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INTRODUCTION: Altered brain activity and functional reorganization patterns during self-initiated movements have been reported in early pre-motor and motor stages of Parkinson's disease. The aim of this study was to investigate whether similar alterations can be observed in patients with idiopathic REM-sleep behavior disorder (RBD). METHODS: 13 polysomnography-confirmed male and right-handed RBD patients and 13 healthy controls underwent a bilateral hand-movement fMRI task including internally selected (INT) and externally-guided (EXT) movement conditions for each hand. We examined functional activity and connectivity differences between groups and task-conditions, structural differences using voxel-based morphometry, as well as associations between functional activity and clinical variables. RESULTS: No group differences were observed in fMRI-task performance or in voxel-based morphometry. Both groups showed faster reaction times and exhibited greater neural activation when movements were internally selected compared to externally-guided tasks. Compared to controls, RBD patients displayed stronger activation in the dorsolateral prefrontal cortex and primary somatosensory cortex during INT-tasks, and in the right fronto-insular cortex during EXT-tasks performed with the non-dominant hand. Stronger activation in RBD patients was associated with cognitive and olfactory impairment. Connectivity analysis demonstrated overall less interregional coupling in patients compared to controls. In particular, patients showed reduced temporo-cerebellar, occipito-cerebellar and intra-cerebellar connectivity, but stronger connectivity in fronto-cerebellar and fronto-occipital pathways. CONCLUSION: The observed stronger activation during hand-movement tasks and connectivity changes in RBD may reflect early compensatory and reorganization patterns in order to preserve motor functioning. Our findings may contribute to a better understanding and prognosis of prodromal stages of α-synucleinopathies.
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Imageamento por Ressonância Magnética , Neurônios Motores/fisiologia , Transtorno do Comportamento do Sono REM/fisiopatologia , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Córtex Pré-Frontal Dorsolateral/diagnóstico por imagem , Córtex Pré-Frontal Dorsolateral/fisiopatologia , Mãos/diagnóstico por imagem , Mãos/fisiopatologia , Humanos , Córtex Insular/diagnóstico por imagem , Córtex Insular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Movimento , Transtornos do Olfato/diagnóstico por imagem , Transtornos do Olfato/etiologia , Transtornos do Olfato/fisiopatologia , Polissonografia , Sintomas Prodrômicos , Transtorno do Comportamento do Sono REM/complicações , Transtorno do Comportamento do Sono REM/diagnóstico por imagem , Córtex Somatossensorial/diagnóstico por imagem , Córtex Somatossensorial/fisiopatologia , Sinucleinopatias/complicações , Sinucleinopatias/diagnóstico por imagem , Sinucleinopatias/fisiopatologia , Análise e Desempenho de TarefasRESUMO
INTRODUCTION: Large studies on cognitive profiles of patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD-MCI) compared to Parkinson's disease (PD-MCI) are rare. METHODS: Data from two multicenter cohort studies in AD and PD were merged using a unified base rate approach for the MCI diagnosis. Cognitive profiles were compared using scores derived from the Consortium to Establish a Registry for Alzheimer's Disease battery. RESULTS: Patients with AD-MCI showed lower standardized scores on all memory test scores and a language test. Patients with PD-MCI showed lower standardized scores in a set-shifting measure as an executive task. A cross-validated logistic regression with test scores as predictors was able to classify 72% of patients correctly to AD-MCI versus PD-MCI. DISCUSSION: The applied test battery successfully discriminated between AD-MCI and PD-MCI. Neuropsychological test batteries in clinical practice should always include a broad spectrum of cognitive domains to capture any cognitive changes.
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INTRODUCTION: The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) is a renowned cognitive test battery, which has been extended in its German version to the CERAD-Plus including tests of executive functions and processing speed. The most commonly used total score (TS) is based on the restricted CERAD version and reflects the sum of selected raw-values (Chandler et al., 2005). The CERAD-Plus extensions might be of particular diagnostic utility for cognitive assessments in Parkinson's Disease (PD), as executive functions and processing speed belong to the most vulnerable domains in PD. OBJECTIVE: The aim was to develop a CERAD-TS based on the extended CERAD-Plus' age-, gender-, and education-corrected z-scores and to evaluate its diagnostic accuracy compared to the established CERAD-Chandler-TS. METHODS: Baseline data of n = 679 patients with PD (69% male, n = 277 PD without cognitive impairment, n = 307 PD-MCI, n = 95 PD-D) from the multicenter, prospective DEMPARK/LANDSCAPE study were analyzed. ROC-analyses were conducted for four different TS that were either based on the original CERAD or CERAD-Plus, on raw-values or z-scores, and equally-weighted or based on factor scores. AUC-comparisons were conducted to determine the best yet most parsimonious TS. RESULTS: The newly designed CERAD-Plus-TS based on equally-weighted z-scores outperformed both the CERAD-Chandler-TS and cognitive screening instruments when differentiating between individuals with PD of varying cognitive impairment (0.78 ≤ AUC ≤ 0.98). CONCLUSION: Results suggest a high relevance of non-amnestic subscales for the cognitive assessment in PD populations. The proposed CERAD-Plus-TS needs further validation. The extensions might offer diagnostic potential for non-PD populations as well.
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Disfunção Cognitiva/diagnóstico , Testes Neuropsicológicos/estatística & dados numéricos , Testes Neuropsicológicos/normas , Doença de Parkinson/psicologia , Idoso , Disfunção Cognitiva/etiologia , Função Executiva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Sistema de Registros , Reprodutibilidade dos TestesRESUMO
STUDY OBJECTIVES: Rapid eye movement sleep behavior disorder (RBD) is considered a prodromal state of Parkinson's disease (PD). We aimed to characterize patterns of structural brain changes in RBD and PD patients using multimodal MRI. METHODS: A total of 30 patients with isolated RBD, 29 patients with PD, and 56 age-matched healthy controls (HC) underwent MRI at 3T, including tensor-based morphometry, diffusion tensor imaging, and assessment of cortical thickness. RESULTS: RBD individuals showed increased volume of the right caudate nucleus compared with HC, and higher cerebellar volume compared with both PD subjects and HC. Similar to PD subjects, RBD patients displayed increased fractional anisotropy (FA) in the corticospinal tracts, several tracts mainly related to non-motor function, and reduced FA of the corpus callosum compared with HC. Further, RBD subjects showed higher FA in the cerebellar peduncles and brainstem compared with both, PD patients and HC. PD individuals exhibited lower than normal volume in the basal ganglia, midbrain, pedunculopontine nuclei, and cerebellum. In contrast, volume in PD subjects was increased in the thalamus compared with both HC and RBD subjects. CONCLUSIONS: We found convergent patterns of structural brain alterations in RBD and PD patients compared with HC. The changes observed suggest a co-occurrence of neurodegeneration and compensatory mechanisms that fail with emerging PD pathology. Our findings strengthen the hypothesis of RBD and PD constituting a continuous disease spectrum.
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Doença de Parkinson , Transtorno do Comportamento do Sono REM , Encéfalo/diagnóstico por imagem , Imagem de Tensor de Difusão , Humanos , Imageamento por Ressonância Magnética , Doença de Parkinson/diagnóstico por imagem , Transtorno do Comportamento do Sono REM/diagnóstico por imagemRESUMO
BACKGROUND: Primary progressive aphasia (PPA) is a neurodegenerative disorder characterized by progressive deterioration of language. Being rare, reports of PPA in multilingual individuals are scarce, despite more than half of the world population being multilingual. METHODS: We describe clinical characteristics of 33 bilingual patients with PPA, including symptom presentation and language deficits pattern in their first (L1) and second language (L2), through a systematic literature review and new cases retrospectively identified in 5 countries. RESULTS: In total, 14 patients presented with nonfluent/agrammatic variant, 6 with semantic variant, and 13 with logopenic variant, with a median symptom onset of 2 years. Word-finding difficulties was the first symptom in 65% of all cases, initially noticed in L2, and not always the dominant language. Our group had 22 different languages as L1, and 9 as L2. At the whole-group level there was a tendency for parallel impairment in both languages, in line with the shared bilingual neural substrate hypothesis, but each PPA variant showed some heterogeneity. DISCUSSION: Each PPA variant showed heterogeneity, showing the need for comprehensive language and cognitive assessment across languages, as well as further clarification on the role of language mediators.
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Afasia Primária Progressiva/diagnóstico , Idioma , Multilinguismo , Idoso , Afasia Primária Progressiva/classificação , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVES: Parkinson's disease (PD) is the second most common neurodegenerative disorder and is further associated with progressive cognitive decline. In respect to motor phenotype, there is some evidence that akinetic-rigid PD is associated with a faster rate of cognitive decline in general and a greater risk of developing dementia.The objective of this study was to examine cognitive profiles among patients with PD by motor phenotypes and its relation to cognitive function. METHODS: Demographic, clinical and neuropsychological cross-sectional baseline data of the DEMPARK/LANDSCAPE study, a multicentre longitudinal cohort study of 538 patients with PD were analysed, stratified by motor phenotype and cognitive syndrome. Analyses were performed for all patients and for each diagnostic group separately, controlling for age, gender, education and disease duration. RESULTS: Compared with the tremor-dominant phenotype, akinetic-rigid patients performed worse in executive functions such as working memory (Wechsler Memory Scale-Revised backward; p=0.012), formal-lexical word fluency (p=0.043), card sorting (p=0.006), attention (Trail Making Test version A; p=0.024) and visuospatial abilities (Leistungsprüfungssystem test 9; p=0.006). Akinetic-rigid neuropsychological test scores for the executive and attentive domain correlated negatively with non-tremor motor scores. Covariate-adjusted binary logistic regression analyses showed significant odds for PD-mild cognitive impairment for not-determined as compared with tremor-dominant (OR=3.198) and akinetic-rigid PD (OR=2.059). The odds for PD-dementia were significant for akinetic-rigid as compared with tremor-dominant phenotype (OR=8.314). CONCLUSION: The three motor phenotypes of PD differ in cognitive performance, showing that cognitive deficits seem to be less severe in tremor-dominant PD. While these data are cross-sectional, longitudinal data are needed to shed more light on these differential findings.