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We describe the clinical, neuropsychological, and neuropathological features of a 21 year old woman with frontotemporal dementia (FTD). The early presentation was of florid behavioural change involving hyperactivity and disinhibition. Magnetic resonance imaging and single photon emission computed tomography of the brain revealed atrophy and severe functional abnormalities of the frontal and temporal lobes, respectively. Electroencephalogram was normal. At autopsy, there was gross frontotemporal brain atrophy and the underlying histology was of a microvacuolar-type degeneration; no tau or ubiquitin immunoreactive, intraneuronal inclusions were seen. There was no family history of dementia and no mutation in the tau gene. We believe this patient represents the youngest (so far) recorded case of FTD associated with this particular histological form of the disorder. [ABSTRACT FROM AUTHOR]

Criterion 4 of the Montreal Process addresses the conservation of soil and water resources as away to assess the sustainability of a nation's forests. For the most part, the indicators under this criterion are relevant to rangelands. The area and percent of rangeland with significant soil erosion apply equally well to both biomes. Percent of streams with flow rates and timing outside its range of historical variation is also equally important, although a measure of proper functioning and condition may provide a better measure of the indicator. The area and percent of rangeland with diminished soil productive capability because of a loss of reduced organic matter or changed physical characteristics can be useful indicators locally and regionally. [ABSTRACT FROM AUTHOR]

Abstract: There is accumulating evidence of preserved arithmetic knowledge in semantic dementia (SD), contrasting with patients’ striking impairment in other domains of semantic memory. This important finding exemplifies domain specificity in the breakdown of semantic memory and supports notions of the functional independence of semantic number knowledge. Nevertheless, evidence for preserved arithmetic knowledge in SD comes largely from single case studies. It is not known whether such preservation is a universal finding, or whether it persists irrespective of disease severity. The present study examined performance of 14 SD patients, varying in the severity of their semantic impairment, on tasks assessing knowledge of arithmetic signs, and on single-digit and multi-digit calculation problems, permitting evaluation of fact retrieval and use of procedures. SD patients performed generally well compared to 10 healthy controls on tests of addition and subtraction. However, abnormalities were elicited, which were not explained by education or hemispheric side of atrophy, but increased as a function of semantic severity. Patients had difficulty identifying arithmetic signs. They used increasingly basic, inflexible strategies to retrieve multiplication table ‘facts’, and in multi-digit calculations they made procedural errors that pointed to a failure to understand the differential weighting of left and right hand columns. The pattern of responses and error types mirrors in reverse that found in children as they acquire arithmetic competence, and suggests a progressive degradation in conceptual understanding of arithmetic. Longitudinal study of two SD patients demonstrated an association between semantic decline and impaired arithmetic performance. The findings challenge the notion of arithmetic knowledge as a totally separate semantic domain and suggest that the temporal lobes play an important role in arithmetic understanding. [Copyright &y& Elsevier]

Background: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the commonest causes of presenile dementia. In the absence of a biological marker, diagnosis is reliant on clinical evaluation. Confirmation is often sought from neuroimaging, including single-photon emission computed tomography (SPECT). Most previous SPECT studies lack pathological validation.Aim: To examine the accuracy of SPECT in differentiating FTD from AD in patients with subsequent pathological confirmation.Methods: Technetium-99-labelled hexamethyl propylene amine oxime SPECT images obtained at initial evaluation in 25 pathologically confirmed cases of FTD were examined. These images were visually rated by an experienced blinded nuclear medicine consultant and compared with those of 31 patients with AD, also with pathological validation.Results: A reduction in frontal cerebral blood flow (CBF) was more common in FTD and was of diagnostic value (sensitivity 0.8, specificity 0.65 and likelihood ratio (LR) 2.25; 95% CI 1.35 to 3.77). A pattern of bilateral frontal CBF reduction without the presence of associated bilateral parietal CBF change is diagnostically more accurate (sensitivity 0.80, specificity 0.81 and +LR 4.13, 95% CI 1.96 to 8.71). Diagnostic categorisation (FTD or AD) on the basis of SPECT alone was less accurate than clinical diagnosis (based on neurology and detailed neuropsychological evaluation). One patient with FTD was initially clinically misdiagnosed as AD, owing to the lack of availability of full neuropsychological assessment. However, SPECT correctly diagnosed this patient, providing a diagnostic gain of 4%.Conclusion: Technetium-99-labelled hexamethyl propylene amine oxime SPECT CBF patterns provide valuable information in the diagnosis of FTD and AD. These data can be better used as an adjunct to clinical diagnosis if pathology is to be correctly predicted in life. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor on coexistence of systemic sclerosis and multiple sclerosis.

Y. S. Davidson, A. C. Robinson, Q. Hu, M. Mishra, A. Baborie, E. Jaros, R. H. Perry, N. J. Cairns, A. Richardson, A. Gerhard, D. Neary, J. S. Snowden, E. H. Bigio and D. M. A. Mann (2013) Neuropathology and Applied Neurobiology 39, 157-165 Nuclear carrier and RNA-binding proteins in frontotemporal lobar degeneration associated with fused in sarcoma (FUS) pathological changes Aims: We aimed to investigate the role of the nuclear carrier and binding proteins, transportin 1 (TRN1) and transportin 2 (TRN2), TATA-binding protein-associated factor 15 (TAF15) and Ewing's sarcoma protein (EWS) in inclusion body formation in cases of frontotemporal lobar degeneration (FTLD) associated with fused in sarcoma protein (FTLD-FUS). Methods: Eight cases of FTLD-FUS (five cases of atypical FTLD-U, two of neuronal intermediate filament inclusion body disease and one of basophilic inclusion body disease) were immunostained for FUS, TRN1, TRN2, TAF15 and EWS. Ten cases of FTLD associated with TDP-43 inclusions served as reference cases. Results: The inclusion bodies in FTLD-FUS contained TRN1 and TAF15 and, to a lesser extent, EWS, but not TRN2. The patterns of immunostaining for TRN1 and TAF15 were very similar to that of FUS. None of these proteins was associated with tau or TDP-43 aggregations in FTLD. Conclusions: Data suggest that FUS, TRN1 and TAF15 may participate in a functional pathway in an interdependent way, and imply that the function of TDP-43 may not necessarily be in parallel with, or complementary to, that of FUS, despite each protein sharing many similar structural elements. [ABSTRACT FROM AUTHOR]

Abstract: A well-documented feature of Huntington''s disease (HD) is disproportionate impairment in the ability to recognise the emotional expression of disgust. However, this finding has been challenged by studies that report no differential disgust impairment and attribute apparent differences across emotions to task difficulty. The present study sought to shed light on disparities in findings through a comparative study of emotion recognition in HD and frontotemporal dementia (FTD). Ten HD, 12 FTD patients and 12 healthy controls were administered 10 tasks assessing facial and vocal recognition of emotions and comprehension of emotion terms. The findings were not consistent with either the ‘selective disgust impairment’ or ‘task difficulty’ view. Both HD and FTD groups were impaired compared to controls, deficits in HD being less severe. Impairments in FTD were elicited for all emotions whereas in HD they were demonstrated predominantly for negative emotions of fear, disgust and anger. Consistency in performance, despite varying task demands, excluded an explanation in terms of item difficulty, and was in keeping with the notion of distinct neural substrates for processing of negative emotions. Contrary to the notion of disproportionate disgust impairment, the most severe deficits in HD were elicited for anger, a finding that may have relevance for the poor anger control that is the hallmark of HD. The data raise the possibility that linguistic influences and conceptual complexities of the emotion of disgust may contribute to the variable finding of selective disgust impairment in HD. [Copyright &y& Elsevier]

Information is sparse on neurotransmitter deficiencies in frontotemporal dementia (FTD), in particular with reference to distinct histological subgroups and Alzheimer’s disease (AD). To evaluate in FTD with the major histologies, and compare with AD and controls, neurotransmission indices, as these may help in developing treatment. Post-mortem grey matter from Brodmann Area 21, 9 and 7 of 51 brains was assayed for ten neurochemical parameters indexing neurotransmission. Repeated measures analyses of variance were carried out for each parameter comparing groups (FTD vs AD vs control) at each anatomical site. In FTD only the indices of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid, serotonin (5-HT)1A and 5-HT2A receptors were significantly reduced from control values. Of the ten parameters only 5-HT1A receptors showed significant group × site interaction. This reflected disproportionate reduction in frontal and temporal compared to parietal cortex. In FTD three other receptors (muscarinic, M1, N-methyl- d-aspartate, NMDA, and kainate), choline acetyltransferase (ChAT) activity, 5-HT and 5-hydroxyindoleacetic acid content and 5-HT reuptake site values were not significantly reduced from control values. Only 5-HT, 5-HT reuptake site and ChAT values were significantly higher in FTD than AD. NMDA receptor and ChAT values were significantly reduced from control only in AD. Neurochemical results in FTD indicate degeneration and loss of pyramidal neurones in frontotemporal neocortex, yet 5-HT afferents and 5-HT concentration, which are inhibitory on pyramidal neurones, were relatively preserved. This could lead to an excess of extraneural 5-HT causing underactivity of surviving pyramidal neurones. Pharmacotherapy with a 5-HT1A receptor antagonist may be indicated. [ABSTRACT FROM AUTHOR]

Abstract: The traditional assumption that classical motor neurone disease (MND) invariably spares cognitive function is now recognised to be incorrect. Deficits have most commonly been demonstrated on executive tasks suggesting impaired function of frontal systems. Yet, crucial aspects of frontal lobe function have not hitherto been explored. The study used tests of theory of mind (ToM) (interpretation of cartoons and stories) to examine the ability of 16 patients with MND to interpret social situations and ascribe mental states to others. Only minor differences were elicited in the MND group as a whole compared to controls, and performance was not differentially affected for cartoons and stories requiring inference of another''s mental state (mental) compared to control (physical) cartoons and stories. However, abnormalities were elicited on both mental and physical tasks in a subgroup of patients with bulbar signs. Moreover, examination of individual patient scores revealed a spectrum of performance ranging from normal to severely impaired. Errors were qualitatively similar to those seen in frontotemporal dementia (FTD). Performance on the ToM tasks was significantly correlated with conventional, untimed measures of executive function, suggesting that ToM deficits in MND are likely to be linked to a more general executive failure. The findings contribute to the understanding of ToM performance in neurodegenerative disease and provide further evidence of the association between MND and FTD. [Copyright &y& Elsevier]

Background: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the commonest causes of presenile dementia. In the absence of a biological marker, diagnosis is reliant on clinical evaluation. Confirmation is often sought from neuroimaging, including single-photon emission computed tomography (SPECT). Most previous SPECT studies lack pathological validation. Aim: To examine the accuracy of SPECT in differentiating FTD from AD in patients with subsequent pathological confirmation. Methods: Technetium-99-labelled hexamethyl propylene amine oxime SPECT images obtained at initial evaluation in 25 pathologically confirmed cases of FTD were examined. These images were visually rated by an experienced blinded nuclear medicine consultant and compared with those of 31 patients with AD, also with pathological validation. Results: A reduction in frontal cerebral blood flow (CBF) was more common in FTD and was of diagnostic value (sensitivity 0.8, specificity 0.65 and likelihood ratio (LR) 2.25; 95% CI 1.35 to 3.77). A pattern of bilateral frontal CBF reduction without the presence of associated bilateral parietal CBF change is diagnostically more accurate (sensitivity 0.80, specificity 0.81 and +LR 4.13, 95% CI 1.96 to 8.71). Diagnostic categorisation (FTD or AD) on the basis of SPECT alone was less accurate than clinical diagnosis (based on neurology and detailed neuropsychological evaluation). One patient with FTD was initially clinically misdiagnosed as AD, owing to the lack of availability of full neuropsychological assessment. However, SPECT correctly diagnosed this patient, providing a diagnostic gain of 4%. Conclusion: Technetium-99-Iabelled hexamethyl propylene amine oxime SPECT CBF patterns provide valuable information in the diagnosis of FTD and AD. These data can be better used as an adjunct to clinical diagnosis if pathology is to be correctly predicted in life. [ABSTRACT FROM AUTHOR]

The age distribution of the 4 allelic form of the apolipoprotein E gene (APOE) was investigated in 630 patients with Alzheimer's disease (AD) with onset age ranging from 35 to 90 years. Overall, mean age at onset in APOE 4 allele bearers was significantly later than that in nonbearers. However, when stratified into early onset AD (EOAD) and late onset (LOAD) groups, mean age at onset in EOAD cases bearing APOE 4 allele was later than that in those EOAD cases without 4 allele, whereas in LOAD mean age at onset in cases bearing APOE 4 allele was earlier than in those without 4 allele. When analysed by decade, it was observed that 37% of the total number of APOE 4 allele bearers, and 43% of total number of cases with APOE 4/4 genotype fell into the 60-69 years age class. Hence, APOE 4 allele frequency, at 0.44, was highest in the 60-69 years age class, progressively decreasing either side of this age group. APOE 4 allele therefore has its maximum impact between onset ages of between 60 and 70 years. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To determine whether polymorphic variations in the apolipoprotein E gene (APOE) are associated with increased risk of frontotemporal lobar degeneration (FTLD) when mutation in tau gene is absent.Methods: The APOE gene was genotyped by polymerase chain reaction from DNA routinely extracted from blood or brain tissues. The APOE epsilon4 allele frequency in 198 patients with FTLD not associated with mutations in tau gene was compared with that of a control group of 756 normal individuals drawn from the same geographical region. Analyses were done according to clinical subtype or sex.Results: The APOE epsilon4 allele frequency (19.4%) was increased (p = 0.01) in FTLD v the whole control group (14.1%), while the APOE epsilon2 allele frequency in FTLD (6.5%) was slightly lower than in controls (8.0%) (NS). The APOE epsilon4 allele frequency in men with FTLD (22.3%) was greater (p = 0.002) than in male controls (12.3%); the frequency in women (16.3%) was similar to that in female controls (14.8%) (NS). The APOE epsilon2 allele frequency in men with FTLD was 4.9% while in male controls it was 9.5% (p = 0.06), but there was no difference in women (7.5% v 7.9%, NS). Neither the APOE epsilon2 nor APOE epsilon4 allele frequency varied significantly between any of the clinical subtypes.Conclusions: In FTLD not associated with mutations in tau gene, possession of APOE epsilon4 allele in men roughly doubles the chances of developing disease, whereas this has no impact upon disease risk in women. [ABSTRACT FROM AUTHOR]

Objective: To determine whether polymorphic variations in the apolipoprotein E gene (APOE) are associated with increased risk of frontotemporal lobar degeneration (FTLD) when mutation in tau gene is absent. Methods: The APOE gene was genotyped by polymerase chain reaction from DNA routinely extracted from blood or brain tissues. The APOE ∈4 allele frequency in 198 patients with FTLD not associated with mutations in tau gene was compared with that of a control group of 756 normal individuals drawn from the same geographical region. Analyses were done according to clinical subtype or sex. Results: The APOE ∈4 allele frequency (19.4%) was increased (p = 0.01 ) in FTLD v the whole control group (14.1%), while the APOE ∈2 allele frequency in FTLD (6.5%) was slightly lower than in controls (8.0%) (NS). The APOE ∈4 allele frequency in men with FTLD (22.3%) was greater (p=0.002) than in male controls (12.3%); the frequency in women (16.3%) was similar to that in female controls (14.8%) (NS). The APOE ∈2 allele frequency in men with FTLD was 4.9% while in male controls it was 9.5% (p = 0.06), but there was no difference in women (7.5% v 7.9%, NS). Neither the APOE ∈2 nor APOE ∈4 allele frequency varied significantly between any of the clinical subtypes. Conclusions: In FTLD not associated with mutations in tau gene, possession of APOE ∈4 allele in men roughly doubles the chances of developing disease, whereas this has no impact upon disease risk in women. [ABSTRACT FROM AUTHOR]

Background: Frontotemporal dementia (FTD) and Alzheimer's disease are clinically distinct disorders, yet neuropsychological studies have had variable success in distinguishing them. A possible reason is that studies typically rely on overall accuracy scores, which may obscure differences in reasons for failure. Objectives: To explore the hypothesis that analysis of qualitative performance characteristics and error types, in addition to overall numerical scores, would enhance the neuropsychological distinction between FTD and Alzheimer's disease. Methods: 38 patients with FTD and 73 with Alzheimer's disease underwent assessment of language, visuospatial abilities, memory, and executive function, using a neuropsychological screening instrument and standard neuropsychological tests. In each of these cognitive domains, performance characteristics and error types were documented, in addition to numerical scores on tests. Results: Whereas comparison of neuropsychological test scores revealed some group differences, these did not occur consistently across tests within cognitive domains. However, analysis of performance characteristics and error types revealed qualitative differences between the two groups. In particular, FTD patients displayed features associated with frontal lobe dysfunction, such as concrete thought, perseveration, confabulation, and poor organisation, which disrupted performance across the range of neuropsychological tests. Conclusions: Numerical scores on neuropsychological tests alone are of limited value in differentiating FTD and Alzheimer's disease, but performance characteristics and error types enhance the distinction between the two disorders. FTD is associated with a profound behavioural syndrome that affects performance on cognitive assessment, obscuring group differences. Qualitative information should be included in neuropsychological research and clinical assessments. [ABSTRACT FROM AUTHOR]

Frontotemporal dementia (FTD) and Huntington’s disease (HD) are degenerative disorders, with predominant involvement, respectively of frontal neocortex and striatum. Both conditions give rise to altered social conduct and breakdown in interpersonal relationships, although the factors underlying these changes remain poorly defined. The study used tests of theory of mind (interpretation of cartoons and stories and judgement of preference based on eye gaze) to explore the ability of patients with FTD and HD to interpret social situations and ascribe mental states to others. Performance in the FTD group was severely impaired on all tasks, regardless of whether the test condition required attribution of a mental state. The HD group showed a milder impairment in cartoon and story interpretation, and normal preference judgements. Qualitative differences in performance were demonstrated between groups. FTD patients made more concrete, literal interpretations, whereas HD patients were more likely to misconstrue situations. The findings are interpreted as demonstrating impaired theory of mind in FTD, as one component of widespread executive deficits. In HD the evidence does not suggest a fundamental loss of theory of mind, but rather a tendency to draw faulty inferences from social situations. It is concluded that social breakdown in FTD and HD may have a different underlying basis and that the frontal neocortex and striatum have distinct contributions to social behaviour. [Copyright &y& Elsevier]

Objective – The occurrence of high signal abnormalities on T2 weighted images is strongly age related. The diagnostic value of these changes in a younger population with dementia is not currently known. We studied the potential of high signal changes on magnetic resonance imaging (MRI) in differentiating Alzheimer's disease (AD), frontotemporal dementia (FTD) and vascular dementia (VaD) in younger patients. Methods – High signal abnormalities were rated, using a previously validated scale, from hard copies of T2 weighted axial images of 102 patients with AD (n =49), VaD (n =31), FTD (n =22) (mean ages 63–65 years). Results – High signal abnormalities were widespread across AD, VaD and FTD. Although they were most frequent and most severe in the VaD group only lacunes and grade III deep white matter hyperintensities (DWMH) were specific for these patients. Conclusions – High signal changes on T2 weighted images on MRI are common across degenerative (AD and FTD) and vascular dementias. Although lacunes and grade III DWMH are specific for VaD, the low sensitivities (sensitivities: for lacunes, 0.32; for grade III DWMH, 0.16) limit their use as diagnostic markers for VaD. High signal changes on MRI should be interpreted with caution in dementias. Their presence, even in younger patients, should not deter one from diagnosing AD or FTD. [ABSTRACT FROM AUTHOR]

Objectives – Alzheimer's disease (AD), frontotemporal dementia (FTD) and vascular dementia (VaD) are the three most common causes of young onset dementias. Most neuroimaging studies of these disorders have involved comparisons with normal controls. The aims of this study were to examine the clinical diagnostic value of magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) (in combination and in isolation) in the differentiation of one form of dementia from another from amongst a␣group of AD, FTD and VaD. Methods – T1 weighted MRI images and 99m Tc-HMPAO SPECT images were obtained from consecutive patients with FTD (n =21), AD (n =23) and VaD (n =20) and rated visually by experienced neuroradiologists and nuclear medicine physicians. Results – Asymmetrical atrophy was seen only in FTD. Frontotemporal dementia patients were the most atrophic whereas severe atrophy was rarely observed in VaD. Severe frontal atrophy (unilaterally or bilaterally) and/or asymmetrical atrophy on MRI is highly diagnostic (sensitivity 0.71, specificity 0.93, LR 10.24) of FTD from within a group of FTD and non-FTD (AD, VaD) patients. Mild or severe parietal atrophy with severe reduction in parietal regional cerebral blood flow on SPECT is diagnostic (sensitivity 0.71, specificity 0.76, LR 3.02) of AD from within a group of AD and non-AD (VaD, FTD) patients. Conclusion – Anatomical (MRI) and functional (SPECT) imaging provide different information and a combination of these modalities improves diagnostic specificity. [ABSTRACT FROM AUTHOR]

The earliest changes in the development of Huntington's disease (HD)remain controversial. Studies of cognitive function in preclinical individualswho have the HD mutation have yielded contradictory results. This study comparedcognitive and motor performance in 51 people with the HD mutation who hadno clinical signs of HD, 85 at-risk individuals without the HD mutation and43 individuals in the early stages of HD. Whereas highly significant differenceswere detected between the preclinical and early-HD groups, only subtle impairmentswere present in at-risk individuals with the HD mutation compared to thosewith normal HD alleles, principally for low-demand psychomotor tasks. Complementingthese observations, longitudinal investigation showed that performance onpsychomotor tasks in people with the mutation who were close to clinical onsetof HD was intermediate between that of individuals many years from onset andthose in the early stages of HD, suggesting a slowly insidious evolution ofdeficit. In contrast, memory performance showed a more precipitous declinearound the time of clinical onset of HD. The findings, which suggest thatHD patients' functional deficits do not evolve uniformly, help to resolvesome of the disparities in the literature on preclinical HD. [ABSTRACT FROM AUTHOR]

Objectives – The study aimed to increase understanding of behavioural changes in frontotemporal dementia (FTD) and identify features that best differentiate FTD from Alzheimer's disease (AD) and cerebrovascular dementia (CvD). Methods – A semi-structured questionnaire was administered to carers of 30 FTD, 75 AD and 34 CvD patients. Results – Behavioural changes that strongly discriminated FTD from AD and to a lesser extent CvD were loss of emotions and insight, selfishness, disinhibition, personal neglect, gluttony and sweet food preference, wandering, motor and verbal stereotypies, loss of pain, echolalia and mutism. Irritability, hyposexuality and hypersomnia did not discriminate. Emotional, eating and stereotyped behaviours correctly classified 95% of patients using regression analysis. Conclusions – Behavioural characteristics accurately differentiate FTD from AD and CvD. The findings highlight the particular importance of affective change in FTD, and underline the role of the frontotemporal lobes in emotion. [ABSTRACT FROM AUTHOR]

Objectives – Dementia with Lewy bodies (DLB) is the second commonest neurodegenerative cause of dementia. While there is consensus on the clinical diagnostic criteria for DLB, the use of EEG to increase the diagnostic sensitivity has not been substantiated. Material and methods – We studied the resting EEG findings in 18 consecutive patients with DLB and compared them with a control group of 20 patients with “probable” Alzheimer's disease (AD). We aimed to evaluate the use of EEG in a representative sample of patients with DLB. Results – All patients with DLB fulfilled accepted clinical criteria for DLB. The DLB group had a more severe dementia than the AD group, as measured by the Mini‐Mental State Examination (MMSE) test (DLB mean MMSE 9.4 and AD mean MMSE 17.2) despite a similar duration of overall severity of illness. The EEG was slow in both groups, predominantly in the 4–7 Hz range. Although there was no statistically significant difference in the EEG findings between the DLB and AD groups, there was a correlation between the EEG score and MMSE score (Spearman Rank correlation rs=-0.61, P<0.001). Conclusion – These findings suggest that although patients with DLB have a more aggressive course than AD, EEG abnormalities do not differ in the 2 groups. However, we believe the EEG provides important supporting diagnostic information in DLB. [ABSTRACT FROM AUTHOR]