Neurological manifestations by sex and age group in COVID-19 inhospital patients.

Introduction: Neurological manifestations have been associated with a poorer prognosis in COVID-19. However, data regarding their incidence according to sex and age groups is still lacking. Methods: This retrospective multicentric cohort collected data from 39 Brazilian hospitals from 17 cities, from adult COVID-19 admitted from March 2020 to January 2022. Neurological manifestations presented at hospital admission were assessed according to incidence by sex and age group. Results: From 13,603 COVID-19 patients, median age was 60 years old and 53.0% were men. Women were more likely to present with headaches (22.4% vs. 17.7%, p < 0.001; OR 1.36, 95% confidence interval [CI] 1.22-1.52) than men and also presented a lower risk of having seizures (OR 0.43, 95% CI 0.20-0.94). Although delirium was more frequent in women (6.6% vs. 5.7%, p = 0.020), sex was not associated with delirium in the multivariable logistc regresssion analysis. Delirium, syncope and coma increased with age (1.5% [18-39 years] vs. 22.4% [80 years or over], p < 0.001, OR 1.07, 95% CI 1.06-1.07; 0.7% vs. 1.7%, p = 0.002, OR 1.01, 95% CI 1.00-1.02; 0.2% vs. 1.3% p < 0.001, OR 1.04, 95% CI 1.02-1.06), while, headache (26.5% vs. 7.1%, OR 0.98, 95% CI 0.98-0.99), anosmia (11.4% vs. 3.3%, OR 0.99, 95% CI] 0.98-0.99 and ageusia (13.1% vs. 3.5%, OR 0.99, CI 0.98-0.99) decreased (p < 0.001 for all). Conclusion: Older COVID-19 patients were more likely to present delirium, syncope and coma, while the incidence of anosmia, ageusia and headaches decreased with age. Women were more likely to present headache, and less likely to present seizures.

Mitochondrial dysfunction in Alzheimer's disease: Therapeutic implications of lithium.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by the accumulation of abnormal tau proteins within neurons and amyloid plaques in the brain parenchyma, which leads to progressive loss of neurons in the brain. While the detailed mechanism of the pathogenesis of AD is still unknown, evidence suggests that mitochondrial dysfunction likely plays a fundamental role in the pathogenesis of this disease. Due to the relevance of mitochondrial alterations in AD, recent works have suggested the therapeutic potential of mitochondrial-targeted lithium. Lithium has been shown to possess neuroprotective and neurotrophic properties that could also be related to the upregulation of mitochondrial function. In the current work, we perform a comprehensive investigation of the significance of mitochondrial dysfunction in AD and pharmacological treatment with lithium as imperative in this pathology, through a brief review of the major findings on the effects of lithium as a therapeutic approach targeting mitochondria in the context of AD.

O espectro clínico e laboratorial da doença de Alzheimer: uma perspectiva neurológica / The clinical and laboratory spectrum of Alzheimer's disease: a neurological perspective / El espectro clínico y de laboratorio de la enfermedad de Alzheimer: una perspectiva neurológica

Esta revisão da literatura tem como objetivo mostrar recentes mudanças relacionadas ao diagnóstico da doença de Alzheimer (DA). O diagnóstico permanece clínico, no entanto, há um entendimento crescente de que biomarcadores específicos no líquido cefalorraquidiano e na neuroimagem molecular possam desempenhar um papel importante na definição etiopatogênica da doença. Os biomarcadores podem ser importantes para o diagnóstico nos estágios iniciais da DA. Considerando que a DA seja um processo fisiopatológico cerebral, a presença de biomarcadores específicos indica o diagnóstico de DA. Atualmente, o uso de biomarcadores é direcionado para pesquisa clínica e para o desenvolvimento de novas drogas.

This narrative review of the literature aims to show the most recent changes related to the diagnosis of Alzheimer's disease (AD). The diagnosis remains clinical, however, there is a growing understanding that specific biomarkers in cerebrospinal fluid and molecular neuroimaging may play an important role in the etiopathogenic definition of the disease. Biomarkers may be particularly important for the diagnosis in the early stages of AD. Considering that AD is a brain pathophysiological process, the presence of AD biomarkers indicates the diagnosis of AD. Currently, the use of biomarkers is directed towards clinical research and the development of new drugs.

Esta revisión narrativa de la literatura tiene como objetivo mostrar los cambios recientes relacionados con el diagnóstico de la enfermedad de Alzheimer (EA). El diagnóstico es clínico, sin embargo, existe una creciente comprensión de que los biomarcadores en el líquido cefalorraquídeo y neuroimagen molecular pueden desempeñar un papel importante en la definición etiopatogénica. Los biomarcadores pueden ser importantes para el diagnóstico en las primeras etapas de la EA. Reconociendo que la EA es un proceso fisiopatológico cerebral, la presencia de biomarcadores indica EA. Actualmente, el uso de biomarcadores está dirigido a la investigación clínica y al desarrollo de nuevos fármacos.

Wnt Signaling Pathway Dysregulation in the Aging Brain: Lessons From the Octodon degus.

Wnt signaling constitutes a fundamental cellular and molecular pathway, necessary from proper embryogenesis to function-maintenance of fully developed complex organisms. In this regard, Wnt pathway plays a crucial role in both the development of the central nervous system and in maintaining the structure and function of the neuronal circuits, and it has been suggested that its dysregulation is critical in the onset of several pathologies including cancer and neurodegenerative disorders, such as Alzheimer's disease (AD). Due to its relevance in the maintenance of the neuronal activity and its involvement in the outbreak of devastating diseases, we explored the age-related changes in the expression of Wnt key components in the cortex and hippocampus of 7 to 72-months-old Octodon degus (O. degus), a Chilean long-living endemic rodent that has been proposed and used as a natural model for AD. We found a down-regulation in the expression of different Wnt ligands (Wnt3a, Wnt7a, and Wnt5a), as well as in the Wnt co-receptor LRP6. We also observed an increase in the activity of GSK-3ß related to the down-regulation of Wnt activity, a fact that was confirmed by a decreased expression of Wnt target genes. Relevantly, an important increase was found in secreted endogenous Wnt inhibitors, including the secreted-frizzled-related protein 1 and 2 (SFRP-1 and SFRP-2) and Dickkopf-1 (Dkk-1), all them antagonists at the cell surface. Furthermore, treatment with Andrographolide, a labdane diterpene obtained from Andrographis paniculata, prevents Wnt signaling loss in aging degus. Taken together, these results suggest that during the aging process Wnt signaling activity decreases in the brain of O. degus.

Oocytes, embryos and pluripotent stem cells from a biomedical perspective

The veterinary and animal science professions are rapidly developing and their inherent and historical connection to agriculture is challenged by more biomedical and medical directions of research. While some consider this development as a risk of losing identity, it may also be seen as an opportunity for developing further and more sophisticated competences that may ultimately feed back to veterinary and animal science in a synergistic way. The present review describes how agriculture-related studies on bovine in vitro embryo production through studies of putative bovine and porcine embryonic stem cells led the way to more sophisticated studies of human induced pluripotent stem cells (iPSCs) using e.g. gene editing for modeling of neurodegeneration in man. However, instead of being a blind diversion from veterinary and animal science into medicine, these advanced studies of human iPSC-derived neurons build a set of competences that allowed us, in a more competent way, to focus on novel aspects of more veterinary and agricultural relevance in the form of porcine and canine iPSCs. These types of animal stem cells are of biomedical importance for modeling of iPSC-based therapy in man, but in particular the canine iPSCs are also important for understanding and modeling canine diseases, as e.g. canine cognitive dysfunction, for the benefit and therapy of dogs.(AU)

Use of clinical form for recognition of cognitive disturbance in elderly dogs / Utilização de formulário clínico para reconhecimento de distúrbio cognitivo em cães idosos

The canine cognitive disorders (DCC) is a neurobehavioral syndrome that affects elderly animals, characterized by deficiencies in learning, memory and space perception, as well as changes in social interactions and sleep pattern. In spite of its common occurrence, it is not diagnosed and treated, since the neu­rocognitive behavioral changes are commonly considered as part of the normal aging process by the owners. This study evaluated the cognitive function in 30 dogs over than 8 years old, through a behavioral form, it was observed that 93% of the animals showed alteration in more than one category. The categories most affected were Category B (relationships and social behavior) with 78,6% (n= 22) of the total of cases and Category C (activity level) also in 78,6% of cases. No differences were observed between gender nor between the age and the pre­sence of signs of DCC.

O distúrbio cognitivo canino (DCC) é uma síndrome neurocomportamental que acomete animais idosos, caracterizado por deficiências na aprendizagem, memória e percepção espacial, bem como alterações em interações sociais e padrão de sono. Apesar de ocorrência comum é pouco diagnosticado e tratado, uma vez que as mudanças comportamentais neuro cognitivas são comumente considerados como parte do processo normal de envelhecimento pelos proprietários. Este estudo avaliou a função cognitiva de 30 cães com mais de oito anos de idade, através de um formulário comportamental, observou-se que 93% dos animais apresentaram alteração em mais de uma categoria. As categorias mais acometidas foram Categoria B (relacionamentos e comportamento social) com 78,6% (n=22) dos casos e Categoria C (nível de atividade) também com 78,6% dos casos. Não foram observadas diferenças entre gênero ou na correção entre idade e presença de sinais de DCC.

Use of clinical form for recognition of cognitive disturbance in elderly dogs / Utilização de formulário clínico para reconhecimento de distúrbio cognitivo em cães idosos

The canine cognitive disorders (DCC) is a neurobehavioral syndrome that affects elderly animals, characterized by deficiencies in learning, memory and space perception, as well as changes in social interactions and sleep pattern. In spite of its common occurrence, it is not diagnosed and treated, since the neu­rocognitive behavioral changes are commonly considered as part of the normal aging process by the owners. This study evaluated the cognitive function in 30 dogs over than 8 years old, through a behavioral form, it was observed that 93% of the animals showed alteration in more than one category. The categories most affected were Category B (relationships and social behavior) with 78,6% (n= 22) of the total of cases and Category C (activity level) also in 78,6% of cases. No differences were observed between gender nor between the age and the pre­sence of signs of DCC.(AU)

O distúrbio cognitivo canino (DCC) é uma síndrome neurocomportamental que acomete animais idosos, caracterizado por deficiências na aprendizagem, memória e percepção espacial, bem como alterações em interações sociais e padrão de sono. Apesar de ocorrência comum é pouco diagnosticado e tratado, uma vez que as mudanças comportamentais neuro cognitivas são comumente considerados como parte do processo normal de envelhecimento pelos proprietários. Este estudo avaliou a função cognitiva de 30 cães com mais de oito anos de idade, através de um formulário comportamental, observou-se que 93% dos animais apresentaram alteração em mais de uma categoria. As categorias mais acometidas foram Categoria B (relacionamentos e comportamento social) com 78,6% (n=22) dos casos e Categoria C (nível de atividade) também com 78,6% dos casos. Não foram observadas diferenças entre gênero ou na correção entre idade e presença de sinais de DCC.(AU)

Alteration of Golgi Structure by Stress: A Link to Neurodegeneration?

The Golgi apparatus is well-known for its role as a sorting station in the secretory pathway as well as for its role in regulating post-translational protein modification. Another role for the Golgi is the regulation of cellular signaling by spatially regulating kinases, phosphatases, and GTPases. All these roles make it clear that the Golgi is a central regulator of cellular homeostasis. The response to stress and the initiation of adaptive responses to cope with it are fundamental abilities of all living cells. It was shown previously that the Golgi undergoes structural rearrangements under various stress conditions such as oxidative or osmotic stress. Neurodegenerative diseases are also frequently associated with alterations of Golgi morphology and many stress factors have been described to play an etiopathological role in neurodegeneration. It is however unclear whether the stress-Golgi connection plays a role in neurodegenerative diseases. Using a combination of bioinformatics modeling and literature mining, we will investigate evidence for such a tripartite link and we ask whether stress-induced Golgi arrangements are cause or consequence in neurodegeneration.

The impact of base excision DNA repair in age-related neurodegenerative diseases.

The aging process and several age-related neurodegenerative disorders have been linked to elevated levels of DNA damage induced by ROS and deficiency in DNA repair mechanisms. DNA damage induced by ROS is a byproduct of cellular respiration and accumulation of damage over time, is a fundamental aspect of a main theory of aging. Mitochondria have a pivotal role in generating cellular oxidative stress, and mitochondrial dysfunction has been associated with several diseases. DNA base excision repair is considered the major pathway for repair of oxidized bases in DNA both in the nuclei and in mitochondria, and in neurons this mechanism is particularly important because non-diving cells have limited back-up DNA repair mechanisms. An association between elevated oxidative stress and a decrease in BER is strongly related to the aging process and has special relevance in age-related neurodegenerative diseases. Here, we review the role of DNA repair in aging, focusing on the implications of the DNA base excision repair pathways and how alterations in expression of these DNA repair proteins are related to the aging process and to age-related neurodegenerative diseases.

Evolución de la categorización semántica en adultos mayores con diagnóstico de DCL-A y DTA y sin patología neurológica / Evolution of semantic categorization in older adults with and without neurological disease

Tradicionalmente la memoria semántica ha sido definida como un tesoro mental que almacena información sobre las palabras, su significado, como así también la relación entre ellas, los hechos y los conceptos. Una de las vías principales para explicar cómo se organiza la información en la memoria semántica (MS) es a través de categorías. La demencia tipo Alzheimer (DTA) suele estar caracterizada por un deterioro en la memoria episódica. Sin embargo, se debate en torno al deterioro de la misma, en qué momento aparece, a qué se debe y si hay una pérdida diferencial en distintos momentos de la enfermedad. El objetivo del trabajo que se informa fue analizar los procesos de categorización semántica en adultos mayores sanos comparándolos con dos grupos de personas con patologías neurológicas: uno con diagnóstico de deterioro cognitivo leve (DCL) y otro con demencia tipo Alzheimer (DTA), emparejados por edad, nivel educativo y género. Para ello, se utilizaron tareas tradicionales para evaluar la memoria semántica y también un método novedoso, el DISTSEM, que permite evaluar las estimaciones que realizan las personas de las distancias semánticas entre los conceptos. Los resultados mostraron que el grupo de personas sin patología tuvo un rendimiento superior en todas las tareas en comparación con los grupos de personas con patología neurológica. Por otro lado, el grupo con DTA mostró un deterioro semántico afectando en primer lugar a la categoría seres vivos. El DCL preservó la estructura categorial sólo con pequeñas intrusiones. El DISTSEM mostró ser un instrumento adecuado para la discriminación entre sujetos sanos y DTA.(AU)

Traditionally, semantic memory has been defined as a mental trove that contains organized information about words and their meaning, as well as relationships between words, facts and concepts.There are different ways of explaining how the information in such memory system is represented and organized. One of the main ways of explaining this organization is through categories. Categorization starts the very moment that any sensorial perception is associated to an abstract category; it is the ability to organize information in equivalence classes, and it is very important because it allows us to summarize the information that we gather through our senses and thus facilitate its manipulation. Alzheimers disease (AD) is the main cause of dementia among older adults, and it is one of the most pressing sanitary, social and cultural problems of the present times. The main risk factor for the illness is age, for its prevalence augments exponentially from 65 to 85 years old, and due to the rise in life expectancy it is considered that it might be transformed into a world-wide epidemic in the coming years. The start of the illness is insidious and slowly progressing, and it is characterized by a loss of episodic memory from its beginnings. With respect to the deterioration of semantic memory in AD, a debate has arisen about its mode of presentation, its causes, and whether there is a differential loss of categories (live or non-live beings) in different moments of the illness. During the 90s, Petersen proposed the concept of mild cognitive impairment (MCI) to label the subjects with a functional cognitive impairment insufficient to diagnose a dementia syndrome. The importance of this syndrome is that between 8 to 15% of those who suffer it evolve to AD annually, while in the general population this evolution is only from 1 to 2%. However, there is a great controversy about the validity and scope of the term MCI, for its etiology can be very varied and it is very difficult to predict its evolution. There are different sub-kinds of MCI, and the amnesic form is the more likely to evolve into AD, for its main characteristic is the subjective deterioration of memory corroborated by standardized test by reference to normative data for the same age and educational level of the subject. The other cognitive functions not present alterations. The main objective of this work was to analyze the semantic categorization processes in healthy older adults comparing them with two groups of people with neurological pathologies, one with diagnosis of MCI and the other with AD, matched by age, educational level and gender. To evaluate this categorization process, two traditional tasks were used together with a novel method, the DISTSEM, which allows the evaluation of the estimation made by people about the semantic distance among a set of given concepts. The results showed that the group of people without pathologies had a superior performance in all the tasks in comparison with the groups of people with neurological pathologies. On the other hand, the group with AD showed a semantic impairment which affected in the first place the category of live beings, which was evident in the all the tasks. The MCI preserved the categorical structure with only minor intrusions. The DISTSEM has shown itself to be a valuable instrument that allows the discrimination between healthy subjects and those with AD. It is expected that this work can provide empirical evidence relevant to the debate surrounding semantic memory, for studies in patients with brain injury offer key information to examine the organizing models of such memory.(AU)

Niveles de aluminio sérico en un grupo de pacientes con enfermedad de Alzheimer / Serum levels of aluminum in a group of patients with Alzheimers disease / Níveis séricos de alumínio em um grupo de pacientes com doenþa de Alzheimer

La Enfermedad de Alzheimer (EA) es una patología neurodegenerativa frecuente en la población senil. Clínicamente se caracteriza por la pérdida progresiva de la memoria y otras habilidades cognitivas. Se han propuesto diversas causas como desencadenantes de la EA, entre las cuales se encuentran factores ambientales como malnutrición, lesiones a nivel craneal y exposición al aluminio (Al), debido a que este metal es una sustancia neurotóxica. El objetivo del presente estudio fue evaluar los niveles de aluminio sérico en pacientes con enfermedad de Alzheimer, internados en un geriátrico en el municipio Veroes, Estado Yaracuy, durante el período mayo-junio de 2013. La muestra estuvo conformada por 22 pacientes con EA, y el grupo control estuvo representado por 12 pacientes sin EA. Las concentraciones de aluminio sérico fueron determinadas por Espectrofotometría de Absorción Atómica Electrotérmica (ETAAS) con horno de grafito. Se obtuvieron valores de la mediana de aluminio sérico de 2,15 mg/L, con un máximo de elevación de 3,0 mg/L para el grupo con EA, mientras que el control fue de 1,60 mg/L, con un máximo de 3,30 mg/L. Ninguno de los pacientes presentaron niveles de Al sérico por encima del límite permisible. Se observaron cifras superiores de este metal en los pacientes con EA en comparación con el grupo control, además de ser significativamente mayores en el género femenino y en aquellos que consumían antiácidos.(AU)

Alzheimers disease (AD) is a common neurodegenerative disorder in the elderly population. It is clinically characterized by progressive loss of memory and other cognitive skills. There are several proposed AD causes as triggers, among which are environmental factors including malnutrition, cranial injuries and exposure level aluminum (Al), because this metal is a neurotoxic substance. The aim of this study was to evaluate serum aluminum levels in patients with Alzheimers disease, institutionalized in Veroes town, Yaracuy state during May-June 2013 period. The sample consisted of 22 patients with AD and the control group was represented by 12 patients without AD. Serum aluminum concentrations were determined by Electrothermal Atomic Absorption Spectrophotometry (ETAAS) with graphite furnace. Median values of serum aluminum of 2.15 mg/L, with a maximum height of 3.0 mg/L for the AD group were obtained, while the control was 1.60 mg/L, with a maximum of 3.30 mg/L. None of the patients had serum Al levels above the allowable limit. Higher figures of this metal were observed in patients with AD compared with the control group, as well as being significantly higher in females and in those eating antacids.(AU)

A doenþa de Alzheimer (DA) é uma desordem neurodegenerativa frequente na populaþÒo idosa. Clinicamente caracteriza-se pela perda progressiva da memória e outras habilidades cognitivas. Várias causas tÛm sido propostas como gatilhos para DA, incluindo fatores ambientais tais como a desnutriþÒo, les§es cranianas e exposiþÒo de alumínio (Al), devido a que este metal é uma substÔncia neurotóxica. O objetivo deste estudo foi avaliar os níveis de alumínio sérico em pacientes com doenþa de Alzheimer, hospitalizados na cidade Veroes, Estado Yaracuy, durante o período maio-junho de 2013. A mostra consistiu de 22 pacientes com DA e o grupo controle foi representado por 12 pacientes sem DA. Concentraþ§es de alumínio sérico foram determinadas por Espectrofotometria de AbsorþÒo At¶mica Eletrotérmica (ETAAS) com forno de grafite. Os valores da mediana de alumínio sérico de 2,15 mg/L, com uma altura máxima de 3,0 mg/L para o grupo DA foram obtidos, enquanto que para o grupo controle foi de 1,60 mg/L, com um máximo de 3,30 mg/L. Nenhum dos pacientes tinha níveis séricos de Al acima do limite permitido. Foram observados valores mais elevados deste metal nos pacientes com DA em comparaþÒo com o grupo controle, além de ser significativamente maior no sexo feminino e nas pessoas que consumiam antiácidos.(AU)

Building capacity for dementia care inLatin America and the Caribbean / Construção de capacidade para atendimento de pacientes com demência em América Latina E no Caribe

Latin America and the Caribbean (LAC) have limited facilities and professionals trained to diagnose, treat, and support people with dementia and other forms of cognitive impairment. The situation for people with dementia is poor, and worsening as the proportion of elderly in the general population is rapidly expanding. We reviewed existing initiatives and provided examples of actions taken to build capacity and improve the effectiveness of individuals, organizations, and national systems that provide treatment and support for people with dementia and their caregivers. Regional barriers to capacity building and the importance of public engagement are highlighted. Existing programs need to disseminate their objectives, accomplishments, limitations, and overall lessons learned in order to gain greater recognition of the need for capacity-building programs.

América Latina e Caribe (ALC) têm instalações e profissionais treinados para diagnosticar, tratar e apoiar as pessoas com demência e outras formas de comprometimento cognitivo limitado. A situação para as pessoas com demência é pobre, e piora quando a proporção de idosos na população em geral está se expandindo rapidamente. Revisamos as iniciativas já existentes, com exemplos de medidas tomadas para fortalecer a capacidade e melhorar a eficácia dos indivíduos, organizações e sistemas nacionais que fornecem tratamento e apoio às pessoas com demência e seus cuidadores. As barreiras regionais ao reforço das capacidades e a importância do engajamento público são realçados. Os programas existentes precisam divulgar seus objetivos, realizações, limitações e lições globais aprendidas a fim de obter maior reconhecimento da necessidade de programas de capacitação.

Brazilian research on cognitive impairment and dementia from 1999 to 2013 / Pesquisa científica em comprometimento cognitivo e demência no Brasil de 1999 a 2013

The phenomenon of demographic transition in recent decades has increased the number of elderly people in Brazil, promoting an escalation in chronic-degenerative conditions, particularly dementia and cognitive related disorders. Objective: The aim of this study was to assess the evolution of the Brazilian scientific publications on dementia and related conditions from 1999 to 2013. Methods: Articles published during the analysis period were searched on three electronic databases: Scopus, Medline (via PubMed) and Lilacs (via BVS). The keywords used were Alzheimers disease, dementia and mild cognitive impairment, with Brazil as the country of affiliation. Results: A total of 1,657 articles met the conditions for inclusion in the study. The output of Brazilian researchers in the area of cognitive disorders increased 11.38-fold in the fifteen-year period of analysis and 4.98-fold from 2003 to 2013. More than half of the articles (53%) were published in international journals. The majority of institutions involved in publications were public universities while 19% were collaborative studies involving Brazilian and international institutions. Conclusion: Despite marked growth, the number of Brazilian scientific publications in the area of cognitive impairment and dementia is still low. More effort is required to improve the output of Brazilian researchers and institutions. Possible strategies to accomplish this increase could be to encourage residents to participate in publications of scientific papers during their residence program and to increase the collaborations between different institutions within Brazil and with the international scientific community.

O fenômeno da transição demográfica nas últimas décadas aumentou o número de indivíduos idosos no Brasil, promovendo um avanço de condições crônico-degenerativas, particularmente demência e outros distúrbios cognitivos relacionados. Objetivo: A intenção deste estudo foi avaliar a evolução da produção científica brasileira em demência e condições relacionadas de 1999 a 2013. Métodos: Pesquisamos artigos publicados durante esse período em três bancos de dados eletrônicos: Scopus, Medline (via PubMed) e Lilacs (via BVS). As palavras-chave utilizadas foram doença de Alzheimer, demência e comprometimento cognitivo leve, com o Brasil como país de afiliação. Resultados: Um total de 1.657 artigos cumpriram as condições para inclusão no estudo. A produção de pesquisadores brasileiros na área de distúrbios cognitivos aumentou 11,38 vezes no período de análise e 4,98 vezes de 2003 a 2013. Mais da metade dos artigos (53%) foi publicada em periódicos internacionais. A maioria das instituições envolvidas em publicações eram universidades públicas e 19% eram estudos colaborativos envolvendo instituições brasileiras e internacionais. Conclusão: Apesar do crescimento expressivo, o número de publicações cientificas brasileiras na área de comprometimento cognitivo e demência é ainda baixo. Mais esforços são necessários para melhorar a produção de pesquisadores e instituições brasileiras. Possíveis estratégias para cumprir essa tarefa poderiam ser encorajar residentes a participar de publicações de artigos científicos durante seu programa de residência e aumentar as colaborações entre diferentes instituições brasileiras e com a comunidade científica internacional.

Demencia semántica y demencia tipo Alzheimer ¿Igual rendimiento en tareas semánticas? / Semantic dementia and Alzheimer´s disease: similar performance in semantic tasks?

Introducción: La Demencia Semántica (DS) y la Demencia de tipo Alzheimer (DTA) presentan deterioro semántico; sin embargo, existen pocos estudios comparativos que investiguen las características de éstos déficits en estas patologías. Objetivos: Comparar perfiles de desempeño en tareas semánticas en pacientes con DS y con DTA. Metodología: Se evaluaron 24 pacientes diagnosticados con DS (N=11) o DTA (N= 13) mediante tareas de denominación de dibujos, asociaciones semánticas y fluidez semántica. Resultados: Se hallaron diferencias significativas de rendimiento en las tres tareas semánticas respecto de los controles en ambos grupos de pacientes. Conclusiones: La DS y DTA poseen perfiles de deterioro semántico diferente. El grupo de pacientes con DS presentó mayor compromiso de la memoria semántica especialmente en la tarea de asociaciones semánticas.

Introduction: Semantic Dementia (SD) and Dementia of the Alzheimer´s type (DAT) have deficits in semantic memory. However there are few comparative studies to determine their characteristic semantic impairments. Objectives: Compare performance of semantic tasks in patients with SD and DAT. Methodology: We evaluated 24 patients diagnosed with SD (N = 11) and DAT (N =13). We administered semantic tasks of picture naming, semantic associations and semantic fluency. Results: Significant differences in performance in the three semantic tasks compared to controls in both patient groups were found. Conclusions: SD and DAT profiles have different semantic impairment. The group of patients with SD had higher commitment of semantic memory especially in the task of semantic associations.

Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD.

Biological markers of Alzheimers disease / Biomarcadores da doenca de Alzheimer

The challenges for establishing an early diagnosis of Alzheimer’s disease (AD) have created a need for biomarkers that reflect the core pathology of the disease. The cerebrospinal fluid (CSF) levels of total Tau (T-tau), phosphorylated Tau (P-Tau) and beta-amyloid peptide (Aβ42) reflect, respectively, neurofibrillary tangle and amyloid pathologies and are considered as surrogate markers of AD pathophysiology. The combination of low Aβ42 and high levels of T-tau and P-Tau can accurately identify patients with AD at early stages, even before the development of dementia. The combined analysis of the CSF biomarkers is also helpful for the differential diagnosis between AD and other degenerative dementias. The development of these CSF biomarkers has evolved to a novel diagnostic definition of the disease. The identification of a specific clinical phenotype combined with the in vivo evidence of pathophysiological markers offers the possibility to make a diagnosis of AD before the dementia stage with high specificity.

O desafio de se estabelecer o diagnóstico precoce de doença de Alzheimer (DA) levou ao desenvolvimento de biomarcadores que reflitam os aspectos patológicos centrais da doença. As dosagens no líquor da proteína Tau total (T-Tau), Tau fosforilada (P-Tau) e peptídeo beta-amiloide (Aβ42) no líquido cefalorraquidiano (LCR) refletem, respectivamente, as patologias Tau e amiloide, sendo consideradas como marcadores da fisiopatologia da DA. Os biomarcadores do LCR podem identificar acuradamente pacientes com DA em estágios precoces da doença, mesmo antes do desenvolvimento da demência. A análise combinada dos biomarcadores permite também fazer o diagnóstico diferencial entre DA e outras demências degenerativas. O desenvolvimento dos biomarcadores de DA conduziu a uma nova definição diagnóstica da doença. A identificação de um fenótipo clínico específico associado a uma evidência fisiopatológica in vivo provida por um biomarcador possibilita estabelecer, com alta especificidade, o diagnóstico de DA antes do estágio demencial.

Treadmill training as an augmentation treatment for Alzheimers disease: a pilot randomized controlled study / Treinamento na esteira como um tratamento adicional para a doenca de Alzheimer: estudo piloto controlado randomizado

Objective To assess the effect of aerobic exercise on the cognition and functional capacity in Alzheimer’s disease (AD) patients. Method Elderly (n=20) with mild dementia (NINCDS-ADRDA/CDR1) were randomly assigned to an exercise group (EG) on a treadmill (30 minutes, twice a week and moderate intensity of 60% VO2max) and control group (GC) 10 patients. The primary outcome measure was the cognitive function using Cambridge Cognitive Examination (CAMCOG). Specifics instruments were also applied to evaluate executive function, memory, attention and concentration, cognitive flexibility, inhibitory control and functional capacity. Results After 16 weeks, the EG showed improvement in cognition CAMCOG whereas the CG declined. Compared to the CG, the EG presented significant improvement on the functional capacity. The analysis of the effect size has shown a favorable response to the physical exercise in all dependent variables. Conclusion Walking on treadmill may be recommended as an augmentation treatment for patients with AD. .

Objetivo Avaliar o efeito do exercício aeróbio na cognição e na capacidade funcional em pacientes com Doença de Alzheimer (DA). Método Idosos (n=20) com demência leve ((NINCDS-ADRDA/CDR1) foram randomizados em grupo exercício (GE) na esteira (30 minutos, 2 vezes por semana e intensidade moderada de 60% VO2max)e grupo controle (GC) 10 pacientes. A medida principal foi a função cognitiva através do Cambridge Cognitive Examination (CAMCOG). Instrumentos específicos também foram aplicados para avaliar a função executiva, atenção e concentração, flexibilidade cognitiva, controle inibitório e capacidade funcional. Resultados Após 16 semanas, o GE mostrou melhora na cognição CAMCOG enquanto o CG declinou. Comparado ao GC, o GE apresentou melhora significativa na capacidade funcional. A análise do tamanho de efeito mostrou resposta favorável do exercício físico em todas as variáveis dependentes. Conclusão Caminhar na esteira pode ser recomendado como um tratamento adicional para pacientes com doença de Alzheimer. .

Overcoming barriers in cognitive assessment of Alzheimers disease / Superando barreiras na avaliação cognitiva da doença de Alzheimer

Diagnosis of Alzheimer's disease (AD) requires a reliable neuropsychological assessment, but major barriers are still encountered when such tests are used across cultures and during the lifespan. This is particularly problematic in developing countries where most of the available assessment tools have been adapted from developed countries. This represents a major limitation as these tests, although properly translated, may not embody the wealth of challenges that a particular culture poses on cognition. This paper centers on two shortcomings of available cognitive tests for AD, namely, their sensitivity to the educational background and to the age of the individual assessed.

O diagnóstico da doença de Alzheimer (DA) necessita de uma avaliação neuropsicológica de confiança, barreiras importantes ainda são encontradas quando esses testes são usados em através de culturas e durante a vida. Isto é particularmente problemático em países em desenvolvimento, onde a maioria das ferramentas de avaliação disponíveis foram adaptadas a partir de países desenvolvidos. Isto representa uma grande limitação, pois mesmo devidamente traduzidas, podem não pode capturar a riqueza de desafios que uma determinada cultura representa na cognição. Neste artigo vou me concentrar em duas falhas de testes cognitivos disponíveis para AD, sensibilidade ao nível educacional e idade do indivíduo avaliado.

Avaliação da qualidade de vida de cuidadores informais de idosos portadores da doença de Alzheimer / Evaluation of quality of life of informal caregivers of elderly patients with Alzheimer's disease / Evaluación de la calidad de vida de cuidadores informales depersonas mayores con Alzheimer

O presente estudo objetivou conhecer a qualidade de vida de cuidadores informais de idosos portadores da doença de Alzheimer e verificar se existe diferença nos aspectos biopsicossociais que interferem na qualidade de vida desses cuidadores. Esta pesquisa é de caráter quantitativo. A amostra constituiu-se de 50 cuidadores informais, sendo 25 adultos e 25 idosos. Para a coleta de dados utilizaram-se os seguintes instrumentos: WHOQOL-Breve, Escala de Depressão Geriátrica e Escala de Rastreamento de Depressão e Escala de Ansiedade. Resultados referentes ao WHOQOL-Breve apresentaram pontuação superior a 60, em uma escala de zero a 100, em todos os domínios, porém, apenas no domínio do meio ambiente houve diferença estatisticamente significativa entre os dois grupos estudados. Constatou-se que a maioria dos participantes apresentou grau médio de ansiedade, mas menos da metade obteve pontuação para depressão. Tais resultados poderão subsidiar trabalhos que visem à melhoria da qualidade de vida de cuidadores informais de idosos.

This study aims to clarify the quality of life of informal caregivers of elderly patients with Alzheimer’s disease and to investigate possible differences in biopsychosocial aspects that affect the quality of life of these caregivers. This research is quantitative in nature. The sample consisted of 50 informal caregivers, being 25 adults and 25 elderly. Data collection used the following instruments: WHOQOL-BREF, Geriatric Depression Scale, Depression Screening Scale and Anxiety Scale. Results for the WHOQOL-Brief showed scores higher than 60 on a scale from 0 to 100 in all areas, but only in the environment area presented a statistically significant difference between the two groups. Less than half of the participants obtained scores for depression and most of them had average degree of anxiety. These results may support work aimed at improving the quality of life of informal caregivers of the elderly.

El presente estudio tuvo como objetivo conocer la calidad de vida de los cuidadores informales de personas mayores con enfermedad de Alzheimer y comprobar si hay diferencias entre los aspectos biopsicosociales que afectan la calidad de vida de dichos cuidadores. Esta investigación es de carácter cuantitativo. La muestra estuvo compuesta de 50 cuidadores informales, entre ellos 25 adultos y 25 personas mayores. Para la recogida de datos se utilizaron los siguientes instrumentos: WHOQOL-Breve, la escala de depresión geriátrica, la escala de seguimiento de depresión y la escala de ansiedad. Los resultados del WHOQOL-Breve fueron superiores a los 60 puntos en una escala de 0 a 100 en todos los dominios; solamente en el dominio del medio ambiente se observaron diferencias estadísticas significativas entre los dos grupos. Se constató que la mayoría de los participantes presentó grado medio de ansiedad y que menos de la mitad obtuvo alguna puntuación en depresión. Estos resultados podrían ayudar a trazar estrategias con miras a mejorar la calidad de vida de los cuidadores informales de personas mayores.

Neurobiology of neuropsychiatric symptoms in Alzheimer?s disease / Neurobiologia dos Sintomas Neuropsiquiátricos na Doença de Alzheimer: Uma revisão crítica com foco na neuroimagem

The objective of this critical review of the literature was to reveal the neural circuits involved in the occurrence of neuropsychiatric symptoms (NPS) in Alzheimer?s disease (AD) patients through the association of these symptoms with neuroimaging findings. The search for articles was performed on PUBMED from January 2000 to May 2013, using thekey words: Dementia AND BPSD; Dementia AND Neuropsychiatric Symptoms; and Dementia AND Psychosis, Delusions, Hallucinations, Agitation, Depression, Anxiety, Apathy, Euphoria, Disinhibition, Irritability, Aberrant Motor Behavior, Sleep or Eating Disorders. Forty-six articles were reviewed and important contributions, especially regarding the psychopathological concepts discussed, were also considered even if not included in this time period. The available evidence suggests thethree most relevant neurobiological models for neuropsychiatric symptoms in Alzheimer?s disease are the frontal-subcortical circuits, the cortico-cortical networks, and the monoaminergic system. We discussed the association of the individual symptoms or syndromes with these models.

O objetivo dessa revisão crítica da literatura é investigar os circuitos neurais envolvidos na ocorrência dos sintomas neuropsiquiátricos nos pacientes com doença de Alzheimer através da associação destes sintomas com achados de neuroimagem. A procura dos artigos foi feita no PUBMED de Janeiro de 2000 a Maio de 2013, usando as palavras chave:Demência E BPSD; Demência E Sintomas Neuropsiquiátricos; e Demência E Psicose, Delírios, Alucinações, Agitação, Depressão, Ansiedade, Apatia, Euforia, Desinibição, Irritabilidade, Comportamento Motor Aberrante, Distúrbios do Sono ou Apetite. Quarenta e seis artigos foram revisados e contribuições importantes, especialmente considerando os conceitospsicopatológicos discutidos, foram também discutidos, mesmo se não incluídos neste período de tempo. As evidências disponíveis sugerem que os três modelos neurobiológicos mais relevantes para os sintomas neuropsiquiátricos na doença de Alzheimer são os circuitos frontal-subcorticais, as redes córtico-corticais, e o sistema monoaminérgico. Nós discutimos a associação dos sintomas individuais ou síndromes com esses modelos.