Effect of prior beliefs and cognitive deficits on learning in first-episode schizophrenia patients.

Introduction: It is known that cognitive deficits are a core feature of schizophrenia and that in the general population, prior beliefs significantly influence learning and reasoning processes. However, the interaction of prior beliefs with cognitive deficits and their impact on performance in schizophrenia patients is still poorly understood. This study investigates the role of beliefs and cognitive variables (CVs) like working memory, associative learning, and processing speed on learning processes in individuals with schizophrenia. We hypothesize that beliefs will influence the ability to learn correct predictions and that first-episode schizophrenia patients (FEP) will show impaired learning due to cognitive deficits. Methods: We used a predictive-learning task to examine how FEP (n = 23) and matched controls (n = 23) adjusted their decisional criteria concerning physical properties during the learning process when predicting the sinking behavior of two transparent containers filled with aluminum discs when placed in water. Results: On accuracy, initial differences by group, trial type, and interaction effects of these variables disappeared when CVs were controlled. The differences by conditions, associated with differential beliefs about why the objects sink slower or faster, were seen in patients and controls, despite controlling the CVs' effect. Conclusions: Differences between groups were mainly explained by CVs, proving that they play an important role than what is assumed in this type of task. However, beliefs about physical events were not affected by CVs, and beliefs affect in the same way the decisional criteria of the control or FEP patients' groups.

Current Understanding of Giardia lamblia and Pathogenesis of Stunting and Cognitive Deficits in Children from Low- and Middle-Income Countries.

Purpose of Review: Giardia lamblia is a common intestinal parasite worldwide, mainly in children from low- and middle-income countries (LMIC). Also, it has been associated with increased intestinal permeability, stunting, and cognitive impairment. Nonetheless, the pathogenesis of long-term consequences is difficult to elucidate. Recent Findings: Recent studies try to understand the long-term consequences of Giardia infections. First, well-characterized studies associate Giardia with intestinal damage and child growth. Second, infections appear not to be associated with inflammation, but "lack of inflammation" may not, however, entirely exclude a pro-inflammatory pathway. Finally, some important amino acids are lower and could contribute to prolongate stunting and cognitive deficit. Summary: Giardia infections in LMIC used to be associated with child growth shortfalls, gut permeability, and cognitive deficits. Multifactorial effects could be associated with Giardia, including nutritional, altered microbiota, and generation of potentially toxic microbial metabolic byproducts, all together increasing risk of long-term outcomes.

Características Cognitivas e Comportamentais Associadas à Distrofia Muscular de Duchenne: Revisão Integrativa / Cognitive and Behavioral Characteristics Associated with Duchenne Muscular Dystrophy: Integrative Review / Características Cognitivas y de Comportamiento Asociadas con la Distrofia Muscular de Duchenne: Revisión Integrativa

A Distrofia Muscular de Duchenne (DMD) é uma doença neuromuscular progressiva recessiva causada por mutações genéticas ligadas ao cromossomo X. Além do enfraquecimento muscular progressivo, a condição é associada a alterações neuropsicológicas. O objetivo deste estudo foi realizar uma revisão sistematizada da temática, para investigar os aspectos cognitivos e comportamentais associados à DMD pela literatura, nos últimos dez anos (2011-2021). Realizou-se uma revisão integrativa da literatura, com o propósito de sintetizar e analisar o conhecimento sobre o tema no campo científico, sendo efetuada busca nas bases de dados e motores de busca Science Direct, SciELO, PubMed e BVS. Após consideração dos critérios de inclusão e exclusão, foram selecionados 29 artigos para análise. Os resultados endossaram que alterações cognitivas e do neurodesenvolvimento, bem como de problemas comportamentais parecem ser mais prováveis na DMD, em comparação com a população geral. Verificou-se escassez de estudos empíricos brasileiros e a necessidade de avaliar e intervir nos âmbitos neuropsicológico e psicossocial, de forma precoce, contínua e multidisciplinar, no intuito de atender às necessidades desse grupo.

Duchenne Muscular Dystrophy (DMD) is a recessive progressive neuromuscular disease caused by X-linked genetic mutations. In addition to progressive muscle weakness, the condition is associated with neuropsychological alterations. The aim of this study was to perform a systematic review about the theme, to investigate the cognitive and behavioral aspects associated with DMD in the literature, over the last ten years (2011-2021). An integrative literature review was carried out, with the purpose of synthesizing and analyzing the knowledge on the subject in the scientific field, with a search in the databases and search engines Science Direct, SciELO, PubMed and BVS. After considering the inclusion and exclusion criteria, 29 articles were selected for analysis. The results endorsed that cognitive and neurodevelopmental alterations and behavioral problems seem to be more likely in DMD, when compared to the general population. There was a lack of brazilian empirical studies and the need to assess and intervene in the neuropsychological and psychosocial spheres was observed, in an early, continuous and multidisciplinary way, in order to meet the needs of this group.

La distrofia muscular de Duchenne (DMD) es una enfermedad neuromuscular progresiva recesiva causada por mutaciones genéticas ligadas al cromosoma X. Además de la debilidad muscular progresiva, la afección se asocia con cambios neuropsicológicos. El objetivo de este estudio fue realizar una revisión sistemática del tema, para investigar los aspectos cognitivos y conductuales asociados a la DMD en la literatura, en los últimos diez años (2011-2021). Se realizó una revisión integradora de la literatura, con el propósito de sintetizar y analizar el conocimiento sobre el tema en el campo científico, mediante una búsqueda en las bases de datos y motores de búsqueda Science Direct, SciELO, PubMed y BVS. Después de considerar los criterios de inclusión y exclusión, se seleccionaron 29 artículos para su análisis. Los resultados respaldaron que alteraciones cognitivas y del neurodesarrollo, así como problemas del comportamiento parecen ser más probables en la DMD en comparación con la población general. Se observó la escasez de estudios empíricos brasileños, así como la necesidad de evaluar e intervenir en los ámbitos neuropsicológico y psicosocial, de forma precoz, continua y multidisciplinar, para atender las necesidades de esta población.

Cognitive Deficits Found in a Pro-inflammatory State are Independent of ERK1/2 Signaling in the Murine Brain Hippocampus Treated with Shiga Toxin 2 from Enterohemorrhagic Escherichia coli.

Shiga toxin 2 (Stx2) from enterohemorrhagic Escherichia coli (EHEC) produces hemorrhagic colitis, hemolytic uremic syndrome (HUS), and acute encephalopathy. The mortality rate in HUS increases significantly when the central nervous system (CNS) is involved. Besides, EHEC also releases lipopolysaccharide (LPS). Many reports have described cognitive dysfunctions in HUS patients, the hippocampus being one of the brain areas targeted by EHEC infection. In this context, a translational murine model of encephalopathy was employed to establish the deleterious effects of Stx2 and the contribution of LPS in the hippocampus. The purpose of this work is to elucidate the signaling pathways that may activate the inflammatory processes triggered by Stx2, which produces cognitive alterations at the level of the hippocampus. Results demonstrate that Stx2 produced depression-like behavior, pro-inflammatory cytokine release, and NF-kB activation independent of the ERK1/2 signaling pathway, while co-administration of Stx2 and LPS reduced memory index. On the other hand, LPS activated NF-kB dependent on ERK1/2 signaling pathway. Cotreatment of Stx2 with LPS aggravated the pathologic state, while dexamethasone treatment succeeded in preventing behavioral alterations. Our present work suggests that the use of drugs such as corticosteroids or NF-kB signaling inhibitors may serve as neuroprotectors from EHEC infection.

Perfil neuropsicológico en pacientes con trauma craneoencefálico atendidos en un hospital de alta complejidad de Medellín, Colombia / Neuropsychological profile of patients with traumatic brain injury evaluated in a high complexity hospital in Medellin, Colombia

RESUMEN INTRODUCCIÓN: El trauma craneoencefálico (TCE) es una de las principales causas de daño cerebral y discapacidad en personas menores de 40 años. Según su severidad, se puede clasificar en leve, moderado o grave, en función de la escala de coma de Glasgow. Muchos pacientes quedan con secuelas neuropsicológicas y comportamentales que pueden afectar en mayor o menor grado su funcionalidad. El objetivo del estudio fue determinar las diferencias en el perfil neuropsicológico, las características clínicas y el compromiso funcional en pacientes con TCE según la clasificación de la severidad. METODOLOGÍA: Se realizó un estudio observacional, analítico, de corte transversal. Se revisaron las historias clínicas y los reportes neuropsicológicos de adultos con TCE evaluados por neuropsicología entre los años 2014 y 2019. Se compararon los resultados de pruebas neuropsicológicas, síndromes neuropsicológicos y funcionalidad según la severidad del TCE. RESULTADOS: Se estudiaron 48 pacientes, 38 de ellos hombres (73 %), con una mediana de edad de 35 años (RI: 25-51). En 14 casos el TCE fue leve, en 18 moderado y en 16 severo. El síndrome neuropsicológico más frente fue el amnésico (100 %), seguido del disejecutivo (79 %) y el compromiso en la atención (77 %). No se encontraron diferencias según severidad del TCE. Cuarenta y un pacientes (85 %) presentaron cambios comportamentales, 14 (29 %) experimentaron alteración en las actividades básicas de la vida diaria y 32 (68 %) en las actividades instrumentales. CONCLUSIONES: Las alteraciones neuropsicológicas, comportamentales y funcionales posteriores a un TCE son frecuentes, sin embargo, no se encontraron diferencias significativas según severidad del trauma.

ABSTRACT INTRODUCTION: Traumatic Brain Injury (TBI) is one of the main causes of brain damage and disability in people under 40 years of age. The severity of TBI can be classified as mild, moderate, or severe based on the Glasgow coma scale. Many patients are left with neuropsychological and behavioral sequelae that can affect functionality to a greater or lesser degree. The objective of the study was to determine the differences in the neuropsychological profile, clinical characteristics and functional impairment in patients with TBI according to severity. METHODOLOGY: An observational, analytical, cross-sectional study was carried out. The clinical records and neuropsychological reports of adults with TBI evaluated between 2014 and 2019 were reviewed. The results of neuropsychological tests, neuropsychological syndromes, and functionality according to severity of TBI were compared. RESULTS: 48 patients were studied, 35 were males (73 %), the median age was 35 years (IR: 25-51). In 14 TBI was mild, in 18 moderate and 16 severe. The most common neuropsychological syndrome was amnesic (100 %) followed by dysexecutive (79 %) and attentional commitment (77 %). No differences were found according to severity of TBI. 41 patients (85 %) presented behavioral changes, 14 (29 %) presented alteration in basic activities of daily life and 32 (68 %) in instrumental activities. CONCLUSIONS: Neuropsychological, behavioral and functional alterations are frequent after TBI; however, no significant differences were found according to the severity of the trauma.

The Role of Perceived and Objective Social Connectedness on Risk for Suicidal Thoughts and Behavior in Late-Life and Their Moderating Effect on Cognitive Deficits.

OBJECTIVE: Impaired cognition increases suicide risk while social connectedness protects against suicide risk in late life. We examined the independent and interactive effects of social connectedness and cognition on suicide risk in late life. METHODS: Participants included 570 individuals aged 50+ from a late-life suicide study. The Interpersonal Support Evaluation List and Social Network Index were used to assess perceived and objective social connectedness, respectively, while the Mattis Dementia Rating Scale and Executive Interview were used to assess cognition. RESULTS: Suicide attempters and ideators reported lower perceived social connectedness and exhibited worse executive function than non-suicidal depressed and healthy comparison participants, while only attempters had worse objective social connectedness relative to the other groups. Executive dysfunction was linked to low objective social connectedness in attempters but higher objective social connectedness in healthy comparisons. CONCLUSION: Interventions targeting suicide risk may consider bolstering social connectedness, particularly in those with low cognitive health.

Female Rats Are Resistant to Cognitive, Motor and Dopaminergic Deficits in the Reserpine-Induced Progressive Model of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease. The main symptoms are motor signs such as resting tremor and difficulty in initializing movements. Non-motor alterations, such as cognitive deficits, can precede the motor symptoms. PD is more frequent in men than women. The mechanisms related to this difference are not completely understood. There is evidence that females present distinct characteristics in dopaminergic function compared to males. While the severity of motor impairments is often compared between sexes, little is known about sex differences in the prodromal stage. Most animal models of PD present acute severe motor impairment, which precludes the study of non-motor symptoms. Our research group have proposed an adaptation of the classic reserpine protocol, using low doses in a chronic treatment. This method allows the observation of progressive motor impairment as well as premotor deficits. Here we investigate possible behavioral and neuronal sex differences in the effects of the repeated treatment with a low dose of reserpine in rats. Male and female Wistar rats received 10-15 injections of reserpine (0.1 mg/kg) or vehicle, on alternate days. We followed-up the estrous cycle phases and conducted motor and cognitive assessments (catalepsy, open field, oral movements and object recognition tests). The euthanasia occurred 48 h after the 10th or 15th injections, with the collection of blood for the quantification of sex hormones and brains for tyrosine hydroxylase (TH) immunohistochemistry in the substantia nigra pars compact (SNpc). Reserpine induced progressive catalepsy, involuntary oral movements and cognitive deficits in male rats. The behavioral effects of reserpine were attenuated (motor) or absent (cognitive) in females. Reserpine decreased TH immunoreactivity in males, but not in females. Estrogen levels in females negatively correlated with catalepsy duration. Our findings show that females present a delay and/or a prevention in the reserpine-induced motor alterations in the progressive PD model, compatible with the lower prevalence of this disease in women. Further, females were protected from the deficit in object recognition at the prodromal stage. The absence of reserpine-induce decrease in TH immunoreactivity suggests that differences in dopaminergic function/plasticity are related to this protection in female sex.

Neurocognitive Disorder and Emotional Symptoms in HIV+ Brazilian Elderly: Influence of Gender, Income, Diet, and Sleep.

The purpose of this study was to identify factors associated with HIV-associated neurocognitive disorder (HAND) and symptoms of anxiety and depression in HIV+ Brazilian elderly on antiretroviral treatments. The study included 112 HIV+ elderly who completed a questionnaire, tests for cognitive screening, attention, problem solving, processing speed, visual perception, memory, and anxiety and depression scales. The results showed presence of HAND (89.3%), pathological anxiety (48.2%) and depression (58%) in the sample. Higher income was a protective factor for HAND (OR = 0.33). Waking up well-rested (OR = 0.63) and better diet quality (OR = 0.62) reduced the chance of pathological anxiety. Higher education (OR = 0.74) and waking up well-rested (OR = 0.61) reduced the chance of depression. Being female (OR = 7.73) increased the chance of depression. It can be concluded that it is important to evaluate cognitive and emotional aspects of HIV+ elders and to consider social and educational status, diet, and sleep in interventions, paying special attention to elderly women.

Early IGF-1 Gene Therapy Prevented Oxidative Stress and Cognitive Deficits Induced by Traumatic Brain Injury.

Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality in adults under 40 years old. Once primary injury occurs after TBI, neuroinflammation and oxidative stress (OS) are triggered, contributing to the development of many TBI-induced neurological deficits, and reducing the probability of critical trauma patients´ survival. Regardless the research investment on the development of anti-inflammatory and neuroprotective treatments, most pre-clinical studies have failed to report significant effects, probably because of the limited blood brain barrier permeability of no-steroidal or steroidal anti-inflammatory drugs. Lately, neurotrophic factors, such as the insulin-like growth factor 1 (IGF-1), are considered attractive therapeutic alternatives for diverse neurological pathologies, as they are neuromodulators linked to neuroprotection and anti-inflammatory effects. Considering this background, the aim of the present investigation is to test early IGF-1 gene therapy in both OS markers and cognitive deficits induced by TBI. Male Wistar rats were injected via Cisterna Magna with recombinant adenoviral vectors containing the IGF-1 gene cDNA 15 min post-TBI. Animals were sacrificed after 60 min, 24 h or 7 days to study the advanced oxidation protein products (AOPP) and malondialdehyde (MDA) levels, to recognize the protein oxidation damage and lipid peroxidation respectively, in the TBI neighboring brain areas. Cognitive deficits were assessed by evaluating working memory 7 days after TBI. The results reported significant increases of AOPP and MDA levels at 60 min, 24 h, and 7 days after TBI in the prefrontal cortex, motor cortex and hippocampus. In addition, at day 7, TBI also reduced working memory performance. Interestingly, AOPP, and MDA levels in the studied brain areas were significantly reduced after IGF-1 gene therapy that in turn prevented cognitive deficits, restoring TBI-animals working memory performance to similar values regarding control. In conclusion, early IGF-1 gene therapy could be considered a novel therapeutic approach to targeting neuroinflammation as well as to preventing some behavioral deficits related to TBI.

Adult hippocampal neurogenesis in the context of lipopolysaccharide-induced neuroinflammation: A molecular, cellular and behavioral review.

The continuous generation of new neurons occurs in at least two well-defined niches in the adult rodent brain. One of these areas is the subgranular zone of the dentate gyrus (DG) in the hippocampus. While the DG is associated with contextual and spatial learning and memory, hippocampal neurogenesis is necessary for pattern separation. Hippocampal neurogenesis begins with the activation of neural stem cells and culminates with the maturation and functional integration of a portion of the newly generated glutamatergic neurons into the hippocampal circuits. The neurogenic process is continuously modulated by intrinsic factors, one of which is neuroinflammation. The administration of lipopolysaccharide (LPS) has been widely used as a model of neuroinflammation and has yielded a body of evidence for unveiling the detrimental impact of inflammation upon the neurogenic process. This work aims to provide a comprehensive overview of the current knowledge on the effects of the systemic and central administration of LPS upon the different stages of neurogenesis and discuss their effects at the molecular, cellular, and behavioral levels.

The effect of sleep medications on prospective and retrospective memory: a population-based study.

Sleep medications, especially benzodiazepines, are known to cause motor and cognitive impairments as side-effects from their use. However, an evaluation of the effects of sleep medications in general on prospective and retrospective memory remains to be seen. Thus, the effects of the different types of sleep medicines were assessed using the total score and the 8 subscales of the Prospective and Retrospective Memory Questionnaire (PRMQ) in a representative sample from the Municipality of São Paulo. The effects of each type of medication on these same parameters were evaluated afterwards. Each analysis was performed controlling for different covariates to observe their degree of interference on the observed results. Impairment due to use of sleep aid medication was observed in 6 of the 8 subscales, as well in the overall score of the PRMQ when compared to non-users. Prospective subscales were particularly affected, even when controlling for highly interfering covariates such as depression and anxiety, and objective sleep variables related to sleep architecture and wakefulness in the night. Few effects were detected between the various types of medication even when controlling for covariates, suggesting that a sample with higher power is necessary to conduct a more detailed analysis. Using pharmacological aids to improve sleep may impair prospective and (to some extent) retrospective memory. Therefore, the relationship between sleep impairment, memory deficits and medication use must be considered by physicians.

Eficacia de la rehabilitación cognitiva en un paciente con esclerosis múltiple progresiva primaria / Efficacy of cognitive rehabilitation in a patient with primary progressive multiple sclerosis

La esclerosis múltiple (EM) es una enfermedad inflamatoria crónica que cursa con la desmielinización y la neurodegeneración a nivel del sistema nervioso central. Existen tres tipos de EM en función de la progresión de la enfermedad, pero la mayor parte de los pacientes tienden a presentar déficits cognitivos. Por lo tanto, resulta imprescindible el desarrollo de programas de entrenamiento cognitivos dirigidos a la mejora de estos déficits y, en definitiva, a la mejora de la calidad de vida de estos pacientes. En este sentido, el objetivo principal de este estudio fue la puesta en marcha de un programa de entrenamiento cognitivo dirigido a un paciente con esclerosis múltiple progresiva primaria (EMPP) a lo largo de un año. Los resultados pusieron de manifiesto que algunos de los déficits cognitivos que presentó inicialmente el paciente mejoraron tras varios meses de intervención. En este sentido, el paciente presentó notables mejoras en el control inhibitorio y la flexibilidad cognitiva. No obstante, los déficits en la velocidad de procesamiento se mantuvieron constantes a lo largo de toda la intervención. Asimismo, aparecieron otros déficits a lo largo de la intervención que remitieron tras la adecuación de los objetivos de intervención. Por todo ello, nuestro estudio reforzó la importancia de la puesta en marcha de los programas de rehabilitación cognitiva dirigidos a pacientes con enfermedades desmielinizantes para paliar las secuelas cognitivas derivadas de las mismas. Además, es importante que estos programas de entrenamiento cognitivo sean revisados periódicamente para adecuar los objetivos del tratamiento.

Multiple sclerosis (MS) is a chronic inflammatory disease that involves demyelination and neurodegeneration at the level of the central nervous system. Despite the different characteristics of each of the three types of MS, most patients with this disease present significant cognitive deficits. Therefore, it is essential to develop cognitive training programs to improve these deficits and, ultimately, increase the quality of life of these patients. Thus, the main objective of this study was to implement a one-year cognitive training program with a patient with progressive primary multiple sclerosis (PPMS). The results showed that some of the cognitive deficits the patient initially presented improved after several months of intervention. In this regard, the patient presented noteworthy improvements in inhibitory control and cognitive flexibility. However, deficits in processing speed remained constant throughout the intervention. Likewise, other deficits appeared during the intervention that remitted after adapting the intervention objectives to the patient's needs. Therefore, our study reinforces the importance of implementing cognitive rehabilitation programs for patients with demyelinating diseases to alleviate the cognitive sequelae they produce. In addition, it is important to evaluate these cognitive training programs periodically in order to adapt the objectives and improve the patient's functionality.

Clinical characteristics of cognitive deficits in major depressive disorder: a 6-month prospective study

Abstract Background Previous studies have shown that major depressive disorder (MDD) is associated with a variety of cognitive deficits, which can persist even in remitted states. Nevertheless, the relationship between the cognitive and affective symptoms in depression remains obscure. The aim of the present study was to explore the clinical characteristics and correlates of the cognitive deficits in patients with MDD. Methods Clinical and neuropsychological assessments were conducted at baseline and 6-month follow-ups. The severity of the disease and the effect of treatment were assessed with the Hamilton Depression Scale-17. Neuropsychological tests, including the digital symbol substitution test and digit span test, were administered to 67 depressed patients and 56 healthy participants. Results MDD patients showed impairments in memory, attention, and executive function at baseline. After the 6-month treatment phase, patients in remission showed significant alleviation of these cognitive deficits, although impairments in attention and executive function were still present when compared to controls. Discussion Significant cognitive deficits are present in MDD. The speed of remission of cognitive functions seems to be slower than and inconsistent with emotional symptoms, which provides new support for the argument that cognitive deficits are independent factors from the emotional symptoms in MDD.

Iron Overload Impairs Autophagy: Effects of Rapamycin in Ameliorating Iron-Related Memory Deficits.

Over the years, iron accumulation in specific brain regions has been observed in normal aging and related to the pathogenesis of neurodegenerative disorders. Many neurodegenerative diseases may involve cognitive dysfunction, and we have previously shown that neonatal iron overload induces permanent cognitive deficits in adult rats and exacerbates age-associated memory decline. Autophagy is a catabolic pathway involved in the removal of toxic protein aggregates, which are a hallmark of neurodegenerative events. In the present study, we investigated whether iron accumulation would interfere with autophagy and also sought to determine the effects of rapamycin-induced stimulation of autophagy in attenuating iron-related cognitive deficits. Male Wistar rats received a single daily oral dose of vehicle or iron carbonyl (30 mg/kg) at postnatal days 12-14. In adulthood, they received daily intraperitoneal injections of vehicle or rapamycin (0.25 mg/kg) for 14 days. Results showed that iron given in the neonatal period impaired inhibitory avoidance memory and induced a decrease in proteins critically involved in the autophagy pathway, Beclin-1 and LC3, in the hippocampus. Rapamycin in the adulthood reversed iron-induced memory deficits, decreased the ratio phospho-mTOR/total mTOR, and recovered LC3 II levels in iron-treated rats. Our results suggest that iron accumulation, as observed in neurodegenerative disorders, hinders autophagy, which might play a role in iron-induced neurotoxicity. Rapamycin, by inducing authophagy, was able to ameliorate iron-induced cognitive impairments. These findings support the use of rapamycin as a potential neuroprotective treatment against the cognitive decline associated to neurodegenerative disorders.

Déficits cognitivos na vida adulta decorrentes da quimioterapia aplicada durante o desenvolvimento neural na infância e na adolescência / Cognitive deficits in adult life induced by chemotherapy during neural development in childhood and adolescence

Although there has been marked progress in the survival rates of children with cancer in recent decades, it is recognized that chemotherapy administered during childhood and adolescence can exert significant central nervous system (CNS) toxicity. It may, for example, affect the neurocognitive functions of the survivors, even with a loss in school/academic performance as children and/or lately in adulthood, thus influencing the quality of life of these individuals. Animal models and clinical studies have allowed the search for an understanding of the pathogenic mechanisms that involve the cognitive deficits induced by chemotherapy in children and adolescents, and also contribute to the development of drugs aiming to prevent or minimize the CNS side effects in these patients. This review aims to present studies describing the cognitive dysfunction induced by chemotherapy applied in the periods of childhood and puberty, discussing the possible incriminated mechanisms, their repercussions in adult life and the importance of pre-clinical studies in vivo in the search for therapeutic protocols that attenuate or prevent the occurrence of this phenomenon.

Embora tenha havido nas últimas décadas um progresso marcante nas taxas de sobrevida de crianças com câncer, é reconhecido que a quimioterapia administrada durante o período da infância e da adolescência pode exercer significativa toxicidade sobre o sistema nervoso central (SNC). Pode, por exemplo, afetar as funções neurocognitivas dos sobreviventes, inclusive com prejuízo no rendimento escolar/acadêmico ainda quando crianças e/ou tardiamente, em idade adulta, dessa forma influenciando de maneira expressiva a qualidade de vida futura desses indivíduos. Modelos animais e estudos clínicos têm permitido a busca da compreensão dos mecanismos patogênicos que envolvem os déficits cognitivos induzidos pela quimioterapia em crianças e adolescentes, contribuindo ainda para o desenvolvimento de drogas que visem a prevenir ou minimizar os efeitos colaterais no SNC desses pacientes. Na presente revisão, busca-se apresentar estudos que descrevem a disfunção cognitiva tardia induzida pela quimioterapia aplicada no período da infância e da adolescência, discutindo os possíveis mecanismos incriminados, suas repercussões na vida adulta e a importância dos estudos pré-clínicos in vivo na busca de protocolos terapêuticos que atenuem ou impeçam a ocorrência desse fenômeno.

Monitoreo de fuente y funcionamiento cognitivo en personas con enfermedades mentales severas / Source monitoring and cognitive functioning in people with severe mental illness

Resumen Monitoreo de Fuente, se define como "establecimiento del origen de memorias, conocimientos y creencias". Por su dependencia del funcionamiento cognitivo, el objetivo de esta investigación es evaluar, en una prueba de Monitoreo de Fuente, a un grupo de personas con trastornos psiquiátricos (esquizofrenia, bipolaridad), caracterizados por la presencia de alteraciones cognitivas significativas. Métodos: 90 sujetos (20-55 años), con diagnóstico de esquizofrenia, trastorno bipolar y controles sanos. Todos los pacientes se encontraban estables en su condición clínica. Los sujetos participantes completaron una evaluación neuropsicológica y una prueba de Monitoreo de Fuente, consistente en identificar el origen propio o ajeno, de una lista de palabras. Resultados: Ambos grupos de pacientes, mostraron un peor desempeño que el grupo control, en la prueba de Monitoreo de Fuente. Los resultados se correlacionaron, con las pruebas de aprendizaje verbal, atención visual y flexibilidad cognitiva. La regresión lineal múltiple, muestra que las fallas en reconocer las palabras ajenas, se explican por el diagnóstico de trastorno afectivo bipolar y el desempeño en la función de aprendizaje verbal, mientras que las fallas del reconocimiento de las palabras propias, se explican por el diagnóstico de los sujetos. Adicionalmente, las personas con esquizofrenia mostraron una mayor tendencia a atribuirse a sí mismas, palabras de origen externo. Conclusiones: Ambos grupos de pacientes, rindieron menos que el grupo control, en la prueba de Monitoreo de Fuente, pero sólo algunos de los resultados se asocian directamente con el funcionamiento cognitivo, por lo que podría tratarse más bien de una habilidad metacognitiva.

Source Monitoring, is defined as "establishing the origin of memories, knowledge and beliefs" Considering its dependence on cognitive functioning, our aim was to assess the performance in a Source Monitoring test, of a group of people with psychiatric disorders (schizophrenia, bipolar disorder), characterized by the presence of significant cognitive deficits. Methods: 90 subjects (20-55 years) with diagnosis of schizophrenia, bipolar disorder and healthy controls. All patients were stable in their clinical condition. Participant completed a neuropsychological evaluation and a Source Monitoring test, in which they were asked to identify the origin (own- other..) of a list of words. Results: Both groups of patients had a worse performance than the control group, in the Source Monitoring test. The results were correlated, with verbal learning, visual attention and cognitive flexibility tests. Multiple linear regression shows that failures in recognizing the foreign words are explained by the diagnosis of bipolar affective disorder and performance in the verbal learning function, whereas the failures of the recognition of the own words are explained by the diagnosis of subjects. In addition, people with schizophrenia showed a greater tendency to attribute to themselves, words of external origin. Conclusions: Both groups of patients performed worse than the control group in the source monitoring test, but only some of the results were directly associated with cognitive functioning. The authors propose that source monitoring may depend of metacognitive abilities.

Predicting Long-term Cognitive Dysfunction in Survivors of Critical Illness with Plasma Inflammatory Markers: a Retrospective Cohort Study.

Persistent inflammation in intensive care unit (ICU) survivors is associated with higher long-term mortality and poorer mobility. However, it is unknown if inflammatory markers are associated with other dysfunctions observed in survivors of critical illness. Thus, it was investigated if plasma levels of interleukin (IL)-6 and IL-10 at hospital discharge were associated with long-term functional and cognitive performance after ICU discharge. Adult patients admitted for > 48 h to a 20-bed mixed ICU in a University Hospital had blood collected within 48 h before hospital discharge to measure IL-6 and IL-10 levels. After a median time of 48 months, cognitive status was determined by the Mini-Mental State Examination (MMSE), and functional status was determined by the Barthel Index. Patients at the higher 25th percentile of both IL-6 and IL-10 had a worse long-term cognitive performance, but not worse functional status, even when adjusted for confounders after long-term follow-up. In conclusion, elevated circulating IL-6 and IL-10 concentrations at hospital discharge were associated with long-term cognitive dysfunction in ICU survivors.

Déficits cognitivos na vida adulta decorrentes da quimioterapia aplicada durante o desenvolvimento neural na infância e na adolescência / Cognitive deficits in adult life induced by chemotherapy during neural development in childhood and adolescence

Although there has been marked progress in the survival rates of children with cancer in recent decades, it is recognized that chemotherapy administered during childhood and adolescence can exert significant central nervous system (CNS) toxicity. It may, for example, affect the neurocognitive functions of the survivors, even with a loss in school/academic performance as children and/or lately in adulthood, thus influencing the quality of life of these individuals. Animal models and clinical studies have allowed the search for an understanding of the pathogenic mechanisms that involve the cognitive deficits induced by chemotherapy in children and adolescents, and also contribute to the development of drugs aiming to prevent or minimize the CNS side effects in these patients. This review aims to present studies describing the cognitive dysfunction induced by chemotherapy applied in the periods of childhood and puberty, discussing the possible incriminated mechanisms, their repercussions in adult life and the importance of pre-clinical studies in vivo in the search for therapeutic protocols that attenuate or prevent the occurrence of this phenomenon.(AU)

Embora tenha havido nas últimas décadas um progresso marcante nas taxas de sobrevida de crianças com câncer, é reconhecido que a quimioterapia administrada durante o período da infância e da adolescência pode exercer significativa toxicidade sobre o sistema nervoso central (SNC). Pode, por exemplo, afetar as funções neurocognitivas dos sobreviventes, inclusive com prejuízo no rendimento escolar/acadêmico ainda quando crianças e/ou tardiamente, em idade adulta, dessa forma influenciando de maneira expressiva a qualidade de vida futura desses indivíduos. Modelos animais e estudos clínicos têm permitido a busca da compreensão dos mecanismos patogênicos que envolvem os déficits cognitivos induzidos pela quimioterapia em crianças e adolescentes, contribuindo ainda para o desenvolvimento de drogas que visem a prevenir ou minimizar os efeitos colaterais no SNC desses pacientes. Na presente revisão, busca-se apresentar estudos que descrevem a disfunção cognitiva tardia induzida pela quimioterapia aplicada no período da infância e da adolescência, discutindo os possíveis mecanismos incriminados, suas repercussões na vida adulta e a importância dos estudos pré-clínicos in vivo na busca de protocolos terapêuticos que atenuem ou impeçam a ocorrência desse fenômeno.(AU)

Perfil neuropsicológico y efectos de la rehabilitación cognitiva en la leucemia linfoblástica aguda: a propósito de un caso / Neuropsychological profile and cognitive rehabilitation training effects on acute lymphoblastic leukaemia: a case study

La Leucemia Linfoblástica Aguda (LLA) infantil es el cáncer pediátrico más frecuente. Actualmente cuenta con un alto porcentaje de supervivencia, pero dichos pacientes presentan secuelas cognitivas secundarias a la enfermedad debidas, principalmente, al tratamiento médico recibido para evitar la recidiva del cáncer. Por lo tanto, resulta necesaria la implementación de programas de rehabilitación cognitiva específicos para este tipo de población. Es por ello que el objetivo del presente estudio fue describir los déficits cognitivos en un varón de 17 años que fue diagnosticado con LLA a los 9 años. Tras la valoración neuropsicológica inicial se desarrolló un programa de rehabilitación cognitiva intensivo durante dos años consecutivos. Realizamos un estudio pre-post en el que administramos el Conners Continuous Performance Test (CPT-II) y la Escala de Inteligencia de Wechsler para niños (WISC-IV). Los resultados, antes de la intervención, mostraron que el paciente manifestaba una menor velocidad de procesamiento y dificultades de atención sostenida y alternante, comprensión verbal y razonamiento perceptivo. Además, también presentó un número considerable de errores perseverativos, signo de dificultades de flexibilidad cognitiva y control inhibitorio. Dichos déficits mejoraron notablemente tras el programa de rehabilitación cognitiva. En conclusión, nuestro estudio pone de manifiesto la necesidad de aplicar programas de rehabilitación cognitiva tempranos para paliar las secuelas cognitivas derivadas de la LLA y de su tratamiento médico, así como mejorar la calidad de vida del paciente, ya que las mejoras cognitivas redundarán en su rendimiento académico y en su funcionamiento cotidiano.

Childhood Acute Lymphoblastic Leukemia (ALL) is the most common pediatric cancer. It currently has a high survival rate, but these patients have cognitive sequelae secondary to the disease, mainly due to the medical treatment received to prevent cancer recurrence. Therefore, it is necessary to implement specific cognitive rehabilitation programs for this type of population. Hence, the main objective of this study was to describe cognitive deficits in a 17-year-old male who was diagnosed with ALL when he was 9 years old. After the initial neuropsychological evaluation, an intensive cognitive rehabilitation program was developed during two consecutive years. We conducted a pre-post study in which we administered the Conners Continuous Performance Test (CPT-II) and the Wechsler Intelligence Scale for Children (WISC-IV). Results, before the intervention, showed that the patient presented a lower processing speed and difficulties of sustained and alternating attention, verbal comprehension and perceptive reasoning; in addition to a large number of perseverative errors, sign of self-monitoring difficulties and inhibitory control. These deficits improved markedly after a program of cognitive rehabilitation. In conclusion, our study highlights the need to apply early cognitive rehabilitation programs to alleviate the cognitive sequelae derived from ALL and its medical treatment. In addition, any improvement in their cognitive capabilities will have a positive impact in their academic performance and quality of life.

Structural and functional papez circuit integrity in amyotrophic lateral sclerosis.

Cognitive impairment in amyotrophic lateral sclerosis (ALS) is heterogeneous but now recognized as a feature in non-demented patients and no longer exclusively attributed to executive dysfunction. However, despite common reports of temporal lobe changes and memory deficits in ALS, episodic memory has been less explored. In the current study, we examined how the Papez circuit-a circuit known to participate in memory processes-is structurally and functionally affected in ALS patients (n = 20) compared with healthy controls (n = 15), and whether these changes correlated with a commonly used clinical measure of episodic memory. Our multimodal MRI approach (cortical volume, voxel-based morphometry, diffusion tensor imaging and resting state functional magnetic resonance) showed reduced gray matter in left hippocampus, left entorhinal cortex and right posterior cingulate as well as increased white matter fractional anisotropy and decreased mean diffusivity in the left cingulum bundle (hippocampal part) of ALS patients compared with controls. Interestingly, thalamus, mammillary bodies and fornix were preserved. Finally, we report a decreased functional connectivity in ALS patients in bilateral hippocampus, bilateral anterior and posterior parahippocampal gyrus and posterior cingulate. The results revealed that ALS patients showed statistically significant structural changes, but more important, widespread prominent functional connectivity abnormalities across the regions comprising the Papez circuit. The decreased functional connectivity found in the Papez network may suggest these changes could be used to assess risk or assist early detection or development of memory symptoms in ALS patients even before structural changes are established.