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1.
Hum Brain Mapp ; 35(5): 2448-58, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24038539

RESUMO

The Stroop interference task is a widely used paradigm to examine cognitive inhibition, which is a key component of goal-directed behavior. With increasing age, reaction times in the Stroop interference task are usually slowed. However, to date it is still under debate if age-related increases in reaction times are merely an artifact of general slowing. The current study was conducted to investigate the role of general slowing, as measured by Trail-Making-Test-A, in age-related alterations of Stroop interference. We applied Diffusion Tensor Imaging (DTI) to determine the topography of neuronal networks underlying Stroop interference under control of general slowing. On the behavioral level, linear regression analysis demonstrated that age accounted for significant variance on Stroop interference, whereas TMT-A performance did not. Controlling for TMT-A, DTI based white matter analyses demonstrated a strong association of Stroop interference with integrity measures of genu of corpus callosum, bilateral anterior corona radiata, and bilateral anterior limb of capsula interna. These pathways are associated with frontal brain regions by either connecting the bilateral dorsolateral prefrontal cortex or the anterior cingulate cortex with frontal and subcortical regions or by containing fibers which are part of cortico-thalamic circuits that cross prefrontal regions. Importantly, results expand our knowledge of the neural basis of Stroop interference and emphasize the importance of white matter integrity of frontal pathways in the modulation of Stroop interference. Combining behavioral and DTI findings our results further suggest that cognitive inhibition, as measured by Stroop task, is a qualitatively distinct cognitive process that declines with age.


Assuntos
Envelhecimento , Mapeamento Encefálico , Cognição/fisiologia , Teste de Stroop , Substância Branca/anatomia & histologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Imagem de Tensor de Difusão , Feminino , Giro do Cíngulo , Humanos , Processamento de Imagem Assistida por Computador , Inibição Psicológica , Masculino , Pessoa de Meia-Idade , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Adulto Jovem
2.
Hum Brain Mapp ; 35(1): 309-18, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22965837

RESUMO

Although cognitive training usually improves cognitive test performance, the capability to transfer these training gains into respective or functionally related cognitive domains varies significantly. Since most studies demonstrate rather limited transfer effects in older adults, aging might be an important factor in transfer capability differences. This study investigated the transfer capability of logical reasoning training gains to a measure of Fluid Intelligence (Gf) in relation to age, general intelligence, and brain structural integrity as measured by diffusion tensor imaging. In a group of 41 highly educated healthy elderly, 71% demonstrated successful transfer immediately after a 4-week training session (i.e. short-term transfer). In a subgroup of 22% of subjects transfer maintained over a 3-month follow-up period (i.e. long-term transfer). While short-term transfer was not related to structural integrity, long-term transfer was associated with increased structural integrity in corpus and genu of the corpus callosum. Since callosal structural integrity was also related to age (in the present and foregoing studies), previously observed associations between age and transfer might be moderated by the structural integrity. Surprisingly, age was not directly associated with transfer in this study which could be explained by the multi-dependency of the structural integrity (modulating factors beside age, e.g. genetics). In this highly educated sample, general intelligence was not related to transfer suggesting that high intelligence is not sufficient for transfer in normal aging. Further studies are needed to reveal the interaction of transfer, age, and structural integrity and delineate mechanisms of age-dependent transfer capabilities.


Assuntos
Envelhecimento , Corpo Caloso/anatomia & histologia , Inteligência/fisiologia , Transferência de Experiência/fisiologia , Idoso , Idoso de 80 Anos ou mais , Imagem de Tensor de Difusão , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade
3.
Cerebrovasc Dis ; 38(6): 448-56, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25502511

RESUMO

BACKGROUND: The central nervous system manifestations in Fabry disease (FD) include progressive white matter lesions (WMLs) and stroke. Due to progressive microvascular involvement, men and women with FD over 35 years of age develop WMLs. Moreover, the prevalence of stroke has been estimated to be 12 times higher in FD compared with the general population. Enzyme replacement therapy (ERT) is available and has shown beneficial effects on renal, cardiac, and peripheral nerve function in FD, but the ERT effect on the progression of WMLs, or the reduction in cerebrovascular events, remains unknown. METHODS: The WML burden and the effect of agalsidase beta 1 mg/kg biweekly on WML progression were assessed longitudinally in a Phase 4 agalsidase-beta placebo-controlled analysis of untreated and treated FD patients with mild-to-moderate renal involvement (serum creatinine measurements of ≥1.2 mg/dl and <3.0 mg/dl). The primary end point was the difference in the number of patients with increased WML burden between the agalsidase beta and placebo groups at the end of treatment. The diameters of the WMLs were determined manually using axial flow-attenuated-inversion-recovery-weighted magnetic resonance imaging (MRI) scans taken at baseline and follow-up. RESULTS: MRI scans from 41 FD patients (mean age 43.9, age range 20-68, 3 females; n=25 on ERT, n=16 on placebo) were analyzed. WML burden was present in 63% of patients at baseline, increased over a mean of 27 months (range 12-33 months) follow-up, and correlated with left ventricular hypertrophy (LVPW). Patients with previous or recent strokes (n=11, 39-68 years) showed an increase in the number of WMLs (p=0.005). A greater proportion of younger patients (≤50 years) on ERT (n=18) had stable WML burden compared with younger patients in the placebo group (n=13): 44% (8 of 18) versus 31% (4 of 13), p=0.014. The number needed to treat was 8. CONCLUSIONS: This FD patient cohort, with mild-to-moderate renal involvement, had a significant WML burden and high inter-individual variability associated with the degree of LVPW but not the degree of kidney dysfunction. These advanced patients with increased LVPW and stroke evidence may have had a higher cerebrovascular risk. The WML burden in patients on ERT was more likely to remain stable, compared with patients on placebo. Thus, ERT may reduce the progression of vascular disease, even in advanced FD patients, suggesting that early treatment may stabilize WML progression and stroke risk.


Assuntos
Terapia de Reposição de Enzimas , Doença de Fabry/tratamento farmacológico , Isoenzimas/uso terapêutico , Leucoencefalopatias/tratamento farmacológico , Substância Branca/patologia , alfa-Galactosidase/uso terapêutico , Adulto , Idoso , Encéfalo/patologia , Progressão da Doença , Doença de Fabry/complicações , Doença de Fabry/patologia , Feminino , Humanos , Leucoencefalopatias/etiologia , Leucoencefalopatias/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Neuroimage ; 76: 167-77, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-23518010

RESUMO

Normal aging is characterized by brain glucose metabolism decline predominantly in the prefrontal cortex. The goal of the present study was to assess whether this change was associated with age-related alteration of white matter (WM) structural integrity and/or functional connectivity. FDG-PET data from 40 young and 57 elderly healthy participants from two research centers (n=49/48 in Center 1/2) were analyzed. WM volume from T1-weighted MRI (Center 1), fractional anisotropy from diffusion-tensor imaging (Center 2), and resting-state fMRI data (Center 1) were also obtained. Group comparisons were performed within each imaging modality. Then, positive correlations were assessed, within the elderly, between metabolism in the most affected region and the other neuroimaging modalities. Metabolism decline in the elderly predominated in the left inferior frontal junction (LIFJ). LIFJ hypometabolism was significantly associated with macrostructural and microstructural WM disturbances in long association fronto-temporo-occipital fibers, while no relationship was found with functional connectivity. The findings offer new perspectives to understand normal aging processes and open avenues for future studies to explore causality between age-related metabolism and connectivity changes.


Assuntos
Encéfalo/metabolismo , Vias Neurais/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Adulto Jovem
5.
Neuroimage ; 79: 184-90, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-23631988

RESUMO

Studies of functional connectivity suggest that the default mode network (DMN) might be relevant for cognitive functions. Here, we examined metabolic and structural connectivity between major DMN nodes, the posterior cingulate (PCC) and medial prefrontal cortex (MPFC), in relation to normal working memory (WM). DMN was captured using independent component analysis of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) data from 35 young healthy adults (27.1 ± 5.1 years). Metabolic connectivity, a correlation between FDG uptake in PCC and MPFC, was examined in groups of subjects with (relative to median) low (n=18) and high (n=17) performance on digit span backward test as an index of verbal WM. In addition, fiber tractography based on PCC and MPFC nodes as way points was performed in a subset of subjects. FDG uptake in the DMN nodes did not differ between high and low performers. However, significantly (p=0.01) lower metabolic connectivity was found in the group of low performers. Furthermore, as compared to high performers, low performers showed lower density of the left superior cingulate bundle. Verbal WM performance is related to metabolic and structural connectivity within the DMN in young healthy adults. Metabolic connectivity as quantified with FDG-PET might be a sensitive marker of the normal variability in some cognitive functions.


Assuntos
Encéfalo/fisiologia , Conectoma/métodos , Fluordesoxiglucose F18/farmacocinética , Memória de Curto Prazo/fisiologia , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiologia , Transdução de Sinais/fisiologia , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética
6.
Am J Geriatr Psychiatry ; 21(7): 646-54, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23567410

RESUMO

OBJECTIVES: Comparability of measures of quality of life in dementia and in other diagnostic groups, such as mild cognitive impairment, normal aging, or other diseases, is highly desirable. However, the impact of cognitive deficits and impaired insight on applicability and validity of generic instruments is sparsely studied. PARTICIPANTS AND MEASUREMENTS: Sixty patients with dementia [38 women; age: mean (SD) = 78.7 (6.4) years; Mini-Mental State Examination (MMSE): mean (SD) = 20.2 (6.0)] recruited as part of the start-modem study, a multicenter care research study in Germany, completed the generic instrument SF-36 and the specific instrument Quality of Life-Alzheimer's Disease (QOL-AD). RESULTS: QOL-AD self-rating scores [mean (SD) = 32.8 (5.9)] and SF-36 subscales indicated moderate to good quality of life in the total group. Reliability and validity of five subdomains of the SF-36 were poor in subgroups of patients with impaired insight or with MMSE scores less than 17 (Cronbach's α <0.7, no significant correlation to the QOL-AD). In contrast, for patients with both adequate insight and MMSE score greater than 16 (n = 33; 55%) Cronbach's α of the subdomains of the SF-36 ranged between 0.920 and 0.676. Seven of the eight subdomains correlated significantly with the QOL-AD self-rating and composite score in this group of patients (0.355 ≤ r ≤ 0.709). CONCLUSIONS: Despite the impact of insight and cognition on self-rated quality of life, we found reliable and valid data for a broad spectrum of patients with dementia. According to the present data, the SF-36 is suitable for dementia patients with both insight into their deficits and an MMSE score greater than 16.


Assuntos
Doença de Alzheimer/psicologia , Demência/psicologia , Qualidade de Vida/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Demência/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria/instrumentação , Reprodutibilidade dos Testes
7.
Neuroimage ; 63(2): 713-22, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-22796505

RESUMO

There is a great deal of heterogeneity in the impact of aging on cognition and cerebral functioning. One potential factor contributing to individual differences among the elderly is the cognitive reserve, which designates the partial protection from the deleterious effects of aging that lifetime experience provides. Neuroimaging studies examining task-related activation in elderly people suggested that cognitive reserve takes the form of more efficient use of brain networks and/or greater ability to recruit alternative networks to compensate for age-related cerebral changes. In this exploratory multi-center study, we examined the relationships between cognitive reserve, as measured by education and verbal intelligence, and cerebral metabolism at rest (FDG-PET) in a sample of 74 healthy older participants. Higher degree of education and verbal intelligence was associated with less metabolic activity in the right posterior temporoparietal cortex and the left anterior intraparietal sulcus. Functional connectivity analyses of resting-state fMRI images in a subset of 41 participants indicated that these regions belong to the default mode network and the dorsal attention network respectively. Lower metabolism in the temporoparietal cortex was also associated with better memory abilities. The findings provide evidence for an inverse relationship between cognitive reserve and resting-state activity in key regions of two functional networks respectively involved in internal mentation and goal-directed attention.


Assuntos
Envelhecimento/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Reserva Cognitiva/fisiologia , Vias Neurais/metabolismo , Idoso , Idoso de 80 Anos ou mais , Atenção/fisiologia , Feminino , Fluordesoxiglucose F18/farmacologia , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Descanso/fisiologia
8.
J Magn Reson Imaging ; 36(1): 84-91, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22359373

RESUMO

PURPOSE: To evaluate the feasibility of multicenter tractography of the cingulate bundle (CB) in Alzheimer's disease (AD). MATERIALS AND METHODS: Automated deterministic tractography of the CB was applied to scans of 45 patients with probable AD and 58 healthy controls (HC) acquired with Siemens Sonata (1.5T; 60 gradients), Trio (3T; 61 gradients), and Avanto (1.5T; 30 gradients). Diagnosis and center effects on the tracking indices fractional anisotropy (FA), mean diffusivity (MD), track density, and volume were estimated with analysis of variance. RESULTS: The multicenter coefficients of variance (CVs) in HC and AD patients were 7% and 7% for FA, 10% and 8% for MD, 18% and 20% for density, and 21% and 21% for volume. Multicenter and single-center CVs were within a similar range. Significant center effects declined in the order MD > FA > density > volume. After adjustment for center and age, the AD group showed significantly higher MD (P < 0.001) and lower FA (P < 0.05) as compared with the HC group. CONCLUSION: Despite strong center effects, we detected significantly altered microstructural integrity of the CB in AD patients. Diffusion-tensor imaging indices of the CB as obtained by automated tractography might qualify as a biologically sustained surrogate marker for diagnostic and monitoring purposes in multicenter AD trials.


Assuntos
Doença de Alzheimer/patologia , Imagem de Tensor de Difusão/métodos , Giro do Cíngulo/patologia , Interpretação de Imagem Assistida por Computador/métodos , Fibras Nervosas Mielinizadas/patologia , Reconhecimento Automatizado de Padrão/métodos , Idoso , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
Alcohol Alcohol ; 47(2): 118-26, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22214998

RESUMO

AIMS: In the last years, refined magnetic resonance diffusion tensor imaging (DTI) methods have become available to study microstructural alterations in the human brain. We investigated to what extent white matter tissue abnormalities are present in male patients after chronic, excessive alcohol consumption and if these alterations are correlated with measures of alcohol consumption and neuropsychological performance. METHODS: Twenty-four detoxified adult male patients with severe alcohol dependence and 23 healthy male control subjects were included in the study. Neuropsychological tests were assessed for executive function, attention, memory and visuospatial function. DTI was acquired and preprocessing of the data was performed using tract-based spatial statistics. Group differences of fractional anisotropy (FA) as well as correlation analyses with neuropsychological measures and drinking history were calculated. RESULTS: Performance in alcoholic patients was significantly poorer in tests of non-verbal reasoning and attention. In detoxified alcoholic patients, lower FA was primarily found in the body of the corpus callosum, but these findings did not correlate directly with behavioral measures. However, executive and psychomotor performance (Trail-Making Test) correlated significantly with FA in right anterior cingulate and left motor areas. CONCLUSION: These findings provide further evidence for reduced integrity of interhemispheric connections in male patients with severe alcohol dependence, and neurocognitive performance was in part correlated with FA.


Assuntos
Alcoolismo/patologia , Alcoolismo/psicologia , Encéfalo/patologia , Imagem de Tensor de Difusão/psicologia , Fibras Nervosas Amielínicas/patologia , Desempenho Psicomotor , Adulto , Consumo de Bebidas Alcoólicas/patologia , Consumo de Bebidas Alcoólicas/psicologia , Anisotropia , Estudos de Casos e Controles , Imagem de Tensor de Difusão/métodos , Função Executiva , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/patologia , Testes Neuropsicológicos/estatística & dados numéricos
10.
Dement Geriatr Cogn Disord ; 30(3): 245-53, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20847555

RESUMO

AIMS: In this study, we aimed to compare cerebrospinal fluid (CSF) levels of total tau (t-tau), phosphorylated tau (p-tau(181)) and positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) in the differential diagnosis of Alzheimer's disease (AD) under clinical conditions. METHOD: In a cross-sectional, blinded, single-center study, we examined a sample of 75 unselected memory clinic patients with clinical diagnoses of dementia of Alzheimer type (DAT; n = 24), amnestic mild cognitive impairment (MCI; n = 16), other dementias (n = 13) and nondemented controls (n = 22). Discriminative accuracy, sensitivity and specificity were calculated and compared using ROC analyses. RESULTS: p-tau(181) and FDG-PET were comparable in separating DAT from controls (sensitivity: 67 vs. 79%; specificity: 91% for both) and patients with other dementias (sensitivity: 71 vs. 79%; specificity: 100% for both). The sensitivity of p-tau(181) in differentiating MCI patients from controls was significantly (p < 0.05) superior to that of FDG-PET (75 vs. 44%) at a comparably high specificity (82 vs. 91%); t-tau measures were less accurate in all analyses. CONCLUSIONS: FDG-PET and CSF p-tau(181) levels are able to discriminate DAT in heterogeneous and unselected samples with a high accuracy. CSF p-tau(181) might be somewhat superior for a sensitive detection of patients with MCI.


Assuntos
Doença de Alzheimer/diagnóstico , Proteínas tau/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico por imagem , Área Sob a Curva , Transtornos Cognitivos/líquido cefalorraquidiano , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Fluordesoxiglucose F18 , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Transtornos da Memória/psicologia , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Curva ROC , Compostos Radiofarmacêuticos
11.
Z Kinder Jugendpsychiatr Psychother ; 38(2): 103-10, 2010 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-20200827

RESUMO

OBJECTIVE: The cognitive phenotype of autism spectrum disorders (ASD) is characterized among other things by local processing (weak central coherence). It was examined whether a test that measures identification of fragmented pictures (FBT) is able to seize this preference for local processing. METHOD: The FBT performance of 15 patients with ASD, 16 with depression, 16 with schizophrenia and of 16 control subjects was compared. In addition, two tests well known to be sensitive to local processing were assessed, namely the Embedded Figures Test (EFT) and the Block Design Test (BDT). RESULTS: ASD patients demonstrated a preference for local processing. Difficulties in global processing, or more specifically in gestalt perception (FBT), were accompanied by good performance on the EFT and BDT as expected. Controlling for age and nonverbal intelligence (ANCOVA) reduced differences to trends. However, the calculation of difference scores (i.e., subtraction of FBT from EFT performance) resulted in significant differences between ASD and control groups even after controlling for of age and intelligence. CONCLUSIONS: The FBT is a suitable exploratory test of local visual processing in ASD. In particular, a difference criterion can be generated (FBT vs. EFT) that discriminates between ASD and clinical as well as healthy control groups.


Assuntos
Atenção , Transtornos Globais do Desenvolvimento Infantil/psicologia , Discriminação Psicológica , Reconhecimento Visual de Modelos , Transtornos da Percepção/psicologia , Adolescente , Adulto , Criança , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Diagnóstico Diferencial , Feminino , Área de Dependência-Independência , Humanos , Inteligência , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos/estatística & dados numéricos , Fechamento Perceptivo , Transtornos da Percepção/diagnóstico , Psicometria , Valores de Referência , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Adulto Jovem
12.
Neuroimage ; 44(1): 43-50, 2009 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-18691659

RESUMO

Statistical comparisons of [(18)F]FDG PET scans between healthy subjects and patients with Alzheimer's disease (AD) or amnestic mild cognitive impairment (aMCI) using Statistical Parametric Mapping (SPM) usually require normalization of regional tracer uptake via ROIs defined using additional software. Here, we validate a simple SPM-based method for count normalization. FDG PET scans of 21 mild, 15 very mild AD, 11 aMCI patients and 15 age-matched controls were analyzed. First, we obtained relative increases in the whole patient sample compared to controls (i.e. areas relatively preserved in patients) with proportional scaling to the cerebral global mean (CGM). Next, average absolute counts within the cluster with the highest t-value were extracted. Statistical comparisons of controls versus three patients groups were then performed using count normalization to CGM, sensorimotor cortex (SMC) as standard, and to the cluster-derived counts. Compared to controls, relative metabolism in aMCI patients was reduced by 15%, 20%, and 23% after normalization to CGM, SMC, and cluster-derived counts, respectively, and 11%, 21%, and 25% in mild AD patients. Logistic regression analyses based on normalized values extracted from AD-typical regions showed that the metabolic values obtained using CGM, SMC, and cluster normalization correctly classified 81%, 89% and 92% of aMCI and controls; classification accuracies for AD groups (very mild and mild) were 91%, 97%, and 100%. The proposed algorithm of fully SPM-based count normalization allows for a substantial increase of statistical power in detecting very early AD-associated hypometabolism, and very high accuracy in discriminating mild AD and aMCI from healthy aging.


Assuntos
Envelhecimento/patologia , Doença de Alzheimer/diagnóstico por imagem , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Idoso , Algoritmos , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Cintilografia , Estudos Retrospectivos
13.
J Geriatr Psychiatry Neurol ; 22(1): 3-9, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19073834

RESUMO

We exploratively measured APPs alpha, a secreted fragment of the non-amyloidogenic cleavage of amyloid precursor protein via a-secretase, and tau protein phosphorylated at threonine 181 (p tau) in the cerebrospinal fluid of 10 patients with mild cognitive impairment, 20 patients with dementia of Alzheimer's type, and 10 controls. Cerebrospinal fluid APPs alpha and p tau levels were correlated with cognitive performance. P tau levels were significantly elevated in mild cognitive impairment and in patients with dementia of Alzheimer's type, APPs alpha levels were significantly reduced in patients with dementia of Alzheimer's type compared to the controls. APPs alpha levels were associated with Mini Mental State Examination total scores but not with Delayed Verbal Recall Test performance. Vice versa, pt au levels correlated only with Delayed Verbal Recall Test in patients with dementia of Alzheimer's type or mild cognitive impairment. Both, an increase in p tau levels and a decrease in cerebrospinal fluid APPs alpha, seem to refer to relevant but functionally different processes in the development of mild cognitive impairment and dementia of Alzheimer's type.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Secretases da Proteína Precursora do Amiloide/líquido cefalorraquidiano , Transtornos Cognitivos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Análise de Variância , Biomarcadores/líquido cefalorraquidiano , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Feminino , Humanos , Masculino , Memória de Curto Prazo , Rememoração Mental , Testes Neuropsicológicos/estatística & dados numéricos , Índice de Gravidade de Doença , Distribuição por Sexo , Análise e Desempenho de Tarefas
14.
J Cereb Blood Flow Metab ; 28(4): 824-31, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17971791

RESUMO

Deficiency of phenylalanine hydroxylase activity in phenylketonuria (PKU) causes an excess of phenylalanine (Phe) throughout the body, predicting impaired synthesis of catecholamines in the brain. To test this hypothesis, we used positron emission tomography (PET) to measure the utilization of 6-[18F]fluoro-L-DOPA [corrected] (FDOPA) in the brain of adult patients suffering from PKU and in healthy controls. Dynamic 2-h long FDOPA emission recordings were obtained in seven adult PKU patients (five females, two males; age: 21 to 27 years) with elevated serum Phe levels, but lacking neurologic deficits. Seven age-matched, healthy volunteers were imaged under identical conditions. The utilization of FDOPA in striatum was calculated by linear graphical analysis (k3S, min(-1)), with cerebellum serving as a nonbinding reference region. The time to peak activity in all brain time-radioactivity curves was substantially delayed in the PKU patients relative to the control group. The mean magnitude of k3S in the striatum of the PKU patients (0.0052+/-0.0004 min(-1)) was significantly lower than in the control group (0.0088+/-0.0009 min(-1)) (P<0.001). There was no significant correlation between individual serum Phe levels and k3S. The unidirectional clearance of FDOPA to brain was impaired in adult patients suffering from PKU, presumably reflecting the competitive inhibition of the large neutral amino acid carrier by Phe. Assuming this competition to be spatially uniform, the relationship between striatum and cerebellum time-activity curves additionally suggests inhibition of DOPA efflux, possibly also due to competition from Phe. The linear graphical analysis shows reduced k3S in striatum, indicating reduced DOPA decarboxylase activity.


Assuntos
Corpo Estriado/metabolismo , Di-Hidroxifenilalanina/metabolismo , Fenilcetonúrias/fisiopatologia , Adulto , Feminino , Radioisótopos de Flúor/metabolismo , Humanos , Masculino , Tomografia por Emissão de Pósitrons
15.
Am J Psychiatry ; 165(4): 507-14, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18316420

RESUMO

OBJECTIVE: All drugs of abuse induce a phasic dopamine release within the striatum that does not undergo habituation. Prolonged substance consumption impairs the natural function of the mesolimbic dopamine system, as shown by a decrease in the availability of striatal dopamine 2 (D(2)) receptors in patients suffering from cocaine, heroin, amphetamine, and alcohol dependence. However, it is unclear whether similar changes can also be observed in heavy-smoking nicotine-dependent smokers. METHOD: In vivo D(2)/D(3) receptor availability was determined with [ (18)F]fallypride positron emission tomography in 17 heavy-smoking nicotine-dependent subjects and in 21 age-matched never-smoking comparison subjects. The smokers were scanned twice: first, during a period of usual consumption and second, 24 hours after smoking cessation. RESULTS: Independent of the withdrawal status, the nicotine-dependent smokers displayed significantly less availability of D(2)/D(3) receptors within the bilateral putamen functionally covering parts of the dorsal striatum, as compared to the never-smoking subjects. Nicotine craving under the consumption condition correlated positively with D(2)/D(3) receptor availability within the ventral striatum but negatively with D(2)/D(3) receptor availability within the anterior cingulate and inferior temporal cortex. CONCLUSIONS: Similar to other types of substance abuse, nicotine dependence is associated with low availability of dorsal striatal D(2)/D(3) receptors. In contrast to previous findings on abstinent alcohol-dependent patients, nicotine craving seems to be maintained by a region-specific shift in D(2)/D(3) receptor availabilities, with higher availability within the ventral striatum but lower availability within the anterior cingulate and inferior temporal cortex.


Assuntos
Gânglios da Base/diagnóstico por imagem , Gânglios da Base/metabolismo , Comportamento Aditivo/metabolismo , Lateralidade Funcional/fisiologia , Tomografia por Emissão de Pósitrons/estatística & dados numéricos , Receptores de Dopamina D2/metabolismo , Tabagismo/diagnóstico por imagem , Tabagismo/metabolismo , Adulto , Gânglios da Base/química , Comportamento Aditivo/diagnóstico , Comportamento Aditivo/diagnóstico por imagem , Benzamidas/metabolismo , Radioisótopos de Carbono , Radioisótopos de Flúor , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/metabolismo , Humanos , Masculino , Pirrolidinas/metabolismo , Receptores de Dopamina D3 , Fumar/efeitos adversos , Fumar/psicologia , Síndrome de Abstinência a Substâncias/diagnóstico , Síndrome de Abstinência a Substâncias/diagnóstico por imagem , Síndrome de Abstinência a Substâncias/metabolismo , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/metabolismo , Tabagismo/diagnóstico
16.
J Nucl Med ; 49(8): 1257-61, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18632824

RESUMO

UNLABELLED: Little is known about the neurobiologic correlates of human personality. On the basis of the key role of the central opioidergic system in addiction and substance abuse, we investigated the relationship between certain personality traits that are supposed to be relevant in addiction and the opioid receptor status in healthy subjects. METHODS: We investigated 23 healthy male volunteers who were extensively clinically tested to exclude substance abuse. All of the subjects underwent 1 PET scan with the subtype-nonselective opioidergic radioligand 18F-fluoroethyl-diprenorphine under resting conditions without sensory or cognitive stimulation. Subsequently, the subjects were psychologically tested for the personality traits novelty seeking, harm avoidance, reward dependence, and persistence, according to Cloninger's biosocial model of personality. The binding potential (BP) as a parameter of regional cerebral opioid receptor availability was computed by means of the modified Logan plot using the occipital cortex as a reference region. Further imaging data analysis was performed using statistical parametric mapping; after stereotactic normalization, the correlations were calculated between the regional BP and the psychologic scores on a voxel-by-voxel basis. RESULTS: The correlation analysis between personality dimensions and opioid receptor availability showed a significant (P < 0.001) positive correlation between the scores of reward dependence and the BP of the bilateral ventral striatum with nucleus accumbens (z scores, 4.52 and 4.33, respectively). The additionally performed region-of-interest-based correlation analysis yielded correlation coefficients of r = 0.84 and r = 0.81 for the left and right ventral striata, respectively. No further significant correlations were detectable between the other personality dimensions and cerebral opioid receptor binding. CONCLUSION: In healthy subjects, personality traits, which might be predisposing for addictive behavior, are correlated to the opioidergic neurotransmission in core structures of the human reward system.


Assuntos
Encéfalo/metabolismo , Diprenorfina/análogos & derivados , Compostos Radiofarmacêuticos , Receptores Opioides/metabolismo , Recompensa , Adulto , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/metabolismo , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Núcleo Caudado/diagnóstico por imagem , Núcleo Caudado/metabolismo , Diprenorfina/metabolismo , Radioisótopos de Flúor , Humanos , Masculino , Pessoa de Meia-Idade , Núcleo Accumbens/diagnóstico por imagem , Núcleo Accumbens/metabolismo , Personalidade , Cintilografia , Compostos Radiofarmacêuticos/metabolismo
17.
Psychiatry Res ; 164(2): 143-53, 2008 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-18930634

RESUMO

At present, there is still no consensus on the choice of the reference area in positron emission tomography (PET) studies of Alzheimer's disease (AD). In this study, PET scans with fluorodeoxyglucose-F18 were carried out in the following groups of subjects: 47 patients with probable AD, 8 patients with mild cognitive impairment, and 15 age-similar healthy subjects. Scans normalized to the cerebral global mean (CGM), cerebellum (CBL), and the primary sensorimotor cortex (SMC). We evaluated the effect of the different count normalization procedures on the accuracy of (18)F-FDG PET to detect AD-specific metabolic abnormalities (voxel-based group comparison) and to differentiate between patients and healthy subjects (ROI-based discriminant analysis) with regard to the degree of clinical deterioration. Metabolic reductions in groups of very mildly, mildly and moderate-to-severely affected patients appeared, respectively, 2.2, 2.6, and 2.7 times greater in spatial extent when tracer uptake was normalized to SMC rather than to CGM. The overall accuracy of discrimination was 94%, 91%, and 80% after normalization to SMC, CBL, and CGM, respectively. In general, normalization to SMC was somewhat superior to cerebellar normalization, allowing the detection of more pronounced metabolic deficits and the more accurate discrimination of patients from non-patients. Normalization to CGM should be used with great caution not only in advanced stages of dementia, but also in very mild AD cases.


Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Cerebelo/metabolismo , Fluordesoxiglucose F18 , Córtex Motor/metabolismo , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Córtex Somatossensorial/metabolismo , Adolescente , Idoso , Transtornos Cognitivos/diagnóstico , Feminino , Lobo Frontal/metabolismo , Giro do Cíngulo/metabolismo , Humanos , Masculino , Testes Neuropsicológicos , Lobo Parietal/metabolismo , Índice de Gravidade de Doença , Lobo Temporal/metabolismo
18.
Psychother Psychosom Med Psychol ; 58(6): 246-52, 2008 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-17926230

RESUMO

SUBJECT: Pilot study on an early-interventional group therapy for patients with incipient Alzheimer disease and their relatives. The present study investigates whether scientific progress in terms of earlier time of diagnostic certainty can be used for psychoeducation, maintenance of positive activities and prevention of comorbid depressive episodes. METHODS: 12 patients (66.8 +/- 5.8 years, MMSE 24.0 +/- 4.0) together with 12 relatives have been treated with a bi-weekly group therapy program. RESULTS: For the patients treatment resulted in reduced anxiety, anergia and withdrawal, for their relatives reduced sleep disturbances, irascibility, and aggressiveness have been found. Only one of the patients suffered from a depressive episode. All participants expressed positive feedback and a high level of quality of life. CONCLUSIONS: By the straightforward psychosocial intervention it seems possible to use the earlier time of diagnostic certainty for early diagnosed patients suffering from incipient Alzheimer disease. However, results have to be replicated by a controlled, prospective study with larger sample sizes.


Assuntos
Doença de Alzheimer/terapia , Cuidadores/psicologia , Psicoterapia de Grupo , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Transtornos de Ansiedade/terapia , Terapia Combinada , Comorbidade , Efeitos Psicossociais da Doença , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Transtorno Depressivo/terapia , Diagnóstico Precoce , Terapia por Exercício , Feminino , Humanos , Masculino , Transtornos da Memória/diagnóstico , Transtornos da Memória/psicologia , Transtornos da Memória/terapia , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Satisfação do Paciente , Projetos Piloto , Qualidade de Vida/psicologia
19.
J Clin Neurosci ; 53: 79-84, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29685411

RESUMO

BACKGROUND: Montreal Cognitive Assessment (MoCA) represents a short screening tool for neuropsychological deficits. The study's aim was to test feasibility and acceptance of MoCA in patients with brain tumours perioperatively. METHODS: Patients with supratentorial located brain tumours were assessed preoperatively (t1, day -1) and postoperatively (t2, day 3-5) using EORTC-QLQ-C30 + BN20, Distress Thermometer (DT) and the MoCA test (different versions). Feasibility was evaluated by a feedback form and patients were asked about perceived discomfort, overstraining or complexity of MoCA. Results of MoCA were correlated with clinical factors. RESULTS: 63 patients participated, 19 were male. Mean age was 56 years. Mean completion time of MoCA was 11 min (both t1 and t2). At t1, in 27% "moderate or major difficulties" occurred during MoCA assessment vs. 41% at t2. Most of the patients (t1, 93% vs. t2, 86%) negated to be overstrained by MoCA. Better "physical function" according to EORTC-QLQ-C30 (p = 0.041, Pearson = 0.321) and higher KPS (p = 0.012, Pearson = 0.578) correlated to higher MoCA scores. Higher distress at t2 was found to be correlated with a stronger deterioration of MoCA at t2 vs. t1 (p = 0.03, Spearman-Rho = .695). CONCLUSION: The MoCA test was well accepted by the patients and implementable in clinical routine. Further investigations evaluating the sensitivity and specificity of the test in brain tumour patients are required.


Assuntos
Transtornos Cognitivos/diagnóstico , Testes Neuropsicológicos , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Neoplasias Supratentoriais/cirurgia , Adulto , Idoso , Transtornos Cognitivos/etiologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
20.
J Autism Dev Disord ; 37(8): 1493-504, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17029017

RESUMO

This study examined gestalt perception in high-functioning autism (HFA) and its relation to tasks indicative of local visual processing. Data on of gestalt perception, visual illusions (VI), hierarchical letters (HL), Block Design (BD) and the Embedded Figures Test (EFT) were collected in adult males with HFA, schizophrenia, depression and normative controls. Individuals with HFA processed gestalt stimuli less in accord with gestalt laws, particularly regarding the principle of similarity. Gestalt processing correlated positively with global processing of the HL. EFT and BD performance correlated negatively with VI susceptibility in HFA. All clinical groups succumbed less to VI than the normative sample. Results suggest decreased gestalt perception in HFA, being associated with a more general local visual processing bias.


Assuntos
Transtorno Autístico/diagnóstico , Área de Dependência-Independência , Inteligência , Reconhecimento Visual de Modelos , Fechamento Perceptivo , Adulto , Atenção , Transtorno Autístico/psicologia , Percepção de Profundidade , Aprendizagem por Discriminação , Feminino , Humanos , Masculino , Ilusões Ópticas , Desempenho Psicomotor , Esquizofrenia Paranoide/diagnóstico , Esquizofrenia Paranoide/psicologia , Escalas de Wechsler
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