Acortamiento de telómeros en enfermedades neurodegenerativas: implicaciones terapéuticas / Telomere attrition in neurodegenerative disorders: therapeutic implications

Introducción: Varias enfermedades neurodegenerativas están asociadas a la ocurrencia de acortamiento de los telómeros, y los convierten en biomarcadores y dianas terapéuticas potenciales. Objetivo: Reflejar la relevancia del acortamiento de los telómeros para enfermedades neurodegenerativas, y destacar sus implicaciones Material y métodos: Se realizó una revisión bibliográfica durante los meses de septiembre de 2019 a enero de 2020. Fueron consultadas bases de datos de referencia, con el uso de descriptores y operadores booleanos. La estrategia de búsqueda avanzada para la selección de los artículos fue empleada, teniendo en cuenta la calidad metodológica o validez de los estudios. Desarrollo: Fueron identificadas evidencias sólidas de asociación entre el acortamiento de los telómeros y las enfermedades de Alzheimer y Huntington, que sugieren un papel relevante de la biología de los telómeros en la fisiopatología de estas enfermedades. Las evidencias disponibles hasta el momento no permiten establecer la relevancia de la biología de los telómeros en la fisiopatología de la Enfermedad de Parkinson o de la esclerosis lateral amiotrófica. Se obtuvieron evidencias de la utilidad de terapias orientadas a la prevención del acortamiento de los telómeros para el tratamiento de enfermedades neurodegenerativas. Conclusiones: El acortamiento de los telómeros es de relevancia fisiopatológica y clínica para las enfermedades de Alzheimer y Huntington, mientras que existen evidencias insuficientes para establecer su importancia en la Enfermedad de Parkinson y la esclerosis lateral amiotrófica. El uso de estrategias para estimular la actividad de la telomerasa tiene potenciales aplicaciones terapéuticas en el contexto de enfermedades neurodegenerativas(AU)

Introduction: Several neurodegenerative disorders are associated with telomere attrition, turning telomeres into potential biomarkers and potential therapeutic targets. Objective: To assess the relevance of telomere attrition for neurodegenerative disorders, highlighting its therapeutic implications. Material and methods: A literature review was carried out from September 2019 to January 2020. Several databases were searched by using descriptors and Boolean operators. Advanced search strategy was used for the selection of articles, taking into account the methodological quality and validity of the studies. Results: Strong evidence for an association between telomere attrition and Alzheimer and Huntington diseases was obtained, suggesting a potential importance of telomere biology in the physiopathology of these diseases. Current evidence does not allow establishing the relevance of telomere attrition in the physiopathology of Parkinson´s disease or Amyotrophic Lateral Sclerosis. Evidence was obtained for the usefulness of therapies for the prevention of telomere attrition in the treatment of neurodegenerative disorders. Conclusions: Telomere attrition has physiopathological and clinical relevance in Alzheimer´s and Huntington´s diseases, though current evidence is not enough to establish its role in Parkinson's disease and Amyotrophic Lateral Sclerosis. Strategies that enhance telomerase activity have therapeutic potential in the context of neurodegenerative disorders(AU)

Effect of fish oil on oxidative stress markers in patients with probable Alzheimer´s disease

High intake of omega-3 fatty acids has been associated with synaptic plasticity, neurogenesis and memory in several experimental models. To assess the efficacy of fish oil supplementation on oxidative stress markers in patients diagnosed with probable Alzheimer´s disease (AD) we conducted a double blind, randomized, placebo controlled clinical trial. AD patients who met the inclusive criteria were given fish oil (containing 0.45 g eicosapentaenoic acid and 1 g docosahexaenoic acid) or placebo daily for 12 months. Oxidative stress markers [lipoperoxides, nitric oxide catabolites levels, oxidized/reduced glutathione ratio, and membrane fluidity] and fatty acid profile in erythrocytes were assessed at enrollment, and 6 and 12 months after the start of the testing period. At the end of the trial, in patients who received fish oil, we detected a decrease in the omega 6/omega 3 ratio in erythrocyte membrane phospholipids. This change was parallel with decreases in plasma levels of lipoperoxides and nitric oxide catabolites. Conversely, the ratio of reduced to oxidized glutathione was significantly increased. In addition, membrane fluidity was increased significantly in plasma membrane samples. In conclusion fish oil administration has a beneficial effect in decreasing the levels of oxidative stress markers and improving the membrane fluidity in plasma(AU)

El alto consumo de ácidos grasos omega-3 se asocia con la plasticidad sináptica, neurogénesis y memoria en varios modelos experimentales. Para evaluar la eficacia de la suplementación con aceite de pescado en los marcadores de estrés oxidativo en pacientes con diagnóstico de la enfermedad de Alzheimer (EA) probable realizamos un ensayo clínico doble ciego, aleatorizado, controlado con placebo. A los pacientes con la EA que cumplían los criterios de inclusión se les administró aceite de pescado (que contenía 0,45 g de ácido eicosapentaenoico y 1 g de ácido docosahexaenoico) o placebo diariamente durante 12 meses. Los marcadores de estrés oxidativo plasmático [niveles de lipoperóxidos y catabolitos del óxido nítrico, cociente de glutatión reducido a glutatiónoxidado) y fluidez de la membrana] y el perfil de ácidos grasos en los eritrocitos se evaluaron al inicio, 6 meses y alos 12 meses. Al final del ensayo, en pacientes que recibieron aceite de pescado detectamos una disminución en el cociente de ácidos grasos omega 6/omega 3 en los fosfolípidos de la membrana eritrocitaria. Este cambio ocurrió en paralelo a la disminución de los niveles plasmáticos de lipoperóxidos y catabolitos del óxido nítrico. Por el contrario, el cociente de glutatión reducido a glutatión oxidado se incrementó significativamente. Además, la fluidez de la membrana aumentó significativamente en las muestras analizadas. En conclusión, la administración de aceite de pescado tiene un efecto beneficioso al disminuir los niveles de marcadores de estrés oxidativo plasmático y mejorar la fluidez de la membrana plasmática(AU)

Reserva Cognitiva: revisión de su conceptualización y relación con la Enfermedad de Alzheimer / Cognitive Reserve: a revision of its conceptualization and its relation with Alzheimer´s Disease

Introducción: La reserva cognitiva permite la activación de conexiones sinápticas adicionales y nuevas redes neurales frente a demandas del ambiente. Objetivo: Delimitar qué variables contribuyen a la formación de la reserva cognitiva y establecer su expresión en el desarrollo de la Enfermedad de Alzheimer. Metodología: Revisión bibliográfica sistemática y evaluativa de tipo cualitativa. Resultados: La educación, actividades de ocio, estilo de vida, estatus socioeconómico e inteligencia son las principales variables que aportan a la formación de la reserva cognitiva. Sujetos con alta reserva tienen menor prevalencia e incidencia de demencia. Aquellos que lleguen a desarrollar la enfermedad lo harán a una edad más tardía y con mayor severidad de síntomas. Conclusión: Las variables que contribuyen a la formación de la reserva cognitiva son, principalmente, variables socio-ambientales. La reserva se considera factor de protección frente a la enfermedad. Además, atrasaría la aparición de la demencia, logrando, en algunos casos, que nunca se llegue a desarrollar la enfermedad(AU)

Introduction: Cognitive reserve allows the activation of additional synaptic connections and new neural networks against environmental demands. Objective: Establish the variables that contribute to the formation of cognitive reserve and its expression in relation with Alzheimer´s Disease. Method: Systematic and evaluative review of qualitative type. Results: Education, leisure activities, lifestyle, socioeconomic status and intelligence are the main variables which contribute to the formation of cognitive reserve. Subjects with high reserve have lower prevalence and incidence of dementia. Those who develop Alzheimer´s Disease will do so at a later age and with more severe symptoms. Conclusions: The variables which contribute to the formation of cognitive reserve are, mainly, socio-environmental variables. The reserve is considered a protective factor against disease. It delays the onset of dementia avoiding, in some cases, the development of the pathology(AU)

Prevalence of dementia among widowed and non-widowed patients and associated clinical and sociodemographic characteristics / Prevalência, características clínicas e sociodemográficas em pacientes viúvos e não viúvos com demência

Abstract Objective: to verify if the prevalence of dementia differs between widowed and non-widowed elderly persons and between genders, and to analyse if there is an association with sociodemographic and clinical characteristics. Method: a retrospective cross-sectional observational study of patients treated at a Behavioral Neurology outpatient clinic from 1999 to 2009 was carried out, employing anamnesis, physical and neurological examination, the Clinical Dementia Rating Scale (CDR) and the Mini Mental State Examination (MMSE). Sociodemographic (schooling and age) and clinical (age of onset of symptoms and time since onset of symptoms, MMSE and CDR) variables were analyzed. The differences were evaluated by the Mann Whitney test, using a significance value of p<0.05. Results: of 208 patients diagnosed with dementia, 73 (35.1%) were widowed and 135 (64.9%) were non-widowed. Those who were widowed were older than those who were non-widowed (p<0.001) when diagnosed with dementia. This difference in age remained when gender (p<0.001), widowed and widowed women (p<0.001) and widowed and non-widowed men (p<0.001) were compared. The time from onset of symptoms to diagnosis was greater in widowed than in non-widowed men [55.6 (± 86.3) vs. 43.4 (± 44.8) months], although the difference was not statistically significant. Widowed patients with dementia had lower schooling, regardless of gender (p<0.05). Conclusion: the prevalence of dementia differed between widowed and non-widowed individuals, being higher among non-widows. There was an association between widowhood and the clinical and sociodemographic characteristics, with differences between the genders. The loss of a spouse can generate different outcomes among men and women, necessitating measures with a specific focus on prevention and strategies of care in dementia.

Resumo Objetivo: Verificar se a prevalência de demência difere entre viúvos e não viúvos, e analisar se há associação com características sociodemográficas e clínicas, bem como diferenças entre os sexos. Método: Estudo observacional transversal retrospectivo que analisou prontuários de pacientes atendidos em um ambulatório de Neurologia do Comportamento de 1999 a 2009 através de anamnese, exame físico e neurológico, Clinical Dementia Rating Scale (CDR) e Miniexame do Estado Mental (MEEM). Avaliou-se variáveis sociodemográficas (escolaridade e idade) e clínicas (idade e tempo do início dos sintomas, MEEM e CDR). As diferenças foram avaliadas pelo teste de Mann Whitney, admitindo-se p<0,05. Resultados: Dos 208 pacientes com diagnóstico de demência, 73 (35,1%) eram viúvos e 135 (64,9%) não viúvos. Os viúvos eram mais velhos que os não viúvos (p<0,001) quando foram diagnosticados com demência. Essa diferença na idade manteve-se comparando os sexos (p<0,001), mulheres viúvas e não viúvas (p<0,001) e homens viúvos e não viúvos (p<0,001). O tempo do início dos sintomas até o diagnóstico foi maior em homens viúvos quando comparado aos não viúvos [55,6 (±86,3) vs 43,4 (±44,8) meses] mas sem significância estatística. Os viúvos com demência tinham menor escolaridade, independente do sexo (p<0,05). Conclusão: A prevalência de demência diferiu entre viúvos e não viúvos, sendo maior nos não viúvos. Houve associação da viuvez com características clínicas e sociodemográficas com diferença entre os sexos. A perda do cônjuge pode gerar diferentes desfechos entre homens e mulheres, necessitando de medidas com enfoque específico na prevenção e estratégias de cuidado na demência.

Neuroprotective effect of melatonin in cerebellums in Alzheimer's disease animal models via MAPK/ERK signaling pathway / 中国药理学通报

Aim: To investigate the effect of melatonin on neuroprotection in cerebellums of rats with Alzheimer' s disease via MAPK/ERK signaling pathway. Methods: Thirty-two male Sprague-Dawley rats were randomly divided into four groups: control group, Aβ1-42 lateral ventricle injection group (AD), and melatonin intraperitoneal injection group (MT), and Aβ1-42 lateral ventricle injection combined with melatonin intraperitoneal injection group (AD + MT). The pathological changes of rat cerebellar cortex were detected by HE staining; the expression of NeuN (neuronal marker), Calbindin(Purkinje cell marker) and p-ERK protein in each group was detected by immunofluorescence; the expression of ERK and p-ERK in each group was determined by Western blot. Results: The HE staining showed that the expression of neurons decreased, followed with the disordered arrangement and morphological alteration of cells in AD. Melatonin could significantly alleviate the pathological damage in cerebellum. Immunofluorescence results showed that compared with AD group, the expression of NeuN (neuronal marker) increased, the number of Purkinje cells marked by Calbindin significantly was up-regulated(P < 0. 01), and the expression of p-ERK was down-regulated in AD + MT group. Western blot showed that the expression of p-ERK was down-regulated by melatonin. Conclusions: Melatonin may exert the neuroprotective effect and relieve the pathological changes by inhibiting the activation of MAPK/ERK signaling pathway.

Small interfering RNA delivery to the neurons near the amyloid plaques for improved treatment of Alzheimer׳s disease

Gene therapy represents a promising treatment for the Alzheimer׳s disease (AD). However, gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have developed an siRNA nanocomplex able to be specifically delivered to the amyloid plaques through surface modification with both CGN peptide for the blood-brain barrier (BBB) penetration and QSH peptide for -amyloid binding. But, whether the as-designed nanocomplex could indeed improve the gene accumulation in the impaired neuron cells and ameliorate AD-associated symptoms remains further study. Herein, we prepared the nanocomplexes with an siRNA against -site amyloid precursor protein-cleaving enzyme 1 (BACE1), the rate-limiting enzyme of A production, as the therapeutic siRNA of AD. The nanocomplexes exhibited high distribution in the A deposits-enriched hippocampus, especially in the neurons near the amyloid plaques after intravenous administration. In APP/PS1 transgenic mice, the nanocomplexes down-regulated BACE1 in both mRNA and protein levels, as well as A and amyloid plaques to the level of wild-type mice. Moreover, the nanocomplexes significantly increased the level of synaptophysin and rescued memory loss of the AD transgenic mice without hematological or histological toxicity. Taken together, this work presented direct evidences that the design of precise gene delivery to the AD lesions markedly improves the therapeutic outcome.

Research on estrogen-like protective effect of quercetin on PC12 cells induced by Aβ25.35 and molecular mechanism / 中国药理学通报

Aim To investigate the estrogen-like pro- tective effect of quercetin and its molecular mechanism via the establishment of a model of AD in vitro by inducing PC 12 cells with Aβ25.35 Methods Cell viability was detected by MTT assay. The expressions of ERot and ERß were detected by immunofluorescence staining. The expressions of ERct and ERβ, p-Akt, total-Akt, p-GSK-3β and total-GSK-3β related proteins were assessed by Western blot. Results MTT assay showed that 20 \imo\ • L-1 Aßyjs could significantly reduce cell viability after treatment with PC 12 cells for 24 h (P 0. 05). The expression levels of total-Akt and total-GSK-3β protein remained basically unchanged. When the estrogen receptor was inhibited by ICI 182, 780, the cell viability of PC 12 cells and the expression of p-Akt and p-GSK-3β protein were significantly decresed (P < 0 . 0 1) . Conclusion All the results indicate that quercetin has a protective effect on Aβ25.35 induced PC 12 cell injury. The estrogen-like neuroprotective mechanism is able to activate PI3K/Akt/GSK-3β signaling pathway by the mediation of estrogen receptor alpha.

Perineuronal nets-a double-edged sword regulating neuropsychiatric disorders / 中国药理学通报

Perineuronal nets (PNNs) are unique extracellular matrix (ECM) structures surrounding parvalbumin (PV) positive intemeurons in the central nervous system (CNS). The intact structure of PNNs is critical to the function of CNS. PNNs regulate the function of GABA neurons, inhibit the damage of neurons induced by reactive oxygen species, and also participate in the regulation of neuroplasticity and the development of central nervous system. They will change in quantity and quality after mental disorders, aging, memory and drug abuse. Here the focus is on how the PNNs protect interneuron and control plasticity , and on the role of PNNs in memory in normal aging, Alzheimer's disease and drug addiction, and the association with altered PNNs formation. Understanding the molecular mechanism on PNNs would offer insights into new treatments of relevant diseases.

Focused ultrasound and Alzheimer's disease: a systematic review / Ultrassonografia focalizada e doença de Alzheimer: uma revisão sistemática

ABSTRACT Alzheimer's disease (AD) affects millions of people, however, there is still no effective treatment. The use of focused ultrasound with microbubbles (FUS-MB) for the opening of the blood-brain barrier has been recently studied and may become a promising therapeutic target. Objective: To discuss the use of FUS-MB for the treatment of AD and to present some of the techniques used. Methods: A systematic review was performed of MEDLINE/PubMed and Biblioteca Virtual em Saúde (BVS) services, using the keywords: focused ultrasound, Alzheimer, amyloid-b. Original articles were included in the study; studies that did not focus on Alzheimer's treatment were excluded. Results: Fifteen original studies were selected. Preclinical trials were able to reduce amyloid-b plaques and tau phosphorylation, improving cognitive performance in AD animals. Conclusion: The results are very promising, but the therapy still requires maturation. Further studies are needed to systematize all the techniques used and their effects in order to enable use in humans.

RESUMO A doença de Alzheimer (DA) afeta milhões de pessoas, porém, ainda não há um tratamento efetivo. O uso de ultrassonografia focalizada com microbolhas (FUS-MB) para a abertura da barreira hematoencefálica (BHE) tem sido objeto de estudos recentes, podendo tornar-se um alvo terapêutico bastante promissor. Objetivo: Discutir o uso da FUS-MB para o tratamento da DA e apresentar algumas das técnicas utilizadas. Métodos: Revisão sistemática através dos serviços MEDLINE/PubMed e Biblioteca Virtual em Saúde (BVS), através das seguintes palavras-chaves: focused ultrasound, Alzheimer, amyloid-b. Foram incluídos no estudo artigos originais. Foram excluídos estudos que não tinham o tratamento do Alzheimer como foco. Resultados: Foram selecionados 15 estudos originais. Os resultados pré-clínicos são positivos para redução de placas amiloides, fosforilação da proteína tau e sobre desempenho cognitivo de animais com DA. Conclusão: Os resultados são promissores, mas terapia ainda necessita de aperfeiçoamento, necessitando de mais estudos que sistematize todas as técnicas e seus efeitos, para ser possível o seu uso em humanos.

Metamemory monitoring in Alzheimer's disease: a systematic review / Monitoramento da metamemória na doença de Alzheimer: uma revisão sistemática

ABSTRACT Metamemory is the awareness of one's own knowledge and control of memory, and refers to the online ability to gather information about the current state of the memory system. Objective: Metamemory is one's own knowledge and control of memory. A systematic review was performed to identify the types of tasks used for evaluating metamemory monitoring, the stimuli used in these tasks, their limitations and the outcomes in people with Alzheimer's disease (PwAD). Methods: This systematic review followed PRISMA methodology. A search of Pubmed, Scopus and Web of Science electronic databases was carried out in September, 2018, identifying experimental investigations of metamemory and dementia. Results: We included 21 studies. The most common tasks used were judgement of learning, feeling of knowing, judgement of confidence and global prediction. The rates of discrepancy between PwAD and caregivers still need further research. The Rey Auditory Verbal Learning Test was the most used list of words. PwAD are able to accurately rate their memory functioning and performance, when the evaluation is done soon afterwards. PwAD tend to overestimate their functioning and performance when the judgement involves forward-looking vision. Conclusion: In the context of metamemory impairment, clinicians and caregivers should seek interventions aiming to identify compensatory styles of functioning. This systematic review provides initial evidence for the use of metamemory measures as part of broader assessments evaluating Alzheimer's disease.

RESUMO Metamemoria é a consciência do próprio conhecimento e controle da memória, e refere-se à capacidade online de reunir informações sobre o estado atual do sistema de memória. Objetivo: Metamemória é a consciência sobre o próprio conhecimento e controle da memória. Nós conduzimos uma revisão sistemática para identificar os tipos de tarefa usadas para avaliar o monitoramento da metamemória, os estímulos usados nessas tarefas, suas limitações e resultados em pessoas com doenças de Alzheimer. Métodos: Esta revisão sistemática usou a metodologia PRISMA. Uma busca nas bases Pubmed, Scopus e Web of Science foi feita em Setembro de 2018. Foram identificados estudos experimentais em metamória e demência. Resultados: Foram incluídos 21 estudos que se enquadravam nos critérios de inclusão. As tarefas mais comuns foram "judgement of learning", "feeling of knowing", "judgement of confidence" and "global prediction". As discrepâncias, em termos de monitoramento de metamemória, ainda necessitam de pesquisas futuras. O Rey Auditory Verbal Learning Test foi a lista de palavras mais usada. Pessoas com doença de Alzheimer são capazes de avaliar de forma acurada o seu funcionamento da memória, quando a avaliação é feita em um momento posterior. Eles tendem a superestimar seu funcionamento quando o julgamento é feito em uma visão de futuro. Conclusão: No contexto do comprometimento da metamemória, é necessário que clínicos e cuidadores procurem intervenções com o objetivo de identificar estilos compensatórios de funcionamento. Assim, esta revisão sistemática fornece evidências iniciais sobre o uso de medidas de metamemória como parte de avaliações mais amplas na doença de Alzheimer.

A program of physical activity improves gait impairment in people with Alzheimer's disease

AIM: This study aimed to identify the effects of aging and Alzheimer's disease (AD) on gait parameters after a four-month period and to investigate the effects of a four-month program of physical activity, with emphasis on the cognitive components of gait during single and dual task, in people with AD. METHODS: Twenty-three people with AD, divided into the Training Group (TG; n=12; aged 79.17±7.62 years) and the Control Group (CG; n=11; aged 77.00±5.57 years), and eleven healthy older adults (Healthy Group - HG; aged 75.82±4.83 years) were included in this study. TG participated in a physical activity program for four months. The CG and HG were instructed not to participate in any kind of regular physical activity in this period. The physical activity program includes motor activities and cognitive tasks simultaneously. The participants attended a 1-h session three times a week. The kinematic parameters of gait were analyzed under two conditions, before and after a physical activity program: single and dual task. Deltas for all dependent variables between pre and post training were calculated. The deltas were compared using two-way ANOVAs with group (TG x CG and CG x HG) and task (single x dual task) as factors, with repeated measures for task. RESULTS: After the training period, the TG improved stride length, duration, velocity and cadence compared to the CG. CONCLUSION: Physical activity with emphasis on cognitive components promotes better reallocation of attention while walking in people with AD, improving attentional focus on the gait and thus resulting in a safer locomotive pattern.(AU)

Dimensiones para la promoción de la salud cognitiva y prevención de demencias / Dimensions for cognitive health´s promotion and prevention of dementias

En la actualidad existe un aumento exponencial en el número de personas que reciben diagnóstico de demencia cada año. Sin embargo el control de determinados factores de riesgo en la población general podría reducir significativamente la tasa global de pacientes que presentan declive cognitivo o algún tipo de demencia (incluida la enfermedad de Alzheimer). Esta realidad convierte a la promoción de salud cognitiva en un campo prioritario desde el cual deben diseñarse acciones encaminadas a potencias el bienestar cognitivo global con énfasis en el envejecimiento. De esta manera el objetivo de este material es discutir un grupo de premisas y dimensiones que deben considerarse para la concepción, diseño e implementación de programas orientados a la promoción de salud cognitiva y la prevención de demencias. Se propone que el diseño de programas orientados a la promoción de salud cognitiva y la prevención de demencias pueden concebirse partiendo de tres dimensiones principales: a) exploración de creencias y conocimiento general, b) educativo-formativo e c) investigación-implementación. La promoción de salud cognitiva está llamada a convertirse en un importante recurso para reducir el declive cognitivo patológico y el riesgo de padecer demencias. Para alcanzar este objetivo la salud cognitiva y prevención de demencias deben constituir una prioridad dentro de los sistemas de salud (y de los profesionales que los integran), concretándose en el diseño de programas dirigidos a reducir los factores de riesgos relacionados con el deterioro cognitivo patológico, y la implementación de intervenciones en función del bien público(AU)

Nowadays, there is an exponential increase in the number of people diagnosed with dementia every year. However, control of certain risk factors in general population could significantly reduce the overall rate of patients with cognitive decline or some form of dementia (including Alzheimer's disease). This reality turns cognitive health´s promotion into a priority field from which actions should be designed to encourage the overall cognitive wellbeing with an emphasis in aging. The objective of this paperwork is to discuss a group of premises and dimensions that must be considered for the conception, design and implementation of programs oriented to cognitive health´s promotions and the prevention of dementias. It is proposed that the design of programs oriented to the promotion of cognitive health and the prevention of dementias can be conceived from three main dimensions: a) exploration of beliefs and general knowledge, b) educational-formative and c) research-implementation. The promotion of cognitive health is called to become an important resource to reduce pathological cognitive decline and the risk of dementias. To achieve this goal, Cognitive Health and Dementia Prevention must be a priority within the health systems (and the professionals that integrate them), focusing on the design of programs aimed to reduce the risk factors related to pathological cognitive impairment , and the implementation of interventions in function of the public good(AU)

Mitochondria-targeting drug conjugates for cytotoxic, anti-oxidizing and sensing purposes: current strategies and future perspectives

Mitochondrial targeting is a promising approach for solving current issues in clinical application of chemotherapy and diagnosis of several disorders. Here, we discuss direct conjugation of mitochondrial-targeting moieties to anticancer drugs, antioxidants and sensor molecules. Among them, the most widely applied mitochondrial targeting moiety is triphenylphosphonium (TPP), which is a delocalized cationic lipid that readily accumulates and penetrates through the mitochondrial membrane due to the highly negative mitochondrial membrane potential. Other moieties, including short peptides, dequalinium, guanidine, rhodamine, and F16, are also known to be promising mitochondrial targeting agents. Direct conjugation of mitochondrial targeting moieties to anticancer drugs, antioxidants and sensors results in increased cytotoxicity, anti-oxidizing activity and sensing activity, respectively, compared with their non-targeting counterparts, especially in drug-resistant cells. Although many mitochondria-targeted anticancer drug conjugates have been investigated and , further clinical studies are still needed. On the other hand, several mitochondria-targeting antioxidants have been analyzed in clinical phases I, II and III trials, and one conjugate has been approved for treating eye disease in Russia. There are numerous ongoing studies of mitochondria-targeted sensors.

Flavonoids from stem and leaf of Scutellaria baicalonsis Georgi inhibit PHF abnormality and regulatory mechanism of protein phosphatase in rats' brain induced by okadaic acid / 中国病理生理杂志

AIM:To investigate the effect of flavonoids from stem and leaf of Scutellaria baicalonsis Georgi(SSF)on paired helical filament(PHF)abnormality and the regulatory mechanism of protein phosphatase(PP)in rats' brain induced by okadaic acid(OA).METHODS:Male Sprague-Dawley(SD)rats were microinjected with OA(200 ng/kg)by the lateral ventricle to establish a memory impairment model.Morris water maze was used to screen the memory impairment model.The successful model rats were continuous intragastric infusion(ig)SSF for 36 days.The relative pro-tein expression of PHF,PP1,PP2A-Cα,PP2A-Cβ,PP2CA and PP2CB in the rat cerebral cortex and hippocampus were detected by Western blot.GinKgo biloba leaf flavonoids(GLF)were used as positive control drug.RESULTS:Compared with the sham-operated rats ,the relative protein expression of PHF in the cerebral cortex and hippocampus and PP 1 in cor-tex of model rats were significantly increased(P<0.01),and the protein expression of PP2A-Cα,PP2A-Cβin the cere-bral cortex and hippocampus and PP2CB in the hippocampus were decreased(P<0.05),while the relative protein expres-sion of PP2CA and PP2CB in the cortex were significantly increased(P<0.01).SSF reversed the abnormality in the pro-tein expression of PHF,PP2A-Cαand PP2A-Cβin rat cortex and hippocampus and PP1 in rat cortex induced by OA(P<0.01),which had no significant effect on the relative protein expression of PP 2CA and PP2CB.GLF also showed similar results to SSF.CONCLUSION:SSF significantly reduces the abnormal formation of PHF in rats ' brain induced by OA ,which may be related to the regulation of PP 1,PP2A-Cαand PP2A-Cβexpression,but not with PP2CA and PP2CB ex-pression.

O Impacto do comportamento do idoso com doença de alzheimer na vida do cuidador / El impacto del comportamiento del anciano con enfermedad de alzheimer en la vida del cuidador / The impact of the behavior of the elder with alzheimer's disease in the caregiver’s life

Objetivo: propor uma reflexão, à luz do Interacionismo Simbólico, sobre o comportamento do idoso com doença de Alzheimer e seus desdobramentos na vida do cuidador. Método: reflexão teórica fundamentada nos preceitos do Interacionismo Simbólico.Optou-se por essa abordagem, pois utiliza como ferramenta a concepção dos próprios atores a respeito do mundo social no qual estão inseridos, atribuindo-lhe significados que refletem nas próprias ações. Resultados: o mundo social do cuidado, vivenciado pelo idoso e seu cuidador não pode ser interpretado em termos de relações determinísticas, pois a natureza dos símbolos é manipulada pelo processo interpretativo e subjetivo de cada cuidador. À medida que ele vivencia sua realidade de cuidado, são estabelecidas transações e interações que se desdobram em demandas de cuidado. Conclusão: Essas demandas apresentam possibilidades reais de intervenção de enfermagem e precisam ser conduzidas a partir da interpretação atribuída e individualizada por cada cuidador.

Objective: to propose a reflection, in the light of Symbolic Interactionism, about the behavior of the elder with Alzheimer's diseaseand its unfolding in the caregiver’s life. Method: theoretical reflection based on the precepts of Symbolic Interactionism. Thisapproach was chosen because it uses as a tool the actors' own conception of the social world in which they are inserted, attributingto it the meanings they reflect in their own actions. Results: the social world of care experienced by the elder and his/her caregivercannot be interpreted in terms of deterministic relations, since the interpretative and subjective process of each caregivermanipulates the nature of the symbols. As he/she experiences his/her care reality, transactions and interactions are established,unfolding into care demands. Conclusion: These demands present real possibilities of nursing intervention and need to be drivenfrom the attributed and individualized interpretation by each caregiver.

Objetivo: proponer una reflexión, a la luz del Interaccionismo Simbólico, sobre el comportamiento del anciano con enfermedad deAlzheimer y sus desdoblamientos en la vida del cuidador. Método: reflexión teórica fundamentada en los preceptos delInteraccionismo Simbólico. Se optó por ese enfoque, pues utiliza como herramienta la concepción de los propios actores a cerca delmundo social en el que están insertados, atribuyéndole significados que reflejan en las propias acciones. Resultados: el mundosocial del cuidado vivido por el anciano y su cuidador no puede ser interpretado en términos de relaciones deterministas, pues lanaturaleza de los símbolos es manipulada por el proceso interpretativo y subjetivo de cada cuidador. A medida que vive su realidadde cuidado, se establecen transacciones e interacciones que se desdoblan en demandas de cuidado. Conclusión: Estas demandaspresentan posibilidades reales de intervención de enfermería y necesitan ser conducidas a partir de la interpretación atribuida eindividualizada por cada cuidador.

A dádiva e o cuidado no tempo vivido em família / La dádiva y el cuidado en el tiempo del vivido en familia / Gifting and care during the time lived with the family

Objetivo: compreender a modelagem do cuidado familiar ao longo do tempo à idosa que vivencia o Alzheimer, inscrevendo-o no circuito da dádiva. Métodos: Estudo de situação, de abordagem compreensiva, empregando história de vida com entrevista em profundidade e observação junto à idosa e à família. Resultados: Apreendemos os laços que unem os entes familiares, possibilitando a modelagem do cuidado “na e para” a vida, ao longo do tempo em família, instaurando o circuito da dádiva, que apresentamos pela imagem da lemniscata. Nessa modelagem evidenciamos o intenso esforço despendido pela família na provisão e no gerenciamento dos cuidados à idosa, cada vez mais aprimorados, atualizando, assim, o dar receber retribuir, em tecitura afetiva e laboriosa. Conclusão: Tal compreensão mostra-se importante aos profissionais de saúde para que reflitam sobre modos de produzir boas práticas que perdurem no tempo, mobilizando recursos para apoiar a família com o substrato necessário ao seu cuidar.

Objective: to understand the modeling of family care provided over time to an elderly who experiences Alzheimer’s, including it in the gifting circuit. Methods: This was a situational study with a comprehensive approach, employing life story with an in-depth interview and observation of the elderly and family. Results: We learned about the ties that bind family members, allowing modeling care “in and for” life, over family time, establishing the gifting circuit that we present through the lemniscate image. In this modeling, we evidenced the intense effort expended by the family to provide and manage the care to the elderly, increasingly improved and updating the give-receive reciprocate in an affective and laborious texture. Conclusion: Such understanding is important for health professionals to reflect on ways to produce good practices that endure over time mobilizing resources to support the family with the necessary substrate for their care.

Objetivo: comprender el modelaje del cuidado familiar a lo largo Del tiempo a la anciana con Alzheimer, inscribiéndolo en el circuito de dádiva. Métodos: Estudio de situación, de enfoque comprensivo, empleando historia de vida con entrevista en profundidad y observación de la anciana y familia. Resultados: Reflexionamos sobre los lazos que unen entes familiares, posibilitando el modelaje del cuidado “en y para” la vida, a lo largo del tiempo en familia, instaurando el circuito de dádiva que presentamos por la imagen de lemniscata. En ese modelaje evidenciamos el intenso esfuerzo despendido por la familia en la provisión y gerenciamiento de lós cuidados, cada vez más mejorados, reactualizando el dar-recibir-retribuir en tesitura afectiva y laboriosa. Conclusión: Tal comprensión es importante para los profesionales de salud para reflexionar sobre modos de producir buenas prácticas que perduren en el tiempo, movilizando recursos para apoyar la familia con el substrato necesario a su cuidar.

Protective effect of fibroin peptides on Aβ25-35-induced injury in SH-SY5Y cells and its mechanism / 中国药科大学学报

This study aimed at exploring the molecular mechanism of fibroin peptide in preventing the Aβ25-35-induced neuronal damages in SH-SY5Y cells.MTT was used to detect the effect of fibroin peptide on the changes of the Aβ25-35-induced injuries in SH-SY5Y cells;Western blot was employed to detect the effect of fibroin peptide on the changes of the Aβ25-35-induced hyperphosphorylation of Tau in SH-SY5Y cells;DCFH-DA probe method was used to detect the effect of fibroin peptide on the Aβ-induced production of intracellular reactive oxygen species (ROS) in SH-SY5Y cells.The results indicated that fibroin peptide could improve the activity of the PP2A and inhibit the activity of GSK-3β to decrease the hyperphosphorylation of Tau induced by Aβ25-35.Fibroin peptide could significantly prevent the Aβ25-35-induced neuronal damages and multisite Tau hyperphosphorylation.In addition,fibroin peptide could also reduce oxidative damage to protect neurons by significantly decreasing the Aβ25-35-induced production of intracellular ROS.

Expressions of amyloid beta peptide and its related metabolic enzymesin the brain of model mice with Alzheimer`s disease and type 2 diabetes mellitus / 基础医学与临床

Objective To examine the changes of Aβ expression and its related metabolic enzymes in the brains of AD and T2DM mice, so as to explore the possible mechanism of type 2 diabetes mellitus combined with AD.Methods Five-month-old APP/PS1 double transgenic mice, ob/ob mice and the wild-type control mice were employed in this study.Immunohistochemical (IHC) staining, Elisa and Western blot were used to detect SP, Aβ and its related metabolic enzymes.Results A certain number of SPs were observed in the cerebral cortex and hip-pocampus of APP/PS1 mice;SPs were occasionally observed in the cortex of ob/ob mice, while no SP appeared in wild-type mice.Aβ40 and Aβ42 levels were significantly increased in APP/PS1 and ob/ob mice brains as compared with controls (P<0.05), thought both Aβ40 and Aβ42 levels in AD mice were significantly higher than those of ob/ob mice (P<0.05).APP expression level was highest in APP/PS1 mice among 3 groups, and its expressed higher in ob/ob mice than that of control mice (P<0.05).BACE1 expression was notably increased in APP/PS1 and ob/ob mice as compared with control(P<0.05), however, it expressed higher in APP/PS1 mice than ob/ob mice (P<0.05).The expression of Aβ degradation enzyme IDE was reduced in APP/PS1 and ob/ob mice(P<0.05), while lowest in ob/ob mice.Conclusions Overexpression of Aβ may be one of main reasons for T2DM combined AD.

Rendimiento en pruebas cognitivas breves, de adultos mayores con demencia en estadios avanzados, residentes de una comunidad urbana de Lima, Perú / Performance of cognitive brief test in elderly patients with dementia in advanced stage living in an urban community of Lima, Peru

RESUMEN Objetivos. Evaluar el rendimiento de la prueba de dibujo de reloj en versión de Manos (PDR-M) y Mini Mental State Examination (MMSE) en su versión peruana, para detectar demencia de cualquier tipo en adultos mayores residentes de una comunidad urbana de Lima, Perú. Materiales y métodos. Análisis secundario de base de datos, de tipo observacional, analítico y transversal; con diseño de prueba diagnóstica, teniendo como prueba estándar a las evaluaciones clínica y neuropsicológica en conjunto. Se evaluó el rendimiento de las pruebas individualmente, así como de forma combinada. Resultados. El rendimiento de MMSE para la evaluación de pacientes con demencia de cualquier tipo presentó sensibilidad de 64,1%, especificidad de 84,1%, VPP de 24,4%, VPN de 96,7%, LR (+) de 4,03 y LR (-) de 0,43. La PDR-M presentó sensibilidad de 89,3%, especificidad de 98,1%, VPP de 79,3%, VPN de 99,1%, LR (+) de 47,79 y LR (-) de 0,11. Cuando se aplicaron ambas pruebas, y al menos una de ellas fue positiva, presentaron sensibilidad de 98,1%, especificidad de 84,1%, VPP de 33,1%, VPN de 99,8%, LR (+) de 6,17 y LR (-) de 0,02. Al realizar el análisis, por separado, de demencia tipo alzhéimer y no alzhéimer, los valores de los parámetros no se diferencian sustancialmente de los obtenidos para demencias de cualquier tipo. Conclusiones. La combinación de MMSE y PDR-M demuestran un buen rendimiento para detectar demencia en estadios moderado y severo en población residente de una comunidad urbana de Lima.

ABSTRACT Objectives. Evaluate the performance of clock drawing test- Manos versión (PDR-M) and Mini Mental State Examination -Peruvian version (MMSE) to detect dementia in a sample based on urban community of Lima, Peru. Materials and methods. This study is a secondary analysis database, observational, analytical and cross-sectional, the gold standard was the clinical and the neuropsychological evaluations together. Performance testing individually and in combination were evaluated.. Data were obtained from prevalence study conducted in 2008 in Cercado de Lima. Results. MMSE performance for evaluation of patients with dementia of any kind showed sensitivity of 64,1%, specificity of 84,1%, PPV of 24.4%, NPV of 96.7%, PLR of 4,03 and NLR of 0,43. PDR-M showed sensitivity of 89,3%, specificity of 98,1%, PPV of 79.3%, NPV of 99.1%, PLR of 47,79 and NLR of 0,11. When both tests were applied, and at least one of them was positive, they showed sensitivity 98.1%, specificity 84.1%, PPV of 33.1%, NPV of 99.8%, PLR of 6,17 and NLR of 0,02. When performing separate analysis of Alzheimer-type dementia and non- Alzheimer dementia, the values of the parameters do not differ substantially from those obtained for dementia of any kind. Conclussions. The combination of MMSE and PDR-M show good discriminative ability to detect moderate and severe dementia in population living in urban community in Lima.

Organização da família no cuidado ao idoso com doença de Alzheimer / Family organization in the care of the elderly with Alzheimer's disease

Objetivo: Analisar como a família se organiza para prestar cuidados ao idoso com doença de Alzheimer no espaço domiciliar. Método: Pesquisa qualitativa, descritiva. Para a avaliação da família foi utilizado o Modelo Calgary de Avaliação Familiar e os dados foram obtidos junto a duas famílias, em que em cada uma delas havia uma pessoa idosa com doença de Alzheimer (DA). As informações foram organizadas e analisadas seguindo os preceitos da análise de conteúdo. Resultados: Identifica-seque o familiar cuidador realiza adequações em seu cotidiano - assume novas funções no ambiente doméstico, abandona determinadas responsabilidades, tarefas e atividades de lazer, para dedicar-se ao cuidado da pessoa com DA. Ainda, apresenta sobrecarga de trabalho, insegurança e, também,adoece necessitando de ajuda de outras pessoas. Considerações finais: Observa-se a importância do vínculo entre os familiares e o idoso com doença de Alzheimer, para que os cuidados sejam efetiva dose sua condição clínica seja preservada. Verifica-se que há mudanças pessoais, físicas, psíquicas e organizacionais na vida do familiar cuidador, para dar conta do cuidado ao idoso que apresenta D Ano espaço domiciliar. Entende-se ser relevante a atenção da equipe de enfermagem neste contexto,prestando cuidado e orientações.

Objective: To analyze how the family is organized to provide care to the elderly with Alzheimer's disease at home. Method: This is a qualitative and descriptive research. For the evaluation of the family we usedthe Calgary Family Assessment Model, and data were obtained from two families, with each of themhaving an elderly person with Alzheimer's disease (AD). Data was organized and analyzed following the precepts of content analysis. Results: We found that the family caregivers make adjustments in their daily lives - take up new duties at home, abandon certain responsibilities, tasks and leisure activities, todevote themselves to the care of the person with AD. They also have work overload, show insecurity, andalso get sick needing help from others. Final Considerations: T importance of a link between the familyand the elderly with Alzheimer's disease is highlighted, in order that care is effectively provided, and thepatient’s clinical condition is preserved. It is found that there are personal, physical, psychological and organizational changes in the family caregivers’ life for the AD elderly to be cared at home. The attention from nursing staff is noted to be relevant in this context, providing care and guidance.