Desorientação topográfica na doença de Alzheimer

Topographical disorientation (TD) has not been as extensively studied as other frequent manifestations of Alzheimer's disease (AD). OBJECTIVE: To verify the occurrence of TD and to identify the neuropsychological dysfunctions associated with TD in AD. METHOD: Thirty patients with probable AD, their caregivers and 30 subjects without dementia (controls) were interviewed with a questionnaire and evaluated with tests related to topographical orientation. RESULTS: AD patients, even those with mild dementia, differ from controls in the questionnaire on topographical orientation and in most neuropsychological tests except for tests of spatial working memory, point localization, three dimension and nonsense figure copy. When the performances in the neuropsychological tests of patients with mild or moderate dementia were compared, only landmark recognition and route description were more impaired in moderate dementia. CONCLUSION: TD occurs even in mild dementia of AD, a finding apparently not explained by the impairments of more elementary spatial functions.Desorientação topográfica (DT) não tem sido tão exaustivamente estudada quanto outros sintomas frequentes da doença de Alzheimer (DA). OBJETIVO: Verificar a ocorrência de DT e identificar as disfunções neuropsicológicas associadas com a DT na DA. Método: Trinta pacientes com DA provável, seus cuidadores e trinta sujeitos sem demência (controles) foram entrevistados com um questionário e testes relacionados à orientação topográfica. RESULTADOS: Pacientes com DA, mesmo aqueles com demência leve, diferiram dos controles no questionário de orientação topográfica e na maioria dos testes neuropsicológicos, exceto nos testes memória operacional espacial, localização de pontos, cópia de figuras sem sentido e de figura em três dimensões. Quando os desempenhos de pacientes com demência leve ou moderada foram comparados, apenas os testes de reconhecimento de marcos e descrição de rotas foram mais comprometidos na demência moderada. CONCLUSÃO: DT ocorre mesmo na demência leve da DA, um achado aparentemente não explicado pelo comprometimento das funções espaciais mais elementares

Avaliação do equilíbrio na doença de Alzheimer leve e moderada: implicações na capacidade funcional e na ocorrência de quedas

OBJECTIVE: To analyze the correlation between balance, falls and loss of functional capacity in mild and moderate Alzheimer's disease(AD). METHOD: 40 subjects without cognitive impairment (control group) and 48 AD patients (25 mild, 23 moderate) were evaluated with the Berg Balance Scale (BBS) and the Disability Assessment for Dementia (DAD). Subjects answered a questionnaire about falls occurrence in the last twelve months. RESULTS: Moderate AD patients showed poorer balance (p=0.001) and functional capacity (p <0.0001) and it was observed a correlation between falls and balance (r= -0.613; p=0.045). CONCLUSION: There is a decline of balance related to AD which is a factor associated to the occurrence of falls, albeit not the most relevant one. The loss of functional capacity is associated with the disease's progress but not to a higher occurrence of falls. The balance impairment did not correlate with functional decline in AD patients.OBJETIVO: Analisar a correlação entre déficit de equilíbrio, ocorrência de quedas e prejuízo funcional na doença de Alzheimer (DA). MÉTODO: 40 idosos sem comprometimento cognitivo (grupo controle) e 48 idosos com DA (25 leves e 23 moderados), avaliados através da Escala de Equilíbrio de Berg (EEB) e Escala de Avaliação de Incapacidade (EAI), e questionados quanto à ocorrência de quedas nos últimos doze meses. RESULTADOS: O equilíbrio no grupo DA moderada foi pior do que no grupo leve (p=0,001), bem como a capacidade funcional (p<0,0001), sem diferença na ocorrência de quedas entre os grupos. Na DA moderada, houve correlação entre ocorrência de quedas e EEB (r= -0,613; p=0,045). CONCLUSÃO: Há um declínio do equilíbrio associado à progressão da DA. O declínio da capacidade funcional não foi associado à maior ocorrência de quedas. O déficit de equilíbrio não se correlacionou ao declínio funcional na DA

A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia

Inclusion body myopathy associated with Paget disease and frontotemporal dementia (IBMPFD) is a progressive and usually misdiagnosed autosomal dominant disorder. It is clinically characterized by a triad of features: proximal and distal myopathy, early onset Paget disease of bone (PDB), and frontotemporal dementia (FTD). It is caused by missense mutations in the valosin-containing protein (VCP) gene. We describe here the clinical and molecular findings of the first Brazilian family identified with IBMPFD. Progressive myopathy affecting the limb girdles was detected by clinical examination followed by muscle biopsy and creatine kinase measurement. PDB was suggested after anatomopathological bone examination and FTD was diagnosed by clinical, neuropsychological and language evaluations. Brain magnetic resonance revealed severe atrophy of the anterior temporal lobes, including the hippocampi. A R93C mutation in VCP was detected by direct sequencing screening in subject W (age 62) and in his mother. Four more individuals diagnosed with "dementia" were reported in this family. We also present a comprehensive genotype-phenotype correlation analysis of mutations in VCP in 182 patients from 29 families described in the literature and show that while IBM is a conspicuously penetrant symptom, PDB has a lower penetrance when associated with mutations in the AAAD1 domain and FTD has a lower penetrance when associated with mutations in the Junction (L1-D1) domain. Furthermore, the R93C mutation is likely to be associated with the penetrance of all the clinical symptoms of the triad

Efeito dos níveis de cortisol no desempenho da memória operacional de idosos com doença de Alzheimer

BACKGROUND: Subjects with Alzheimer's disease (AD) have elevated cortisol levels as a result of hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Acute administration of hydrocortisone has been associated with working memory (WM) performance in young adults. OBJECTIVE: To investigate whether cortisol levels are associated with WM performance in subjects with AD. METHOD: Eighty subjects were included, comprising 40 patients with mild AD and 40 healthy elderly controls. WM was assessed using the Digit Span Backward test (DSB). Saliva samples were collected to determine cortisol levels. RESULTS: AD subjects had poorer performance on the DSB than controls (p=0.002) and also presented higher levels of cortisol than control group (p=0.04). No significant correlation was observed between the DSB and cortisol levels in both groups (r= -0.29). CONCLUSION: In this study, elevated cortisol levels were not associated with poorer WM performance in patients with AD or in healthy elderly subjects.INTRODUÇÃO: Idosos com doença de Alzheimer (DA) apresentam elevados níveis de cortisol como resultado de uma disfunção no eixo hipotálamo-pituitária-adrenal (HPA). A administração aguda de hidrocortisona tem sido associada ao desempenho da memória operacional (WM) em adultos jovens. OBJETIVO: Investigar se os níveis de cortisol estão associados com o desempenho na WM em pacientes com DA. MÉTODO: Oitenta indivíduos foram incluídos, sendo 40 pacientes com DA leve e 40 idosos saudáveis controles. WM foi avaliada a partir do teste de Extensão de Dígitos na ordem direta (DSB). Amostras de saliva foram coletadas para determinar os níveis de cortisol. RESULTADOS: Indivíduos com DA apresentaram pior desempenho no DSB (p=0,002) e maiores níveis de cortisol (p=0,04) do que os controles. Não foi observada correlação significativa entre DSB e níveis de cortisol em nenhum dos grupos (r= -0,29). CONCLUSÃO: Neste estudo, níveis de cortisol elevados não estão associados com pior desempenho da WM em pacientes com DA ou em idosos cognitivamente saudáveis

Morphometric brain changes during aging: Results from a Brazilian necropsy sample.

The present study aimed to establish the morphometric brain changes during aging in a necropsy series from Brazil and determine whether sexual dimorphisms interfere in these changes. Methods:A cross-sectional study was conducted at the São Paulo Autopsy Service in Brazil where, after informed consent, data was gathered from next of kin interview with reference to clinical status prior to death. Brain weight, volume and density measurements were taken and then adjusted for head circumference. Descriptive statistics and tests of hypothesis and correlations were applied, considering a p-value of 0.05. Results:414 subjects, mostly men (60.4%), with a mean age of 67.1 years, were included. The mean brain weight of the sample was 1219.2g±140.9and mean volume was 1217mL±152.3. The mean brain density of the sample was 1.0g/mL±0.09. Values differed between males and females in terms of weight and volume. Brain weight decreased during aging by about 45g per decade (r= -0.300; p&lt;0.01) and volume by about 43mL (r= -0.278; p&lt;0.00). Mean density of the sample was 1.0 g/mL in both genders. Conclusions:Brain weight and volume (with or without corrections) decreased during aging, and these reductions were more pronounced in women. Density remained unchanged for both genders. Further studies are needed to investigate factors associated to these reductions

A revelação do diagnóstico de doença de Alzheimer: opiniões de cuidadores em uma amostra brasileira

BACKGROUND: Disclosure of the diagnosis of Alzheimer's disease (AD) remains a contentious issue, and has been little studied in developing countries. OBJECTIVE: To investigate the influence of socio-demographic factors and the experience of being a caregiver on opinion about disclosing AD diagnosis to the patient in a Brazilian sample. METHOD: Caregivers of 50 AD patients together with 50 control participants that did not have the experience of being a caregiver of AD patient were interviewed using a structured questionnaire. RESULTS: Most of the participants (73.0%) endorsed disclosure of the diagnosis, while caregivers were less prone to disclose (58.0%) than controls (88.0%; p=0.0007). Logistic regression confirmed that only the experience of being a caregiver was associated with a lesser tendency for disclosure endorsement. CONCLUSION: The majority of participants was in favor of disclosing the diagnosis, but caregivers were less willing to disclose the diagnosis to the AD patient.FUNDAMENTO: A revelação do diagnóstico de doença de Alzheimer (DA) tem sido tema polêmico e pouco estudado em países em desenvolvimento. OBJETIVO: Investigar a influência de fatores sócio-demográficos e a experiência de ter sido cuidador na opinião sobre a revelação do diagnóstico em uma amostra brasileira. MÉTODO: Cuidadores de 50 pacientes com DA e 50 indívíduos controle que não tinham tido experiência como cuidadores de pacientes com DA foram entrevistados com o uso de um questionário estruturado. RESULTADOS: A maioria dos participantes (73,0%) manifestou-se a favor da revelação diagnóstico aos pacientes, mas cuidadores foram menos favoráveis (58,0%) que controles (88,0%; p=0,0007). Regressão logística demonstrou que apenas a experiência como cuidador foi associada com menor tendência a apoiar a revelação do diagnóstico. CONCLUSÃO: A maioria dos participantes foi a favor da revelação do diagnóstico ao paciente, mas aqueles com experiência como cuidadores de pacientes com DA foram menos favoráveis

Atividade periódica generalizada no EEG em dois casos de neurossífilis

Neurosyphilis is a recognized cause of epileptic seizures and cognitive impairment, but is not usually associated with the finding of generalized periodic activity in the EEG. We report two similar cases characterized by progressive cognitive impairment followed by partial complex seizures, in whom the EEG showed generalized periodic activity. Both cerebrospinal fluid and the response to penicillin therapy confirmed the diagnoses of neurosyphilis in the two cases. The finding of EEG generalized periodic activity in patients with cognitive or behavioral disorders is usually associated with Creutzfeldt-Jakob disease, although there are other conditions, some of them potentially reversible, which may also present this EEG abnormality. Neurosyphilis has tended not to be included among them, and our present findings support the importance of first ruling out neurosyphilis in those patients with cognitive or behavioral disorders associated with generalized periodic epileptiform discharges.Neurossífilis é uma causa conhecida de crises convulsivas e de comprometimento cognitivo, mas não é associada geralmente a atividade periódica generalizada no eletroencefalograma (EEG). Relatamos dois casos similares caracterizados por declínio cognitivo progressivo seguido de crises parciais complexas, em que o EEG mostra a atividade periódica generalizada. O líquido cefalorraquidiano e uma boa resposta à terapia com penicilina confirmaram os diagnósticos de neurossífilis nos dois casos. Achados de atividade periódica generalizada no EEG de pacientes com distúrbios cognitivos ou de comportamento são associados geralmente com a doença de Creutzfeldt-Jakob, embora haja outras circunstâncias, algumas delas potencialmente reversíveis, que podem também apresentar esta anormalidade no EEG. A neurossífilis tende a não ser incluída entre eles, e nossos achados sustentam a importância de afastar o diagnóstico de neurossífilis naqueles pacientes com declínio cognitivo ou comportamental associados com as descargas periódicas generalizadas no EEG.Universidade de São Paulo Faculdade de Medicina Departamento de NeurologiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Serviço de Neurofisiologia ClínicaUNIFESP, EPM, Serviço de Neurofisiologia ClínicaSciEL

A síndrome de tremor e ataxia associada ao X frágil (FXTAS)

FXTAS (Fragile X-associated tremor and ataxia syndrome) is a late- onset neurodegenerative disorder affecting mainly men, over 50 years of age, who are carriers of the FMR1 gene premutation. The full mutation of this gene causes the fragile X syndrome (FXS), the most common cause of inherited mental retardation. Individuals affected by FXTAS generally present intention tremor and gait ataxia that might be associated to specific radiological and/or neuropathological signs. Other features commonly observed are parkinsonism, cognitive decline, peripheral neuropathy and autonomic dysfunction. Nearly a decade after its clinical characterization, FXTAS is poorly recognized in Brazil. Here we present a review of the current knowledge on the clinical, genetic and diagnostic aspects of the disease.A FXTAS (síndrome de tremor e ataxia associada ao X frágil) é uma doença neurodegenerativa de início tardio que afeta principalmente homens acima dos 50 anos de idade, portadores de pré-mutação do gene FMR1. A mutação completa desse gene é responsável pela síndrome do cromossomo X frágil (SXF), a causa mais comum de deficiência mental herdada. Indivíduos afetados pela FXTAS geralmente apresentam tremor de intenção e ataxia de marcha que podem estar associados a sinais radiológicos ou neuropatológicos específicos. Outras características comumente observadas são parkinsonismo, declínio cognitivo, neuropatia periférica e disfunções autonômicas. Quase uma década após sua caracterização clínica, a FXTAS é mal conhecida por médicos no Brasil. Esta revisão apresenta o conhecimento atual sobre os aspectos clínicos, genéticos e diagnósticos da síndrome.FAPESP - Center for the Study of Human Genom

Selecting the most relevant brain regions to discriminate Alzheimer's disease patients from healthy controls using multiple kernel learning: A comparison across functional and structural imaging modalities and atlases

BACKGROUND: Machine learning techniques such as support vector machine (SVM) have been applied recently in order to accurately classify individuals with neuropsychiatric disorders such as Alzheimer's disease (AD) based on neuroimaging data. However, the multivariate nature of the SVM approach often precludes the identification of the brain regions that contribute most to classification accuracy. Multiple kernel learning (MKL) is a sparse machine learning method that allows the identification of the most relevant sources for the classification. By parcelating the brain into regions of interest (ROI) it is possible to use each ROI as a source to MKL (ROI-MKL). METHODS: We applied MKL to multimodal neuroimaging data in order to: 1) compare the diagnostic performance of ROI-MKL and whole-brain SVM in discriminating patients with AD from demographically matched healthy controls and 2) identify the most relevant brain regions to the classification. We used two atlases (AAL and Brodmann's) to parcelate the brain into ROIs and applied ROI-MKL to structural (T1) MRI, 18F-FDG-PET and regional cerebral blood flow SPECT (rCBF-SPECT) data acquired from the same subjects (20 patients with early AD and 18 controls). In ROI-MKL, each ROI received a weight (ROI-weight) that indicated the region's relevance to the classification. For each ROI, we also calculated whether there was a predominance of voxels indicating decreased or increased regional activity (for 18F-FDG-PET and rCBF-SPECT) or volume (for T1-MRI) in AD patients. RESULTS: Compared to whole-brain SVM, the ROI-MKL approach resulted in better accuracies (with either atlas) for classification using 18F-FDG-PET (92.5% accuracy for ROI-MKL versus 84% for whole-brain), but not when using rCBF-SPECT or T1-MRI. Although several cortical and subcortical regions contributed to discrimination, high ROI-weights and predominance of hypometabolism and atrophy were identified specially in medial parietal and temporo-limbic cortical regions. Also, the weight of discrimination due to a pattern of increased voxel-weight values in AD individuals was surprisingly high (ranging from approximately 20% to 40% depending on the imaging modality), located mainly in primary sensorimotor and visual cortices and subcortical nuclei. CONCLUSION: The MKL-ROI approach highlights the high discriminative weight of a subset of brain regions of known relevance to AD, the selection of which contributes to increased classification accuracy when applied to 18F-FDG-PET data. Moreover, the MKL-ROI approach demonstrates that brain regions typically spared in mild stages of AD also contribute substantially in the individual discrimination of AD patients from controls

Cross-cultural adaptation of the disability assessment for dementia (DAD)

The original version of the Disability Assessment for Dementia (DAD) was translated into Portuguese and back translated to English. The divergences of translation were identified and discussed, resulting in a version that was used in a preliminary investigation for cross-cultural adaptation. The final version was administered to 29 patients with mild to moderate probable Alzheimer's disease. The correlation coefficients of DAD were 0.929 and 0.932 for the inter-examiner and test-retest evaluations respectively. The reliability indexes were also high (Kappa 0.72 p<0.001 inter-examiners and 0.85 p<0.001 test-retest). The Brazilian version of DAD was easy to administer and had good reliability to assess the functional status of demented patients. It will contribute to the follow-up of these patients in our population. Moreover, it can be used in transcultural studies on functional abilities in dementia.A versão original da Escala de Avaliação de Incapacidade em Demência (Disability Assessment for Dementia, DAD) foi traduzida para a língua portuguesa e retrotraduzida para o inglês. Divergências de tradução foram identificadas e discutidas, chegando-se a uma versão que foi submetida a pré-teste para adaptação sócio-cultural. A versão final foi administrada a amostra de 29 pacientes com doença de Alzheimer provável de leve a moderada. Os coeficientes de correlação da DAD foram 0,929 e 0,932 nas avaliações inter e intra-examinadores respectivamente. Os índices de confiabilidade também foram elevados (Kappa=0,72; p<0,001 inter-examinadores e Kappa=0,85; p<0,001 intra-examinadores). A versão brasileira da escala DAD mostrou-se um instrumento de fácil aplicação e boa confiabilidade para avaliação funcional de pacientes com demência e poderá contribuir para o acompanhamento desses pacientes em nosso meio. Esta versão também poderá ser utilizada em estudos transculturais sobre habilidades funcionais de pacientes com demência.Universidade de São Paulo Faculdade de Medicina Hospital das ClínicasUniversidade Federal de São Paulo (UNIFESP) Escola de Paulista de Medicina Departamento de Neurologia e NeurocirurgiaUNIFESP, Escola de Paulista de Medicina Depto. de Neurologia e NeurocirurgiaSciEL