The first genome-wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease.

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.

Adaptación argentina del Cuestionario de Reserva Cognitiva: CRC-a / Argentinian adaptation of the Cognitive Reserve Questionnaire: CRQ-a

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.

Three verbal fluency tasks: Normative data and convergent validity in Argentines over 50 years.

Verbal fluency tasks are frequently used in neuropsychological assessment, standing out for their easy application and good sensitivity to early cognitive impairment. However, in Argentina, the availability of updated norms is limited, especially for the action fluency variant. There is also little evidence of validity. Objectives: The aim of this study was to obtain Argentine norms for three verbal fluency tasks and to analyze their convergent validity. Methods: Using a nonprobability sampling method, 303 Argentines from a nonclinical population (age mean=66.8, 50-91 years) were recruited to participate in this study. Those with medical conditions that could compromise neuropsychological performance were excluded. Three verbal fluency tasks (i.e., phonological, semantic, and action), the Montreal Cognitive Assessment (MoCA) test, and the Digit Span-WAIS III test were administered. Correlations and multiple regressions were subsequently performed. Results: Education and age significantly explained 11.8% of the variance in phonological fluency, 15.8% of the variance in semantic fluency, and 20.2% of the variance in action fluency. Hence, the normative data varied according to educational level and age group, with normal performance limit values between 9 and 14 for phonological fluency, 11 and 18 for semantic fluency, and 8 and 17 for action fluency. Positive correlations were obtained between all verbal fluency tasks, as well as between the MoCA test and the Digit Span test. Conclusions: This study supports the applicability of three verbal fluency tasks in an Argentine context by providing age- and education-corrected norms and acceptable evidence of convergent validity.

As tarefas de fluência verbal são frequentemente utilizadas na avaliação neuropsicológica, destacando-se pela facilidade de aplicação e boa sensibilidade ao comprometimento cognitivo incipiente. No entanto, na Argentina, a disponibilidade de padrões atualizados é limitada, especialmente pela variante de fluência de ações. Assim sendo, a evidência de validade é escassa. Objetivos: Obter normas argentinas para três tarefas de fluência verbal e analisar sua validade convergente. Métodos: Usando um método de amostragem não probabilística, 303 argentinos de uma população não clínica (idade M=66,8, 50­91 anos) foram recrutados para participar deste estudo. Foram excluídos aqueles com condições médicas que pudessem comprometer o desempenho neuropsicológico. Três tarefas de fluência verbal (ou seja, fonológica, semântica e ações), o teste Montreal Cognitive Assessment (MoCA) e o teste Digit Span-WAIS III foram administrados. Correlações e regressão múltipla foram realizadas posteriormente. Resultados: A escolaridade e a idade explicaram significativamente 11,8% da variância da fluência fonológica, 15,8% da variância da fluência semântica e 20,2% da variância da fluência de ações. Assim, os dados normativos variaram de acordo com a escolaridade e a faixa etária, com limite de desempenho normal entre 9 e 14 para fluência fonológica, 11 e 18 para fluência semântica e 8 e 17 para fluência de ações. Foram obtidas correlações positivas entre todas as tarefas de fluência verbal, bem como entre estas, o teste MoCA e o Digit Span. Conclusões: Este estudo apoia a aplicabilidade de três tarefas de fluência verbal no contexto argentino, fornecendo normas corrigidas por idade e educação e evidências aceitáveis de validade convergente.

Three verbal fluency tasks: Normative data and convergent validity in Argentines over 50 years / Três tarefas de fluência verbal: dados normativos e validade convergente em argentinos com mais de 50 anos

ABSTRACT Verbal fluency tasks are frequently used in neuropsychological assessment, standing out for their easy application and good sensitivity to early cognitive impairment. However, in Argentina, the availability of updated norms is limited, especially for the action fluency variant. There is also little evidence of validity. Objectives: The aim of this study was to obtain Argentine norms for three verbal fluency tasks and to analyze their convergent validity. Methods: Using a nonprobability sampling method, 303 Argentines from a nonclinical population (age mean=66.8, 50-91 years) were recruited to participate in this study. Those with medical conditions that could compromise neuropsychological performance were excluded. Three verbal fluency tasks (i.e., phonological, semantic, and action), the Montreal Cognitive Assessment (MoCA) test, and the Digit Span-WAIS III test were administered. Correlations and multiple regressions were subsequently performed. Results: Education and age significantly explained 11.8% of the variance in phonological fluency, 15.8% of the variance in semantic fluency, and 20.2% of the variance in action fluency. Hence, the normative data varied according to educational level and age group, with normal performance limit values between 9 and 14 for phonological fluency, 11 and 18 for semantic fluency, and 8 and 17 for action fluency. Positive correlations were obtained between all verbal fluency tasks, as well as between the MoCA test and the Digit Span test. Conclusions: This study supports the applicability of three verbal fluency tasks in an Argentine context by providing age- and education-corrected norms and acceptable evidence of convergent validity.

RESUMO As tarefas de fluência verbal são frequentemente utilizadas na avaliação neuropsicológica, destacando-se pela facilidade de aplicação e boa sensibilidade ao comprometimento cognitivo incipiente. No entanto, na Argentina, a disponibilidade de padrões atualizados é limitada, especialmente pela variante de fluência de ações. Assim sendo, a evidência de validade é escassa. Objetivos: Obter normas argentinas para três tarefas de fluência verbal e analisar sua validade convergente. Métodos: Usando um método de amostragem não probabilística, 303 argentinos de uma população não clínica (idade M=66,8, 50-91 anos) foram recrutados para participar deste estudo. Foram excluídos aqueles com condições médicas que pudessem comprometer o desempenho neuropsicológico. Três tarefas de fluência verbal (ou seja, fonológica, semântica e ações), o teste Montreal Cognitive Assessment (MoCA) e o teste Digit Span-WAIS III foram administrados. Correlações e regressão múltipla foram realizadas posteriormente. Resultados: A escolaridade e a idade explicaram significativamente 11,8% da variância da fluência fonológica, 15,8% da variância da fluência semântica e 20,2% da variância da fluência de ações. Assim, os dados normativos variaram de acordo com a escolaridade e a faixa etária, com limite de desempenho normal entre 9 e 14 para fluência fonológica, 11 e 18 para fluência semântica e 8 e 17 para fluência de ações. Foram obtidas correlações positivas entre todas as tarefas de fluência verbal, bem como entre estas, o teste MoCA e o Digit Span. Conclusões: Este estudo apoia a aplicabilidade de três tarefas de fluência verbal no contexto argentino, fornecendo normas corrigidas por idade e educação e evidências aceitáveis de validade convergente.

Tracking the impact of multiple sclerosis on employment status: the development of a questionnaire.

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.

Tracking the impact of multiple sclerosis on employment status: the development of a questionnaire / Avaliação do impacto da esclerose múltipla na situação laboral: desenvolvimento de um questionário

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.

Reproductive aging and executive functions in healthy women.

The aim of this study was to analyze the influence of reproductive aging on executive functions. We assessed executive functions in three groups of healthy women in the premenopausal (n = 45, mean age = 30.89, SD = 10.5), perimenopausal (n = 31, mean age = 50.06, SD = 3.6) and postmenopausal (n = 24, mean age = 63.39, SD = 6.5) phase. No differences between groups were observed in working memory, verbal fluency, inhibitory control, planning, and cognitive flexibility. However, when the analyses were repeated with participants with occupations with lower intellectual demands, perimenopausal and postmenopausal women performed worse than premenopausal women in semantic verbal fluency. This study provides important evidence to understand the effects of reproductive aging on cognitive performance in healthy women. Our findings indicate that cognitive reserve-related factors may be important to understand the differences in executive functions associated with reproductive aging.

[Systematic revision of the neural bases of dissociative amnesia]. / Las bases neurales de la Amnesia Disociativa (AD): una revisión sistemática de la bibliografía.

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.

Análisis psicométrico del cuestionario de memoria prospectiva y retrospectiva / Psychometric Analysis of the Prospective and Retrospective Memory Questionnaire

Resumen Para poder cuantificar e investigar científicamente las quejas mnésicas de los pacientes, se hace necesario contar con un instrumento adaptado y que presente análisis psicométricos adecuados. El objetivo del presente trabajo fue estudiar propiedades psicométricas de una versión argentina del Cuestionario de Memoria Prospectiva y Retrospectiva. Para ello se administró el Cuestionario de Memoria Prospectiva y Retrospectiva de forma individual a 192 participantes sanos con más de 27 puntos en el Mini Mental State Examination. La media de edad fue de 39.67 años (DE = 12.3). La media de escolaridad fue de 14.5 años (DE = 2.72). A un subgrupo de participantes (n = 45) denominado Subgrupo A, también se les administraron pruebas de memoria prospectiva y retrospectiva. El Índice Global del Cuestionario presentó una distribución normal. Según el análisis factorial exploratorio se estableció la extracción de un factor que explicó el 35.19 % de la varianza. El coeficiente α de Cronbach fue de .87. La confiabilidad estimada por el método de la división por mitades fue de .73 y de .84 luego de la corrección con la fórmula de Spearman-Brown. No hubo correlación significativa entre las respuestas del cuestionario y los test de memoria retro y prospectiva en el subgrupo A. Estos resultados permiten concluir que el Cuestionario de Memoria Prospectiva y Retrospectiva presenta adecuados índices de confiabilidad y una estructura de un solo factor. Si bien no se asocia con el rendimiento objetivo en pruebas de memoria, muestra ser apropiado para el registro de las quejas subjetivas de los pacientes en la región de estudio.

Abstract Memory complaints are the reason for consultation in many cases of neurological injuries and in the majority of aged people who attend the neurological clinic. The presence of memory complaints is a diagnostic criterion for mild cognitive impairment, for which it is necessary to have an appropriate and specific instrument, which would allow us to quantify and scientifically investigate it. The aim of the present study is to analyze the psychometric properties of an Argentine version of the Prospective and Retrospective Memory Questionnaire: the factorial structure of the test; its internal consistency; correlations of the questionnaire with an objective measurement of retro and prospective memory; and correlations of the questionnaire with affective-emotional variables. The Mexican version of the Prospective and Retrospective Memory Questionnaire was administered individually to 192 healthy participants who achieved more than 27 point in the Mini Mental State Examination. A modification was made to the syntax of two sentences in order to increase the comprehensibility. A Global, Prospective and a Retrospective Index of the questionnaire was calculated for each participant. Anxiety (the State-Trait Anxiety Inventory: STAI) and depression (the Beck's Depression Inventory-II) scales were also administered. The mean age was 39.67 years (SD = 12.3). The average of schooling was 14.5 years (SD = 2.72). We also selected a subgroup of participants (n = 45) with a mean age of 37.58 years (SD = 11.4), and an average schooling in years of 14.36 (SD = 3). In addition to the memory questionnaire, this subgroup, called the A Subgroup, was administered prospective (El Cóndor test) and retrospective (The Selective Memory Test) objective memory tests. The mean in the Global Index was 32.25 (SD = 8.49), in the Prospective Index it was 17.3 (SD = 5.01) and in the Retrospective Index it was 14.95 (SD = 4.07). The test for normality of the distribution of the Global Index Kolmogorov-Smirnov (K-S) was Z = 1.031, p = .238. In the same way, the other two scores of the questionnaire show a normal curve, K-S of the Prospective Index Z = 1.109, p = .171; K-S of the Retrospective Index Z = 1.264, p = .082. According to the exploratory factor analysis through the Maximum Likelihood extraction method, a single factor explained 35.19 % of the variance. The Cronbach's α coefficient was .87. The reliability estimated by the split-half method was .73 and .84 after correction with the Spearman-Brown formula. There was a significant positive correlation of mild degree between the Global Questionnaire Index and the STAI Trait, r = .33, p = .013, and with the IDB-II, e = .23, p = .127. There was no significant correlation between the questionnaire responses and the retro and prospective memory objective tests in the A Subgroup. The Prospective and Retrospective Memory Questionnaire presents adequate reliability indexes and a single factor structure. The results indicate that the questionnaire associates with anxiety and depression in a positive way, but not with the objective measures of retro and prospective memory, in coincidence with the literature about the relationship between cognitive complaints and cognitive tests performance. In sum, this study shows that the questionnaire is an appropriate instrument to quantify patient's memory complaints and particularly for its use in the study region. This study is the first in the country to investigate the psychometric properties of the Prospective and Retrospective Memory Questionnaire, widely used in neuropsychological clinic and research around the world. Efforts should be made to obtain normative data and validation in the pathological population of interest.

[Mini Mental State Examination (MMSE): Normative data for the Rosario Metropolitan Area, Argentina]. / Mini Mental State Examination (MMSE): valores normativos para el área metropolitana de la ciudad de Rosario, Argentina.

INTRODUCTION: It is estimated that population aging will continue to rise over the next few years, increasing cases of cognitive impairment. This requires having short, reliable and low-cost tests aimed at the early detection of cognitive disorders. The Mini Mental State Examination (MMSE) is a widely used test that allows an initial screening of cognitive disorders. Regarding this test, there is no normative data for the Rosario Metropolitan Area, Argentina, in elderly subjects. OBJECTIVE: Obtain normative values for the MMSE test (language Spanish rioplatense version) in inhabitants of the Rosario Metropolitan Area, with ages 50 years and older. MATERIALS AND METHODS: The MMSE was administered to 1126 subjects in the context of a campaign to prevent cognitive impairment. When applying the exclusion criteria, the sample was reduced to 824 subjects. RESULTS: Schooling and age influence the performance of the test, while gender had no incidence. The means and standard deviations are reported according to levels of schooling and age ranges. CONCLUSIONS: These norms indicate an unprecedented local frame of reference for the purpose of researching cognitive disorders in subjects 50 years of age and older.

[Emotional valence effect on prospective memory in relapsing remitting Multiple Sclerosis]. / Efecto de valencia emocional sobre la memoria prospectiva en pacientes con esclerosis múltiple recaídas y remisiones.

INTRODUCTION: prospective memory is the ability to remember to perform actions in the future. Currently there is no consensus about the relationship between prospective memory and emotional processing. OBJECTIVE: The aim of this work is to determine the influence of the emotional valence of prospective memory signals on prospective recall in patients diagnosed with multiple sclerosis. METHOD: 37 patients with multiple sclerosis and 32 healthy volunteers were recruited. An experimental test was made where the concurrent task consisted in a 2-back working memory activity and the prospective component consisted of remembering to press a key on the computer when an image of positive, negative or neutral emotional content appears on the screen. RESULTS: An intra-group comparison was made between the memory of emotional and neutral stimuli, and it was obtained that the differences are significant in both groups in favor of the recall of stimuli with neutral valence (Z = -3.39, p = .001 for the control group and Z = -2.63, p = .008 for multiple sclerosis). DISCUSSION: The results indicate that emotionally neutral target stimuli benefits prospective memory in normal people and in multiple sclerosis patients. The limitations of the implemented method are discussed.

Reserva Cognitiva: revisión de su conceptualización y relación con la Enfermedad de Alzheimer / Cognitive Reserve: a revision of its conceptualization and its relation with Alzheimer´s Disease

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)

Reconocimiento de emociones básicas y sus principales confusores en la demencia tipo Alzheimer / Recognition of basic emotions and their main confusers in Alzheimer-type dementia

Introducción: En la demencia tipo Alzheimer se suele observar alteración en el reconocimiento de las emociones básicas. Aunque existe cierto consenso en que las emociones básicas son seis, trabajos más recientes concluyen que puede haber una combinación entre miedo/sorpresa y asco/enojo. Este patrón no está investigado en la demencia tipo Alzheimer. Objetivos: Evaluar si los principales confusores son significativos para determinar la cantidad de emociones básicas y estudiar cuáles son los principales confusores entre emociones que se manifiestan en los pacientes con demencia tipo Alzheimer. Pacientes y métodos: Se evaluó a 28 pacientes con la batería de reconocimiento facial de emociones básicas. Resultados: Los porcentajes más elevados de elección para cada emoción, que proceden de las respuestas correctas, corresponden a los principales factores de confusión (miedo × sorpresa, sorpresa × miedo y asco × enojo). Se encontraron diferencias significativas entre miedo correcto/sorpresa × miedo, sorpresa correcta/miedo × sorpresa, enojo correcto/asco × enojo y asco correcto/enojo × asco. Conclusiones: Estos resultados estarían apoyando la teoría clásica planteada sobre la existencia de seis emociones básicas. Respecto a los confusores emocionales, nuestros resultados coinciden parcialmente con estudios que encontraron que los principales errores se presentan entre enojo/asco y sorpresa/miedo. Como excepción, en nuestra muestra encontramos que cuando la respuesta correcta es enojo, la respuesta más común de los pacientes es miedo

Introduction: An alteration in the recognition of basic emotions is usually observed in Alzheimer's type dementia. Although there is some consensus that basic emotions are six, more recent studies conclude that there may be a combination between fear/ surprise and disgust/anger. This pattern has not yet been investigated in the Alzheimer's type dementia. Aims: To evaluate if the main confusers are significant as to determine the amount of basic emotions, and to study which are the main confusers, between emotions, that are manifested in patients with Alzheimer's type dementia. Patients and methods: Twenty-eight patients were evaluated with the Battery of Facial Recognition of Basic Emotions. Results: The highest percentages of choice for each emotion, proceeding those of correct answers, correspond to the main confusers (fear × surprise, surprise × fear, and disgust × anger). Significant differences were found between fear correct/surprise × fear, surprise correct/fear × surprise, anger correct/disgust × anger, and disgust correct/anger × disgust. Conclusions: These results support the classical theory raised on the existence of six basic emotions. As regard as emotional confusers, our results coincide partially with studies which found that the main errors are between anger/disgust and surprise/fear. As an exception, we found in our sample that when the correct answer is anger, the most common response by patients is fear

Transethnic meta-analysis of rare coding variants in PLCG2, ABI3, and TREM2 supports their general contribution to Alzheimer's disease.

Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer's disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) were genotyped in 419 AD cases and 486 controls. Meta-analysis with European population was performed. Ancestry was estimated from genome-wide genotyping results. All variants show similar frequencies and odds ratios to those previously reported. Their association with AD reach statistical significance by meta-analysis. Although the Argentinian population is an admixture, variant carriers presented mainly Caucasian ancestry. Rare coding variants in TREM2, PLCG2, and ABI3 also modulate susceptibility to AD in populations from Argentina, and they may have a European heritage.

Prospective memory in patients with relapsing remitting Multiple Sclerosis

La Memoria Prospectiva (MP) es un conjunto de habilidades cognitivas que permite recordar y realizar acciones planeadas o intenciones demoradas. El objetivo de este estudio fue investigar la MP en pacientes con Esclerosis Múltiple Recaídas y Remisiones (EMRR) con dos pruebas experimentales que evalúan distintos aspectos de la MP. Se evaluaron 36 pacientes con EMRR y un grupo control de 35 voluntarios sanos (GC), apareados por edad y escolaridad. Se administró una batería de tests neuropsicológicos que incluye dos técnicas que evalúan la MP: El Cóndor y el Test de Memoria Prospectiva de Tareas Múltiples (MTPM). Los pacientes obtuvieron un puntaje más bajo que el GC (en puntaje total de El Cóndor, p = .007, d = 0.7). En el MTPM, el GC obtuvo significativamente más puntos en la Fase de Formación de la intención (p = .027, d = .5). El 63% de los pacientes versus el 88.5% del GC, autoiniciaron la intención (p = .014). Los pacientes que obtuvieron mejor puntaje en Formación, autoiniciaron más la acción proyectada (p = .012). La educación, la duración de la enfermedad y la depresión correlacionaron leve y significativamente con el Cóndor y el MTPM. La discapacidad física se relacionó sólo con la capacidad de autoiniciar del MTPM. Se concluye que la MP parece estar afectada negativamente en pacientes con EMRR. Se encontró un deterioro de la planificación y la autoiniciación de la intención. La autoniciación fue influenciada por la calidad de la planificación. Los resultados destacan la necesidad de evaluar objetivamente la MP en pacientes con EMRR para poder detectar cualquier alteración en las etapas iniciales de la enfermedad y comenzar una rehabilitación apropiada.

Prospective Memory (PM) is a set of cognitive abilities that allow us to remember to perform planned actions or delayed intentions. It requires the recall of the content of the planned task in the form of an intention to be able to execute it at the appropriate moment. Previous studies have yielded conflicting results as some show that MS patients have difficulty in remembering the content of intentions and others in the process of self-initiation of delayed intentions. Moreover, the relationship between PM and clinical variables also remains unclear. The aim of this study was to investigate PM in Relapsing-Remitting Multiple Sclerosis (RRMS) with two experimental tests that evaluate different aspects of the MP. Another aim of the current study was to analyse the relationship between PM and demographic variables and clinical variables. 36 outpatients with a diagnosis of RRMS attending to two centers specialized in multiple sclerosis clinics, were recruited. Thirty five healthy volunteers formed the contrast group (CG), matched for age, gender and education with the MS patients. A neuropsychological test battery that included two techniques for measuring PM was administered. The Condor Test consists of reading a text whilst simultaneously executing many actions. In the Multitask Prospective Memory (MTPM), the participant must remember to initiate a complex intention, which was previously planned. The test yields formation scores of the intention, initiation, plan retention capacity and finally two execution scores. A depression scale (Beck Depression Inventory, BDI-II) was administered and physical disability was revealed using the Expanded Disability Status Scale. In the RRMS group, the majority of patients (80.6%) had none or minimal signs of depression according to BDI-II classification criteria. Seventy five % of patients were in full- or half-time employment, 13.9% were unemployed or in occasional employment and 11.1% were house wives or retired on grounds of age. With respect to cognitive performance 47.2% of MS patients presented cognitive impairment. RRMS patients and the CG did not differ significantly on age and years of formal education. Groups showed no significant differences in distribution of Gender. Patients scored significantly lower than the CG on the Condor's total score, p = .007, d = .7. On the MTPM, the CG obtained significantly more points for intention formation than patients, p = .027, d = .5. Sixty-three percent of patients versus 88.5% of the CG self-initiated the intention, p = .014. Patients who obtained a higher score on Formation, self-initiated more often, p = .012. Education, disease progression and depression measure with the Beck Depression Inventory, significantly and mildly correlated with the Condor and the MTPM. Physical disability was only associated with the intention planning phase of MTPM. PM appears to be impaired in patients with RRMS. A deficit was found in planning and self-initiation of planned actions. Self-initiation was influenced by planning quality. Education, disease progression and depression were shown to influence recall and execution of future intentions. Physical disability was only associated with the intention planning phase. Some previous studies have not found a significant relationship between physical disability and cognitive measures. This study suggests that PM can be affected in patients with a low level of physical impairment. Results highlight the need for objective assessment of PM in RRMS patients to be able to detect any disorder in the initial stages of the disease and start appropriate rehabilitation. Amongst the limitations of this study, the observational, non-blind design must be acknowledged, as well as the small sample size. Also, the instruments used to assess PM are relatively new and studies of their psychometric properties are lacking. Nevertheless, the use of an instrument like The Condor is notable, given that it was developed for local population.

¿Cuántas son las emociones básicas? Estudio preliminar en una muestra de adultos mayores sanos / How many are the basic emotions? Preliminary study in a sample of healthy old adults

Hay dos posturas sobre cuáles son las emociones básicas. La clásica plantea que las mismas son asco, tristeza, alegría, enojo, miedo y sorpresa; y la postura actual concluye que las emociones básicas son tristeza, alegría y la combinación de miedo/sorpresa por un lado y enojo/asco por otro. El objetivo será estudiar las fallas en el reconocimiento de asco, enojo, miedo y sorpresa, y la relación en el tipo de error producido en una muestra de sujetos mayores sanos. Se evaluaron 18 sujetos con la batería de Reconocimiento Facial de Emociones Básicas considerando las respuestas correctas y las elecciones incorrectas. Los resultados obtenidos muestran que hay diferencias significativas entre los pares "miedo correcta-miedo por sorpresa"," sorpresa correcta-sorpresa por miedo","enojo correcta-enojo por asco" y "asco correcta-asco por enojo". Estos hallazgos apoyan la postura clásica sobre la existencia de las seis emociones básicas.

There are two main positions about what the basic emotions are. The standard posture establishes that the basic emotions are disgust, sadness, joy, anger, fear and surprise; however, the current position concludes that these basic emotions are sadness, joy and the combination of fear and surprise on one hand, and on the other, anger and disgust. The purpose will be to study the flaws on the recognition of the expressions of disgust, anger, fear and surprise, and the connection in the type of error produced in a cohort of healthy old subjects. 18 subjects were evaluated with the battery of Facial Recognition of Basic Emotions considering the correct answers and the incorrect selections. The results obtained show that there are significant differences between the pairs of ¨correct fear and fear by surprise¨, ¨correct surprise and surprise by fear¨, ¨correct anger and anger by disgust¨ and ¨correct disgust and disgust by anger¨. These findings support the standard posture about the existence of the 6 basic emotions.

[Objective and subjective prospective memory in patients with relapsing remitting multiple sclerosis]. / Memoria prospectiva objetiva y subjetiva en pacientes con esclerosis múltiple, recaídas y remisiones.

INTRODUCTION: prospective memory is the ability to remember actions in the future or remember delayed intentions. OBJECTIVE: to study the relationship between prospective memory complaints with an objective measure of prospective memory and affective-emotional variables such as depression and anxiety. SUBJECTS AND MATERIALS: 51 patients with multiple sclerosis relapsing-remitting and 46 participants in the control group were evaluated with a prospective memory task called El Condor, a questionnaire on subjective complaints of prospective memory, a depression inventory and an anxiety inventory. RESULTS: the control group performed better in El Condor than patients with multiple sclerosis, t = 6263, df = 95, p = 0.000. The prospective memory questionnaire correlated with the depression and the anxiety inventories, but not with El Condor. CONCLUSIONS: subjective prospective memory is associated with depression and anxiety and not with the objective prospective memory in a group of multiple sclerosis patients. The results indicate that the subjective and objective prospective memory must be studied as separate entities or different phenomena.

Reconocimiento facial de emociones básicas y su relación con la teoría de la mente en la variante conductual de la demencia frontotemporal / Recognition of basic emotion and their relation with theory of mind in the behavioral variant of frontotemporal dementia

Las emociones básicas están biológicamente determinadas y ligadas a conductas fundamentales para la supervivencia. Las emociones secundarias son aquellas que para su reconocimiento, requieren la elaboración cognitiva de un contexto social, por lo tanto, de la Teoría de la Mente (TdM). La TdM fue definida como la habilidad de conceptualizar estados mentales de otros individuos para explicar y predecir gran parte de su comportamiento. No es un concepto unitario, existen disociaciones entre los componentes cognitivo y el emocional de la TdM. Han sido establecidas las alteraciones en el reconocimiento facial de emociones básicas (RFEB) y en las tareas de TdM en la variante conductual de la demencia frontotemporal (DFTvc). El objetivo del trabajo que se informa fue estudiar el reconocimiento de emociones básicas o primarias y su relación con la TdM en pacientes con DFTvc. El 81% de los pacientes mostró alteraciones en por lo menos uno de los tests de RFEB y el 35% en el reconocimiento de la prosodia emocional. El subtest Denominación y el Puntaje Total Emociones mostraron correlaciones con el Test Lectura de la Mente en los Ojos, mientras que todas las tareas de RFEB correlacionaron con la tarea de falsa creencia. Se encontraron dobles disociaciones entre TdM emocional y cognitiva, con mayor afectación del componente emocional. Como conclusión se corrobora la presencia de alteraciones en el RFEB con prosodia emocional conservada en la DFTvc. La ausencia de correlaciones entre emociones básicas y secundarias parecería indicar que se trata de procesos independientes entre sí.

Behavioral variant of frontotemporal dementia (bvFTD) is associated with dramatic changes in personality. The behavioral manifestations that show these patients may be due, to one hand, to abnormal emotional processing as a result of the anatomical regions concerned, and on the other, to alterations in Theory of Mind (ToM). Basic emotions are biologically determined. Joy, sadness, anger, disgust and fear are the emotional states that have received most agreement. ToM allows representing, inferring and interpreting mental and emotional states of others. It has been suggested that it is not a unitary concept. Cognitive Theory of Mind refers to the representations regarding the cognitive status of others. Affective ToM refers to the representation of emotional and motivational states. The objectives were to study the presence of alterations in the recognition of basic emotions in the face and voice in patients with bvFTD, aswell as examine the relation ships that exist between the recognition of basic emotions and TdM, to know if there are, or not, independent processes. To study, finally, the presence of dissociations between emotional and cognitive ToM, to know which one of these types of ToM shows greater alteration in our population. 26 bvFTD patients were assessed, diagnosed on the basis of the criteria proposed by the International Consortium Behavioral Variant FTD Criteria, and 23 control subjects. A battery for facial recognition of basic emotions (FRBE) was administered, selecting 60 photographs of the Pictures of Facial Affect. Three tasks were created, comprising 60 sheets each, 10 forevery basic emotion. A test for recognition of emotional prosody was also administered. Among the ToM tests were Reading the Mind in the Eyes (RME), Faux Pas, and Firs Order False Belief Task (FOFBT). 81% of the patients showed alterations in at least one of the tests RFEB, and 35% in emotional prosody recognition. All RFEB tasks showed a significantly moderate statistical correlation with the emotional prosody task. The Naming subtest and the Total Emotions Score (RFEB) showed correlations with RME test, while all tasks RFEB correlated with FC1ºO. Finally, 10 simple dissociations between altered FRBE and preserved emotional prosody were found, and double dissociations between emotional and cognitive ToM, with greater impairment of the emotional component of ToM Discussion: A decreased performance is corroborated in the bvFTD patients group, relative to a control group, in all FRBE tasks. The recognition of emotional prosody is preserved. The presence of correlations between RME and all FRBE tasks may be explained by the neuropsychological structure of the tasks. The correlations found between RME and under standing of emotional prosody may be due to the fact that both tests assess emotional comprehension. As for the correlations found between FC1ºO and all FRBE tasks, taking into account that there seems to be no bibliographic outcome regarding to this correlation, that the neuropsychological tasks structure is completely different, and that FC1ºO showed no correlations with the emotional prosody task, it seems not possible for us to explain this result, leaving open the possibility for the development of a acceptable conclusion. Because of the absence of significant correlations between all of the recognition of basic and complex emotions tasks, we infer that the basic emotions are a qualitatively different kind of emotional state that secondary emotions, this lasts ones processed through ToM.

[Mental simulation in frontotemporal dementia]. / Simulación mental en Demencia Frontotemporal.

There is a common network for perception and execution of actions necessary for the acquisition of Theory of Mind, and the mirror neuron system could be the neural substrate. OBJECTIVE: To study the presence of apraxia and their relationship to Theory of Mind in patients with behavioral variant of Frontotemporal Dementia. METHODS: 24 patients were assessed, and the cognitive praxis assessment battery and theory of mind were administered. RESULTS: All the tasks of the cognitive praxis assessment battery showed a significant correlation with the first order False Believe task, while Faces Test showed correlations with all the battery tasks except Auditory verbal income. Significant correlations were also found between Reading the Mind in the Eyes and Income of visual objects and Imitation of familiar gestures, and between Faux Pas and Use of tools, Gestural decision and Naming by function. DISCUSSION: These findings reinforce the hypothesis that the processes of Theory of Mind are based, according to mental simulation theory, in a matching execution/observation of actions system, whose neural substrate may correspond to the mirror neuron system.

[Impact of facial emotional recognition alterations in Dementia of the Alzheimer type]. / Impacto de las alteraciones del reconocimiento facial emocional en la demencia tipo Alzheimer.

Face recognition of basic emotions is independent of other deficits in dementia of the Alzheimer type. Among these deficits, there is disagreement about what emotions are more difficult to recognize. Our aim was to study the presence of alterations in the process of facial recognition of basic emotions, and to investigate if there were differences in the recognition of each type of emotion in Alzheimer's disease. With three tests of recognition of basic facial emotions we evaluated 29 patients who had been diagnosed with dementia of the Alzheimer type and 18 control subjects. Significant differences were obtained in tests of recognition of basic facial emotions and between each. Since the amygdala, one of the brain structures responsible for emotional reaction, is affected in the early stages of this disease, our findings become relevant to understand how this alteration of the process of emotional recognition impacts the difficulties these patients have in both interpersonal relations and behavioral disorders.