The Effects of Methylfolate on Cognitive Decline and Dementia: A Protocol for Systematic Review and Meta-Analysis.

INTRODUCTION: Dementia and cognitive decline are highly prevalent in later life and are growing public health concerns worldwide due to the increasing aging population. Individuals diagnosed with dementia have reduced mental function, resulting in social and cognitive skill deficits, increased dependence, and reduced autonomy-all of which are conditions associated with higher mortality rates. This systematic review aims to assess the effectiveness of treating dementia and cognitive decline with methylfolate. The main outcomes analyzed will be dementia and changes in cognitive function measured by different instruments in older adults treated with methylfolate. Secondary outcomes, such as inflammatory markers, plasma folic-acid levels, and total homocysteine, will also be assessed. METHODS AND ANALYSIS: This study will be carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This protocol is registered in the International Prospective Registry of Systematic Reviews, under the code CRD42021275755. We will include clinical trials conducted with older adults diagnosed with dementia or cognitive decline and treated with folic acid. The searches will be conducted on the PubMed, Scopus, and Embase databases, and the articles will be selected by reading their titles and abstracts first, followed by the full text. The quality of the selected studies will be assessed using GRADE and the risk of bias will be assessed using the Downs-and-Black method. ETHICS AND DISSEMINATION: The results will be presented at scientific conferences and disseminated by publishing a scientific article in an international English-language journal. We hope to find robust and significant evidence regarding the effectiveness of methylfolate supplementation in improving dementia symptoms and cognitive decline among older adults. By systematizing this evidence and possibly performing a meta-analysis study, we expect to significantly contribute to the treatment of this health problem, reduce mortality, and improve the quality of life and health of this population, boosting the development of medical protocols capable of reducing the financial effects of public health.

A randomized pharmacokinetic and pharmacodynamic trial of two regular human insulins demonstrates bioequivalence in type 1 diabetes and availability of biosimilar insulin may improve access to this medication.

AIMS: To compare the pharmacokinetic (PK) and pharmacodynamic (PD) effects and safety of therapeutic dosages of a regular insulin (experimental drug) produced by Bioton S.A. (Warsaw, Poland) versus Humulin® R, a regular insulin (reference drug) produced by Eli Lilly (Indianapolis, Indiana). MATERIALS AND METHODS: In a single-centre, randomized, double-blinded phase 1 crossover study, we used the manual euglycaemic clamp technique to compare PK and PD profiles between single subcutaneous doses (0.3 units/kg) of the two regular insulins in participants with type 1 diabetes (T1DM) with a washout period of 14 (± 7) days between tests. RESULTS: We evaluated 56 participants. The mean participant age and body mass index were 32.9 years and 22.9 kg/m2 , respectively. The ratios (experimental/reference) of the geometric means of maximum plasma insulin concentration and for plasma insulin area under the curve (AUC) were 0.909 (90% confidence interval [CI] 0.822-1.01) and 0.993 (90% CI 0.944-1.04), respectively. The ratios of the geometric means of maximum glucose infusion rate (GIR) and for GIR AUC were 0.999 (95% CI 0.912-1.09) and 1.04 (95% CI 0.962-1.12), respectively. CONCLUSIONS: The experimental product regular human insulin and comparator Humulin® R are bioequivalent in patients with T1DM. Wider entry to the pharmaceutical market of affordable, biosimilar regular insulins may substantially improve access to insulin for many socioeconomically disadvantaged patients with diabetes.

Gross anatomy of the longitudinal fascicle of Sapajus sp.

Opposing genetic and cultural-social explanations for the origin of language are currently the focus of much discussion. One of the functions linked to the longitudinal fascicle is language, which links Wernicke's area and Broca's area in the brain, and its size should indicate the brain increase in the evolution. Sapajus is a New World primate genus with high cognition and advanced tool use similar to that of chimpanzees. A study of the gross anatomy of the longitudinal fascicle of Sapajus using Kingler's method found it to differ from other studied primates, such as macaques and chimpanzees, mainly because its fibers join the cingulate fascicle. As in other non-human primates, the longitudinal fascicle of Sapajus does not reach the temporal lobe, which could indicate a way of separating these fascicles to increase white matter in relation to individual function. The study of anatomical structures seems very promising for understanding the basis of the origin of language. Indeed, socio-historical-cultural philosophy affirms the socio-cultural origin of speech, although considering the anatomical structures behind it working as a functional system.

Suggestive diagnosis of attention-deficit/hyperactivity disorder in indigenous children and adolescents from the Brazilian Amazon.

The prevalence of attention-deficit/hyperactivity disorder (ADHD) symptoms has been scarcely studied in indigenous cultures that preserve ancestral cultural characteristics. The objective of the study is to estimate the prevalence of suggestive diagnosis of ADHD among indigenous children and adolescents from villages in the Amazon. This is an analytical cross-sectional study using instruments to track ADHD symptoms (the Child Behaviour Checklist for ages 6-18: CBCL/6-18 and the teacher report form for ages 6-18: TRF/6-18) and to investigate their negative impact on the patients (using the Strengths and Difficulties Questionnaire-SDQ). The prevalence of a suggestive ADHD diagnosis according to the CBCL/TRF DSM-IV ADHD subscale without and with negative impact as assessed by the SDQ was 4.3% and 1.1%, respectively. Comorbid oppositional-defiant, conduct problems and anxious symptoms were present in all cases screening positive for ADHD. We also presented a case report as an illustration of the observed clinical presentation. ADHD is a recognizable disorder even in a culture that preserves millennial characteristics. Furthermore, the presence of ADHD symptoms was associated with significant impairment.

The Confrontation between Ethnopharmacology and Pharmacological Tests of Medicinal Plants Associated with Mental and Neurological Disorders.

For neurological disorders, pharmacological tests have shown promising results in the reduction of side effects when using plants with known therapeutic effects in the treatment of some types of dementia. Therefore, the goals of this study are to gather data about the major medicinal plants used in the nervous system as described in ethnopharmacological surveys from South America and Brazil and to compare this data with the results from pharmacological tests on the active principles of those same plants found in the scientific literature. After collecting the data about each plant, their respective popular indication was compared with the results found through pharmacological tests. The discrepancy rate between the effects observed by ethnopharmacological and pharmacological methods in this study is greater than 50%. In conclusion, despite the importance of ethnopharmacological data, it is important to make comparisons with pharmacological tests for the same plants, since the pharmacological studies, although few, have shown a high rate of discrepancy in the results.

Anatomical Study of Intrahemispheric Association Fibers in the Brains of Capuchin Monkeys (Sapajus sp.).

Previous studies suggest that the complexity of fiber connections in the brain plays a key role in the evolutionary process of the primate brain and behaviors. The patterns of brain fiber systems have been studied in detail in many nonhuman primates, but not in Sapajus sp. Behavioral studies indicated that Sapajus sp. (bearded capuchins) show highly cognitive behaviors such as tool use comparable to those in other nonhuman primates. To compare the brain fiber systems in capuchins with those in other nonhuman primates and humans, the intrahemispheric fibers systems in 24 cerebral hemispheres of Sapajus were dissected by a freezing-thawing procedure. Dissection of the hemispheres in lateral view indicated short arcuate fibers, uncinate fasciculus, and inferior longitudinal fasciculus, while that in a medial view indicated short arcuate fibers, the cingulum united with the superior longitudinal fasciculus, and inferior longitudinal fasciculus. The results showed that the fiber systems in Sapajus are comparable to those in rhesus and humans, except for a lack of independent superior longitudinal fasciculus and cingulum in Sapajus.

Posterior cortical atrophy--a prototypical case of dementia beginning with visual symptoms: case report.

Dementia presenting with prominent higher order visual symptoms may be observed in a range of neurodegenerative conditions and is often challenging to diagnose. We describe a case of progressive dementia presenting with prominent visual cortical symptoms. A 55-year-old, right-handed, woman with early onset of visual impairment not associated with anterior visual pathology, presenting with dyslexia, visual agnosia, Balint's syndrome, and spatial disorientation. Ophthalmologists should consider this condition especially in presenile patients with slowly progressive higher-order visual symptoms. Although described in association with different conditions, it may also occur in Alzheimer disease.

Posterior cortical atrophy - a prototypical case of dementia beginning with visual symptoms: case report / Atrofia cortical posterior - um caso prototípico de demência iniciando com sintomas visuais: relato de caso

Dementia presenting with prominent higher order visual symptoms may be observed in a range of neurodegenerative conditions and is often challenging to diagnose. We describe a case of progressive dementia presenting with prominent visual cortical symptoms. A 55-year-old, right-handed, woman with early onset of visual impairment not associated with anterior visual pathology, presenting with dyslexia, visual agnosia, Balint's syndrome, and spatial disorientation. Ophthalmologists should consider this condition especially in presenile patients with slowly progressive higher-order visual symptoms. Although described in association with different conditions, it may also occur in Alzheimer disease.

As demências que se apresentam predominantemente com sintomas visuais associativos podem ser observadas em diferentes condições neurodegenerativas, sendo seu diagnóstico muitas vezes desafiador. Descrevemos um caso com demência progressiva que se apresentam com sintomas visuais proeminentes. Mulher de 55 anos, destra, com início precoce de déficits visuais não associados a patologia visual anterior, apresentando dislexia, agnosia visual, síndrome de Balint e desorientação espacial. Os oftalmologistas devem ter em mente essa condição especialmente em pacientes pré-senis com queixas visuais complexas e lentamente progressivas. Apesar de descritas em diferentes condições, pode ocorrer na doença de Alzheimer.

HIV-associated dementia in older adults: clinical and tomographic aspects.

BACKGROUND: Elderly adults with human immunodeficiency virus (HIV) are at greater risk of developing cognitive impairment. The purpose of this study was to describe clinical and tomographic characteristics of HIV-1 associated dementia (HIVD) in older adults. METHODS: A descriptive study was carried out involving eight HIVD patients. Seven tests were employed for cognitive assessment and transformed to whole number z-scores using appropriate normative sets. RESULTS: The average age of the patients was 71 years; seven cases described the route of HIV infection as being heterosexual; and mean schooling was 6.5 years. Six subjects were using highly active anti-retroviral therapy (HAART), with an average CD4 count of 407.8 cells/mm3. Mild dementia was detected in most cases (87.5%). Deficits on neuropsychological tests showed results similar to multi-center transversal studies on HIVD. The classic HIVD triad observed in younger adults was also seen in this population: i.e. cognitive changes, psychiatric changes and motor impairment. Cortical injury shown by dyscalculia, visual-spatial change and language deficits were frequent. Brain images showed cortical atrophy in all patients but was restricted to frontal lobes in five cases. CONCLUSION: The findings on brain imaging were non-specific, revealing images similar to those of the elderly brain and to HIVD in younger adults. HIVD in the elderly is a challenge and become an increasingly significant differential diagnosis for cognitive loss in old age. This dementia must be clinically suspected and image exams are useful in excluding other central disorders. Prospective studies of HIV-positive elderly people are warranted to better understand HIVD.

The prefrontal areas and cerebralhemispheres of the neotropicalCebus apella and their correlationswith cognitive processes / Áreas pré-frontais e hemisférios cerebrais do Cebus apella neotropical e suas correlações aos processos cognitivos

The organization of the prefrontal cortex can hold important clues to understanding its functioning. The Cebus apella present cerebral particularities and behavioral and cognitive flexibility, possessing abilities that demonstrate an overlap with those of big primates. Objectives: To provide evidence of correlations between anatomical particularities of the brain areas analyzed and some cognitive abilities previously described in these simians. Methods: The relative size of the cerebral hemispheres and prefrontal areas (PFA) were measured using a Universal caliper, in 24 hemispheres of C. apella fixed with 10% formaldehyde and kept in 70% alcoholic solution. Results: Data gathered allowed the calculation of the approximate volume (cm3) of the areas under study: right antimere 35.2 cm3 (±5.3), left antimere 31.3 cm3 (±5.4) and of the left PFA 6.0 cm3 (±1.5) and right PFA 6.9 cm3 (±1.7). Conclusions: We concluded that the PFA represents about 20% of the cerebral volume of this primate. No significant differences were found in the antimeres in terms of volume and area of the hemispheres and likewise for the PFA. These animals have a proportionally bigger brain than that of other neotropical primates in the literature. This allows us to infer that the frontal lobe of C. apella is also larger; possibly related to its maturity and developed cognitive functions indicative of the culture transfers characteristic of this species.

A organização do córtex pré-frontal pode conter dados importantes para a compreensão de seu funcionamento. Os Cebus apella apresentam particularidades cerebrais e flexibilidade comportamental e cognitiva, possuindo habilidades que demonstram destacada sobreposição sobre grandes primatas. Objetivos: Fornecer subsídios para realização de correlações entre particularidades anatômicas das regiões encefálicas analisadas e algumas habilidades cognitivas já descritas nestes símios. Métodos: Analisamos o tamanho relativo dos hemisférios cerebrais e da região pré-frontal (RPF), utilizando paquímetro universal, em 24 hemisférios cerebrais de C. apella fixados em formol a 10% e conservados em solução alcoólica a 70%. Resultados: Os dados obtidos permitiram-nos calcular o volume (cm3) aproximado das áreas estudadas: antímero direito 35,2 cm3 (±5,3), antímero esquerdo 31,3 cm3 (±5,4) e das RPF esquerda 6,0 cm3 (±1,5) e a direita 6,9 cm3 (±1,7). Conclusões: Concluímos que a RPF representa aproximadamente 20% do volume cerebral deste primata. Não constatamos diferenças significativas nos antímeros em relação aos volumes e às áreas tanto dos hemisférios cerebrais como das RPF. Estes animais apresentaram tamanho cerebral proporcionalmente maior que os demais primatas neotropicais quando comparamos nossos achados com a literatura disponível, permitindo-nos inclusive inferir que há uma grande amplitude do lobo frontal em C. apella; possivelmente relacionada à maturidade e às funções cognitivas elaboradas indicativas de transferência de cultura características deste animal.

Prevalência e estudo neuropsicológico de transtornos cognitivos decorrentes de neuroinfecções em hospital de referência / Prevalence and neuropsychology study of cognition diseases in neuroinfections in a reference hospital

JUSTIFICATIVA E OBJETIVOS: Várias doenças infecciosas e parasitárias foram descritas como possíveis causadoras de prejuízos cognitivos, destacando-se as neuroinfecções que, pela localização no sistema nervoso central (SNC), podem evoluir para quadros demenciais francos (embora passíveis de reversão). As vastas possibilidades etiológicas tem como resultado grande heterogeneidade de sintomas neuropsiquiátricos, o que pode dificultar a avaliação clínica, mas se forem utilizados os recursos de testes neuropsicológicos, aumenta-se as probabilidades de detecção de sintomas cognitivos e comportamentais e consequentemente a precisão diagnóstica. O estudo teve como objetivo estimar a prevalência de alterações cognitivas nas neuroinfecções.MÉTODO: A amostra foi composta por 60 pacientes portadores de infecção do SNC no intuito de identificar possíveis alterações do desempenho no Mini-Exame do Estado Mental (MEEM).RESULTADOS: Através da aplicação do MEEM verificou-se que 20 pacientes (33,3%) apresentaram transtornos cognitivos sem demência e 23 pacientes foram diagnosticados com demências, sendo este o quadro neuropsicológico mais prevalente (38,3). CONCLUSÃO: Observou-se alta prevalência de transtornos cognitivos entre os quadros de neuroinfecções, demonstrando a necessidade de investigação de aspectos cognitivos nos pacientes portadores de infecções do SNC.(AU)

BACKGROUND AND OBJECTIVES: Several infectious and parasitics diseases were described as possible causes of cognition losses, mainly neuroinfections, which, due to their location in the CNS, can evolve to dementia (although possible of reversal). The wide etiologic possibilities are a result of a large number of neuropsychiatric symptoms, which may complicate clinical evaluation. However, by using neuropsychological tests, the chances of detecting cognitive and behavioral symptoms are increased as well as precision in diagnosis. The study estimates the prevalence of cognition disorders in neuroinfection.METHOD: We evaluated patients with infection in CNS for identification of possible alterations in Mini Mental State (MMSE).RESULTS: based on MMSE, it was observed that 20 patients (33.3%) presented cognition diseases without dementia, and 23 patients were diagnosed with dementia, which was the most common neuropsychological alteration (38.3%).CONCLUSION: Through this study, high prevalence of cognition disorders was found among neuroinfections, which shows the need of cognitive aspects investigation in infection of the CNS.(AU)

The prefrontal areas and cerebral hemispheres of the neotropical Cebus apella and its correlations with cognitive processes.

The organization of the prefrontal cortex can hold important clues to understanding its functioning. The Cebus apella present cerebral particularities and behavioral and cognitive flexibility, possessing abilities that demonstrate an overlap with those of big primates. OBJECTIVES: To provide evidence of correlations between anatomical particularities of the brain areas analyzed and some cognitive abilities previously described in these simians. METHODS: The relative size of the cerebral hemispheres and prefrontal areas (PFA) were measured using a Universal caliper, in 24 hemispheres of C. apella fixed with 10% formaldehyde and kept in 70% alcoholic solution. RESULTS: Data gathered allowed the calculation of the approximate volume (cm3) of the areas under study: right antimere 35.2cm3 (±5.3), left antimere 31.3cm3 (±5.4) and of the left PFA 6.0cm3 (±1.5) and right PFA 6.9cm3 (±1.7). CONCLUSIONS: We concluded that the PFA represents about 20% of the cerebral volume of this primate. No significant differences were found in the antimeres in terms of volume and area of the hemispheres and likewise for the PFA. These animals have a proportionally bigger brain than that of other neotropical primates in the literature. This allows us to infer that the frontal lobe of C. apella is also larger; possibly related to its maturity and developed cognitive functions indicative of the culture transfers characteristic of this species.

A organização do córtex pré-frontal pode conter dados importantes para a compreensão de seu funcionamento. Os Cebus apella apresentam particularidades cerebrais e flexibilidade comportamental e cognitiva, possuindo habilidades que demonstram destacada sobreposição sobre grandes primatas. OBJETIVOS: Fornecer subsídios para realização de correlações entre particularidades anatômicas das regiões encefálicas analisadas e algumas habilidades cognitivas já descritas nestes símios. MÉTODOS: Analisamos o tamanho relativo dos hemisférios cerebrais e da região pré-frontal (RPF), utilizando paquímetro universal, em 24 hemisférios cerebrais de C. apella fixados em formol a 10% e conservados em solução alcoólica a 70%. RESULTADOS: Os dados obtidos permitiram-nos calcular o volume (cm3) aproximado das áreas estudadas: antímero direito 35,2cm3 (±5,3), antímero esquerdo 31,3cm3 (±5,4) e das RPF esquerda 6,0cm3 (±1,5) e a direita 6,9cm3 (±1,7). CONCLUSÕES: Concluímos que a RPF representa aproximadamente 20% do volume cerebral deste primata. Não constatamos diferenças significativas nos antímeros em relação aos volumes e às áreas tanto dos hemisférios cerebrais como das RPF. Estes animais apresentaram tamanho cerebral proporcionalmente maior que os demais primatas neotropicais quando comparamos nossos achados com a literatura disponível, permitindo-nos inclusive inferir que há uma grande amplitude do lobo frontal em C. apella; possivelmente relacionada à maturidade e às funções cognitivas elaboradas indicativas de transferência de cultura características deste animal.

Estudos epidemiológicos em neuropsiquiatria infantil com ênfase no transtorno de déficit de atenção e hiperatividade / Epidemiologic studies in childhood neuropsychiatry with emphasis on attention deficit disorder with hyperactivity

As estimativas de prevalência mundial em neuropsiquiatria infantil são muito heterogêneas. As razões desta discrepância permanecem malcompreendidas. Localização geográfica desempenha um papel limitado nas razões da grande variabilidade nas prevalências mundiais de transtornos em neuropsiquiatria infantil. Em vez disso, esta variabilidade parece ser explicada principalmente pelas características metodológicas dos estudos. Estimativas da prevalência do transtorno de déficit de atenção e hiperatividade (TDAH) e da taxa de persistência dos sintomas em toda a vida são heterogêneas, o que levanta dúvidas sobre a validade do diagnóstico. As melhores estimativas disponíveis sobre a prevalência de TDAH é de cerca de 5,29%, para crianças e adolescentes. As estimativas de prevalência e taxa de TDAH parecem ser muito afetados pelas características metodológicas dos estudos.

The worldwide prevalence estimates of neuropsychiatric disorders in childhood are highly heterogeneous. The reasons for this discrepancyremain poorly understood. Geographic location plays a limited role in the reasons for the large variability of neuropsychiatric disordersprevalence in childhood estimates worldwide. Instead, this variability seems to be explained primarily by the methodological characteristics ofstudies. Prevalence estimates of the attention-deficit hyperactivity disorder (ADHD) and the rate of persistence of symptoms across the lifespan are heterogeneous, raising questions about the validity of the diagnosis. The best available estimates of ADHD prevalence are around 5.29% for children and adolescents. Estimates of ADHD prevalence seem to be highly affected by methodological characteristics of the studies.

Do attention deficit/hyperactivity disorder symptoms exist among Brazilian indigenous children?

The validity of the clinical constructs of attention deficit hyperactivity disorder (ADHD) has been generalized for all human populations of different cultures worldwide. Yet important population groups have yet to be adequately studied so as to definitively confirm this generalization. OBJECTIVE: To investigate the presence of symptoms of ADHD in children living within an indigenous community. METHODS: We performed interviews in a bid to screen for symptoms of ADHD among settlement-dwelling indigenous children of the Karajá ethnic group in the Brazilian Amazonian Region. RESULTS: Three narratives are presented highlighting the classical symptomatological triad of ADHD: inattentiveness, hyperactivity and impulsiveness. CONCLUSIONS: Some of ADHD's major characteristics, described in the most common disease classification worldwide, are clearly described by children of this population. We concluded that ADHD symptoms are present in this population which diverges greatly in cultural issues compared to the Western world.

A validade dos construtos clínicos do transtorno de déficit de atenção e hiperatividade (TDAH) tem sido generalizados para todas as populações humanas de diferentes culturas pelo mundo afora. Ainda importantes grupos populacionais continuam exigindo estudos adequados de forma a confirmar definitivamente tal generalização. OBJETIVO: Investigar a presença de sintomas do TDAH entre crianças de comunidade indígena. MÉTODOS: Realizamos entrevistas nas quais se explora a possibilidade da existência de sintomas do TDAH entre crianças indígenas da etnia Karajá, aldeiadas, na região da Amazônia Brasileira. RESULTADOS: Três narrativas são apresentadas e evidenciam a tríade sintomatológica clássica do TDAH: desatenção, hiperatividade e impulsividade. CONCLUSÕES: Alguns dos sintomas característicos do TDAH, descritos nas classificações de doenças mais utilizadas no mundo, são claramente referidos por crianças dessa população. Concluímos que existem sintomas do TDAH nessa população, tão distinta culturalmente do mundo ocidental.

Hanseníase: revisão para o neurologista / Hanseniasis: review for the neurologist

A hanseníase (mal de Hansen, lepra) é uma doença infecto-contagiosa crônica endêmica no Brasil, causada pelo Mycobacterium leprae, e constitui um sério problema de Saúde Pública em muitos países. Caracteriza-se por manifestações neurológicas e dermatológicas que acarretam, em geral após longa evolução, deformidades e mutilações que tanto concorrem para a estigmatização dessa moléstia. Muito embora já exista tratamento eficaz para a hanseníase (poliquimioterapia), o estigma persiste. Podem ocorrer episódios inflamatórios agudos ou subagudos, cutâneos e/ou extra-cutâneos, antes, durante ou após o tratamento, que são chamados estados ou episódios reacionais.

Hansen's disease (leprosy) is a chronic, endemic infectious disease, caused by M. leprae, and a problem of Public Health in many countries, like Brazil. Most often involves the skin and peripheral nerves, with a broad range of clinical presentations, which may acquire clinical and immunological aspects at each pole. Sometimes this can lead to disabilities and morbidity characterized by the historical stigma typical to leprosy, that persists nowadays in spite of new treatments (polychemotherapy) and cure. Leprosy reactions are considered acute and inflammatory complications that may occur before, during and/or after specific treatment.