الملخص
Objective: To assess the influence of migration on the psychopathological presentation of individuals at ultra-high risk for psychosis (UHR) in São Paulo, Brazil. Methods: This study is part of the Subclinical Symptoms and Prodromal Psychosis (SSAPP) project, a cohort study in São Paulo, Brazil, designed to follow individuals at UHR. After screening with the Prodromal Questionnaire (PQ) and a clinical interview, the Global Assessment of Functioning (GAF) was administered, a neuropsychological assessment was performed, sociodemographic and migration data were obtained. We then analyzed UHR individuals who had migration data to see if migration had any effect on their cognition and psychopathology. Chi-square tests were used for categorical variables, and Student's t test or analysis of variance (ANOVA) were used for nonparametric and parametric distributions, respectively. Results: The sample was composed of 42 at-risk subjects, of whom 5 had a migration history in the past two generations. Those with migration history showed significantly more formal thought disturbances (p = 0.012) and sleeping problems (p = 0.033) compared to those without. Conclusions: Our data reinforce migration as a risk factor for psychosis in developing countries as well, and highlights the importance of studying the specific effect of this factor in UHR psychopathology.
الموضوعات
Humans , Psychotic Disorders/diagnosis , Psychotic Disorders/epidemiology , Schizophrenia , Psychiatric Status Rating Scales , Brazil/epidemiology , Risk Factors , Cohort Studies , Prodromal Symptoms , Neuropsychological Testsالملخص
Abstract Background Current evidence suggests that upregulation of polyamines system plays a role both in cognitive deficit and synaptic loss observed in Alzheimer's disease (AD). Objective The aim of this study was to determine the plasmatic concentration of polyamines in mild cognitive impairment (MCI) and AD patients in comparison with healthy controls (HC). Methods Plasmatic polyamines were quantified using the AbsoluteIDQ® p180 and liquid chromatography coupled to tandem mass spectrometry (LC/MS-MS). Results The study group comprised 34 AD patients, 20 MCI and 25 HC. All individuals were followed for 4 years. During this period 8 amnestic MCI patients (40% of the MCI sample at baseline) converted to AD. Spermidine level was lower in both patient groups (AD; MCI) compared to HC (p = 0.007). Plasma levels of spermine were higher in the MCI group (p < 0.001), but decreased in the sub-sample of MCI patients who converted to AD (p = 0.043). No statistically significant differences were found in ornithine and putrescine levels (p = 0.056 and p = 0.126, respectively). Discussion Our results suggest dynamic changes in the expression of polyamines in the MCI-AD continuum.
الموضوعات
Humans , Male , Female , Aged , Aged, 80 and over , Polyamines/blood , Spermine/blood , Alzheimer Disease/physiopathology , Cognitive Dysfunction/physiopathology , Ornithine/blood , Polyamines/metabolism , Biomarkers/blood , Putrescine/blood , Spermidine/blood , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods , Metabolomics/methods , Alzheimer Disease/diagnosis , Cognitive Dysfunction/diagnosisالملخص
Objective:To assess the relationship between cognitive function, a proposed schizophrenia endophenotype, and two genetic polymorphisms related to dopamine function, catechol-O-methyl transferase (COMT) Val158Met and dopamine receptor 3 (DRD3) Ser9Gly.Methods:Fifty-eight outpatients with schizophrenia/schizoaffective disorder and 88 healthy controls underwent neurocognitive testing and genotyping. Analyses of covariance (ANCOVAs) using age, sex, and years of education as covariates compared cognitive performance for the proposed genotypes in patients and controls. ANCOVAs also tested for the epistatic effect of COMT and DRD3 genotype combinations on cognitive performance.Results:For executive functioning, COMT Val/Val patients performed in a similar range as controls (30.70-33.26 vs. 35.53-35.67), but as COMT Met allele frequency increased, executive functioning worsened. COMT Met/Met patients carrying the DRD3 Ser/Ser genotype performed poorest (16.184 vs. 27.388-31.824). Scores of carriers of this COMT/DRD3 combination significantly differed from all DRD3 Gly/Gly combinations (p < 0.05), from COMT Val/Met DRD3 Ser/Gly (p = 0.02), and from COMT Val/Val DRD3 Ser/Ser (p = 0.01) in patients. It also differed significantly from all control scores (p < 0.001).Conclusion:Combined genetic polymorphisms related to dopamine neurotransmission might influence executive function in schizophrenia. Looking at the effects of multiple genes on a single disease trait (epistasis) provides a comprehensive and more reliable way to determine genetic effects on endophenotypes.
الموضوعات
Adult , Female , Humans , Male , Middle Aged , Young Adult , Catechol O-Methyltransferase/genetics , Cognition/physiology , Epistasis, Genetic , Polymorphism, Single Nucleotide , /genetics , Schizophrenia/genetics , Analysis of Variance , Case-Control Studies , Educational Status , Executive Function/physiology , Gene Frequency , Genetic Association Studies , Neuropsychological Tests , Real-Time Polymerase Chain Reaction , Schizophrenia/physiopathologyالملخص
Objective: To critically review and evaluate existing knowledge on the conceptual limits and clinical usefulness of the diagnosis of mild cognitive impairment (MCI) and the neuropsychological assessment and short- and long-term prognosis thereof. Methods: We conducted a systematic search of the PubMed and Web of Science electronic databases, limited to articles published in English between 1999 and 2012. Based on the search terms mild cognitive impairment or MCI and epidemiology or diagnosis, we retrieved 1,698 articles, of which 248 were critically eligible (cross-sectional and longitudinal studies); the abstracts of the remaining 1,450 articles were also reviewed. Results: A critical review on the MCI construct is provided, including conceptual and diagnostic aspects; epidemiological relevance; clinical assessment; prognosis; and outcome. The distinct definitions of cognitive impairment, MCI included, yield clinically heterogeneous groups of individuals. Those who will eventually progress to dementia may present with symptoms consistent with the definition of MCI; conversely, individuals with MCI may remain stable or return to normal cognitive function. Conclusion: On clinical grounds, the cross-sectional diagnosis of MCI has limited prognostic relevance. The characterization of persistent and/or progressive cognitive deficits over time is a better approach for identification of cases at the pre-dementia stages, particularly if these cognitive abnormalities are consistent with the natural history of incipient Alzheimer's disease. .
الموضوعات
Aged , Humans , Middle Aged , Dementia/diagnosis , Cognitive Dysfunction/diagnosis , Dementia/physiopathology , Disease Progression , Cognitive Dysfunction/physiopathology , Neuropsychological Tests , Prognosis , Risk Factorsالملخص
In this study, we investigated the associations between single-nucleotide polymorphisms in GAB2 (rs2373115), GSK3B (rs6438552) and SORL1 (rs641120) and Alzheimer's disease (AD), both alone and in combination with the APOE*4 allele.
الموضوعات
Aged , Female , Humans , Male , Adaptor Proteins, Signal Transducing/genetics , Alzheimer Disease/genetics , /genetics , Cytoskeletal Proteins/genetics , LDL-Receptor Related Proteins/genetics , Membrane Transport Proteins/genetics , Nuclear Proteins/genetics , Polymorphism, Single Nucleotide/genetics , Age of Onset , Risk Factorsالموضوعات
Humans , Male , Aged , Faculty, Medical/history , Medical Oncology , Research Personnel/historyالملخص
Alzheimer disease is the most common cause of dementia among the elderly, accounting for ~60-70 percent of all cases of dementia. The neuropathological hallmarks of Alzheimer disease are senile plaques (mainly containing p-amyloid peptide derived from amyloid precursor protein) and neurofibrillary tangles (containing hyperphosphorylated Tau protein), along with neuronal loss. At present there is no effective treatment for Alzheimer disease. Given the prevalence and poor prognosis of the disease, the development of animal models has been a research priority to understand pathogenic mechanisms and to test therapeutic strategies. Most cases of Alzheimer disease occur sporadically in people over 65 years old, and are not genetically inherited. Roughly 5 percent of patients with Alzheimer disease have familial Alzheimer disease-that is, related to a genetic predisposition, including mutations in the amyloid precursor protein, presenilin 1, and presenilin 2 genes. The discovery of genes for familial Alzheimer disease has allowed transgenic models to be generated through the overexpression of the amyloid precursor protein and/or presenilins harboring one or several mutations found in familial Alzheimer disease. Although none of these models fully replicates the human disease, they have provided valuable insights into disease mechanisms as well as opportunities to test therapeutic approaches. This review describes the main transgenic mouse models of Alzheimer disease which have been adopted in Alzheimer disease research, and discusses the insights into Alzheimer disease pathogenesis from studies in such models. In summary, the Alzheimer disease mouse models have been the key to understanding the roles of soluble b-amyloid oligomers in disease pathogenesis, as well as of the relationship between p-amyloid and Tau pathologies.
الموضوعات
Animals , Humans , Mice , Alzheimer Disease/genetics , Amyloid beta-Protein Precursor/genetics , Disease Models, Animal , Mutation/genetics , Amyloid beta-Protein Precursor/metabolism , Mice, Transgenicالملخص
OBJECTIVE: To identify predictors of the progression from pre-dementia stages of cognitive impairment in Alzheimer's disease is relevant to clinical management and to substantiate the decision of prescribing antidementia drugs. METHOD: Longitudinal study of a cohort of elderly adults with amnestic mild cognitive impairment and healthy controls, carried out to estimate the risk and characterize predictors of the progression to Alzheimer's disease. RESULTS: Patients with amnestic mild cognitive impairment had a higher risk to develop Alzheimer's disease during follow-up (odds ratio = 4.5, CI95 percent [1.3-13.6], p = 0.010). At baseline, older age, lower scores on memory tests and presence of the APOE*4 allele predicted the progression from amnestic mild cognitive impairment to Alzheimer's disease. In a sub sample of amnestic mild cognitive impairment patients, those who progressed to Alzheimer's disease had lower cerebrospinal fluid concentrations of amyloid-beta peptide (Aβ42, p = 0.020) and higher concentrations of total TAU (p = 0.030) and phosphorylated TAU (p = 0.010), as compared to non-converters. DISCUSSION: This is the first Brazilian study to report cerebrospinal fluid biomarkers in the prediction of the conversion from MCI to Alzheimer's disease. Our data are in accordance with those reported in other settings. The measurement of cerebrospinal fluid total-TAU, phospho-TAU and Aβ42 may help identify patients with mild cognitive impairment at higher risk for developing Alzheimer's disease.
OBJETIVO: A identificação de preditores da conversão para a doença de Alzheimer em pacientes com comprometimento cognitivo leve é relevante para o manejo clínico e para decidir sobre a prescrição de drogas antidemência. MÉTODO: Estudo longitudinal em coorte de indivíduos idosos com comprometimento cognitivo leve amnéstico e controles saudáveis; estimativa do risco da progressão para doença de Alzheimer nos dois grupos; determinação das variáveis preditivas desse desfecho. RESULTADOS: Pacientes com comprometimento cognitivo leve amnéstico apresentaram maior risco de desenvolver doença de Alzheimer ao longo do seguimento (odds ratio = 4,5, CI95 por cento [1,3-13,6], p = 0,012). Na avaliação inicial, idade mais avançada, escores mais baixos nos testes cognitivos e do alelo APOE*4 foram preditores da conversão do comprometimento cognitivo leve amnéstico para doença de Alzheimer. Em uma subamostra de pacientes com comprometimento cognitivo leve amnéstico, aqueles que progrediram para doença de Alzheimer tinham concentrações liquóricas mais baixas do peptídeo beta-amilóide (Aβ42, p = 0,020) e mais altas da proteína TAU total (p = 0,030) e TAU fosforilada (p = 0,010) do que os pacientes que não progrediram para doença de Alzheimer. DISCUSSÃO: Este é o primeiro estudo brasileiro com biomarcadores liquóricos a relatar preditores da conversão comprometimento cognitivo leve-doença de Alzheimer. Nossos dados biológicos (aumento de TAU total e fosfo-TAU; redução de Aβ42), e podem auxiliar na identificação dos pacientes com comprometimento cognitivo leve com maior risco de evolução para demência.
الموضوعات
Aged , Female , Humans , Male , Alzheimer Disease/diagnosis , Amnesia/diagnosis , Amyloid beta-Peptides/cerebrospinal fluid , Cognition Disorders/diagnosis , tau Proteins/cerebrospinal fluid , Alzheimer Disease/cerebrospinal fluid , Amnesia/cerebrospinal fluid , Biomarkers/cerebrospinal fluid , Cognition Disorders/cerebrospinal fluid , Disease Progression , Epidemiologic Methodsالملخص
Patients with schizophrenia have a two- to three-fold increased risk of premature death as compared to patients without this disease. It has been established that patients with schizophrenia are at a high risk of developing cardiovascular disease. Moreover, an important issue that has not yet been explored is a possible existence of a "cerebral" focus that could trigger sudden cardiac death in patients with schizophrenia. Along these lines, several structural and functional alterations in the thalamic complex are evident in patients with schizophrenia and have been correlated with the symptoms manifested by these patients. With regard to abnormalities on the cellular and molecular level, previous studies have shown that schizophrenic patients have fewer neuronal projections from the thalamus to the prefrontal cortex as well as a reduced number of neurons, a reduced volume of either the entire thalamus or its subnuclei, and abnormal glutamate signaling. According to the glutamate hypothesis of schizophrenia, hypofunctional corticostriatal and striatothalamic projections are directly involved in the pathophysiology of the disease. Animal and post-mortem studies have provided a large amount of evidence that links the sudden unexpected death in epilepsy (SUDEP) that occurs in patients with schizophrenia and epilepsy to thalamic changes. Based on the results of these prior studies, it is clear that further research regarding the relationship between the thalamus and sudden cardiac death is of vital importance.
الموضوعات
Humans , Death, Sudden, Cardiac/etiology , Schizophrenia/mortality , Thalamic Nuclei/abnormalities , Antipsychotic Agents/adverse effects , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Epilepsy/etiology , Glutamine/metabolism , Prefrontal Cortex/abnormalitiesالملخص
OBJECTIVE: To describe the neuropsychological profile of mild cognitive impairment subtypes (amnestic, non-amnestic and multiple-domain) of a clinical sample. We further address the diagnostic properties of the Mini-Mental State Examination and the Cambridge Cognitive Examination for the identification of the different mild cognitive impairment subtypes in clinical practice. METHOD: Cross-sectional clinical and neuropsychological evaluation of 249 elderly patients attending a memory clinic at a university hospital in Sao Paulo, Brazil. RESULTS: The performance of patients with mild cognitive impairment was heterogeneous across the different subtests of the neuropsychological battery, with a trend towards an overall worse performance for amnestic (particularly multiple domain) mild cognitive impairment as compared to non-amnestic subtypes. Screening tests for dementia (Mini-Mental State Examination and Cambridge Cognitive Examination) adequately discriminated cases of mild Alzheimer's disease from controls, but they were not accurate to discriminate patients with mild cognitive impairment (all subtypes) from control subjects. CONCLUSIONS: The discrimination of mild cognitive impairment subtypes was possible only with the aid of a comprehensive neuropsychological assessment. It is necessary to develop new strategies for mild cognitive impairment screening in clinical practice.
OBJETIVO: Descrever o perfil neuropsicológico dos subtipos de comprometimento cognitivo leve, amnéstico, não-amnéstico e múltiplos domínios, de uma amostra clínica. Além disto, avaliou-se as propriedades diagnósticas do Mini-exame do Estado Mental e do Cambridge Cognitive Examination na identificação dos diferentes subtipos de comprometimento cognitivo leve na prática clínica. MÉTODO: Avaliação clínica e neuropsicológica transversal de 249 idosos em uma clínica de memória de um hospital universitário em São Paulo, Brasil. RESULTADOS: Testes de rastreio para demência (Mini-exame do Estado Mental e Cambridge Cognitive Examination) identificam corretamente casos de doença de Alzheimer leve, mas não apresentam boa acurácia para diferenciar os diversos subtipos de comprometimento cognitivo leve. A performance dos sujeitos portadores de comprometimento cognitivo leve foi heterogênea nos diferentes testes da bateria neuropsicológica, com uma tendência a uma pior performance global nos pacientes com o subtipo amnéstico (especialmente os com envolvimento de múltiplos domínios cognitivos) em relação ao comprometimento cognitivo leve não-amnéstico. CONCLUSÕES: A discriminação dos diferentes subtipos de comprometimento cognitivo leve foi possível somente a partir de uma avaliação neuropsicológica detalhada. Desta maneira, é necessário o desenvolvimento de novas estratégias de rastreio para esta condição na prática clínica.
الموضوعات
Aged , Female , Humans , Male , Alzheimer Disease/diagnosis , Amnesia/diagnosis , Cognition Disorders/diagnosis , Neuropsychological Tests , Case-Control Studies , Geriatric Assessment/methods , Mental Status Schedule , Multivariate Analysis , Reproducibility of Resultsالملخص
Estas diretrizes para o tratamento biológico da esquizofrenia foram desenvolvidas pela Força-Tarefa da Federação Mundial das Sociedades de Psiquiatria Biológica (World Federation of Societies of Biological Psychiatry, WFSBP). A meta fixada durante o desenvolvimento destas diretrizes foi rever sistematicamente todas as evidências disponíveis referentes ao tratamento da esquizofrenia, tanto no âmbito clínico como científico, e chegar a um consenso sobre as principais recomendações para a prática psiquiátrica. Estas diretrizes são destinadas a todos os médicos que atendem e tratam de pacientes portadores de esquizofrenia. Os dados usados para desenvolver estas diretrizes foram extraídos primariamente de vários painéis e diretrizes nacionais de tratamento para esquizofrenia, assim como de metanálises, revisões e estudos clínicos randomizados sobre a eficácia do tratamento farmacológico e de outras intervenções terapêuticas biológicas, identificadas por uma busca nas bases de dados MedLine e Biblioteca Cochrane. A literatura identificada foi avaliada no que diz respeito à solidez das evidências a favor da eficácia de uma dada intervenção e, então, categorizada em quatro níveis de evidências (de A a D). A primeira parte das diretrizes abrange a definição da doença, sua classificação, a epidemiologia e o curso da esquizofrenia, assim como o manejo terapêutico de fase aguda. Estas diretrizes são primariamente relacionadas ao tratamento biológico de adultos esquizofrênicos, incluindo medicação antipsicótica, outras opções de tratamento farmacológico, terapia eletroconvulsiva, estratégias terapêuticas recentes e complementares.
These guidelines for the biological treatment of schizophrenia were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal during the development of these guidelines was to review systematically all available evidence pertaining to the treatment of schizophrenia, and to reach a consensus on a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating people with schizophrenia. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for schizophrenia, as well as from meta-analyses, reviews and randomised clinical trials on the efficacy of pharmacological and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into four levels of evidence (A/D). This first part of the guidelines covers disease definition, classification, epidemiology and course of schizophrenia, as well as the management of the acute phase treatment. These guidelines are primarily concerned with the biological treatment (including antipsychotic medication, other pharmacological treatment options, electroconvulsive therapy, adjunctive and novel therapeutic strategies) of adults suffering from schizophrenia.
الموضوعات
Practice Guidelines as Topic , Schizophrenia/therapy , Crisis Intervention , Antipsychotic Agents/therapeutic use , Evidence-Based Medicine , Psychiatry , Societies, Medicalالملخص
Estas diretrizes para o tratamento biológico da esquizofrenia foram desenvolvidas pela Força-Tarefa da Federação Mundial das Sociedades de Psiquiatria Biológica (World Federation of Societies of Biological Psychiatry, WFSBP). As metas fixadas durante o desenvolvimento destas diretrizes foi a revisão sistemática de todas as evidências disponíveis referentes ao tratamento da esquizofrenia, tanto no âmbito clínico como no científico, e o estabelecimento de um consenso sobre as principais recomendações para a prática psiquiátrica. Estas diretrizes são destinadas a todos os médicos que atendem e tratam de pacientes portadores de esquizofrenia. Os dados usados para desenvolver estas diretrizes foram extraídos primariamente de vários painéis e diretrizes nacionais para o tratamento da esquizofrenia, assim como de metanálises, revisões e estudos clínicos randomizados sobre a eficácia do tratamento farmacológico e de outras intervenções terapêuticas biológicas, identificadas por uma busca nas bases de dados MedLine e na Biblioteca Cochrane. A literatura identificada foi avaliada quanto à solidez das evidências a favor da eficácia de determinada intervenção, sendo, então, categorizada em quatro níveis de evidência (de A a D). A segunda parte das diretrizes abrange o tratamento de longo prazo, bem como o controle dos efeitos colaterais relevantes. Essas diretrizes são primariamente relacionadas ao tratamento biológico de adultos esquizofrênicos, incluindo medicação antipsicótica, outras opções de tratamento farmacológico, eletroconvulsoterapia, estratégias terapêuticas recentes e complementares.
These guidelines for the biological treatment of schizophrenia were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal during the development of these guidelines was to review systematically all available evidence pertaining to the treatment of schizophrenia, and to reach a consensus on a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating people with schizophrenia. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for schizophrenia, as well as from meta-analyses, reviews and randomised clinical trials on the efficacy of pharmacological and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and then categorised into four levels of evidence (A/D). This second part of the guidelines covers the long-term treatment as well as the management of relevant side effects. These guidelines are primarily concerned with the biological treatment (including antipsychotic medication, other pharmacological treatment options, electroconvulsive therapy, adjunctive and novel therapeutic strategies) of adults suffering from schizophrenia.
الموضوعات
Practice Guidelines as Topic , Schizophrenia/therapy , Crisis Intervention , Antipsychotic Agents/therapeutic use , Evidence-Based Medicine , Psychiatry , Follow-Up Studies , Societies, Medicalالملخص
Os autores apresentam uma revisäo da literatura sobre a síndrome de Münchhausen, ilustrada pela descriçäo de um caso clínico bastante característico do transtôrno. Discute-se o diagnóstico e o diagnóstico diferencial com a simulaçäo, a esquizofrenia e transtornos somatoformes tais como somatizaçäo e conversäo. É importante que o clínico e o cirurgiäo estejam alertas para o diagnóstico de Münchhausen, porque esses pacientes se expöem a graves complicações de procedimentos clínicos e cirúrgicos desnecessários. Devido à baixa adesäo ao tratamento, o manejo clínico da síndrome de Münchhausen é difícil. O diagnóstico precoce pode, de maneira considerável, excluir estes riscos iatrogênicos. Recomendamos que os pacientes com as características psicopatológicas da síndrome de Münchhausen sejam observados de forma cautelosa. Deve-se tentar clarificar tanto o diagnóstico clínico quanto psiquiátrico antes de se realizar qualquer procedimento invasivo