavioural variant frontotemporal dementia requires three of six clinically discriminating features (disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative/compulsive behaviours, hyperorality and dysexecutive neuropsychological profile). ‘Probable’ behavioural variant frontotemporal dementia adds functional disability and characteristic neuroimaging, while behavioural variant frontotemporal dementia ‘with definite frontotemporal lobar degeneration’ requires histopathological confirmation or a pathogenic mutation. Sixteen brain banks contributed cases meeting histopathological criteria for frontotemporal lobar degeneration and a clinical diagnosis of behavioural variant frontotemporal dementia, Alzheimer’s disease, dementia with Lewy bodies or vascular dementia at presentation. Cases with predominant primary progressive aphasia or extra-pyramidal syndromes were excluded. In these autopsy-confirmed cases, an experienced neurologist or psychiatrist ascertained clinical features necessary for making a diagnosis according to previous and proposed criteria at presentation. Of 137 cases where features were available for both proposed and previously established criteria, 118 (86%) met ‘possible’ criteria, and 104 (76%) met criteria for ‘probable’ behavioural variant frontotemporal dementia. In contrast, 72 cases (53%) met previously established criteria for the syndrome (P < 0.001 for comparison with ‘possible’ and ‘probable’ criteria). Patients who failed to meet revised criteria were significantly older and most had atypical presentations with marked memory impairment. In conclusion, the revised criteria for behavioural variant frontotemporal dementia improve diagnostic accuracy compared with previously established criteria in a sample with known frontotemporal lobar degeneration. Greater sensitivity of the proposed criteria may reflect the optimized diagnostic features, less restrictive exclusion features and a flexible structure that accommodates different initial clinical presentations. Future studies will be needed to establish the reliability and specificity of these revised diagnostic guidelines.

Background

Posterior cortical atrophy (PCA) may represent a discrete syndrome of Alzheimer’s disease (AD) rather than amnestic AD with visual deficits.

Methods

We separated 30 patients with PCA based on ventral and dorsal visual symptoms using cluster analysis and analyzed the demographic, cognitive, and functional imaging features.

Results

This analysis revealed subgroups of 26 dorsal and 4 ventral patients. The ventral subgroup had greater confrontational naming impairment, and the dorsal subgroup had greater hypofunction in the parietal regions. The PCA cohort had memory retrieval rather than encoding deficits, and clinical follow-up showed relative isolation of dorsal and ventral visual manifestations.

Conclusion

These results support 2, mostly nonoverlapping syndromes in patients with PCA, with the commonest affecting the dorsal visual pathway; moreover, the memory retrieval difficulty in the patients with PCA was dissimilar to the amnestic pattern in typical AD. These results suggest that, in most cases, PCA syndromes are discrete clinical variant of AD.

Frontotemporal lobar degeneration (FTLD) often presents with asymmetric atrophy. We assessed whether premorbid occupations in FTLD patients were associated with these hemispheric asymmetries. In a multi-center chart review of 588 patients, occupation information was related to location of tissue loss or dysfunction. Patients with atrophy lateralized to the right had professions more dependent on verbal abilities than patients with left-lateralized or symmetrical atrophy. In a subgroup of 96 well-characterized patients with quantified neuroimaging data, the lateralization effect was localized to the temporal lobes and included verbal and mathematical ability. Patients whose professions placed high demands on language and mathematics had relatively preserved left temporal relative to right temporal volumes. Thus, occupation selection occurring in early adulthood is related to lateralized brain asymmetry in patients who develop FTLD decades later in the relatively deficient hemisphere. The finding suggests that verbal and mathematical occupations may have been pursued due to developmental right-lateralized functional impairment that precedes the neurodegenerative process. Alternatively, long-term engagement of activities associated with these occupations contributed to left-lateralized reserve, right-lateralized dysfunction, or both.

Objective

Myelination of the human brain results in roughly quadratic trajectories of myelin content and integrity, reaching a maximum in mid-life and then declining in older age. This trajectory is most evident in vulnerable later myelinating association regions such as frontal lobes and may be the biological substrate for similar trajectories of cognitive processing speed. Speed of movement, such as maximal finger tapping speed (FTS), requires high-frequency action potential (AP) bursts and is associated with myelin integrity. We tested the hypothesis that the age-related trajectory of FTS is related to brain myelin integrity.

Methods

A sensitive in vivo MRI biomarker of myelin integrity (calculated transverse relaxation rates (R2)) of frontal lobe white matter (FLwm) was measured in a sample of very healthy males (N = 72) between 23 and 80 years of age. To assess specificity, R2 of a contrasting early-myelinating region (splenium of the corpus callosum) was also measured.

Results

FLwm R2 and FTS measures were significantly correlated (r = .45, p < .0001) with no association noted in the early-myelinating region (splenium). Both FLwm R2 and FTS had significantly quadratic lifespan trajectories that were virtually indistinguishable and both reached a peak at 39 years of age and declined with an accelerating trajectory thereafter.

Conclusions

The results suggest that in this very healthy male sample, maximum motor speed requiring high-frequency AP burst may depend on brain myelin integrity. To the extent that the FLwm changes assessed by R2 contribute to an age-related reduction in AP burst frequency, it is possible that other brain functions dependent on AP bursts may also be affected. Non-invasive measures of myelin integrity together with testing of basic measures of processing speed may aid in developing and targeting anti-aging treatments to mitigate age-related functional declines.

Morality may be innate to the human brain. This review examines the neurobiological evidence from research involving functional magnetic resonance imaging of normal subjects, developmental sociopathy, acquired sociopathy from brain lesions, and frontotemporal dementia. These studies indicate a “neuromoral” network for responding to moral dilemmas centered in the ventromedial prefrontal cortex and its connections, particularly on the right. The neurobiological evidence indicates the existence of automatic “prosocial” mechanisms for identification with others that are part of the moral brain. Patients with disorders involving this moral network have attenuated emotional reactions to the possibility of harming others and may perform sociopathic acts. The existence of this neuromoral system has major clinical implications for the management of patients with dysmoral behavior from brain disorders and for forensic neuropsychiatry.

Background

Extrapyramidal signs (EPS) may vary across 3 major subtypes of primary progressive aphasia (PPA): progressive nonfluent aphasia (PNFA), semantic dementia (SD), and progressive logopenic aphasia (PLA).

Methods

We reviewed initial neurological examinations from a clinical PPA cohort (PNFA = 49, SD = 26, PLA = 28) to determine the prevalence of specific categories of EPS.

Results

The presence of any EPS was more common in PNFA (38.8%) and PLA (35.7%) than in SD (3.8%). The PNFA group exhibited the highest prevalence of bradykinesia (PNFA: 22.4%, SD: 3.8%, PLA: 0.0%) and rigidity (PNFA: 30.6%, SD: 0.0%, PLA: 10.7%). Calculated positive likelihood ratios indicated bradykinesia (12.1) or rigidity (5.5) was more strongly associated with PNFA than other PPAs.

Conclusion

These findings suggest that on initial presentation, specific EPS may help distinguish PPA subtypes when linguistic and/or neuroimaging profiles are indistinct. Moreover, EPS could represent a marker of underlying tauopathy, linking clinical presentation to neuropathology in PPA.

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 τ-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.

Objective

There are no Food and Drug Administration (FDA)-approved medications indicated for the treatment of frontotemporal dementia (FTD). We sought to determine the most commonly used drugs used to treat behavioral variant FTD (bvFTD) in specialized dementia clinics.

Methods

Medication and demographic data from the Alzheimer’s Disease Research Centers of California (ARCC) and a multicenter FTD natural history study (NHS) data set were compared in bvFTD and Alzheimer’s disease (AD), and effects of demographic variables were assessed using logistic regression.

Results

Overall, the percentage of patients taking one or more FDA-approved AD or psychiatric medications was similar in bvFTD and AD; however, after controlling for demographic variables, acetylcholinesterase inhibitor (AChI) use was less common in bvFTD, whereas memantine use remained similar in the 2 groups.

Conclusions

Despite lack of evidence for efficacy, the use of AChIs and memantine is common in bvFTD. Clinical trials should be pursued to determine the optimal therapeutic interventions for bvFTD.

To design clinical trials for the frontotemporal lobar degenerations (FTLD), knowledge about measurement of disease progression is needed to estimate power and enable the choice of optimal outcome measures. The aim here was to conduct a multicentre, 1 year replica of a clinical trial in patients with one of four FTLD syndromes, behavioural variant frontotemporal dementia (bvFTD), progressive nonfluent aphasia (PNFA), progressive logopenic aphasia (PLA) and semantic dementia (SMD). Patients with one of the four FTLD syndromes were recruited from five academic medical centres over a 2 year period. Standard operationalized diagnostic criteria were used. In addition to clinical inclusion and exclusion criteria, patients were required to exhibit focal frontal, temporal or insular brain atrophy or dysfunction by neuroimaging. Patients underwent neuropsychological, functional, behavioural, neurological and MR imaging assessment at baseline and approximately 12 months later. Potential outcome measures were examined for their rates of floor and ceiling values at baseline and end of study, their mean changes and variances. The neuropsychological tests were combined into two cognitive composites—one for language functions and the other for executive functions. There were 107 patients who underwent baseline assessment and 78 who completed a follow-up assessment within 10–16 months. Two global measures, the FTLD-modified Clinical Dementia Rating (FTLD-modified CDR) and the Clinical Global Impression of Change (CGIC) demonstrated decline in the majority of patients. Several cognitive measures showed negligible floor or ceiling scores either at baseline or follow-up. Scores declined at follow-up in the majority of patients. The cognitive, executive and combined composites were shown to be sensitive to change across all FTLD syndromes. Patients improved at follow-up on the behavioural scales—the Frontal Behavioural Inventory (22%) and the Neuropsychiatric Inventory (28%)—suggesting that these instruments may not be ideal for clinical trial use. It was feasible to recruit FTLD patients in a simulated multi-centre trial. There are several candidate outcome measures—including the FTLD-CDR and the cognitive composites— that could be used in clinical trials across the spectrum of FTLD.

We compared demographics of subjects diagnosed with frontotemporal degeneration (FTD) at a group of 5 clinics specializing in this non-Alzheimer dementia against those subjects diagnosed at standard Alzheimer disease centers, to determine any differences in referral patterns between such clinics.

Of the two major phenotypes of FTD, behavior and language, the latter more frequently presented to the specialty clinics (46% of FTD diagnoses versus 19%, P < 0.001). Mean age at onset for the behavioral presentation phenotype was one year younger at the specialty clinics (P < 0.01). Mean age at onset for the language phenotype was 3 years older (P < 0.001) than for the behavioral phenotype at standard centers but did not differ between the two evaluating groups.

Cases with FTD referred to all of the dementia evaluation sites in this study did not differ significantly from those previously reported in the literature. Clinics specializing in FTD recruit more language presentation cases. There were statistical but not clinically significant differences in ages at onset.

Although familial Alzheimer’s disease (FAD) is an early onset AD (EAD), most patients with EAD do not have a familial disorder. Recent guidelines recommend testing for genes causing FAD only in those EAD patients with two first-degree relatives. However, some patients with FAD may lack a known family history or other indications for suspecting FAD but might nonetheless be carriers of FAD mutations. The study was aimed to identify clinical features that distinguish FAD from non-familial EAD (NF-EAD). A retrospective review of a university-based cohort of 32 FAD patients with PSEN1-related AD and 81 with NF-EAD was conducted. The PSEN1 patients, compared to the NF-EAD patients, had an earlier age of disease onset (41.8 ± 5.2 vs. 55.9 ± 4.8 years) and, at initial assessment, a longer disease duration (5.1 ± 3.4 vs. 3.3 ± 2.6 years) and lower MMSE scores (10.74 ± 8.0 vs. 20.95 ± 5.8). Patients with NF-EAD were more likely to present with non-memory deficits, particularly visuospatial symptoms, than were FAD patients. When age, disease duration, and MMSE scores were controlled in a logistical regression model, FAD patients were more likely to have significant headaches, myoclonus, gait abnormality, and pseudobulbar affect than those with NF-EAD. In addition to a much younger age of onset, FAD patients with PSEN1 mutations differed from those with NF-EAD by a history of headaches and pseudobulbar affect, as well as myoclonus and gait abnormality on examination. These may represent differences in pathophysiology between FAD and NF-EAD and in some contexts such findings should lead to genetic counseling and appropriate recommendations for genetic testing for FAD.

Nine families with autosomal dominant Alzheimer’s disease (AD), all of whom had the Ala431Glu substitution in the PSEN1 gene and came from Jalisco State in Mexico, have been previously reported. As they shared highly polymorphic flanking dinucleotide marker alleles, this strongly suggests that this mutation arose from a common founder. In the current letter, we expand this observation by describing an additional 15 independent families with the Ala431Glu substitution in the PSEN1 gene and conclude that this mutation is not an uncommon cause of early-onset autosomal dominant AD in persons of Mexican origin.