Las orexinas como biomarcadores para demencia tipo Alzheimer y relación con síntomas neuropsiquiátricos / Orexins as biomarkers for Alzheimer dementia and their relationship with neuropsychiatric symptoms

RESUMEN: Los biomarcadores más estudiados en la demencia tipo Alzheimer (DA) son los niveles elevados de Aβ42 y de proteína Tau en líquido cefalorraquídeo. Dada la complejidad de la sintomatología cognitiva y síntomas neuropsiquiátricos (SNP) de esta patología, algunos estudios recientes proponen sustancias como las orexinas, como blanco terapéutico de DA y SNP. El presente trabajo tiene como objetivo revisar publicaciones científicas recientes que hayan analizado la asociación entre orexinas, SNP y DA en humanos, algunos modelos animales y que hayan evaluado a las orexinas como posibles biomarcadores tanto para investigación como en el área clínica. En esta revisión también se describen los estudios que sugieren a las orexinas como un posible biomarcador en la DA, dada su relación con el Aβ42 y la proteína Tau, y otros estudios que las asocian con presencia de SNP, especialmente alteración del sueño. Se plantea la hipótesis de que la presencia de SNP en DA se asocia con las orexinas, debido a que este sistema influye en el funcionamiento hipotalámico y de forma indirecta en áreas cerebrales que regulan el comportamiento. Sin embargo, aún falta mayor investigación, principalmente de estudios longitudinales para conocer claramente la influencia de las orexinas en los SNP.

ABSTRACT The most studied biomarkers in Alzheimer's dementia (AD) are elevated levels of Aβ42 and Tau protein in cerebrospinal fluid. Given the complexity of the cognitive symptomatology and neuropsychiatric symptoms (NPS) of this pathology, some recent studies propose substances such as orexins as a therapeutic target for AD and NPS. The present work aims to review recent scientific publications that have analyzed the association between orexins, PNS and AD in humans. There are some animal models that have evaluated orexins as possible biomarkers both for research and in the clinical area. This review also describes studies that suggest orexins as possible biomarkers in AD, given their relationship with Aβ42 and Tau protein, and other studies that associate them with the presence of SNPs, especially sleep disturbance. It is hypothesized that the presence of SNPs in AD is associated with orexins, because this system influences hypothalamic functioning and indirectly in brain areas that regulate behavior. However, further research is still lacking, mainly longitudinal studies to clearly know the influence of orexins on SNPs.

Os impactos da neuroinflamação na doença de Alzheimer / The impacts of neuroinflamation on Alzheimer's disease

A Doença de Alzheimer (DA) consiste em um grande problema de saúde pública no Brasil e no mundo. Trata-se de uma doença neurodegenerativa, em que ocorre perda progressiva de neurônios e atrofia das regiões cerebrais. Essa degeneração está associada principalmente ao depósito de duas proteínas tóxicas: a proteína beta-amiloide e a proteína Tau, uma vez que estas proteínas se encontram acumuladas, elas prejudicam a ocorrência de sinapses nervosas. Apesar de extremamente prevalente na população mais idosa, suas causas ainda não estão bem esclarecidas, sendo que vários fatores já foram apontados como possíveis motivos para o surgimento do depósito destas proteínas, levando assim a neurodegeneração. Recentemente, tem se estudado o papel da inflamação, que é fundamental durante todo o curso da doença, tanto para a eliminação das proteínas tóxicas quanto para a proteção de neurônios. Um funcionamento anormal do processo inflamatório poderia dificultar a eliminação das proteínas e acentuar a perda neuronal. Com isso essa revisão de literatura tem como objetivo descrever os principais fatores imunológico que se encontram alterados na Doença de Alzheimer e como isso pode contribuir para o quadro neurodegenerativo.

Alzheimer's Disease (AD) is a major public health problem in Brazil and worldwide. It is a neurodegenerative disease, in which there is a progressive loss of neurons and atrophy of brain regions. This degeneration is mainly associated with the deposition of two toxic proteins, the beta-amyloid protein and the Tau protein, once these proteins are accumulated, they impair the occurrence of nerve synapses. Despite being extremely prevalent in the older population, its causes are still not well understood, and several factors have already been pointed out as possible reasons for the emergence of the deposit of these proteins, thus leading to neurodegeneration. Recently, the role of inflammation, which is fundamental throughout the course of the disease, has been studied, both for the elimination of toxic proteins and for the protection of neurons. An abnormal functioning of the inflammatory process could hinder the elimination of proteins and accentuate the neuronal loss Thus, this literature review aims to describe the main immunological factors that are altered in Alzheimer's Disease and how this can contribute to the neurodegenerative picture.

Disfunción inmunológica en enfermedad de Alzheimer; proinflamatoria en etapas iniciales y regulatoria, y exhausta en etapas avanzadas / Immune dysfunction in disease Alzheimer's; proinflammatory in stages initial and regulatory, and exhaustive in advanced stages

Alzheimer disease (AD) is the main cause of dementia worldwide and a source of important population morbidity and mortality. It is estimate that its prevalence will increase dramatically in the upcoming years. The classical clinical presentation of AD is an amnesic hippocampal syndrome, and Mild Cognitive impairment (MCI) is considered the initial stage between normal cognition and dementia. The most accepted pathogenesis establishes amyloid beta (Ab) deposition in brain parenchyma as the initial mechanism, followed by the intracellular accumulation of hyperphosphorylated tau finally leading to the loss of synapses and neurons. Recently, the study of AD pathogenesis is focusing on immune mechanisms as main actors of disease development. Microglia is the macrophagic resident cell in the central nervous system (CNS), and initiates the inflammatory response and Ab phagocytosis, interacting with other glia and recruiting diverse immune cells to the CNS. The role of the adaptive immune system, and, especially T lymphocytes' role, is still controversial. We hypothesize that the pathogenesis of AD is dynamic; with a preponderant proinflammatory activity initially, but later on, the persistent presence of Ab due to the lack of its proper elimination leads to a phenomena of lymphocyte dysfunction and immunological tolerance that have a deleterious role at advanced stages of the disease. (AU)

Avaliação do Impacto do Nível Educacional na Doença de Alzheimer: Artigo Original / Evaluation of the Impact of Educational Level on Alzheimer's Disease: Original Article

A doença de Alzheimer (DA) consiste em uma doença neurodegenerativa progressiva, irreversível e de aparecimento insidioso. O grau de escolaridade formal, assim como a reserva cognitiva, vem sendo proposto como fator protetor da DA, interagindo com a predisposição genética na gênese e curso evolutivo da doença. Tal estudo tem como objetivo buscar associações da escolaridade formal e outras variáveis, que possam estabelecer relação com valores reduzidos do MEEM. Foram coletados dados como idade, sexo, estado civil, raça, escolaridade e pontuação no MEEM no período do diagnóstico da DA dos pacientes que se encontravam em fase inicial da doença. Os pacientes foram divididos em três grupos de acordo com a idade: 60-69 anos, 70-79 anos e = 80 anos. Após análise estatística, a comparação MEEM versus escolaridade se mostrou significativa (r=0,39; P=0,0001), enquanto MEEM versus idade não apresentou significância (r=-0,13; P=0,86), tal como para associação de MEEM e sexo (P=0,46). Na separação realizada por grupos etários, o nível de escolaridade foi significativamente maior nos indivíduos com idade entre 60-69 anos versus 70-79 versus = 80 anos, todavia, sem diferenças significativas entre os escores do MEEM (13 ± 6,2 versus 13± 6 versus 15 ± 5; mediana ± intervalo interquartil; P = 0,34). Assim sendo, esse estudo aponta relevante relação entre a escolaridade e pontuações obtidas no teste cognitivos, determinando associação entre o nível educacional mais elevado e maior habilidade cognitiva dos pacientes com DA. (AU)

Alzheimers disease (AD) consists of a progressive, irreversible and insidious neurodegenerative disease. The degree of formal schooling, as well as the cognitive reserve, has been proposed as a protective factor of AD, interacting with the genetic predisposition in the genesis and evolutionary course of the disease. This study aims to seek associations of formal schooling and other variables, which may establish a relationship with reduced MMSE values. Data such as age, sex, marital status, race, schooling and MMSE score were collected during the diagnosis of AD in patients who were in the initial phase of the disease. Patients were divided into three groups according to age: 60-69 years, 70-79 years and = 80 years. After statistical analysis, the MMSE versus schooling comparison was significant (r = 0.39, P = 0.0001), while MMSE versus age did not present significance (r = -0.13, P = 0.86), as for association of MEEM and sex (P = 0.46). In the separation by age groups, the educational level was significantly higher in individuals aged 60-69 years versus 70-79 versus = 80 years, however, without significant differences between the MMSE scores (13 ± 6.2 versus 13 ± 6 versus 15 ± 5, median ± interquartile range, P = 0.34). Therefore, this study points out a relevant relationship between schooling and scores obtained in the cognitive test, determining the association between the higher educational level and the greater cognitive ability of patients with AD. (AU)

Impacto de las emociones sobre la memoria declarativa en la enfermedad de Alzheimer / Impact of emotions on declarative memory in Alzheimer's disease / Impacto das emoções na memória declarativa na doença de Alzheimer

Esta investigación tuvo como objetivo determinar la influencia de las emociones en los procesos de memoria declarativa en personas con enfermedad de Alzheimer. Para esto, se planteó un estudio con diseño comparativo-correlacional y modelo no probabilístico. Participaron 160 adultos mayores, 80 con diagnóstico de enfermedad de Alzheimer y 80 con envejecimiento normal, homólogos en edad, género y nivel escolar. Se encontró que, de forma general, las emociones negativas favorecen la codificación, almacenamiento y evocación de la información en personas con Alzheimer, más que las positivas, y la mayor influencia se haya en contenidos de información asociados a emociones como miedo y tristeza. Asimismo, el brindar claves semánticas posibilita una mayor cantidad de información a ser evocada. La memoria en el envejecimiento normal y patológico se beneficia de los vínculos establecidos entre la información y las emociones contextuales al momento de registrarla y almacenarla, por lo que, siendo la memoria uno de los principales deterioros en la enfermedad de Alzheimer, este vínculo es clave en el abordaje de la patología y los programas de intervención clínica.

The objective of this research was to determine the influence of emotions on declarative memory processes in people with Alzheimer's disease. A study with a comparative-correlational design and a non-probabilistic model was proposed. 160 elderly people participated, 80 with a diagnosis of Alzheimer's disease and 80 with normal aging, homologous in age, gender and school level. It was found that in general negative emotions favor the coding storage and evocation of information in people with Alzheimer's disease, rather than positive ones, and the greatest influence is on information content associated with emotions such as fear and sadness. Likewise, providing semantic keys allows a greater amount of information to be evoked. Memory in normal and pathological aging benefits from the links established between information and contextual emotions at the time of recording and storing it since memory is one of the main impairments in Alzheimer's disease, this link is key in the approach of pathology and clinical intervention programs.

O objetivo desta pesquisa foi determinar a influência das emoções nos processos de memória declarativa em pessoas com doença de Alzheimer. Para isso, foi proposto um estudo com modelo comparativo-correlacional e não probabilístico. Participaram 160 idosos, sendo 80 com diagnóstico de doença de Alzheimer e 80 com envelhecimento normal, homólogos em idade, sexo e nível escolar. Achou-se que, em geral, as emoções negativas favorecem a codificação, armazenamento e evocação de informações em pessoas com doença de Alzheimer, ao invés das positivas, e a maior influência está no conteúdo de informação associado a emoções como medo e tristeza. Da mesma forma, fornecer chaves-semânticas permite que uma quantidade maior de informações seja evocada. A memória no envelhecimento normal e patológico se beneficia das ligações estabelecidas entre a informação e as emoções contextuais no momento de registrála e de armazená-la, de modo que, como a memória é um dos principais prejuízos na doença de Alzheimer, essa ligação é fundamental na abordagem da patologia e dos programas de intervenção clínica.

Alzheimer's disease and sleep disturbances: a review / Doença de Alzheimer e distúrbios do sono: uma revisão

ABSTRACT The association between Alzheimer's disease (AD) and sleep disturbances has received increasing scientific attention in the last decades. However, little is known about the impact of sleep and its disturbances on the development of preclinical AD stages, such as mild cognitive impairment. This review describes the evolution of knowledge about the potential bidirectional relationships between AD and sleep disturbances exploring recent large prospective studies and meta-analyses and studies of the possible mechanisms through which sleep and the neurodegenerative process could be associated. The review also makes a comprehensive exploration of the sleep characteristics of older people, ranging from cognitively normal individuals, through patients with mild cognitive impairment, up to the those with dementia with AD.

RESUMO A associação entre Doença de Alzheimer (DA) e distúrbios do sono vem recebendo atenção crescente nas últimas décadas. No entanto, pouco se sabe sobre o impacto do sono e suas alterações no desenvolvimento de estágios pré-clínicos da doença, como é o caso do Comprometimento Cognitivo Leve (CCL). Esta revisão descreve a evolução do conhecimento sobre as relações potencialmente bidirecionais entre DA e distúrbios do sono, explorando grandes estudos prospectivos e meta-análises, assim como estudos dos possíveis mecanismos da associação entre o sono e as doenças neurodegenerativas. Também revisamos amplamente as características do sono de pessoas idosas, incluindo indivíduos cognitivamente normais, com CCL e com demência por DA.

Decreased plasmatic spermidine and increased spermine in mild cognitive impairment and Alzheimer's disease patients

Abstract Background Current evidence suggests that upregulation of polyamines system plays a role both in cognitive deficit and synaptic loss observed in Alzheimer's disease (AD). Objective The aim of this study was to determine the plasmatic concentration of polyamines in mild cognitive impairment (MCI) and AD patients in comparison with healthy controls (HC). Methods Plasmatic polyamines were quantified using the AbsoluteIDQ® p180 and liquid chromatography coupled to tandem mass spectrometry (LC/MS-MS). Results The study group comprised 34 AD patients, 20 MCI and 25 HC. All individuals were followed for 4 years. During this period 8 amnestic MCI patients (40% of the MCI sample at baseline) converted to AD. Spermidine level was lower in both patient groups (AD; MCI) compared to HC (p = 0.007). Plasma levels of spermine were higher in the MCI group (p < 0.001), but decreased in the sub-sample of MCI patients who converted to AD (p = 0.043). No statistically significant differences were found in ornithine and putrescine levels (p = 0.056 and p = 0.126, respectively). Discussion Our results suggest dynamic changes in the expression of polyamines in the MCI-AD continuum.

Exploratory analysis of rare and novel variants in Mexican patients diagnosed with schizophrenia and dementia

Abstract Background Schizophrenia (SCZ) and dementia, often related, are two of the most common neuropsychiatric diseases; epidemiological studies have shown that SCZ patients present a 2-fold increased risk for dementia compared to non-schizophrenic individuals. We explored the presence of rare and novel damaging gene variants in patients diagnosed with late-onset dementia of Alzheimer’s type (DAT) or SCZ. Methods We included 7 DAT and 12 SCZ patients and performed high-depth targeted sequencing of 184 genes. Results We found novel and rare damaging variants in 18 genes in these Mexican patients. Carriers of these variants showed extreme phenotypes, including, treatment-resistant SCZ or cognitive decline. Furthermore, we found a variation on ABCC1 as a possible link between psychosis and cognitive impairment. Discussion As an exploratory analysis, we report some interesting variations that should be corroborated in larger sample size studies.

Evaluación neuropsicológica de la memoria semántica en demencia presenil y declive cognitivo atípico: ¿estamos preparados? / Neuropsychological assessment of semantic memory in presenile dementia and atypical cognitive decline: ¿are we prepared?

El envejecimiento de la población es un fenómeno demográfico de preocupación mundial. Junto al aumento de la población mayor, aumenta también el número de enfermedades neurodegenerativas. La enfermedad de Alzheimer y la demencia frontotemporal, son las principales causas del envejecimiento cognitivo patológico, diferenciando dentro de su progresión al Deterioro Cognitivo Leve (DCL) y la demencia. La memoria semántica permite el procesamiento, almacenamiento y representación de información que subyace la comprensión y uso del significado de todo lo que nos rodea, permitiendo la autonomía en el desempeño de actividades de la vida diaria, por lo tanto, su compromiso conlleva a un estado de demencia. Uno de los principales objetivos de estudio clínico y de impacto en salud pública es la detección precoz de la demencia, dirigido hacia un tratamiento farmacológico, no-farmacológico y manejo psicosocial oportuno. Actualmente, los casos de demencias preseniles y las presentaciones iniciales con perfiles atípicos han aumentado, siendo la memoria semántica una de estas manifestaciones. En Chile existen efectivas herramientas para la detección de un envejecimiento cognitivo patológico, sin embargo, no se cuenta con herramientas evaluativas para un diagnóstico efectivo en casos atípicos.

Population ageing is a demographic phenomenon of global concern. As the elderly population increases, so does the number of neurodegenerative diseases. Alzheimer's disease and frontotemporal dementia are the main causes of pathological cognitive aging, differentiating between Mild Cognitive Impairment (MCI) and dementia. Semantic memory allows the processing, storage and representation of information that underlies the understanding and use of the meaning of everything that surrounds us, allowing autonomy in the performance of activities of daily life, therefore, it's commitment leads to a state of dementia. One of the main objectives of clinical studies and public health impact is the early detection of dementia, aimed at a pharmacological treatment, non-pharmacological, and timely psychosocial management. Currently, cases of presenile dementias and initial presentations with atypical profiles have increased, with semantic memory being one of these manifestations. In Chile, there are effective tools for detection of a pathological cognitive aging, however, there are no evaluative tools for an effective diagnosis in atypical cases.

Nutritional and hematological factors associated with the progression of Alzheimer's disease: a cohort study

SUMMARY OBJECTIVE: We studied the users of the Specialized Drug Distribution Program of the public health network. METHODS: A prospective cohort examined the elderly at two intervals of three years and included 30 patients in phase I and 16 in phase II. The methodology was composed of home visits, anthropometric, nutritional and hematological evaluation. For the progression of AD, the Clinical Dementia Rating (CDR) scale was used. RESULTS: According to the CDR, the disease evolved, since in 2014 most of the patients were in CDR 3. In the analysis of the micronutrients, only the B vitamins (B1, B2, B3, B5, B6) presented a significant reduction in 2014. The consumption of carbohydrates and lipids increased in the 2014 evaluation, and protein consumption decreased. As for the average weight of the elderly, there was an increase in 2014, 65.9 (± 15.6) Kg, with a BMI of 26.75 (± 4, 5), in 2011 the average weight was 62.44 kg (± 14, 36), BMI 24.64 (± 4.97). CONCLUSION: The hypothesis that patients are likely to be overweight or obese before the development of AD and that this may be associated with an increased risk of dementia is suggested.

RESUMO OBJETIVO: Foram estudados os usuários do programa de distribuição de medicamentos especializados da rede pública de saúde de Guarapuava, Paraná, Brasil. MÉTODOS: Uma coorte prospectiva, em que os idosos foram examinados em dois momentos, com um intervalo de três anos, com 30 pacientes na fase I e 16 na fase II. A metodologia foi composta por visitas domiciliares, avaliação antropométrica; avaliação nutricional e hematológica. Para a progressão da DA, utilizou-se a escala Clinical Demential Rating (CDR). Os testes de Shapiro-Wilk, teste de Wilcoxon e correlações com associações (Δ%), p < 0,05 para as análises estatísticas. RESULTADOS: A progressão da doença, segundo o CDR, evoluiu, pois, em 2014, a maioria dos pacientes encontrava-se em CDR 3. Na análise dos micronutrientes, somente as vitaminas do complexo B (B1, B2, B3, B5, B6) apresentaram redução significativa em 2014. O consumo de carboidratos e lipídeos aumentou na avaliação de 2014, e o consumo de proteínas diminuiu. Quanto ao peso médio dos idosos, houve um aumento em 2014, 65,9 (± 15,6) kg, com IMC 26,75 (± 4, 5); em 2011, o peso médio foi 62,44 kg (± 14,36), IMC 24,64 (± 4,97). CONCLUSÃO: Não foram encontrados pacientes anêmicos ou desnutridos na amostra. A hipótese de que os pacientes provavelmente já apresentavam sobrepeso ou obesidade antes do desenvolvimento da DA, e que isso pode estar associado com um aumento de risco de demência, pode ser sugerida.

Accuracy of praxis test from Cambridge Cognitive Examination (CAMCOG) for Alzheimer's disease: a cross-sectional study

ABSTRACT BACKGROUND: Praxis impairment may be one of the first symptoms manifested in dementia, primarily in cortical dementia. The Cambridge Cognitive Examination (CAMCOG) evaluates praxis, but little is known about the accuracy of CAMCOG for diagnosing dementia. The aims here were to investigate the accuracy of praxis and its subitems in CAMCOG (constructive, ideomotor and ideational subitems) for diagnosing Alzheimer's disease (AD) among elderly patients. DESIGN AND SETTING: Cross-sectional study on community-dwelling elderly people. METHODS: 158 elderly patients were evaluated. CAMCOG, Mini-Mental State Examination and Pfeffer Functional Activities Questionnaire were used. ROC curve analysis was used to establish cutoff points. RESULTS: The total scores for praxis and the constructive subitem presented significant differences (P < 0.0001) between healthy elderly people and AD patients. Stage of dementia (clinical dementia rating, CDR = 0, 1 and 2) showed that total and constructive praxis can be used to classify the stages of dementia (mild and moderate cases), i.e. constructive praxis classified 88% of the patients with mild dementia (P < 0.0001) while total praxis classified 56% with moderate dementia. Comparison of normal controls (NC) and mild dementia cases showed specificity of 71% and sensitivity of 88% (AUC = 0.88; P < 0.0001). CONCLUSION: Some praxis subtests can have higher predictive diagnostic value for detecting Alzheimer's disease in mild stages (total praxis AUC = 0.858; P < 0.0001; constructive AUC = 0.972; P < 0.0001). Constructive praxis as measured using CAMCOG may contribute towards diagnosing dementia, because occurrence of impairment of praxis may help in recognizing an evolving dementia syndrome.

Performances on the Timed Up and Go Test and subtasks between fallers and non-fallers in older adults with cognitive impairment / Performances no teste Timed Up and Go e subtarefas em idosos com comprometimento cognitivo, caidores e não caidores

ABSTRACT This work aimed to compare performances on the Timed Up and Go (TUG) test and its subtasks between faller and non-faller older adults with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). A prospective study was conducted, with 38 older adults with MCI and 37 with mild AD. Participants underwent an assessment at baseline (the TUG and its subtasks using the Qualisys ProReflex system) and the monitoring of falls at the six-month follow up. After six months, 52.6% participants with MCI and 51.3% with AD fell. In accordance with specific subtasks, total performance on the TUG distinguished fallers from non-fallers with AD, fallers from non-fallers with MCI and non-fallers with MCI from non-fallers with AD. Although no other difference was found in total performances, non-fallers with MCI and fallers with AD differed on the walking forward, turn and turn-to-sit subtasks; and fallers with MCI and non-fallers with AD differed on the turn-to-sit subtask.

RESUMO O objetivo deste trabalho foi comparar o desempenho do Timed up and go test (TUG) e suas subtarefas entre idosos caidores e não caidores com comprometimento cognitivo leve (CCL) e doença de Alzheimer (DA) leve. Um estudo prospectivo foi conduzido, com 38 idosos com CCL e 37 com DA leve. Foi realizada uma avaliação inicial (TUG e subtarefas por meio do sistema Qualisys Pro Reflex) e um monitoramento de quedas por 6 meses. Após 6 meses, 52.6% pessoas com CCL e 51.3% com DA caíram. Em concordância com subtarefas específicas, a performance total do TUG distinguiu caidores de não caidores com DA, caidores de não caidores com CCL e não caidores com CCL de não caidores com DA. Embora nenhuma outra diferença foi encontrada na performance total do TUG, não caidores com CCL e caidores com DA apresentaram diferenças nas performances das subtarefas marcha ida, retornar e virar-se para sentar; e caidores com CCL e não caidores com DA diferiram na subtarefa virar-se para sentar.

Anesthesia and Alzheimer disease - Current perceptions / Anestesia e doença de Alzheimer - Percepções atuais

Abstract Background and objectives: It has been speculated that the use of anesthetic agents may be a risk factor for the development of Alzheimer disease. The objective of this review is to describe and discuss pre-clinical and clinical data related to anesthesia and this disease. Content: Alzheimer disease affects about 5% of the population over 65 years old, with age being the main risk factor and being associated with a high morbidity. Current evidence questions a possible association between anesthesia, surgery, and long-term cognitive effects, including Alzheimer disease. Although data from some animal studies suggest an association between anesthesia and neurotoxicity, this link remains inconclusive in humans. We performed a review of the literature in which we selected scientific articles in the PubMed database, published between 2005 and 2016 (one article from 1998 due to its historical relevance), in English, which address the possible relationship between anesthesia and Alzheimer disease. 49 articles were selected. Conclusion: The possible relationship between anesthetic agents, cognitive dysfunction, and Alzheimer disease remains to be clarified. Prospective cohort studies or randomized clinical trials for a better understanding of this association will be required.

Resumo Justificativa e objetivos: Tem sido especulado que o uso de agentes anestésicos possa ser um fator de risco para o desenvolvimento de doença de Alzheimer. O objetivo desta revisão é descrever e discutir dados pré-clínicos e clínicos relacionados com a anestesia e essa doença. Conteúdo: A doença de Alzheimer afeta cerca de 5% da população com mais de 65 anos, a idade é o principal fator de risco e está associada a uma elevada morbidade. A evidência atual questiona uma possível associação entre anestesia, cirurgia e efeitos cognitivos em longo prazo, o que inclui a doença de Alzheimer. Embora os dados obtidos em alguns dos estudos animais sugiram uma associação entre anestesia e neurotoxicidade, esse elo permanece inconclusivo em humanos. Fizemos uma revisão da literatura em que foram selecionados artigos científicos na base de dados Pubmed, publicados entre 2005 e 2016 (um de 1998 pela relevância histórica), em inglês, que abordam a eventual relação entre anestesia e doença de Alzheimer. Foram eleitos 49 artigos. Conclusão: A possível relação entre agentes anestésicos, disfunção cognitiva e doença de Alzheimer permanece por esclarecer. Serão necessários estudos de coorte prospetivos ou ensaios clínicos randomizados para melhor compreensão dessa associação.

Naming and verbal learning in adults with Alzheimer's disease, mild cognitive impairment and in healthy aging, with low educational levels / Nomeação e aprendizagem verbal na doença de Alzheimer, no comprometimento cognitivo leve e no envelhecimento sadio com baixa escolaridade

ABSTRACT Language assessment seems to be an effective tool to differentiate healthy and cognitively impaired aging groups. This article discusses the impact of educational level on a naming task, on a verbal learning with semantic cues task and on the MMSE in healthy aging adults at three educational levels (very low, low and high) as well as comparing two clinical groups of very low (0-3 years) and low education (4-7 years) patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) with healthy controls. The participants comprised 101 healthy controls, 17 patients with MCI and 19 with AD. Comparisons between the healthy groups showed an education effect on the MMSE, but not on naming and verbal learning. However, the clinical groups were differentiated in both the naming and verbal learning assessment. The results support the assumption that the verbal learning with semantic cues task is a valid tool to diagnose MCI and AD patients, with no influence from education.

RESUMO A linguagem tem se mostrado uma ferramenta eficiente para diferenciar grupos de idosos saudáveis dos com deficiências cognitivas. O artigo objetiva discutir o impacto do nível educacional na nomeação, na aprendizagem verbal (AV) com pistas semânticas e no MEEM no envelhecimento saudável em três níveis de escolaridade (muito baixa: 0-3 anos, baixa: 4-7 anos e alta: >8 anos) e em dois grupos clínicos de escolaridade muito baixa e baixa (Doença de Alzheimer - DA - e Comprometimento Cognitivo Leve - CCL), comparados a controles saudáveis. Participaram 101 controles, 17 CCL e 19 DA. Comparações entre grupos saudáveis demonstraram um efeito da escolaridade no MEEM, mas não nas tarefas de nomeação e de AV. Considerando as comparações entre os grupos clínicos, tanto a nomeação quanto a AV os diferenciaram. Os resultados corroboram a pressuposição de que a tarefa de AV com pistas semânticas é válida para diagnosticar CCL e DA, não sendo influenciada pela escolaridade.

Tempo de trânsito oral na demência de Alzheimer / Oral transit time in Alzheimer's disease

RESUMO Objetivo Avaliar o tempo de trânsito oral de alimento na consistência pudim, nos diferentes estágios da demência de Alzheimer. Métodos Estudo de caráter descritivo e observacional do tipo transversal, com uma amostra de 34 idosos com idade entre 65 e 98 anos, com demência de Alzheimer em diferentes estágios. Os participantes foram observados por avaliação de videofluoroscopia da deglutição, enquanto ingeriam alimento na consistência pudim, usando o programa de cronometragem Kinovea. Os dados foram analisados estatisticamente, em nível de significância de 5%. Resultados Os participantes com o Clinical Dementia Rating CDR 3 apresentaram maior tempo de trânsito oral, quando comparados àqueles com CDR 1, média de 3,09s (desvio padrão = 0,91) e 1,17s (desvio padrão = 1,10), respectivamente. Participantes na faixa etária de 90a 100 anos apresentaram maior tempo de trânsito oral do que os mais jovens, entre 60 e 79 anos, média de 3,90s e 1,28s. Conclusão Indivíduos com demência e idade avançadas apresentam tempo de trânsito oral aumentado para alimento na consistência pudim, devendo ser alvo de atenção de familiares e cuidadores.

ABSTRACT Purpose Evaluate oral transit time (OTT) with pudding consistency at the different stages of Alzheimer's disease (AD). Methods Descriptive, cross-sectional, observational study conducted with a sample of 34 elderly aged 65-98 years, with AD at different stages. Participants were observed using videofluoroscopy of swallowing while ingesting pudding consistency, using the Kinovea timing program. Data were statistically analyzed at 5% significance level. Results Participants with Clinical Dementia Rating - CDR 3 presented longer OTT compared with those with CDR 1, with means of 3.09 s (SD = 0.91) and 1.17 s (SD = 1.10), respectively. Individuals aged 90-100 years presented longer OTT than those aged 60-79 years, means of 3.90 s and 1.28 s, respectively. Conclusion Individuals with dementia and advanced aged present longer OTT for pudding consistency and should receive special attention from family members and caregivers.

Thiamine deficiency contributes to synapse and neural circuit defects

BACKGROUND: The previous studies have demonstrated the reduction of thiamine diphosphate is specific to Alzheimer's disease (AD) and causal factor of brain glucose hypometabolism, which is considered as a neurodegenerative index of AD and closely correlates with the degree of cognitive impairment. The reduction of thiamine diphosphate may contribute to the dysfunction of synapses and neural circuits, finally leading to cognitive decline. RESULTS: To demonstrate this hypothesis, we established abnormalities in the glucose metabolism utilizing thiamine deficiency in vitro and in vivo, and we found dramatically reduced dendrite spine density. We further detected lowered excitatory neurotransmission and impaired hippocampal long-term potentiation, which are induced by TPK RNAi in vitro. Importantly, via treatment with benfotiamine, Aß induced spines density decrease was considerably ameliorated. CONCLUSIONS: These results revealed that thiamine deficiency contributed to synaptic dysfunction which strongly related to AD pathogenesis. Our results provide new insights into pathogenesis of synaptic and neuronal dysfunction in AD.

Role of aquaporin-4 in the change of interstitial fluid drainage in Alzheimer's disease / 北京大学学报(医学版)

OBJECTIVE@#To observe the characteristics of the interstitial fluid (ISF) drainage in the Alzheimer's disease (AD) rats through magnetic resonance imaging (MRI) tracer gadolinium-diethylene triamine pentacetic acid (Gd-DTPA)spread in the brain extracellular space (ECS) and to discuss the role of aquaporin-4 (Aqp4) in the AD.@*METHODS@#Wild type SD rats (300-350 g) and Aqp4 gene knock out (Aqp4-/-) SD rats (300-350g) were divided into Sham group, AD group, Aqp4-/--Sham group and Aqp4-/--AD group. Sham group and Aqp4-/--Sham group were injected with saline by intraperitoneal each day for 6 weeks, and the AD group and Aqp4-/--AD group were injected with D-galactose by intraperitoneal each day for 6 weeks. MRI tracer Gd-DTPA (10 mmol/L, 2 μL) was injected into the hippocampus of the rats. MRI scan was performed at the end of 0.5 h, 1.5 h, 1 h, 2 h, and 3 h to observe the dynamic distribution of the Gd-DTPA in the hippocampus and the diffusion rate D*, clearance rate k' and half-life t1/2 measured.@*RESULTS@#The diffusion rate D* in Sham group was (2.66±0.36)×10-6 mm2/s, the diffusion rate D* in AD group was (2.72±0.62)×10-6 mm2/s, the diffusion rate D* in Aqp4-/--Sham group was (2.75±0.47)×10-6 mm2/s, the diffusion rate D* in Aqp4-/--AD group was (2.802±0.55)×10-6 mm2/s, and there was no statistically significant difference in the four groups (One-Way ANOVA, P>0.05).The clearance rate k' in Sham group was (4.57±0.14)×10-4/s, the clearance rate k' in AD group was (3.68±0.22)×10-4/s, the clearance rate k' in Aqp4-/--Sham group was (3.17±0.16)×10-4/s, the clearance rate k' in Aqp4-/--AD group was (2.59±0.19)×10-4/s, and there was significant difference in the four groups (One-Way ANOVA, P<0.05). The half-life t1/2 in Sham group was (0.67±0.12) h, the half-life t1/2 in AD group was (0.88±0.08) h, the half-life t1/2 in Aqp4-/--Sham group was (1.12±0.15) h, the half-life t1/2 in Aqp4-/--AD group was (1.58±0.11) h, and there was significance difference in the four groups(one-way ANOVA,P<0.05).@*CONCLUSION@#The ISF drainage is slow after AD and the loss of Aqp4 in the AD makes the ISF drainage obviously slow down, Aqp4 plays an important role in AD to remove the metabolism of waste out of the brain.

Doença de Alzheimer e diabetes mellitus tipo 2: qual a relação? / Alzheimer's disease and diabetes mellitus type 2: what is the relationship?

Fundamento: a Doença de Alzheimer (DA) é o tipo mais comum de demência, sendo histologicamente caracterizada pela deposição de peptídeo ß-amiloide, hiperfosforilação da proteína tau, neuroinflamação e perda neuronal, favorecida por diferentes mecanismos fisiopatológicos. O diabetes mellitus tipo 2 (DM2) ocorre devido à resistência periférica à insulina e à insuficiência insulínica (em fases mais avançadas da doença). Dados epidemiológicos sugerem relação entre DA e DM2, embora os supostos mecanismos fisiopatológicos comuns dessa inter-relação sejam obscuros. Objetivos: revisar os principais mecanismos fisiopatológicos compartilhados pela DA e DM2. Métodos: foram pesquisados artigos de 2000 a 2017 nas bases de dados do Portal CAPES/MEC, utilizando as palavras-chave: doença de Alzheimer, diabetes mellitus tipo 2, lesão vascular, resistência à insulina e estresse oxidativo. Resultados: 127 publicações foram analisadas e 73 incluídas. Lesão endotelial, resistência à insulina e estresse oxidativo foram os aspectos fisiopatológicos mais importantes e comuns à DA e DM2. Conclusão: há indícios de relação entre DA e DM2, embora não esteja clara se a relação é causal. Consequentemente, há a necessidade de estudos mais aprofundados sobre marcadores e mecanismos relacionados, visando o desenvolvimento de programas de prevenção e intervenção nas duas doenças em conjunto. (AU)

Introduction: Alzheimer's Disease (AD) is the most common type of dementia and is histologically characterized by deposition of ß-amyloid peptide, hyperphosphorylation of tau protein, neuronal loss and neuroinflammation, favored by different pathophysiological mechanisms. The type 2 diabetes mellitus (T2DM) occurs due to peripheral insulin resistance and insulin insufficiency (in later stages of the disease). Epidemiological data suggest a relationship between AD and T2DM, although the supposed common pathophysiological mechanisms of this interrelation are obscure. Objectives: to review the main pathophysiological mechanisms possibly shared by AD and T2DM. Methods: articles were searched from 2000 to 2017 in the databases of Portal CAPES / MEC, using the key words: Alzheimer's disease, type 2 diabetes mellitus, vascular injury, insulin resistance and oxidative stress. Results: we selected 73 from 127 articles. Endothelial injury, insulin resistance and oxidative stress are pathophysiological aspects common to AD and T2DM. Conclusion: there is evidence of a relationship between AD and T2DM, although it is unclear whether the relation is causal. There is a need for more studies about markers and related mechanisms, aiming at the development of prevention and intervention programs in both diseases. (AU)

Biomarcadores y marcadores de imagen de la enfermedad de Alzheimer / Biomarkers and image markers of Alzheimer's disease

Este artículo presenta un análisis desde el punto de vista bibliográfico de marcadores y biomarcadores de la enfermedad de Alzheimer (EA). Las metodologías usadas fueron los marcadores de imágenes (Resonancia Magnética y Tomografía por emisión de positrones) y biomarcadores de la proteína BA42, de la proteína Tau y de la Apoliproteína E (ALPE). De esta manera, son de importancia los niveles de BA42 disminuidos, la Tau incrementada, los polimorfismos de ALPE y las alteraciones constatadas en los marcadores de imagen, como factores de riesgo esenciales para el desarrollo de la EA. Se realiza una revisión de la literatura con respecto a los hallazgos clínicos de esta enfermedad.

This article presents a bibliographical analysis of markers and biomarkers of Alzheimer's disease (AD). The methodologies used were the imaging markers (Magnetic Resonance and Positron Emission Tomography) and biomarkers of the BA42 protein, Tau protein and Apoliprotein E (ALPE). Thus, decreased levels of BA42, increased Tau, ALPE polymorphisms, and alterations in imaging markers are important as risk factors for the development of AD. A review of the literature is made regarding the clinical findings of this disease.