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INTRODUCTION: Genome-wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities. METHODS: We performed GWAS on sporadic Alzheimer's disease (AD) including 539 patients and 854 controls from Argentina and Chile. We combined our results with those from the European Alzheimer and Dementia Biobank (EADB) in a meta-analysis and tested their genetic risk score (GRS) performance in this admixed population. RESULTS: We detected apolipoprotein E ε4 as the single genome-wide significant signal (odds ratio = 2.93 [2.37-3.63], P = 2.6 × 10-23 ). The meta-analysis with EADB summary statistics revealed four new loci reaching GWAS significance. Functional annotations of these loci implicated endosome/lysosomal function. Finally, the AD-GRS presented a similar performance in these populations, despite the score diminished when the Native American ancestry rose. DISCUSSION: We report the first GWAS on AD in a population from South America. It shows shared genetics modulating AD risk between the European and these admixed populations. HIGHLIGHTS: This is the first genome-wide association study on Alzheimer's disease (AD) in a population sample from Argentina and Chile. Trans-ethnic meta-analysis reveals four new loci involving lysosomal function in AD. This is the first independent replication for TREM2L, IGH-gene-cluster, and ADAM17 loci. A genetic risk score (GRS) developed in Europeans performed well in this population. The higher the Native American ancestry the lower the GRS values.
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Doença de Alzheimer , Azidas , Estudo de Associação Genômica Ampla , Humanos , Chile , Doença de Alzheimer/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
Resumen La reserva cognitiva (RC) se refiere al nivel de adaptabilidad de la cognición frente a cambios cerebrales. Varios estudios la han considerado un factor de protección de la enfermedad de Alzheimer (EA). En la región argentina no se cuenta con un instrumento validado que permita medir este constructo. El objetivo del presente trabajo es adaptar el Cuestionario de Reserva Cognitiva (CRC) a la población argentina, establecer puntajes de corte para determinar desde niveles bajos a superiores de RC y analizar qué variables predicen el puntaje total de la reserva. Las modificaciones introducidas a la adaptación fueron evaluadas a través de un proceso de juicio de expertos. Un total de 177 sujetos sanos completaron el Cuestionario de Reserva Cognitiva en su adaptación argentina (CRC-a). Mediante la medida de cuartiles, se establecieron puntajes de corte para determinar niveles bajos, medios, altos y superiores de la reserva. Se realizó una regresión lineal para evaluar si el sexo, la edad y la escolaridad predicen el nivel de RC. En la adaptación argentina del CRC se modificaron 3 de las 8 dimensiones totales y 16 de los 33 ítems totales con respecto al cuestionario original. La media del puntaje total obtenido por la muestra a partir del cuestionario fue de 15.06 con DS = 3.42. Puntajes menores a 13 reflejaron niveles bajos de RC, puntajes entre 13 y 16, niveles medios, puntajes entre 16 y 20, niveles altos, y puntajes superiores a 20, niveles superiores. La escolaridad resultó ser la única variable de predicción del nivel de RC. Si bien se encontraron diferencias entre grupos respecto a la variable sexo, esta no demostró ser predictiva. El CRC-a es el primer instrumento desarrollado en esta región para medir el nivel de RC. Contar con su validación abriría futuras líneas de investigaciones sobre posibles intervenciones para la prevención de enfermedades, tales como la EA.
Abstract Cognitive reserve (CR) refers to the level of adaptability of cognition after brain changes. It is based on processes that allow the activation of new synaptic connections after neurodegeneration, which permits to better withstand the consequences. This reserve is constituted by the interaction of innate individual characteristics (intrauterine or genetically determined) and the exposure to different life experiences. It begins its development in early stages of life and continues its transformation up to advances ages. The sociodemographic variables reported as the main ones to build the reserve are education, leisure activities, lifestyle, socioeconomic level and intelligence. Several studies have considered it as a protective factor for Alzheimer's Disease (AD). Subjects with high levels of CR have lower prevalence and incidence of AD in comparison to those with low levels of reserve. CR would lead to a late onset of symptoms, despite not having any effect on the underlying pathophysiological process of the disease. The reserve would not prevent AD from developing, but it would compensate the symptoms and, therefore, delay their onset. In some cases, there is such compensation that the symptoms do not manifest. There is no validated instrument available for the Argentinian region that allows to measure this construct. The aim of this study is to adapt the Cognitive Reserve Questionnaire to the Argentinian population, to establish cut-off scores to distinguish between low, medium, high and superior levels of CR and analyze which variables could predict the total reserve score. The modifications introduced in the adaptation were evaluated through an expert judgment process. A total of 177 healthy subjects completed the Cognitive Reserve Questionnaire in its Argentinian adaptation (CRQ-a). Through the measure of quartiles, cut-off scores were established to determine low, medium, high and superior levels of the reserve. A lineal regression was made to evaluate if age, education, and sex might predict the level of CR. Three of the eight total dimensions and 16 of the 33 total items that make up the original questionnaire were modified. The mean of the total score obtained by the sample from the questionnaire was 15.06 with SD = 3.42. Scores under 13 reflected low CR levels, scores between 13 and 16 reflected medium levels, scores between 16 and 20 reflected high levels, and scores above 20 reflected superior levels. Education turned out to be the only predictor variable for the level of CR. Although differences were found between groups of different sex, this variable turned out to be not predictive. The CRQ-a is the first instrument for the Argentinian population to measure the level of the reserve. It allows to quickly explore different dimensions, considered as the most relevant for its formation. These are: formal education, courses, parents' formal education, employment, musical training, languages, reading activity and intellectual games. In patients with AD, is particularly important to have a measure for CR to prepare interventions for those subjects whose reserve levels are perceived as low, aiming to delay and, when possible, prevent the clinical manifestation of the disease. Its validation would open future lines of research on possible interventions for the prevention of diseases such as AD.
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BACKGROUND: Multiple sclerosis (MS) has a negative effect on employment status. OBJECTIVE: To present the preliminary results of a special questionnaire designed to collect employment information on patients with MS. METHODS: The questionnaire on the impact of MS on employment status was completed by 63 patients. Fatigue, cognition, and depression were also evaluated, and 33 healthy participants were recruited as a control group. RESULTS: Regarding the patients' employment status, we found rates of 31.7% of full-time employment, 28.6% of part-time employment, 7.9% of unemployment due to MS, 4.8% of housewives, 1.6% retirement due to age, 15.9% of retirement due to disability, 7.9% of medical leave due to MS, and 1.6% of medical leave for other reasons. The rate of unemployment among the patients was significantly higher compared with that of the control group. Out of 38 working patients, 31% had been absent from work for the previous 3 months due to MS, and 50% had to make changes in their work to remain employed. Out of the 19 unemployed patients, 78% said that walking difficulties were the cause of unemployment, while 52% thought cognitive impairment was the cause. CONCLUSIONS: The questionnaire provides a record of the employment status of patients with MS and describes the impact on work from their point of view.
ANTECEDENTES: A esclerose múltipla (EM) tem um efeito negativo na situação laboral. OBJETIVO: Apresentar os resultados preliminares de um questionário elaborado para coletar informações sobre a situação laboral de pacientes com EM. MéTODOS: O questionário sobre o impacto da EM na situação laboral foi preenchido por 63 pacientes. Fadiga, cognição e depressão também foram avaliadas, e 33 pacientes saudáveis foram incluídos como grupo controle. RESULTADOS: Quanto à situação laboral dos pacientes, foram encontradas taxas de 31,7% de emprego em tempo integral, 28,6% de emprego em meio período, 7,9% de desemprego por EM, 4,8% de donas de casa, 1,6% aposentadoria por idade, 15,9% de aposentadoria por invalidez, 7,9% por licença médica por EM, e 1,6% de licença médica por outros motivos. A taxa de desemprego entre os pacientes foi significativamente mais alta em comparação com a do grupo controle. Dos 38 pacientes empregados, 31% tiveram que se afastar do trabalho nos 3 meses anteriores por causa da EM, e 50% tiveram que fazer mudanças em seu trabalho para permanecer empregado. Dos 19 pacientes desempregados, 78% mencionaram que as dificuldades de locomoção foram a causa do desemprego, enquanto 52% reportaram que a deterioração cognitiva foi a causa. CONCLUSõES: Este questionário fornece um registro da situação laboral dos pacientes com EM e descreve o seu impacto no emprego do ponto de vista deles.
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Pessoas com Deficiência , Esclerose Múltipla , Humanos , Adolescente , Esclerose Múltipla/complicações , Emprego , Inquéritos e Questionários , Fadiga/etiologiaRESUMO
Abstract Background Multiple sclerosis (MS) has a negative effect on employment status. Objective To present the preliminary results of a special questionnaire designed to collect employment information on patients with MS. Methods The questionnaire on the impact of MS on employment status was completed by 63 patients. Fatigue, cognition, and depression were also evaluated, and 33 healthy participants were recruited as a control group. Results Regarding the patients' employment status, we found rates of 31.7% of fulltime employment, 28.6% of part-time employment, 7.9% of unemployment due to MS, 4.8% of housewives, 1.6% retirement due to age, 15.9% of retirement due to disability, 7.9% of medical leave due to MS, and 1.6% of medical leave for other reasons. The rate of unemployment among the patients was significantly higher compared with that of the control group. Out of 38 working patients, 31% had been absent from work for the previous 3 months due to MS, and 50% had to make changes in their work to remain employed. Out of the 19 unemployed patients, 78% said that walking difficulties were the cause of unemployment, while 52% thought cognitive impairment was the cause. Conclusions The questionnaire provides a record of the employment status of patients with MS and describes the impact on work from their point of view.
Resumo Antecedentes A esclerose múltipla (EM) tem um efeito negativo na situação laboral. Objetivo Apresentar os resultados preliminares de um questionário elaborado para coletar informações sobre a situação laboral de pacientes com EM. Métodos O questionário sobre o impacto da EM na situação laboral foi preenchido por 63 pacientes. Fadiga, cognição e depressão também foram avaliadas, e 33 pacientes saudáveis foram incluídos como grupo controle. Resultados Quanto à situação laboral dos pacientes, foram encontradas taxas de 31,7% de emprego em tempo integral, 28,6% de emprego em meio período, 7,9% de desemprego por EM, 4,8% de donas de casa, 1,6% aposentadoria por idade, 15,9% de aposentadoria por invalidez, 7,9% por licença médica por EM, e 1,6% de licença médica por outros motivos. A taxa de desemprego entre os pacientes foi significativamente mais alta em comparação coma do grupo controle. Dos 38 pacientes empregados, 31% tiveram que se afastar do trabalho nos 3 meses anteriores por causa da EM, e 50% tiveram que fazer mudanças em seu trabalho para permanecer empregado. Dos 19 pacientes desempregados, 78% mencionaram que as dificuldades de locomoção foram a causa do desemprego, enquanto 52% reportaram que a deterioração cognitiva foi a causa. Conclusões Este questionário fornece um registro da situação laboral dos pacientes com EM e descreve o seu impacto no emprego do ponto de vista deles.
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INTRODUCTION: Dissociative amnesia (DA) is a retrograde amnesia characterized by an alteration in episodic memory. AIM: Establish the neural bases which underlie the development of dissociative amnesia. METHODS: Systematic and evaluative bibliographic review of qualitative type. RESULTS: The bibliography found suggested functional inhibition in the hippocampus, amygdala, temporal lobes, prefrontal cortex and thalamus. Also, hypoglycemia was observed in right cerebral cortex, at the fronto-temporal junction. An inhibition in the potential action P300 was also stated. CONCLUSIONS: There is enough evidence to say that dissociative amnesia is an objectifiable biologically based pathology. There is a need to review the current conceptualization of this syndrome and to establish new criteria that would allow us to distinguish DA from organic amnesias.
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Amnésia Retrógrada , Amnésia , Amnésia/etiologia , HumanosRESUMO
Introducción: La reserva cognitiva permite la activación de conexiones sinápticas adicionales y nuevas redes neurales frente a demandas del ambiente. Objetivo: Delimitar qué variables contribuyen a la formación de la reserva cognitiva y establecer su expresión en el desarrollo de la Enfermedad de Alzheimer. Metodología: Revisión bibliográfica sistemática y evaluativa de tipo cualitativa. Resultados: La educación, actividades de ocio, estilo de vida, estatus socioeconómico e inteligencia son las principales variables que aportan a la formación de la reserva cognitiva. Sujetos con alta reserva tienen menor prevalencia e incidencia de demencia. Aquellos que lleguen a desarrollar la enfermedad lo harán a una edad más tardía y con mayor severidad de síntomas. Conclusión: Las variables que contribuyen a la formación de la reserva cognitiva son, principalmente, variables socio-ambientales. La reserva se considera factor de protección frente a la enfermedad. Además, atrasaría la aparición de la demencia, logrando, en algunos casos, que nunca se llegue a desarrollar la enfermedad(AU)
Introduction: Cognitive reserve allows the activation of additional synaptic connections and new neural networks against environmental demands. Objective: Establish the variables that contribute to the formation of cognitive reserve and its expression in relation with Alzheimer´s Disease. Method: Systematic and evaluative review of qualitative type. Results: Education, leisure activities, lifestyle, socioeconomic status and intelligence are the main variables which contribute to the formation of cognitive reserve. Subjects with high reserve have lower prevalence and incidence of dementia. Those who develop Alzheimer´s Disease will do so at a later age and with more severe symptoms. Conclusions: The variables which contribute to the formation of cognitive reserve are, mainly, socio-environmental variables. The reserve is considered a protective factor against disease. It delays the onset of dementia avoiding, in some cases, the development of the pathology(AU)
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Humanos , Reserva Cognitiva , Doença de AlzheimerRESUMO
The technical capability of different methods to diagnose Plasmodium in maternal peripheral blood, placenta, and umbilical cord blood has not been assessed in Colombia and seldom explored in other malaria-endemic regions. We designed a study to compare the technical and the operational-economical performances of light microscopy (LM), nested polymerase chain reaction (nPCR), and histopathology (HP). In maternal blood, LM had 41% sensitivity and 100% specificity and in placental blood, 35% and 100%, respectively, compared with nPCR. In placental tissue, LM had 33% sensitivity and 95% specificity; and nPCR 47% and 77%, respectively; compared with HP. Light microscopy had the best operational-economical qualification. We concluded that nPCR and HP performed better compared with LM, but field implementation of these two techniques remains a problem. Therefore, LM is recommended as the gold standard for diagnosis of gestational malaria and placental blood infection in the field.