Inhibition of subicular seizure-labeled c-fos+ neurons alleviates cognitive deficit in epilepsy / 中国药理学与毒理学杂志

OBJECTIVE Cognitive deficit is a com-mon comorbidity in temporal lobe epilepsy(TLE)and that is not well controlled by current therapeutics.Currently,how epileptic seizure affects cognitive performance remains largely unclear.The subiculum is the major out-put of the hippocampus,which projects to entorhinal cor-tex and other more distinct brain regions.Physiologically,the subiculum codes spatial working memory and naviga-tion information including place,speed,and trajectory.Importantly,prior studies have noted the importance of the subiculum in the beginning,spreading,and generaliz-ing process of hippocampal seizure.How seizure-activated neurons in subiculum participate in cognitive impairment remains largely elusive.METHODS In this study,we sought to label the subicular seizure-activated c-fos+ neu-rons with a special promoter with enhanced synaptic activity-responsive element E-SARE in the subiculum,combined with chemogenetics and designer receptors exclusively activated by designer drugs(DREADDs),Ca2+ fiber photometry approaches,and behavioral tasks,to reveal the role of these neurons in cognitive impairment in epilepsy.RESULTS We found that chemogenetic inhibi-tion of subicular seizure-tagged c-fos+ neurons(mainly CaMK Ⅱ α+ glutamatergic neurons)alleviates seizure generalization and improves cognitive performance in the hippocampal CA3 kindling TLE model.While inhibition of seizure-labeled c-fos+ GABAergic interneuron shows no effect on seizure and cognition.As a comparison,che-mogenetic inhibition of the whole subicular CaMK Ⅱ α+ neuron impairs cognitive function in na?ve mice in basal condition.Notably,inhibition of subicular seizure-tagged c-fos+ neurons enhances the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks.CONCLUSION Our results dem-onstrate that subicular seizure-activated c-fos+ neurons contribute to cognitive impairment in TLE,suggesting sei-zure-tagged c-fos+ neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.

The function and drug development progress of free fatty acid receptor 1 in chronic inflammatory diseases / 药学学报

As a member of G protein coupled-receptors superfamily, free fatty acid receptor 1 (FFAR1), is also known as GPR40, has been shown to regulate numerous pathophysiological processes in a variety of tissues and organs. The activated FFAR1 has a variety of biological functions. For instance, it can not only regulate metabolism of fatty acids and glucose, but also play an important role in immune inflammatory response, it may be a potential drug target for the treatment of various chronic inflammatory diseases. In this review, we focus on the recent researches of FFAR1's action in the regulation of pathophysiological processes, its molecular mechanism and new agonists development. At the same time, this review will take the discovery of series FFAR1 agonists as examples, and display the applied prospects of FFAR1.

Declínio cognitivo e uso de medicamentos na população de idosos institucionalizados de uma cidade do interior de Minas Gerais, Brasil / Neurocognitive disorders and medication used by the institutionalized elderly population of the interior of Minas Gerais, Brazil

Resumo Introdução Idosos institucionalizados possuem maiores riscos para a prescrição de cinco ou mais medicamentos, ou polifarmácia, e, por consequência, de eventos adversos, por apresentarem problemas de saúde limitantes, fragilidade e baixa funcionalidade. Esse risco é ainda maior quanto maior o declínio cognitivo. Objetivo Determinar a prevalência de declínio cognitivo (DC) e a relação com o uso de medicamentos em idosos institucionalizados. Método Estudo transversal descritivo realizado por análise de prontuários dos idosos institucionalizados portadores ou não de DC, conforme resultados de testes validados. Foram levantados os medicamentos utilizados e os medicamentos potencialmente inadequados (MPI) por meio dos Critérios de Beers (2015). Resultados Foram avaliados 88 idosos, com idade média de 77,6 (9,2) anos. A prevalência de DC foi de 75%, sendo maior no sexo feminino (82,5%, p = 0,01) e em idosos acima de 80 anos (85%, p = 0,04). Antieméticos e inibidores de bomba de prótons foram significativamente mais utilizados nos idosos com DC. A prevalência de polifarmácia foi de 69,3%, e 71 idosos (80,68%) utilizavam pelo menos um MPI, com maior prevalência do uso de MPI na faixa etária de 60 a 79 anos (p = 0,004). Os idosos que utilizavam pelo menos um MPI também usavam maior número de medicamentos (p = 0,014). Conclusão A presença de DC teve relação com a maior utilização de antieméticos e inibidores de bomba de prótons, mas não com o maior uso de MPI. Além disso, foi observada elevada prevalência de polifarmácia e MPI em prescrições dos idosos institucionalizados.

Abstract Background Institutionalized elderly are at greater risk of prescribing five or more medications and consequently of higher occurence of adverse events, as they have limiting health problems, frailty and low functionality. This risk is even greater if they also have cognitive decline. Objective To determine the prevalence of cognitive disorders (CDs) and its association with the medication used by the institutionalized elderly population of the interior of Minas Gerais, Brazil. Method Descriptive cross-sectional study for analysis of medical records of institutionalized elderly with or without CDs, according to validated tests. The medicine used and the potentially inappropriate medications (PIMs) were determined as per the Beers criteria (2015). Results Eighty eight elderly people, with mean age of 77.6 (9.2) years, were included. CD prevalence was 75% higher in females (82.5%, p = 0.01) and in older age groups, with 80 years and above (85%, p = 0.04). Antiemetics and proton pump inhibitors were significantly more used by the elderly with CDs. The prevalence of polypharmacy was 69.3%, 71 elderlies (80.7%) used at least one PIM, and a higher prevalence of PIM use was observed in elderly people of 60 to 79 years old (p = 0.004). The elderly who used at least one PIM was also observed to use a higher number of medications (p = 0.014). Conclusion CDs was found to be related to the higher use of antiemetics and proton pump inhibitors, but not to the use of PIMs in regards to the institutionalized elderlies. Furthermore, a high prevalence of polypharmacy and PIMs were detected in the prescriptions of the institutionalized elderly subjects.

Verbal learning in schizophrenia in remission, first-degree relatives, and correlation to symptoms

Background: Cognitive impairments are fundamental in schizophrenia with verbal memory impairments commonly occurring not only in patients but also in unaffected genetically susceptible individuals. Deficits in verbal memory produce difficulty in problem-solving, emotional distress, and worsening of daily life skills resulting in a poor quality of life. Objectives: This study aims to evaluate the verbal memory in unaffected first-degree relatives of patients of schizophrenia in comparison to healthy controls as well as patients of schizophrenia in remission and to find correlation to symptom domains. Methods: It was a hospital-based, descriptive, cross-sectional case-control study. Three groups (n=40, each group) of patients, first-degree relatives, and controls were taken. Subjects were screened for mental retardation and remission was ascertained in the patient group by the Positive and Negative Syndrome Scale (PANSS). Rye’s Auditory Verbal Learning (RAVL) test was used to assess verbal leaning. Results: Verbal memory impairments were significant both in patients and unaffected first-degree relatives. Further, these impairments showed a strong correlation to negative symptoms. Conclusion: Significant (p<0.05) verbal learning impairments were noted in patients and first-degree relatives which showed a correlation to negative symptoms.

Factores asociados al funcionamiento global en pacientes con esquizofrenia de un hospital general del Perú / Factors associated with overall functioning in patients with schizophrenia in a general hospital in Peru

RESUMEN Objetivo: Evaluar la influencia de los factores asociados al funcionamiento global en pacientes con esquizofrenia que acuden a la consulta externa del Hospital Nacional de la Policía "Luis Nicasio Saenz" durante los arios 2018-2019. Metodología: Estudio cuantitativo observacional de tipo descriptivo transversal correlacional. La muestra fue por conveniencia y estuvo constituida por 53 pacientes con esquizofrenia. Se utilizó el Functioning Assessment Short Test (FAST) para valorar el funcionamiento global, el Screen for Cognitive Impairment (SCIP) para el funcionamiento cognitivo y una ficha de recolección de datos sociodemográficos y de historia de la enfermedad. Resultados: Se encontró que 34 (62.2%) pacientes fueron varones; 52 (98.1%), solteros; 39 (73.6%), sin un trabajo actual. Se halló un peor funcionamiento global en los pacientes con menor nivel educativo (p = 0.005) y sin un trabajo actual (p = 0.004). El total del FAST se correlacionó con el tiempo de la enfermedad (p=0.334, p < 0.05), el número de episodios psicóticos previos (p=0.354, p< 0.01), el puntaje total del SCIP (p=0.542, p< 0.01) y su dimensión memoria de trabajo (VMT) (p=-0.523, p<0.05). En el modelo de regresión lineal múltiple se encontró que las variables que más influyeron en el FAST fueron el puntaje total del SCIP (Beta = -0.528) y el número de episodios psicóticos previos (Beta = 0.278). Conclusión: Los factores asociados que más influyen en el funcionamiento global en esta muestra de pacientes con esquizofrenia peruanos son el funcionamiento cognitivo y el número de episodios psicóticos previos.

ABSTRACT Objective: To evaluate the influence of the factors associated with overall functioning in patients with schizophrenia who attended the outpatient clinic of the Hospital Nacional de la Policía [National Police Hospital] "Luis Nicasio Saenz" in 2018-2019. Methodology: Non-experimental quantitative study of a descriptive cross-sectional correlational type. Convenience sampling was carried out, and consisted of 53 patients with schizophrenia. Functioning Assessment Short Test (FAST) was used to assess overall functioning, the Screen for Cognitive Impairment in Psychiatry (SCIP) for cognitive functioning, and a data collection sheet with sociodemographic data and a history of the disease. Results: It was found that 34 (62.2%) patients were male; 52 (98.1%), single; 39, (73.6%) without a current job. We found worse overall functioning in patients with a lower educational level (p = 0.005) and without a current job (p = 0.004). The total FAST was correlated with the time of the disease (p = 0.334, p <0.05), the number of previous psychotic episodes (p = 0.354, p <0.01), the total SCIP score (p = 0.542, p <0.01) and their working memory dimension (VMT) (p = -0.523, p < 0.05). In the multiple linear regression model, it was found that the variables that most influenced the FAST were the total SCIP score (Beta = -0.528) and the number of previous psychotic episodes (Beta = 0.278). Conclusion: The associated factors that most influence overall functioning in this sample of Peruvian patients with schizophrenia are cognitive functioning and the number of previous psychotic episodes.

Synaptic pruning mediated by glia in Alzheimer's disease / 药学学报

Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive impairment. To date, however, no disease-modifying strategies to prevent or cure AD exist. Synapses are involved in the connection of neurons and present as the key component for the memory and other neural activities. Synapse loss is a critical hallmark of AD pathology. In brain, glia cells, including microglia and astrocytes, are a group of highly specific cell types other than neurons. Microglia and astrocytes play a key role in maintaining the healthy neural circuit and regulating synaptic plasticity. Under development and physiological conditions, glial cells contribute to construct and maintain mature central neural networks via synaptic pruning. However, during AD pathogenesis, glial cells engulf synapses excessively, which leads to synapse loss, neuronal dysfunction, and cognitive impairment. Here, we review recent advances in our understanding of the underlying mechanisms for glia-mediated synaptic pruning in AD, and provide a novel strategy for the development of AD drugs.

Retraso del diagnóstico en un paciente con Hakim Adams / Delayed diagnosis in a patient with Hakim Adams

La hidrocefalia normotensiva es una patología caracterizada por alteración en la marcha, incontencia vesical, déficit cognitivo, hallazgos imagenológicos de ventriculomegalia comunicante y, presión normal de líquido cefalorraquídeo. Por la ambigüedad de sus síntomas y por la falta de criterios imagenológicos muy concluyentes es una patología de difícil diagnóstico inicial; el paciente muchas veces acude a distintos especialistas por síntomas aislados hasta que se relacionan los mismos y, se deriva el caso a Neurología / Neurocirugía. Se presenta el caso de un paciente de 65 años que presentó un cuadro de 2 años de evolución de incontinencia urinaria tratado como alteración de la micción secundaria a una hiperplasia prostática benigna sin mejoría alguna en ese intervalo de tiempo. Luego se agregó al cuadro una alteración en la marcha que fue poco valorada por el paciente y su entorno, sin ser conscientes del déficit cognitivo hasta que se realizó la evaluación neuropsicológica. Si bien el paciente presentaba la triada clásica que caracteriza a la hidrocefalia de presión normal, no fue hasta dos años luego del inicio del cuadro que se llegó al diagnóstico y, fue intervenido quirúrgicamente. Se colocó una válvula de derivación ventrículo peritoneal de presión media, con la cual presentó una evolución favorable y, resolución absoluta de los síntomas.

Normotensive hydrocephalus is a pathology characterized by impaired gait, bladder incontinence, cognitive deficit, images findings of communicating ventriculomegaly and normal cerebrospinal fluid pressure. Due to the ambiguity of its symptoms and the lack of conclusive images criteria, it is difficult initial diagnosis pathology; the patient often goes to different specialists for isolated symptoms until they are related, and the case is referred to Neurology / Neurosurgery. We present the case of a patient who presented a 2-year history of urinary incontinence treated as an alteration of urination secondary to a benign prostatic hyperplasia without any improvement in that time interval. Then a gait disturbance was added to the picture that was poorly valued by the patient and his environment, without being aware of the cognitive deficit until a neuropsychological evaluation. Although the patient presented the classic triad that characterizes normal pressure hydrocephalus, it was not until two years after the onset of the condition that the diagnosis was reached and underwent surgery. A peritoneal ventricular shunt of medium pressure was placed, presenting a favorable evaluation and complete resolution of symptoms.

Prevalência e fatores associados ao deficit cognitivo em idosos na comunidade / Prevalence and associated factors to the cognitive deficit in community-dwelling elderly

Resumo Objetivo Estimar a prevalência do deficit cognitivo e verificar associações com variáveis sociodemográficas e de saúde em idosos de Unidades Básicas de Saúde (UBSs) de uma cidade no interior do nordeste brasileiro. Método Estudo transversal de prevalência e associação a respeito da população idosa. Os instrumentos utilizados para coleta dos dados foram Miniexame do Estado Mental (função cognitiva), Escala de Depressão Geriátrica Abreviada (sintomas depressivos), Escala de Lawton (capacidade funcional), Miniavaliação Nutricional (estado nutricional) e teste Timed Get Up and Go (risco de quedas). A associação bivariada entre o deficit cognitivo e as variáveis independentes foi avaliada pelo teste qui-quadrado. A análise multivariada foi feita usando um modelo de regressão logística com as razões de prevalência (RP) e intervalo de confiança de 95% (IC95%). Resultados Foram avaliados 818 idosos. A prevalência de deficit cognitivo foi de 65,9% (IC95%=62,50 - 69,10). Ao compor o modelo de análise multivariada, verificou-se maior ocorrência de deficit cognitivo em indivíduos mais velhos (RP=1,48; IC95%=1,07-2,05), funcionalmente dependentes (RP=3,27; IC95%=2,01-5,10), analfabetos (RP=1,66; IC95%=1,15-2,40) e com risco de desnutrição ou desnutridos (RP=2,09; IC95%=1,47-2,96). Conclusão O presente trabalho evidenciou alta prevalência de deficit cognitivo e que foi associada à idade, escolaridade, capacidade funcional e estado nutricional. É possível questionar se isso se deve à grande quantidade de pessoas com comprometimento cognitivo leve sem demência com remissão posterior dos sintomas, ou pela ocorrência de demência de início precoce.

Abstract Objective To estimate the prevalence of cognitive deficit and verify associations with sociodemographic and individual health variables in senior patients from units in the primary health system. Method Prevalence and association study about the elderly population. The instruments used were the Mini-Mental State Examination (cognitive function), Shorten Geriatric Depression Scale (depression symptoms), Lawton Scale (functional capacity), Mini-Nutritional Assessment (nutritional state), and Timed Up and Go Test (fall risk). The association between cognitive deficit and independent variables was verified by the Chi-square test. Multivariate analysis was performed using a logistic regression model with the prevalence ratio (PR) and 95% confidence interval (95%CI). Results The data were collected from 818 old-aged patients. The cognitive deficit had a prevalence of 65.9% (95%CI= 62.50-69.10). In the multivariate analysis model, it was verified a larger occurrence of cognitive deficit individuals, with risks of malnutrition (PR=2.09; CI95%=1.47-2.96), illiteracy (PR=1.66; 95%CI=1.15-2.40), dependents (PR=3.27; 95%CI=2.01-5.10), and with more than 70 years old (PR=1.48; 95%CI=1.07-2.05). Conclusion The present study showed a high prevalence of cognitive deficit and was associated with age, education, functional capacity, and nutritional status. It is possible to question if it is caused by the big amount of people with mild cognitive impairment without dementia with posterior remission of the symptoms, or by the occurrence of early start dementia.

Complejo de esclerosis tuberosa: perfil neuropsicológico y propuesta de intervención / Tuberous Sclerosis Complex: neuropsychological profile and intervention proposal

El Complejo de Esclerosis Tuberosa (CET) es un trastorno genético de heren-cia autosómica dominante causado por la mutación en uno de los genes TSC1 o TSC2. Los pacientes con una afectación CET grave de tipo neurológica posible-mente presentarán epilepsia, discapacidad intelectual, problemas específicos del aprendizaje y trastornos de la conducta, por lo que la evaluación neuropsicológica en individuos con esta patología cobra un carácter importante al proporcionar información sobre los déficits cognitivos que subyacen en la afectación cerebral, que alteran el funcionamiento intelectual y los aspectos adaptativos. El actual tra-bajo presenta el perfil de una paciente adulta femenina con antecedente de CET, epilepsia y discapacidad intelectual, así como la descripción de una propuesta de intervención neuropsicológica basada en el funcionamiento ejecutivo dorsolateral.

Tuberous Sclerosis Complex (TSC) is an autosomal dominant inherited genetic disorder caused by mutation in one of the TSC1 or TSC2 genes. Patients with severe neurological-type CET involvement may have epilepsy, intellectual disability, specific learning problems, and behavioral disorders. For this reason, the neuropsychological evaluation in individuals with this pathology becomes an important character by providing information on the cognitive deficits that underlie brain involvement that alter intellectual functioning and adaptive aspects. The current work presents the cognitive profile of a female adult patient with a history of TSC, epilepsy and intellectual disability and the description of a proposed neuropsychological intervention based on dorsolateral executive functioning.

Rastreio cognitivo em estruturas residenciais para pessoas idosas no Concelho de Miranda do Corvo, Portugal / Cognitive screening for elderly people in long-term care institutions in the Miranda do Corvo municipality, Portugal

Resumo Com o objetivo de efetuar o rastreio do perfil cognitivo dos residentes em Estruturas Para Idosos no Concelho de Miranda do Corvo, avaliaram-se 174 participantes recorrendo ao Mini-Mental State Examination (MMSE) (n=96) e ao diagnóstico de demência reportado nos prontuários dos pacientes (n=78). Verificou-se, através do MMSE, que 41,7% dos inquiridos apresentavam pontuações sugestivas de déficit cognitivo. Adicionando a este resultado o diagnóstico de demência reportado nos prontuários dos pacientes, a percentagem subiu para 67,8% (n=118). A comparação dos nossos resultados com os obtidos a nível nacional revelou que essa percentagem foi significativamente superior (p<0,001). A escolaridade foi um fator preditivo da pontuação do MMSE (p=0,001). Conclui-se que a elevada prevalência de suspeita de déficit cognitivo e de demência revelada no nosso estudo deve remeter para a reflexão sobre a adequação dos cuidados prestados e sobre a ausência/escassez de programas de estimulação cognitiva nas estruturas residenciais para idosos. Nesse sentido, torna-se imperativo implementar avaliação cognitiva regular e instituir programas de intervenção que promovam a conservação e melhoria do funcionamento cognitivo em pessoas idosas institucionalizadas de zonas desfavorecidas.

Abstract This study aimed to screen the cognitive profile elderly people living in long-term care institutions in the municipality of Miranda do Corvo by evaluating 174 participants with the Mini Mental State Examination (MMSE) (n=96) and the clinical dementia diagnosis (n=78). According to the MMSE, 41.7% of respondents had scores suggestive of cognitive impairment. The percentage rose to 67.8% (n=118) by adding the diagnosis of dementia reported in individual medical records to this result. The comparison of our results with those obtained nationwide showed that this proportion was significantly higher (p<0.001). The educational level was a predictive factor for MMSE scores (p=0.001). We can conclude that the high prevalence of suspected cognitive impairment and dementia revealed in our study should lead us to reflect on the quality of care provided and on the lack/scarcity of cognitive stimulation programs in long-term care institutions for seniors. Thus, it is imperative to implement regular cognitive assessment and to apply intervention programs for the preservation and improvement of the cognitive functioning of institutionalized elderly of deprived areas.

Secuelas neurofuncionales por déficit de cobalamina (vitamina B12) en un adulto joven: estudio de caso / Neurofunctional sequelae by cobalamin deficiency (vitamin B12) in a young adult: case study / Sequelas neurofuncionales por défice de cobalamina (vitamina B12) em um adulto jovem: estudo de caso

El objetivo del presente artículo fue caracterizar las principales alteraciones neurofuncionales en un adulto joven en condición de déficit de vitamina B12. Para esto, se utilizó un estudio de caso único con enfoque cuantitativo, de corte descriptivo. Los resultados arrojados por las pruebas, dieron cuenta de alteraciones en la memoria de trabajo, para la memoria verbal y visual, con una mayor afectación en la memoria de contenido verbal, además de dificultades en comprensión y en la fluidez verbal y fonológica. De igual manera, el sujeto presentó deterioro en la atención sostenida, selectiva y alternante, y se dieron fenómenos como las perseveraciones, intrusiones, errores de denominación y alteraciones en la planeación y organización, esto referente a las funciones ejecutivas. Por otra parte, no se halló compromiso en la capacidad de repetición, ni dificultades en las praxias, grafestesias y esterognosias, sumado a la ausencia de signos negativos para los componentes generales de la Teoría de la Mente.

The aim of the present article was to characterize the main neurofunctional alterations of vitamin B12 deficits in young adults. To do this, we used a single case study with a quantitative approach, of descriptive criteria. The results of the tests showed alterations in working memory, for verbal and visual memory, with a greater involvement in the memory of verbal content, as well as difficulties in comprehension of verbal and phonological fluency. Likewise, the subject presented deterioration in sustained, selective and alternating attention, and phenomenas such as: perseverations, intrusions, naming errors and alterations in planning and organization, this refers to executive functions. On the other hand, there was no compromise in the ability to repeat, nor difficulties in praxis, graphesthesia and steerognosies, and this is added to the absence of negative signs for the general components of Theory of Mind.

O objetivo do presente artigo foi caracterizar as principais alterações neurofuncionales num jovem adulto em condição de deficiência de vitamina B12. Para isto, utilizouse um estudo de caso único com abordagem quantitativa, de corte descritivo. Os resultados para as provas, deram conta de distúrbios na memória de trabalho, para a memória verbal e visual, com uma maior envolvimento na memória de conteúdo verbal, além de dificuldades na compreensão ena fluidez verbal e fonológica. Da mesma forma, o sujeito apresentou deterioração na atenção sustentada, seletiva e alternada, e deu-se fenômenos como as perseverações, intrusões, erros de denominação e alterações no planejamento e organização, isto se refere às funções executivas. Por outro lado, não foi encontrado nenhum compromisso na capacidade de repetição, nem dificuldades nas praxias, grafestesias e esterognosias, somado à ausência de sinais negativos para os componentes gerais da teoria da mente.

Perfiles cognitivos en pacientes con hipotiroidismo congénito detectado y tratado en forma temprana / Cognitive profiles of patients with early detected and treated congenital hypothyroidism

Introducción. Los niños con hipotiroidismo congénito (HC) detectados por pesquisa neonatal y tratados adecuadamente presentarían defectos cognitivos leves. Objetivos. Evaluar el coeficiente intelectual de niños con HC e identificar la presencia de déficits cognitivos específicos. Población y métodos. Se seleccionó un grupo de 60 niños con HC, de entre 9 y 10 años, detectados por pesquisa neonatal y tratados adecuadamente desde el primer mes de vida, y se comparó con un grupo control de 60 niños sin HC de la misma edad. Fueron criterios de inclusión la ausencia de patología intercurrente, concurrencia a jornada escolar simple y padres con nivel escolar mínimo de secundaria completa. En entrevistas individuales, se administraron la escala de inteligencia Wechsler para niños, tercera edición, figura compleja de Rey, test Woodcock-Muñoz revisado, Conners Continuous Performance Test II, test Illinois de aptitudes psicolingüísticas, test de fluidez verbal, test de cubos de Knox, Trail Making Test, test de caras y test de los 5 dígitos. Se realizó el análisis estadístico con pruebas t de Student (muestras independientes) ajustado por Bonferroni (p < 0,002). Resultados. Aun dentro del rango normal promedio, hubo diferencias significativas entre grupos en el coeficiente intelectual total y de ejecución (tamaño del efecto pequeño y moderado, respectivamente). Los niños hipotiroideos presentaron, en el área de ejecución, significativamente menor desempeño en velocidad de procesamiento, tiempos de reacción, atención, flexibilidad cognitiva, visoconstrucción y memoria a largo plazo. No hubo diferencia significativa entre grupos en el área verbal. Conclusiones. Los niños hipotiroideos congénitos, sin discapacidad mental, presentaron defectos cognitivos leves, que deben ser tenidos en cuenta para su atención integral.

Introduction. Children with congenital hypothyroidism (CH) detected by newborn screening and adequately treated may have mild cognitive deficits. Objectives. To assess the intelligence quotient of children with CH and identify the presence of specific cognitive deficits. Population and methods. A group of 60 children with CH detected by newborn screening, who were aged 9-10 years old and received adequate treatment since their first month of life was selected and compared to a control group of 60 children without CH in the same age range. Inclusion criteria: children without concurrent diseases, who were attending school in a single shift, and whose parents had at least completed secondary education. The following tests were administered during individual interviews: the Wechsler Intelligence Scale for Children (third edition), the Rey complex figure test, the Woodcock-Muñoz revised test, the Conners Continuous Performance Test II, the Illinois Test of Psycholinguistic Abilities, the verbal fluency test, the Knox Cube Test, the Trail Making Test, the faces test, and the 5 digit test. The statistical analysis was done using Student's t tests (for independent samples) with Bonferroni's correction (p < 0.002). Results. Even within the normal average range, significant differences were observed between both groups in terms of total intelligence quotient and performance intelligence quotient (small and moderate effect sizes, respectively). In terms of performance, children with hypothyroidism had a significantly poorer performance in processing speed, reaction times, attention, cognitive flexibility, visuoconstruction, and long-term memory. No significant differences were found between both groups in the verbal area. Conclusions. Children with congenital hypothyroidism and without mental disability had mild cognitive deficits, which should be taken into account for a comprehensive patient care.

Research progress of antipsychotics / 药学学报

Epidemiology indicates that schizophrenia affects approximately 8‰ of the world's population. The atypical (second and third generation) antipsychotics generally endowed with D2/5-HTHT2 receptors antagonism properties are commonly used as first-line drugs for the treatment of schizophrenia presently. They have been proven effective in the treatment of positive and negative symptoms of schizophrenia, but they are largely ineffective in the treatment of cognitive deficit. Moreover, the atypical antipsychotics are usually associated with cardiovascular and metabolic side effects such as QT prolongation and weight gain. To develop more potent antipsychotics with fewer side effects, more targets have been identified such as D3, glutamate, H3 receptors and PDE10A in recent years. Herein, the research progress of antipsychotics is reviewed.

Valoración del estado cognitivo en el adulto mayor: áreas más afectadas / Assessment of cognitive status in the elderly: most affected areas

Introducción: La alteración del estado cognitivo vuelve al adulto mayor dependiente, limita su autocuidado y genera cuidados a largo plazo. Objetivo: Valorar el estado cognitivo del adulto mayor, identificar las capacidades cognitivas más afectadas según género, edad y escolaridad. Metodología: Se realizó un estudio descriptivo transversal no probabilístico con enfoque cuantitativo en una casa de rehabilitación y reposo en México D.F. La población fue de 78 adultos mayores de 60 años (41 mujeres y 37 hombres). Se valoró el estado cognitivo con ayuda del (Mini-Mental) cuyo objetivo es establecer un diagnóstico presuntivo de las funciones cognitivas. Se utilizaron cuatro variables: estado cognitivo, género, edad y escolaridad. Resultados: De las 78 personas el 47.4% fueron hombres y el 52.6% mujeres, el 40.5% tienen de 60 a 69 años, el 32.1% obtuvo un título universitario, el 23.1% de la población mostro deterioro severo, el 44.9% deterioro leve. Las áreas más afectadas fueron: abstracción (cálculo) con 46.2% de deterioro severo, memoria a corto plazo con 47.4% de deterioro severo y lenguaje con 11.5% de deterioro. Conclusiones: Evaluar y detectar alteraciones cognitivas permitirá concientizar a la familia, buscar modelos de atención y cuidado fortaleciendo el bienestar del adulto mayor.

Introduction: Altered mental state becomes the elderly dependent, limited self-care and generates long-term care. Objective: To assess the cognitive status of the elderly and identify the cognitive abilities most affected by gender, age and education. Methodology: A cross-sectional study of non-probabilistic descriptive quantitative approach was conducted in a rehabilitation and rest house in Mexico DF. The sample was 78 adults over 60 years, 41 women and 37 men. We made an assessment of cognitive status using the Minimental which objective to establish a diagnosis of cognitive functions. Were considered four variables: Cognitive status, gender, age and education. Results: Of the 78 people found that 47.4% were male and 52.6% female, 40.5% was found in the group of 60-69 years, 32.1% of seniors earned a university degree in 23.1% of the population severe deterioration was observed, 44.9% mild deterioration. The Areas with more impairment were the area of abstraction (calculation) 46.2% had severe deterioration in the area of short-term memory 47.4% severe cognitive impairment was found and in the language area was 11.5%. Conclusions: Evaluate and detect cognitive impairment will allow awareness to the family, look for models of care and attention to strengthen the welfare of the elderly.

Percepción subjetiva del déficit cognitivo y desempeño en una batería neuropsicológica en personas con esquizofrenia / Subjective perception of cognitive deficit and performance in a neuropsychological battery in people with schizophrenia

Los resultados contradictorios de las investigaciones respecto a la capacidad de las personas con esquizofrenia, para percibir sus déficits cognitivos, podrían explicarse por factores metodológicos, en especial, por diferencias en los instrumentos empleados y las funciones evaluadas. Esta investigación reporta los resultados obtenidos comparando directamente, el desempeño cognitivo, con el reporte subjetivo de dificultades cotidianas derivadas del mismo. Método: Participaron 57 personas con diagnóstico de esquizofrenia, entre 18 y 55 años, clínicamente estables y con un déficit cognitivo demostrado. El funcionamiento cognitivo fue evaluado con la batería CogState, mientras que la percepción de los pacientes fue registrada con la Escala Subjetiva para Investigar la Cognición en la Esquizofrenia (SSTICS). Se correlacionó específicamente, los desempeños en cada función cognitiva con los ítems correspondientes de la escala. Resultados: Los puntajes reportados en la escala SSTICS, indican un grado de dificultad leve a moderado, en todos los funciones evaluadas, sin diferencias por edad o género. El análisis de correlación entre la batería Cogstate y la escala SSTICS, sólo muestra una asociación directa, estadísticamente significativa, entre las preguntas referidas a dificultades en la vida diaria y las evaluaciones de atención y resolución de problemas. Al examinar por funciones cognitivas específicas y puntación total en la SSTICS, no se encuentran asociaciones significativas. Discusión: La falta de correlación entre el desempeño en la batería Cogstate y la autoevaluación en la encuesta SSTICS, podría explicarse por la falta de percepción de los pacientes de sus déficits cognitivos...

The contradictory results of investigations into the ability of persons with schizophrenia, to perceive their cognitive deficits, could be explained by methodological factors, especially, differences in the instruments used and the functions evaluated. This study reports the results obtained by directly comparing, cognitive performance, and subjective report of daily difficulties arising from the same in a group of people with schizophrenia. Methods: 57 participants with a diagnosis of schizophrenia, between 18 and 55 years, clinically stable and with a demonstrated cognitive deficit. Cognitive performance was evaluated with the CogState battery, while the perception of patients was registered with the SSTICS scale. The performance in each cognitive function was specifically, correlated with the corresponding items of the scale. Results: The scores reported in the SSTICS scale, indicate a degree of mild to moderate difficulty, in all the functions assessed, without differences by age or gender. The analysis of correlation between the Cogstate battery and SSTICS scale, only shows a direct, statistically significant association, between the questions referring to difficulties in daily life and evaluations of attention and resolution of problems. Examining specific cognitive functions and the total score in the SSTICS, did not yield any significant associations. Discussion: The lack of correlation between the performance in the Cogstate battery and self-evaluation in the SSTICS scale, could be explained by the lack of perception of patients of their cognitive deficits...

Modulation of cerebral malaria by curcumin as an adjunctive therapy

Cerebral malaria is the most severe and rapidly fatal neurological complication of Plasmodium falciparum infection and responsible for more than two million deaths annually. The current therapy is inadequate in terms of reducing mortality or post-treatment symptoms such as neurological and cognitive deficits. The pathophysiology of cerebral malaria is quite complex and offers a variety of targets which remain to be exploited for better therapeutic outcome. The present review discusses on the pathophysiology of cerebral malaria with particular emphasis on scope and promises of curcumin as an adjunctive therapy to improve survival and overcome neurological deficits.

Cognitive rehabilitation and head injury / Reabilitação cognitiva no traumatismo cranioencefálico

The present study aims to present the cognitive benefits and the importance of the use of compensatory strategies for a better functional adaptation and for the quality of life in patient that underwent cognitive rehabilitation (CR), after a severe cranioencephalic trauma. A 24 years-old male carried out neuropsychological evaluation after eight months of car accident. CR program developed for one year and four months, with constant establishment of goal, cognitive training and use of compensatory strategies for the difficulties in the daily tasks. It is possible to notice through the neuropsychological revaluation that the cognitive profits with the CR were global, including reaching expected performance for his age group in some functions. There was also observed, reach of great part of the stipulated goals, adaptation to the difficulties in the daily activities through the use of the strategies and consequently improves in the quality of life. This is a case that shows the contribution of the CR for patients who suffered CET, even after the process of spontaneous recuperation, in a moment that, from the clinical point of view, constant sequels keeps in mind.

O presente estudo tem como objetivo apresentar os benefícios cognitivos e a importância do uso de estratégias compensatórias, para uma melhor adaptação funcional e para a qualidade de vida, em um paciente que foi submetido à reabilitação cognitiva (RC) após um trauma cranioencefálico grave. Após oito meses do acidente automobilístico, um jovem de 24 anos foi submetido a uma avaliação neuropsicológica, iniciando-se, em seguida, um programa de RC. Este programa foi realizado durante um ano e quatro meses, com o treino cognitivo, o uso de estratégias compensatórias para as dificuldades nas tarefas diárias e com constante avaliação das metas. Foi possível observar por meio da reavaliação neuropsicológica que os lucros com a RC foram globais, alcançando o desempenho esperado para a sua idade em algumas funções cognitivas. Pode-se observar também o alcance de grande parte das metas estipuladas, melhor adaptação às dificuldades anteriormente apresentadas nas atividades diárias com o uso das estratégias e, consequentemente, melhora na qualidade de vida. Este é um caso que mostra a contribuição do RC para pacientes que sofreram TCE, mesmo após o processo de recuperação espontânea, em um momento que, do ponto de vista clínico, já seriam consideradas sequelas.

Neurophysicological findings after anterior communicant artery aneurysm surgery (AcomA): a literature review / Alterações neuropsicológicas após cirurgia de aneurisma de artéria comunicante anterior

Objective: To present a literature review of cognitive disorders in patients operated on anterior communicant artery aneurysm (AcomA). Methods: Literature was searched (PubMed) from 1996 to 2009 using "aneurysm", "surgery" and "neuropsychological evaluation" as keywords. Only papers describing postoperative neuropsychological findings were included in this review. Results: A great deal of the retrieved papers noted alterations of intellectual, executive functions and memory (episodic and semantic). Some authors explain these memory deficits as secondary to the executive dysfunction or ischemia in related areas. Other papers noted secondary alterations after temporary clipping (worse alert and selective attention). Majority of deficits improve with time, however, long periods of temporary clip are associated with persistent deficits. Conclusion: The studies are scarce in the Brazilian literature that valued thoroughly neuropsychological alterations after AcomA surgery, correlating data with the resection or not of the straight gyrus, with the presence or not of vasoespasm and alterations in the quality of life. There were not found, up to the moment, studies in which these patients were valued pre and post surgery.

Objetivo: Apresentar extensa revisão de literatura sobre alterações cognitivas em pacientes operados de aneurismas de artéria comunicante posterior. Métodos: Realizou-se pesquisa na base de dados PubMed utilizando as palavras-chave "aneurysm", "surgery" e "neuropsychological evaluation". Somente trabalhos publicados entre 1996 e 2009 descrevendo achados pós-operatórios foram incluídos. Resultados: Grande número de artigos descrevem alterações de funções intelectuais, executivas e de memória (episódica e semântica). Déficits de memória podem ser secundários à disfunção executiva ou isquemia. Outros artigos relatam alterações ocorridas após clipagem temporária, principalmente na função de atenção seletiva. A maioria dos déficits melhora com o tempo, contudo períodos prolongados de clipagem temporária têm sido associados com disfunções permanentes. Conclusão: Não há estudos até o momento incluindo avaliações pré e pós-operatórias e os estudos em literatura nacional são escassos. O papel da hemorragia, do vasoespasmo, da hidrocefalia, da ressecção do giro reto e da clipagem temporária ainda não está estabelecido.

Cerebral Perfusion Abnormalities in Cases of Down Syndrome.

A SPECT (single photon emission computed tomography using Tc-99m HMPAO) study of brain with segmental quantitative analysis was conducted to access the cerebral perfusion in cases of Down’s syndrome (DS). Varying level of brain hypo-perfusion was documented, probably explaining the neurophysiologic basis of cognitive and neuropsychological deficits, which are not well understood in DS.

Animal models of intellectual disability: towards a translational approach

Intellectual disability is a prevalent form of cognitive impairment, affecting 2-3 percent of the general population. It is a daunting societal problem characterized by significant limitations both in intellectual functioning and in adaptive behavior as expressed in conceptual, social and practical adaptive skills. Intellectual disability is a clinically important disorder for which the etiology and pathogenesis are still poorly understood. Moreover, although tremendous progress has been made, pharmacological intervention is still currently non-existent and therapeutic strategies remain limited. Studies in humans have a very limited capacity to explain basic mechanisms of this condition. In this sense, animal models have been invaluable in intellectual disability investigation. Certainly, a great deal of the knowledge that has improved our understanding of several pathologies has derived from appropriate animal models. Moreover, to improve human health, scientific discoveries must be translated into practical applications. Translational research specifically aims at taking basic scientific discoveries and best practices to benefit the lives of people in our communities. In this context, the challenge that basic science research needs to meet is to make use of a comparative approach to benefit the most from what each animal model can tell us. Intellectual disability results from many different genetic and environmental insults. Taken together, the present review will describe several animal models of potential intellectual disability risk factors.