Different patterns of gray matter atrophy in behavioral variant frontotemporal dementia with and without episodic memory impairment.

BACKGROUND: Differentiating patients with behavioral variant frontotemporal dementia (bvFTD) from Alzheimer's disease (AD) is important as these two conditions have distinct treatment and prognosis. Using episodic impairment and medial temporal lobe atrophy as a tool to make this distinction has been debatable in the recent literature, as some patients with bvFTD can also have episodic memory impairment and medial temporal lobe atrophy early in the disease. OBJECTIVES: To compare brain atrophy patterns of patients with bvFTD with and without episodic memory impairment to that of patients with AD. METHODS: We analyzed 19 patients with bvFTD, 21 with AD and 21 controls, matched by age, sex, and years of education. They underwent brain MRI and the memory test from the Brief Cognitive Battery (BCB) to assess episodic memory. We then categorized the bvFTD group into amnestic (BCB delayed recall score <7) and non-amnestic. RESULTS: The amnestic bvFTD group (n = 8) had significant gray matter atrophy in the left parahippocampal gyrus, right cingulate and precuneus regions compared with the nonamnestic group. Compared with AD, amnestic bvFTD had more atrophy in the left fusiform cortex, left insula, left inferior temporal gyrus and right temporal pole, whereas patients with AD had more atrophy in the left hippocampus, left frontal pole and left angular gyrus. CONCLUSIONS: There is a group of amnestic bvFTD patients with episodic memory dysfunction and significant atrophy in medial temporal structures, which poses a challenge in considering only these features when differentiating bvFTD from AD clinically.

Papez Circuit Gray Matter and Episodic Memory in Amyotrophic Lateral Sclerosis and Behavioural Variant Frontotemporal Dementia.

Amyotrophic lateral sclerosis and behavioural variant frontotemporal dementia are two different diseases recognized to overlap at clinical, pathological and genetic characteristics. Both conditions are traditionally known for relative sparing of episodic memory. However, recent studies have disputed that with the report of patients presenting with marked episodic memory impairment. Besides that, structural and functional changes in temporal lobe regions responsible for episodic memory processing are often detected in neuroimaging studies of both conditions. In this study, we investigated the gray matter features associated with the Papez circuit in amyotrophic lateral sclerosis, behavioural variant frontotemporal dementia and healthy controls to further explore similarities and differences between the two conditions. Our non-demented amyotrophic lateral sclerosis patients showed no episodic memory deficits measured by a short-term delayed recall test while no changes in gray matter of the Papez circuit were found. Compared with the amyotrophic lateral sclerosis group, the behavioural variant frontotemporal dementia group had lower performance on the short-term delayed recall test and marked atrophy in gray matter of the Papez circuit. Bilateral atrophy of entorhinal cortex and mammillary bodies distinguished behavioural variant frontotemporal dementia from amyotrophic lateral sclerosis patients as well as atrophy in left cingulate, left hippocampus and right parahippocampal gyrus. Taken together, our results suggest that sub-regions of the Papez circuit could be differently affected in amyotrophic lateral sclerosis and behavioural variant frontotemporal dementia.

Challenges in the diagnosis of dementia: insights from the United Kingdom-Brazil Dementia Workshop.

In July 2019, a group of multidisciplinary dementia researchers from Brazil and the United Kingdom (UK) met in the city of Belo Horizonte, Minas Gerais, Brazil, to discuss and propose solutions to current challenges faced in the diagnosis, public perception and care of dementia. Here we summarize the outcomes from the workshop addressing challenges in diagnosis. Brazil faces a major problem in dementia underdiagnosis, particularly involving the population in an adverse socioeconomic context. There is poor availability of resources and specialists, and the knowledge of general practitioners and other healthcare professionals is far from satisfactory. Low education level is a further obstacle in diagnosing dementia, as the most commonly used screening tests are not designed to evaluate this population. Patients and their families must overcome the stigma of a diagnosis of dementia, which is still prevalent in Brazil and increases the burden of this condition. Whilst the UK has greater resources, dedicated memory services and a National Dementia Strategy plan, the National Health Service (NHS) has limited funding. Therefore, some challenges regarding diagnosis are common across both countries. The authors suggest possible solutions to confront these, with the goal of improving assessment and recognition of dementia and reducing misdiagnosis.

Em julho de 2019, um grupo multidisciplinar de pesquisadores em demência do Brasil e do Reino Unido se reuniu em Belo Horizonte para discutir e propor soluções para os desafios no diagnóstico, percepção pública e tratamento dessa condição. Neste artigo, sintetizamos as conclusões do workshop sobre os desafios no diagnóstico de demência. O Brasil enfrenta um grande problema no subdiagnóstico de demência, principalmente entre a população em condições socioeconômicas adversas. Há pouca disponibilidade de recursos e de especialistas e o conhecimento de médicos generalistas e de outros profissionais de saúde é pouco abrangente. Baixa escolaridade é também um obstáculo no diagnóstico de demência, uma vez que os testes de rastreio mais utilizados na prática clínica não são estruturados para avaliar a população com esse perfil. Os pacientes com demência e suas famílias ainda têm que superar o estigma do diagnóstico, que é ainda muito prevalente no Brasil e colabora para a piora da qualidade de vida. O Reino Unido, por outro lado, dispõe de mais recursos financeiros e de pessoal, possui serviços dedicados à avaliação de problemas de memória e um plano estratégico nacional para demência. Contudo, o National Health Service (NHS) tem verbas limitadas, o que faz com que alguns dos desafios no diagnóstico de demência sejam comuns aos dois países. Os autores sugerem possíveis soluções para enfrentá-los, com o objetivo de melhorar a avaliação e o reconhecimento da demência e reduzir os erros de diagnóstico.

Challenges in the diagnosis of dementia: insights from the United Kingdom-Brazil Dementia Workshop / Desafios no diagnóstico de demência: conclusões do Workshop de Demência Reino Unido-Brasil

ABSTRACT. In July 2019, a group of multidisciplinary dementia researchers from Brazil and the United Kingdom (UK) met in the city of Belo Horizonte, Minas Gerais, Brazil, to discuss and propose solutions to current challenges faced in the diagnosis, public perception and care of dementia. Here we summarize the outcomes from the workshop addressing challenges in diagnosis. Brazil faces a major problem in dementia underdiagnosis, particularly involving the population in an adverse socioeconomic context. There is poor availability of resources and specialists, and the knowledge of general practitioners and other healthcare professionals is far from satisfactory. Low education level is a further obstacle in diagnosing dementia, as the most commonly used screening tests are not designed to evaluate this population. Patients and their families must overcome the stigma of a diagnosis of dementia, which is still prevalent in Brazil and increases the burden of this condition. Whilst the UK has greater resources, dedicated memory services and a National Dementia Strategy plan, the National Health Service (NHS) has limited funding. Therefore, some challenges regarding diagnosis are common across both countries. The authors suggest possible solutions to confront these, with the goal of improving assessment and recognition of dementia and reducing misdiagnosis.

RESUMO. Em julho de 2019, um grupo multidisciplinar de pesquisadores em demência do Brasil e do Reino Unido se reuniu em Belo Horizonte para discutir e propor soluções para os desafios no diagnóstico, percepção pública e tratamento dessa condição. Neste artigo, sintetizamos as conclusões do workshop sobre os desafios no diagnóstico de demência. O Brasil enfrenta um grande problema no subdiagnóstico de demência, principalmente entre a população em condições socioeconômicas adversas. Há pouca disponibilidade de recursos e de especialistas e o conhecimento de médicos generalistas e de outros profissionais de saúde é pouco abrangente. Baixa escolaridade é também um obstáculo no diagnóstico de demência, uma vez que os testes de rastreio mais utilizados na prática clínica não são estruturados para avaliar a população com esse perfil. Os pacientes com demência e suas famílias ainda têm que superar o estigma do diagnóstico, que é ainda muito prevalente no Brasil e colabora para a piora da qualidade de vida. O Reino Unido, por outro lado, dispõe de mais recursos financeiros e de pessoal, possui serviços dedicados à avaliação de problemas de memória e um plano estratégico nacional para demência. Contudo, o National Health Service (NHS) tem verbas limitadas, o que faz com que alguns dos desafios no diagnóstico de demência sejam comuns aos dois países. Os autores sugerem possíveis soluções para enfrentá-los, com o objetivo de melhorar a avaliação e o reconhecimento da demência e reduzir os erros de diagnóstico.

Disinhibition in Frontotemporal Dementia and Alzheimer's Disease: A Neuropsychological and Behavioural Investigation.

OBJECTIVE: Cognitive tests of inhibitory control show variable results for the differential diagnosis between behavioural variant of Frontotemporal Dementia (bvFTD) and Alzheimer's disease (AD). We compared the diagnostic accuracies of tests of inhibitory control and of a behavioural questionnaire, to distinguish bvFTD from AD. METHODS: Three groups of participants were enrolled: 27 bvFTD patients, 25 AD patients, and 24 healthy controls. Groups were matched for gender, education, and socio-economic level. Participants underwent a comprehensive neuropsychological assessment of inhibitory control, including Hayling Test, Stroop, the Five Digits Test (FDT) and the Delay Discounting Task (DDT). Caregivers completed the Barratt Impulsiveness Scale 11th version (BIS-11). RESULTS: bvFTD and AD groups showed no difference in the tasks of inhibitory control, while the caregiver questionnaire revealed that bvFTD patients were significantly more impulsive (BIS-11: bvFTD 76.1+9.5, AD 62.9+13, p < .001). CONCLUSIONS: Neuropsychological tests of inhibitory control failed to distinguish bvFTD from AD. On the contrary, impulsivity caregiver-completed questionnaire provided good distinction between bvFTD and AD. These results highlight the current limits of cognitive measures of inhibitory control for the differential diagnosis between bvFTD and AD, whereas questionnaire information appears more reliable and in line with clinical diagnostics.

Alzheimer's Disease or Behavioral Variant Frontotemporal Dementia? Review of Key Points Toward an Accurate Clinical and Neuropsychological Diagnosis.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the most common neurodegenerative early-onset dementias. Despite the fact that both conditions have a very distinctive clinical pattern, they present with an overlap in their cognitive and behavioral features that may lead to misdiagnosis or delay in diagnosis. The current review intends to summarize briefly the main differences at the clinical, neuropsychological, and behavioral levels, in an attempt to suggest which aspects would facilitate an adequate diagnosis in a clinical setting, especially in Latin American and low- and middle-income countries, where the resources needed for a differential diagnosis (such as MRI or biomarkers) are not always available. A timely diagnosis of AD and FTD have significant implications for the medical management and quality of life of patients and careers.

Mapping the neuroanatomy of functional decline in Alzheimer's disease from basic to advanced activities of daily living.

BACKGROUND: Impairments in activities of daily living (ADL) are a criterion for Alzheimer's disease (AD) dementia. However, ADL gradually decline in AD, impacting on advanced (a-ADL, complex interpersonal or social functioning), instrumental (IADL, maintaining life in community), and finally basic functions (BADL, activities related to physiological and self-maintenance needs). Information and communication technologies (ICT) have become an increasingly important aspect of daily functioning. Yet, the links of ADL, ICT, and neuropathology of AD dementia are poorly understood. Such knowledge is critical as it can provide biomarker evidence of functional decline in AD. METHODS: ADL were evaluated with the Technology-Activities of Daily Living Questionnaire (T-ADLQ) in 33 patients with AD and 30 controls. ADL were divided in BADL, IADL, and a-ADL. The three domain subscores were covaried against gray matter atrophy via voxel-based morphometry. RESULTS: Our results showed that three domain subscores of ADL correlate with several brain structures, with a varying degree of overlap between them. BADL score correlated mostly with frontal atrophy, IADL with more widespread frontal, temporal and occipital atrophy and a-ADL with occipital and temporal atrophy. Finally, ICT subscale was associated with atrophy in the precuneus. CONCLUSIONS: The association between ADL domains and neurodegeneration in AD follows a traceable neuropathological pathway which involves different neural networks. This the first evidence of ADL phenotypes in AD characterised by specific patterns of functional decline and well-defined neuropathological changes. The identification of such phenotypes can yield functional biomarkers for dementias such as AD.

Regional Dynamics of the Resting Brain in Amyotrophic Lateral Sclerosis Using Fractional Amplitude of Low-Frequency Fluctuations and Regional Homogeneity Analyses.

Resting-state functional magnetic resonance imaging has been playing an important role in the study of amyotrophic lateral sclerosis (ALS). Although functional connectivity is widely studied, the patterns of spontaneous neural activity of the resting brain are important mechanisms that have been used recently to study a variety of conditions but remain less explored in ALS. Here we have used fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) to study the regional dynamics of the resting brain of nondemented ALS patients compared with healthy controls. As expected, we found the sensorimotor network with changes in fALFF and ReHo, and also found the default mode network (DMN), frontoparietal network (FPN), and salience network (SN) altered and the cerebellum, although no structural changes between ALS patients and controls were reported in the regions with fALFF and ReHo changes. We show an altered pattern in the spontaneous low-frequency oscillations that is not confined to the motor areas and reveal a more widespread involvement of nonmotor regions, including those responsible for cognition.

Frontostriatal grey matter atrophy in amyotrophic lateral sclerosis A visual rating study.

Amyotrophic lateral sclerosis (ALS) is characterised by frontostriatal grey matter changes similar to those in frontotemporal dementia (FTD). However, these changes are usually detected at a group level, and simple visual magnetic resonance imaging (MRI) cortical atrophy scales may further elucidate frontostriatal changes in ALS. OBJECTIVE: To investigate whether frontostriatal changes are detectable using simple visual MRI atrophy rating scales applied at an individual patient level in ALS. METHODS: 21 ALS patients and 17 controls were recruited and underwent an MRI scan. Prefrontal cortex sub-regions of the medial orbitofrontal cortex (MOFC), lateral orbitofrontal cortex (LOFC) and anterior cingulate cortex (ACC), striatal sub-regions of the caudate nucleus (CN) and nucleus accumbens (NAcc) were rated using visual grey matter atrophy 5-point Likert scales. RESULTS: Significantly higher atrophy ratings in the bilateral MOFC only in ALS patients versus controls was observed (p<.05). Patients with greater MOFC atrophy had significantly higher atrophy of the CN (p<.05) and LOFC (p<.05). CONCLUSION: Use of simple visual atrophy rating scales on an individual level reliably detects frontostriatal deficits specific to ALS, showing MOFC atrophy differences with associated CN and LOFC atrophy. This is an applicable method that could be used to support clinical diagnosis and management.

A esclerose lateral amiotrófica (ELA) é caracterizada por alterações na substância cinzenta frontostriatal, semelhantes às da demência frontotemporal (DFT). No entanto, essas alterações geralmente são detectadas em nível de grupo, e as escalas simples de atrofia cortical por ressonância magnética visual (MRI) podem elucidar ainda mais as alterações frontostriatais na ELA. OBJETIVO: Investigar se as alterações frontostriatais são detectáveis usando escalas de classificação de atrofia MRI visuais simples aplicadas em um nível de paciente individual em ELA. MÉTODOS: 21 pacientes com ELA e 17 controles foram recrutados e submetidos a uma ressonância magnética. Sub-regiões do córtex pré-frontal do córtex orbitofrontal medial (MOFC), córtex orbitofrontal lateral (LOFC) e córtex cingulado anterior (ACC), sub-regiões estriadas do núcleo caudado (NC) e nucleus accumbens (NAcc) foram classificadas usando escalas de atrofia de substância cinzenta visuais de Likert de 5 pontos. RESULTADOS: Observações de atrofia significativamente maiores no MOFC bilateral em pacientes com ELA versus controles foram observadas apenas (p <0,05). Pacientes com maior atrofia do MOFC tiveram atrofia significativamente maior do CN (p <0,05) e LOFC (p <0,05). CONCLUSÃO: O uso de escalas de avaliação de atrofia visuais simples em um nível individual detecta de forma confiável déficits frontostriatais específicos para ELA, mostrando diferenças de atrofia MOFC com atrofia associada de CN e LOFC. Este é um método aplicável que pode ser usado para apoiar o diagnóstico e o gerenciamento clínico.

Frontostriatal grey matter atrophy in amyotrophic lateral sclerosis: a visual rating study / Atrofia da massa cinzenta frontostriatal na esclerose lateral amiotrófica: um estudo de avaliação visual antes da publicação

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is characterised by frontostriatal grey matter changes similar to those in frontotemporal dementia (FTD). However, these changes are usually detected at a group level, and simple visual magnetic resonance imaging (MRI) cortical atrophy scales may further elucidate frontostriatal changes in ALS. Objective: To investigate whether frontostriatal changes are detectable using simple visual MRI atrophy rating scales applied at an individual patient level in ALS. Methods: 21 ALS patients and 17 controls were recruited and underwent an MRI scan. Prefrontal cortex sub-regions of the medial orbitofrontal cortex (MOFC), lateral orbitofrontal cortex (LOFC) and anterior cingulate cortex (ACC), striatal sub-regions of the caudate nucleus (CN) and nucleus accumbens (NAcc) were rated using visual grey matter atrophy 5-point Likert scales. Results: Significantly higher atrophy ratings in the bilateral MOFC only in ALS patients versus controls was observed (p<.05). Patients with greater MOFC atrophy had significantly higher atrophy of the CN (p<.05) and LOFC (p<.05). Conclusion: Use of simple visual atrophy rating scales on an individual level reliably detects frontostriatal deficits specific to ALS, showing MOFC atrophy differences with associated CN and LOFC atrophy. This is an applicable method that could be used to support clinical diagnosis and management.

RESUMO: A esclerose lateral amiotrófica (ELA) é caracterizada por alterações na substância cinzenta frontostriatal, semelhantes às da demência frontotemporal (DFT). No entanto, essas alterações geralmente são detectadas em nível de grupo, e as escalas simples de atrofia cortical por ressonância magnética visual (MRI) podem elucidar ainda mais as alterações frontostriatais na ELA. Objetivo: Investigar se as alterações frontostriatais são detectáveis usando escalas de classificação de atrofia MRI visuais simples aplicadas em um nível de paciente individual em ELA. Métodos: 21 pacientes com ELA e 17 controles foram recrutados e submetidos a uma ressonância magnética. Sub-regiões do córtex pré-frontal do córtex orbitofrontal medial (MOFC), córtex orbitofrontal lateral (LOFC) e córtex cingulado anterior (ACC), sub-regiões estriadas do núcleo caudado (NC) e nucleus accumbens (NAcc) foram classificadas usando escalas de atrofia de substância cinzenta visuais de Likert de 5 pontos. Resultados: Observações de atrofia significativamente maiores no MOFC bilateral em pacientes com ELA versus controles foram observadas apenas (p <0,05). Pacientes com maior atrofia do MOFC tiveram atrofia significativamente maior do CN (p <0,05) e LOFC (p <0,05). Conclusão: O uso de escalas de avaliação de atrofia visuais simples em um nível individual detecta de forma confiável déficits frontostriatais específicos para ELA, mostrando diferenças de atrofia MOFC com atrofia associada de CN e LOFC. Este é um método aplicável que pode ser usado para apoiar o diagnóstico e o gerenciamento clínico.

Diagnostic relevance of spatial orientation for vascular dementia: A case study.

Spatial orientation is emerging as an early and reliable cognitive biomarker of Alzheimer's disease (AD) pathophysiology. However, no evidence exists as to whether spatial orientation is also affected in vascular dementia (VaD). OBJECTIVE: To examine allocentric (map-based) and egocentric (viewpoint-based) spatial orientation in an early stage VaD case. METHODS: A spatial test battery was administered following clinical and neuropsychological cognitive evaluation. RESULTS: Despite the patient's complaints, little evidence of episodic memory deficits were detected when cueing was provided to overcome executive dysfunction. Similarly, medial temporal lobe-mediated allocentric orientation was intact. By contrast, medial parietal-mediated egocentric orientation was impaired, despite normal performance on standard visuospatial tasks. CONCLUSION: To our knowledge, this is the first in-depth investigation of spatial orientation deficits in VaD. Isolated egocentric deficits were observed. This differs from AD orientation deficits which encompass both allocentric and egocentric orientation deficits. A combination of egocentric orientation and executive function tests could serve as a promising cognitive marker for VaD pathophysiology.

A orientação espacial está emergindo como um biomarcador cognitivo precoce e confiável da fisiopatologia da doença de Alzheimer (DA). No entanto, não existe evidência de que a orientação espacial também seja afetada na demência vascular (DVa). OBJETIVO: Examinar a orientação espacial alocêntrica (baseada em mapas) e egocêntrica (baseada no ponto de vista) em um caso de DVa em fase incial. MÉTODOS: Uma bateria de testes espaciais foi administrada após avaliação clínica e neuropsicológica cognitiva. RESULTADOS: Apesar das queixas do paciente, poucas evidências de déficits de memória episódica foram detectadas quando foram fornecidas pistas para superar a disfunção executiva. Da mesma forma, a orientação alocêntrica mediada pelo lobo temporal medial estava intacta. Em contrapartida, a orientação egocêntrica mediada pela região parietal medial estava comprometida, apesar do desempenho normal em tarefas visuoespaciais padrão. CONCLUSÃO: Pelo nosso conhecimento, esta é a primeira investigação aprofundada dos déficits de orientação espacial na DVa. Foram observados déficits egocêntricos isolados. Isso difere dos déficits de orientação da DA que abrangem déficits de orientação alocêntricos e egocêntricos. Uma combinação de orientação egocêntrica e testes de função executiva poderia servir como um marcador cognitivo promissor para a fisiopatologia de DVa.

Diagnostic relevance of spatial orientation for vascular dementia: A case study / Relevância da orientação espacial para o diagnóstico de demência vascular: um estudo de caso

ABSTRACT Spatial orientation is emerging as an early and reliable cognitive biomarker of Alzheimer's disease (AD) pathophysiology. However, no evidence exists as to whether spatial orientation is also affected in vascular dementia (VaD). Objective: To examine allocentric (map-based) and egocentric (viewpoint-based) spatial orientation in an early stage VaD case. Methods: A spatial test battery was administered following clinical and neuropsychological cognitive evaluation. Results: Despite the patient's complaints, little evidence of episodic memory deficits were detected when cueing was provided to overcome executive dysfunction. Similarly, medial temporal lobe-mediated allocentric orientation was intact. By contrast, medial parietal-mediated egocentric orientation was impaired, despite normal performance on standard visuospatial tasks. Conclusion: To our knowledge, this is the first in-depth investigation of spatial orientation deficits in VaD. Isolated egocentric deficits were observed. This differs from AD orientation deficits which encompass both allocentric and egocentric orientation deficits. A combination of egocentric orientation and executive function tests could serve as a promising cognitive marker for VaD pathophysiology.

RESUMO A orientação espacial está emergindo como um biomarcador cognitivo precoce e confiável da fisiopatologia da doença de Alzheimer (DA). No entanto, não existe evidência de que a orientação espacial também seja afetada na demência vascular (DVa). Objetivo: Examinar a orientação espacial alocêntrica (baseada em mapas) e egocêntrica (baseada no ponto de vista) em um caso de DVa em fase incial. Métodos: Uma bateria de testes espaciais foi administrada após avaliação clínica e neuropsicológica cognitiva. Resultados: Apesar das queixas do paciente, poucas evidências de déficits de memória episódica foram detectadas quando foram fornecidas pistas para superar a disfunção executiva. Da mesma forma, a orientação alocêntrica mediada pelo lobo temporal medial estava intacta. Em contrapartida, a orientação egocêntrica mediada pela região parietal medial estava comprometida, apesar do desempenho normal em tarefas visuoespaciais padrão. Conclusão: Pelo nosso conhecimento, esta é a primeira investigação aprofundada dos déficits de orientação espacial na DVa. Foram observados déficits egocêntricos isolados. Isso difere dos déficits de orientação da DA que abrangem déficits de orientação alocêntricos e egocêntricos. Uma combinação de orientação egocêntrica e testes de função executiva poderia servir como um marcador cognitivo promissor para a fisiopatologia de DVa.

Structural and functional papez circuit integrity in amyotrophic lateral sclerosis.

Cognitive impairment in amyotrophic lateral sclerosis (ALS) is heterogeneous but now recognized as a feature in non-demented patients and no longer exclusively attributed to executive dysfunction. However, despite common reports of temporal lobe changes and memory deficits in ALS, episodic memory has been less explored. In the current study, we examined how the Papez circuit-a circuit known to participate in memory processes-is structurally and functionally affected in ALS patients (n = 20) compared with healthy controls (n = 15), and whether these changes correlated with a commonly used clinical measure of episodic memory. Our multimodal MRI approach (cortical volume, voxel-based morphometry, diffusion tensor imaging and resting state functional magnetic resonance) showed reduced gray matter in left hippocampus, left entorhinal cortex and right posterior cingulate as well as increased white matter fractional anisotropy and decreased mean diffusivity in the left cingulum bundle (hippocampal part) of ALS patients compared with controls. Interestingly, thalamus, mammillary bodies and fornix were preserved. Finally, we report a decreased functional connectivity in ALS patients in bilateral hippocampus, bilateral anterior and posterior parahippocampal gyrus and posterior cingulate. The results revealed that ALS patients showed statistically significant structural changes, but more important, widespread prominent functional connectivity abnormalities across the regions comprising the Papez circuit. The decreased functional connectivity found in the Papez network may suggest these changes could be used to assess risk or assist early detection or development of memory symptoms in ALS patients even before structural changes are established.

Neuroanatomical Comparison of the "Word" and "Picture" Versions of the Free and Cued Selective Reminding Test in Alzheimer's Disease.

Episodic memory tests with cued recall, such as the Free and Cued Selective Reminding Test (FCSRT), allow for the delineation of hippocampal and prefrontal atrophy contributions to memory performance in Alzheimer's disease (AD). Both Word and Picture versions of the test exist but show different profiles, with the Picture version usually scoring higher across different cohorts. One possible explanation for this divergent performance between the different modality versions of the test might be that they rely on different sets of neural correlates. The current study explores this by contrasting the neural correlates of the Word and Picture versions of the FCSRT with voxel-based morphometry (VBM) in AD and healthy subjects. We predicted that the Picture version would be associated with different cortical regions than the Word version, which might be more hippocampal-centric. When comparing 35 AD patients and 34 controls, AD patients exhibited impairments on both versions of the FCSRT and both groups performed higher in the Picture version. A region of interest analysis based on prior work revealed significant correlations between free recall of either version with atrophy of the temporal pole and hippocampal regions. Thus, contrary to expectations, performance on both the Word and the Picture version of the FCSRT is associated with largely overlapping networks. Free recall is associated with hippocampal volume and might be properly considered as an indicator of hippocampal structural integrity.

Fronto-striatal atrophy correlates of neuropsychiatric dysfunction in frontotemporal dementia (FTD) and Alzheimer's disease (AD) / Correlatos de atrofia fronto-estriatal e disfunção neuropsiquiátrica em demência frontotemporal (DFT) e doença de ALZHEIMER (DA)

Behavioural disturbances in frontotemporal dementia (FTD) are thought to reflect mainly atrophy of cortical regions. Recent studies suggest that subcortical brain regions, in particular the striatum, are also significantly affected and this pathology might play a role in the generation of behavioural symptoms. OBJECTIVE: To investigate prefrontal cortical and striatal atrophy contributions to behavioural symptoms in FTD.METHODS: One hundred and eighty-two participants (87 FTD patients, 39 AD patients and 56 controls) were included. Behavioural profiles were established using the Cambridge Behavioural Inventory Revised (CBI-R) and Frontal System Behaviour Scale (FrSBe). Atrophy in prefrontal (VMPFC, DLPFC) and striatal (caudate, putamen) regions was established via a 5-point visual rating scale of the MRI scans. Behavioural scores were correlated with atrophy rating scores. RESULTS: Behavioural and atrophy ratings demonstrated that patients were significantly impaired compared to controls, with bvFTD being most severely affected. Behavioural-anatomical correlations revealed that VMPFC atrophy was closely related to abnormal behaviour and motivation disturbances. Stereotypical behaviours were associated with both VMPFC and striatal atrophy. By contrast, disturbance of eating was found to be related to striatal atrophy only. CONCLUSION: Frontal and striatal atrophy contributed to the behavioural disturbances seen in FTD, with some behaviours related to frontal, striatal or combined fronto-striatal pathology. Consideration of striatal contributions to the generation of behavioural disturbances should be taken into account when assessing patients with potential FTD.

Distúrbios de comportamento na demência frontotemporal (DFT) parecem refletir principalmente atrofia de regiões corticais. Estudos recentes sugerem que regiões cerebrais subcorticais, em particilar o estriado, são também são significativamente afetados e esta patologia pode ter um papel na geração dos sintomas comportamentais. OBJETIVO: Investigar a contribuição da atrofia cortical prefrontal e estriatal para os sintomas da DFT. MÉTODOS: 182 participantes (87 pacienjtes com DFT, 39 pacientes com DA e 56 controles) foram incluídos. Os perfis cognitivos foram estabelecidos usando o Cambridge Behavioural Inventory Revised (CBI-R) e Frontal System Behaviour Scale (FrSBe). Atrofia nas regiões prefrontal (VMPFC, DLPFC) e estriatal (caudado e putamen) foi estabelecida através de uma escala visual de 5 pontos nas imagens de ressonância magnética. Os escores de comportamento foram correlacionados aos escores de atrfoia. RESULTADOS: Os resultados comportamentais e de atrofia demonstraram que os pacientes estavam significativamente mais comprometidos do que os controles, com os pacientes com DFT mais gravemente afetados. As correlações anátomo-comportamentais revelaram que a atrofia do VMPFC foi intimamente relacionada ao comportamento anormal e distúrbios de motivação. Comportamentos estereotipados estiveram associados com atrofia do VMPFC e estriatal. Em contraste, distúrbios da alimentação foram relacionados somente a atrofia estriatal. CONCLUSÃO: A atrofia frontal e estriatal contribuíram para os distúrbios vistos na DFT, com alguns comportamentos relacionados a patologia frontal, estriatal ou combinadas. Considerações quanto à contribuição estriatal na gênese dos distúrbios de comportamento devem ser levados em conta quando se avalia pacientes com DFT em potencial.

Cultural differences are reflected in variables associated with carer burden in FTD: A comparison study between India and Australia / Diferenças culturais se refletem nas variáveis associadas à sobrecarga do cuidador em DFT: um estudo comparativo entre Índia e Austrália

ABSTRACT There is great need to understand variables behind carer burden, especially in FTD. Carer burden is a complex construct, and its factors are likely to vary depending on the type of dementia, carer characteristics and cultural background. Objective: The present study aimed to compare profiles and severity of carer burden, depression, anxiety and stress in carers of FTD patients in India in comparison to Australia; to investigate which carer variables are associated with carer burden in each country. Methods: Data of 138 participants (69 dyads of carers-patients) from India and Australia (India, n=31; Australia, n=38). Carer burden was assessed with the short Zarit Burden Inventory; carer depression, anxiety and stress were measured with the Depression, Anxiety and Stress-21. Dementia severity was determined with the Frontotemporal Dementia Rating Scale (FTD-FRS), and a range of demographic variables regarding the carer and patient were also obtained. Results: Overall, levels of carer burden were not significantly different across India and Australia, despite more hours delivering care and higher dementia severity in India. Variables associated with burden, however, differed between countries, with carer depression, anxiety and stress strongly associated with burden in India. By contrast, depression, stress, and dementia severity were associated with burden in Australia. Conclusion: This study demonstrated that variables associated with carer burden in FTD differ between cultures. Consequently, cultural considerations should be taken into account when planning for interventions to reduce burden. This study suggests that addressing carers' skills and coping mechanisms are likely to result in more efficacious outcomes than targeting patient symptoms alone.

RESUMO Há uma grande necessidade de se entender as variáveis por trás da sobrecarga do cuidador, especialmente em DFT. A sobrecarga é um construto complexo e os fatores provavelmente estão ligados ao tipo de demência, características do cuidador e origens culturais. Objetivo: O presente estudo objetivou comparar perfis e gravidade da sobrecarga, depressão, ansiedade e estresse nos cuidadores dos pacientes com DFT da Índia em comparação aos da Austrália; investigar que variáveis do cuidador estão associadas à sobrecarga em cada país. Métodos: Dados de 138 participantes (69 pares cuidadores-pacientes) da Índia e Austrália (Índia, n=31) e Austrália (n=38). A sobrecarga do cuidador foi avaliada através da versão curta do Inventário de Sobrecarga de Zarit; depressão, ansiedade e estresse do cuidador através com o Depression, Anxiety and Stress-21. A gravidade da demência foi determinada com a Frontotemporal Dementia Rating Scale (FTD-FRS), e uma gama de variáveis demográficas do cuidador e do paciente foram também obtidas. Resultados: De modo geral os níveis de sobrecarga do cuidador não foram significativamente diferentes entre Índia e Austrália, apesar do maior tempo despendido no cuidado e gravidade da demência na Índia. As variáveis associadas à sobrecarga, todavia, diferiram entre os países, com depressão do cuidador, ansiedade e estresse fortemente associados com sobrecarga na Índia. Em contraste, depressão, estresse e gravidade da demência foram associados à sobrecarga na Austrália. Conclusão: Este estudo demonstrou que variáveis associadas à sobrecarga do cuidador na DFT difere entre culturas. Consequentemente, aspectos culturais devem ser levados em consideração quando se planeja intervenções para redução da sobrecarga. Este estudo sugere que programas direcionados às habilidades e meios de se lidar com a situação dos cuidadores são provavelmente mais eficazes do que aqueles só aos sintomas do paciente.

Fronto-striatal atrophy correlates of neuropsychiatric dysfunction in frontotemporal dementia (FTD) and Alzheimer's disease (AD).

Behavioural disturbances in frontotemporal dementia (FTD) are thought to reflect mainly atrophy of cortical regions. Recent studies suggest that subcortical brain regions, in particular the striatum, are also significantly affected and this pathology might play a role in the generation of behavioural symptoms. OBJECTIVE: To investigate prefrontal cortical and striatal atrophy contributions to behavioural symptoms in FTD. METHODS: One hundred and eighty-two participants (87 FTD patients, 39 AD patients and 56 controls) were included. Behavioural profiles were established using the Cambridge Behavioural Inventory Revised (CBI-R) and Frontal System Behaviour Scale (FrSBe). Atrophy in prefrontal (VMPFC, DLPFC) and striatal (caudate, putamen) regions was established via a 5-point visual rating scale of the MRI scans. Behavioural scores were correlated with atrophy rating scores. RESULTS: Behavioural and atrophy ratings demonstrated that patients were significantly impaired compared to controls, with bvFTD being most severely affected. Behavioural-anatomical correlations revealed that VMPFC atrophy was closely related to abnormal behaviour and motivation disturbances. Stereotypical behaviours were associated with both VMPFC and striatal atrophy. By contrast, disturbance of eating was found to be related to striatal atrophy only. CONCLUSION: Frontal and striatal atrophy contributed to the behavioural disturbances seen in FTD, with some behaviours related to frontal, striatal or combined fronto-striatal pathology. Consideration of striatal contributions to the generation of behavioural disturbances should be taken into account when assessing patients with potential FTD.

Distúrbios de comportamento na demência frontotemporal (DFT) parecem refletir principalmente atrofia de regiões corticais. Estudos recentes sugerem que regiões cerebrais subcorticais, em particilar o estriado, são também são significativamente afetados e esta patologia pode ter um papel na geração dos sintomas comportamentais. OBJETIVO: Investigar a contribuição da atrofia cortical prefrontal e estriatal para os sintomas da DFT. MÉTODOS: 182 participantes (87 pacienjtes com DFT, 39 pacientes com DA e 56 controles) foram incluídos. Os perfis cognitivos foram estabelecidos usando o Cambridge Behavioural Inventory Revised (CBI-R) e Frontal System Behaviour Scale (FrSBe). Atrofia nas regiões prefrontal (VMPFC, DLPFC) e estriatal (caudado e putamen) foi estabelecida através de uma escala visual de 5 pontos nas imagens de ressonância magnética. Os escores de comportamento foram correlacionados aos escores de atrfoia. RESULTADOS: Os resultados comportamentais e de atrofia demonstraram que os pacientes estavam significativamente mais comprometidos do que os controles, com os pacientes com DFT mais gravemente afetados. As correlações anátomo-comportamentais revelaram que a atrofia do VMPFC foi intimamente relacionada ao comportamento anormal e distúrbios de motivação. Comportamentos estereotipados estiveram associados com atrofia do VMPFC e estriatal. Em contraste, distúrbios da alimentação foram relacionados somente a atrofia estriatal. CONCLUSÃO: A atrofia frontal e estriatal contribuíram para os distúrbios vistos na DFT, com alguns comportamentos relacionados a patologia frontal, estriatal ou combinadas. Considerações quanto à contribuição estriatal na gênese dos distúrbios de comportamento devem ser levados em conta quando se avalia pacientes com DFT em potencial.

Cultural differences are reflected in variables associated with carer burden in FTD: a comparison study between India and Australia.

There is great need to understand variables behind carer burden, especially in FTD. Carer burden is a complex construct, and its factors are likely to vary depending on the type of dementia, carer characteristics and cultural background. OBJECTIVE: The present study aimed to compare profiles and severity of carer burden, depression, anxiety and stress in carers of FTD patients in India in comparison to Australia; to investigate which carer variables are associated with carer burden in each country. METHODS: Data of 138 participants (69 dyads of carers-patients) from India and Australia (India, n=31; Australia, n=38). Carer burden was assessed with the short Zarit Burden Inventory; carer depression, anxiety and stress were measured with the Depression, Anxiety and Stress-21. Dementia severity was determined with the Frontotemporal Dementia Rating Scale (FTD-FRS), and a range of demographic variables regarding the carer and patient were also obtained. RESULTS: Overall, levels of carer burden were not significantly different across India and Australia, despite more hours delivering care and higher dementia severity in India. Variables associated with burden, however, differed between countries, with carer depression, anxiety and stress strongly associated with burden in India. By contrast, depression, stress, and dementia severity were associated with burden in Australia. CONCLUSION: This study demonstrated that variables associated with carer burden in FTD differ between cultures. Consequently, cultural considerations should be taken into account when planning for interventions to reduce burden. This study suggests that addressing carers' skills and coping mechanisms are likely to result in more efficacious outcomes than targeting patient symptoms alone.

Há uma grande necessidade de se entender as variáveis por trás da sobrecarga do cuidador, especialmente em DFT. A sobrecarga é um construto complexo e os fatores provavelmente estão ligados ao tipo de demência, características do cuidador e origens culturais. OBJETIVO: O presente estudo objetivou comparar perfis e gravidade da sobrecarga, depressão, ansiedade e estresse nos cuidadores dos pacientes com DFT da Índia em comparação aos da Austrália; investigar que variáveis do cuidador estão associadas à sobrecarga em cada país. MÉTODOS: Dados de 138 participantes (69 pares cuidadores-pacientes) da Índia e Austrália (Índia, n=31) e Austrália (n=38). A sobrecarga do cuidador foi avaliada através da versão curta do Inventário de Sobrecarga de Zarit; depressão, ansiedade e estresse do cuidador através com o Depression, Anxiety and Stress-21. A gravidade da demência foi determinada com a Frontotemporal Dementia Rating Scale (FTD-FRS), e uma gama de variáveis demográficas do cuidador e do paciente foram também obtidas. RESULTADOS: De modo geral os níveis de sobrecarga do cuidador não foram significativamente diferentes entre Índia e Austrália, apesar do maior tempo despendido no cuidado e gravidade da demência na Índia. As variáveis associadas à sobrecarga, todavia, diferiram entre os países, com depressão do cuidador, ansiedade e estresse fortemente associados com sobrecarga na Índia. Em contraste, depressão, estresse e gravidade da demência foram associados à sobrecarga na Austrália. CONCLUSÃO: Este estudo demonstrou que variáveis associadas à sobrecarga do cuidador na DFT difere entre culturas. Consequentemente, aspectos culturais devem ser levados em consideração quando se planeja intervenções para redução da sobrecarga. Este estudo sugere que programas direcionados às habilidades e meios de se lidar com a situação dos cuidadores são provavelmente mais eficazes do que aqueles só aos sintomas do paciente.

Neural correlates of behavioural symptoms in behavioural variant frontotemporal dementia and Alzheimers disease: employment of a visual MRI rating scale / Correlatos neuronais de sintomas de comportamento em demência frontotemporal e demência de Alzheimer: aplicação de uma escala visual clínica em ressonância magnética

Frontotemporal dementia (FTD) patients often present with severe behavioural disturbances and concomitant lack of insight. The underlying neural correlates of these disturbances are mostly attributed to prefrontal cortex dysfunction,but are still poorly understood. Objectives: The current study explores whether a simple visual magnetic resonance imaging(MRI) rating scale in combination with the Frontal System Behaviour Scale (FrSBe) can be used to identify the prefrontal correlates of behavioural symptoms in behavioural variant frontotemporal dementia (bvFTD) and Alzheimers disease (AD).Methods: Forty-eight patients with a clinical diagnosis of bvFTD and AD participated in the study. Their behavioural profiles were assessed using the Frontal System Behaviour Scale (FrSBe) and cross-correlated to the atrophy of the sub-regions inthe prefrontal cortex using a 5-point visual rating scale of MRI scans. Results: Patients with bvFTD showed higher incidenceof behavioural disturbances than AD with apathy being the most significant. BvFTD patients also showed the highestincidence of atrophy in the orbital frontal cortex and this atrophy was correlated with the apathetic features. Conclusions: Employment of a simple visual MRI rating scale can be used in combination with a behavioural screening test to identifyreliably the behavioural symptoms in bvFTD and AD. These findings will inform the diagnostic accuracy of the neural correlates of behavioural dysfunction in bvFTD in the future.

Pacientes com demência frontotemporal (DFT) frequentemente se apresentam com graves distúrbios comportamentais e concomitante falta de insight. Os correlatos neurais subjacentes a estes distúrbios são em sua maioria atribuídos a disfunção do córtex pré-frontal, porém, ainda são pouco compreendidos. Objetivos: O presente estudo explorase uma escala de mensuração visual de ressonância magnética (RM) em combinação com a Escala Comportamental doSistema Frontal podem ser usadas para identificar os correlatos pré-frontais de sintomas comportamentais na variantecomportamental da DFT (cDFT) e na doença de Alzheimer (DA). Métodos: Quarenta e oito pacientes com diagnóstico clínicode cDFT e DA participaram do estudo. Seus perfis comportamentais foram avaliados usando a Escala Comportamentaldo Sistema Frontal (ECSF) e correlacionada a atrofia das sub-regiões no córtex pré-frontal utilizando uma escala demensuração visual de 5 pontos na RM. Resultados: Os pacientes com cDFT mostraram uma maior incidência de distúrbioscomportamentais do que os com DA, sendo a apatia o sintoma mais significativo. Os pacientes com cDFT tambémdemonstraram uma maior incidência de atrofia no córtex orbito-frontal e esta atrofia correlacionou-se às característicasapáticas. Conclusões: O emprego de uma escala simples de mensuração visual de RM pode ser usada em combinação a um teste de rastreio comportamental para identificar de forma confiável os sintomas comportamentais na cDFT e DA. Estes achados informarão a acurácia diagnóstica dos correlatos neurais da disfunção comportamental na cDFT no futuro.

Neural correlates of behavioural symptoms in behavioural variant frontotemporal dementia and Alzheimer's disease: Employment of a visual MRI rating scale.

Frontotemporal dementia (FTD) patients often present with severe behavioural disturbances and concomitant lack of insight. The underlying neural correlates of these disturbances are mostly attributed to prefrontal cortex dysfunction, but are still poorly understood. OBJECTIVES: The current study explores whether a simple visual magnetic resonance imaging (MRI) rating scale in combination with the Frontal System Behaviour Scale (FrSBe) can be used to identify the prefrontal correlates of behavioural symptoms in behavioural variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD). METHODS: Forty-eight patients with a clinical diagnosis of bvFTD and AD participated in the study. Their behavioural profiles were assessed using the Frontal System Behaviour Scale (FrSBe) and cross-correlated to the atrophy of the sub-regions in the prefrontal cortex using a 5-point visual rating scale of MRI scans. RESULTS: Patients with bvFTD showed higher incidence of behavioural disturbances than AD with apathy being the most significant. BvFTD patients also showed the highest incidence of atrophy in the orbital frontal cortex and this atrophy was correlated with the apathetic features. CONCLUSIONS: Employment of a simple visual MRI rating scale can be used in combination with a behavioural screening test to identify reliably the behavioural symptoms in bvFTD and AD. These findings will inform the diagnostic accuracy of the neural correlates of behavioural dysfunction in bvFTD in the future.

Pacientes com demência frontotemporal (DFT) frequentemente se apresentam com graves distúrbios comportamentais e concomitante falta de insight. Os correlatos neurais subjacentes a estes distúrbios são em sua maioria atribuídos a disfunção do córtex pré-frontal, porém, ainda são pouco compreendidos. OBJETIVOS: O presente estudo explora se uma escala de mensuração visual de ressonância magnética (RM) em combinação com a Escala Comportamental do Sistema Frontal podem ser usadas para identificar os correlatos pré-frontais de sintomas comportamentais na variante comportamental da DFT (cDFT) e na doença de Alzheimer (DA). MÉTODOS: Quarenta e oito pacientes com diagnóstico clínico de cDFT e DA participaram do estudo. Seus perfis comportamentais foram avaliados usando a Escala Comportamental do Sistema Frontal (ECSF) e correlacionada a atrofia das sub-regiões no córtex pré-frontal utilizando uma escala de mensuração visual de 5 pontos na RM. RESULTADOS: Os pacientes com cDFT mostraram uma maior incidência de distúrbios comportamentais do que os com DA, sendo a apatia o sintoma mais significativo. Os pacientes com cDFT também demonstraram uma maior incidência de atrofia no córtex orbito-frontal e esta atrofia correlacionou-se às características apáticas. CONCLUSÕES: O emprego de uma escala simples de mensuração visual de RM pode ser usada em combinação a um teste de rastreio comportamental para identificar de forma confiável os sintomas comportamentais na cDFT e DA. Estes achados informarão a acurácia diagnóstica dos correlatos neurais da disfunção comportamental na cDFT no futuro.