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Objective To investigate the relieving effects of knockdown of long non-coding RNA(lncRNA)taurine up-regulated gene 1 (TUG1) on inhibiting nucleotide binding oligomerization domain like receptor protein 1 (NLRP1) inflammasome and the progression of Alzheimer’ s disease. Methods Wild-type (WT group, 10 mice) or amyloid precursor protein (APP) / presenilin-1 (PS1) transgenic mice (30 mice) with a genetic background of C57 / BL6 aged 9-10 weeks were used in this study. APP / PS1 transgenic mice were randomly divided into model group, model+lncRNA TUG1 short hairpin RNA (shRNA) group and model + shRNA non target (NT) group (n = 10) . Blood samples, cerebral cortex tissues, primary microglial cells and primary astrocytes were collected from mice 12 weeks of age on day 1 (3-month-old) and 32 weeks of age on day 1 (8-month-old), with 5 mice per group at each time point. Real-time PCR analysis was used to detect the expression levels of lncRNA TUG1 and macrophage migration inhibitory factor (MIF) mRNA in cerebral cortex tissues and primary microglial cells, and C1r and C1s mRNA levels in primary astrocytes of 3-month-old and 8-month-old mice in the above 4 groups, respectively. ELISA was used to determine the MIF in plasma samples of the above 4 groups of mice. Primary microglia and astrocytes from the cerebral cortex of 3-month-old and 8-month-old mice were co-cultured. CCK-8 method was used to determine the proliferation ability of the above cells. Western blotting was used to determine the expression levels of MIF, pro interleukin-1β (pro-IL-1β), apoptosis associated speck-like protein containing a caspase recrult domain(ASC), Caspase-1 (p20), Caspase-1 (full), NLRP1 and NLRP3 in cerebral cortex tissues of 3-month-old and 8-month-old mice. Immunofluorescent staining was used to determine amyloid beta(Aβ) in cerebral cortex of 8-month-old mice. Results At the age of 3-month-old and 8-month-old, compared with the WT group, the relative expression level of lncRNA TUG1 and MIF in cerebral cortex tissues and primary microglia of model group mice was significantly up-regulated, with primary microglial cells and astrocytes proliferation ability enhanced (P0. 05) . There was no significant difference between the model group and the model+shRNA NT group mice of all the above factors (P>0. 05) . Conclusion In APP / PS1 transgenic mice, up-regulation of lncRNA TUG1 and MIF are positively associated with the activation of NLRP1 inflammasome in mice cerebral cortex tissues and primary microglia. Knock-down of lncRNA TUG1 can ameliorate the progression of Alzheimer’ s disease.
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Alzheimer' s disease (AD) is a progressive neurodegenerative disorder histologically characterized by the presence of senile plaques and neurofibrillary tangles (NFTs) found in and around pyramidal neurons in cortical tissue. Mounting evidence suggests regional increased iron load and dyshomeostasis have been associated with oxidative stress, oxidation of proteins and lipids, and cell death, and appears to be a risk factor for more rapid cognitive decline, thereby involved in multiple aspects of the pathophysiology of AD. Ferroptosis is a newly identified iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD. Notably, some novel compounds targeting ferroptosis can relieve AD-related pathological symptoms in AD cells and animal model and exhibit potential clinical benefits in AD patients. This review systematically summarizes the growing molecular and clinical evidence implicating ferroptosis in the pathogenesis of AD, and then reviews the application of ferroptosis inhibitors in mouse/cell models to provide valuable information for future treatment and prevention of AD.
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Alzheimer’s disease (AD) is a progressive neurodegenerative disease with the early symptom of A β plaque, tau hyperphosphorylation neuronal tangle formation in cells. At present, accumulated evidence shows that the changes of GABA receptors are closely related to AD. Some studies have shown that the expression level of each subunit of the GABA receptor changes in AD patients. Therefore, it is speculated that the changes of GABA subunits may be related to the pathogenesis of AD, but there is no better methods to improve AD by targeting GABA receptors. In order to further understand the relationship between the changes of GABA receptors and AD, this paper first reviewed the changes of GABA receptors in AD patients and animal models’ brains and found that there was differential expression in GABA(A) receptor subunits in AD patients. Then we summarized the changes of GABA receptor subunits in Alzheimer database. Based on the data, we found that a few GABA subunits had significant changes. The evidence shows that the change of GABA receptors alters the neural activity in the brain. Other studies have found that the treatment of mice with GABA receptor agonists and antagonists can improve the cognitive ability of mice. We hope that understanding the differential expression of GABA receptors in AD will provide a more accurate target for the treatment of AD.
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Aim To investigate the effects of baicalin on the inflammatory response and Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD 88)/nuclear factor kappa B (N F-K B) signaling pathway in Alzheimer' s disease (AD) rat model induced by lateral ventricular injection of streptozotocin (STZ). Methods The AD animal model was constructed by lateral ventricular injection of STZ in SD rats, and divided into sham operation group, model group, low-dose (60 mg
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Objective To study the effect of velvet antler polypeptides (VAP) on Rho/ROCK pathway in APP/ PSl double transgenic mice. Methods APP/PSl double transgenic mice were randomly divided into model group and velvet antler polypeptide group, 20 mice in each group, and control group consisting of 20 mice of the same litter and the same gender negative. The mice in VAP group were given velvet antler polypeptide 100 mg/kg by intragastric administration once a day for 28 days. After treatment, the water maze experiment was detected and recorded the escape latency and the number of crossing platforms of the mice; the ultrastructures of the synapse were observed by transmission electron microscopy; the expression of Rhs homolog gene family member A(RhoA) and Rho associated coiled-coil forming protein kinase II(ROCKII) in the hippocampal CAI area were observed by immunofluorescence. The expression levels of RhoA and ROCKII protein in the hippocampus were detected by Western blotting. The contents of hippocampus amyloid (3-protein(A(3),
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Objective To study the effect of velvet antler polypeptides (VAP) on antioxidant in Alzheimer' s disease model mice. Methods Eight months old male amyloid precursor protein (APP)/presenilin-l (PS1) double transgenic mice were selected as Alzheimer' s disease (AD) model and divided into the model group and the VAP intervention group, 12 in each group. Besides, normal mice of the same brood (with no transgene) were recruited as a control group (n= 12).After 6 months of intragastric administration, behavior, morphology and oxidative stress related indicators were detected.SH-SY5 cells were used to establish AD model of damaged by Ap2535. The expression levels of APP and p-secreatase-l(BACE1) protein in mouse hippocampus were detected by Western blotting. VAP intervention group SH-SY5Y cells was cultured with VAP (500 g/L) and amyloid P(Ap) 2535(25 ixmol/L) for 24 hours. Control group cells were normally cultured by DMEM medium. Cell apoptosis, membrane potential, reactive oxygen species (ROS) levels and oxidative stress related indexes were detected. Results In animal models, compared with the model group, the escape latency of mice in the VAP intervention group was shortened (P<0. 05). The neuronal cells in the CA1 region of the hippocampus of the model group were reduced and arranged disorderly. The arrangement of the VAP intervention group was relatively regular, and the morphology was significantly improved. Compared with the model group, senile plaques were decreased in the VAP intervention group. Compared with the model group, the malondialdehyde (MDA) content ol the VAP intervention group increased, and the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) content increased, the difference was statistically significant. Compared with the control group, the APP and BACE1 content in the model group increased. Compared with the model group, the contents of APP and BACE1 in the VAP intervention group decreased, and the difference was statistically significant (P<0. 05). In the cell model, the apoptosis rates of the VAP intervention group decreased. Compared with the model group, the mitochondrial membrane potential of the VAP intervention group increased, the content ol ROS decreased, the content of MDA decreased, and the content of SOD and GSH-Px increased. The difference were statistically significant (P<0. 05). Conclusion VAP has a protective effect on oxidative stress damage caused by Alzheimer' s disease model animals and cells, which may be achieved by reducing ROS production and increasing the activity of antioxidant enzymes to reduce Ap deposition.
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Recently p75 neurotrophin receptor (p75NTR) has been found to play a critical role in the pathology of neurodegen¬erative! diseases including Alzheimer's disease (AD) , Parkin¬son' s disease ( PI)), Huntington's disease ( HI)) , amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS).This arti¬cle reviews the research progress of p75NTR in regulating neuron apoptosis, axon degeneration and cognitive impairment, explo¬ring the application of p75NTR as a potential therapeutic target for the treatment of neurodegenerative diseases.
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Alzheimer’s disease (AD) is a prevalent progressive neurodegenerative disorder among the elderly. In the scientific community, the β-amyloid (Aβ) hypothesis is currently a widely-accepted model for AD pathogenesis. Removing Aβ, inhibiting Aβ aggregation and depolymerizing Aβ fibrils are proposed to provide useful strategies for the treatment of AD. However, most current drugs used for anti-Aβ therapy usually have inherent drawbacks that may limit their clinical applications. With the rise of nanotechnology nowadays, the application of two-dimensional nanomaterials in medicine has rapidly attracted much attention from researchers. Two-dimensional nanomaterials not only have excellent physical and chemical properties, as well as good biocompatibility, but also can easily cross either the cell membrane or blood-brain barrier. Recently, it has been found that many two-dimensional nanomaterials can inhibit Aβ aggregation or depolymerize Aβ fibrils by intermolecular interaction, near-infrared photothermal effect, photocatalytic oxidation, chelation of copper ions, drug delivery and other mechanisms, implying its great potential in treating AD. This review will focus on the research of graphene and graphene-like two-dimensional nanomaterials such as molybdenum disulfide, graphitic carbon nitride, and black phosphorus used for anti-Aβ therapy in the treatment of AD.
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Alzheimer's disease (AD) has become one of the major diseases that plague human health and seriously affect the quality of life of patients. Up to present there is no specific treatment drug for Alzheimer' s disease, which still needs research and development. Ginseng is an important traditional Chinese medicine in the prescription for treating of Alzheimer's disease, which contains saponins, polysaccharides, volatile components, proteins, vitamins, amino acids and other compounds. Saponins are the main active components, which have a good effect on improving learning and memory ability and preventing AD. In this paper, the effect and the mechanism of ginsenosides for treating AD are reviewed in order to provide ideas for developing ginsenosides into drugs with better clinical compliance and more effective treatment of AD.
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The ubiquitin-proteasome pathway is one of the most important pathways of cell protein degradation in eukaryotes, and plays an important role in the regulation of cell proliferation, differentiation, apoptosis, DNA repair and other physiological activities. E3 ubiquitin ligase is the major component of ubiquitinproteasome system, which is responsible for substrate recognition. The abnormal regulation of E3 ubiquitin ligase may cause many diseases such as cancer, Alzheimer's disease and Parkinson's disease. Here, we summarizes the progress of drugs targeting E3 ubiquitin ligase in cancer, Alzheimer's disease, Parkinson's disease, diabetic complications, atherosclerosis, and inflammatory bowel diseases. At present, only a few of small molecule antagonists or agonists targeting E3 ubiquitin ligase are under development. The study of natural products in China is leading the way in the world, and numerous natural products have been identified for pharmacological effects on E3 ubiquitin ligase, which may open up a new avenue for multiple complex diseases.
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Aim To investigate the effect of methyl salicylate lactoside (MSL) on the spatial memory and learning of Alzheimer' s disease mice. Methods APP/PS1 double transgenic mice were used as AD animal model to evaluate behavioral changes by Morris water test. At the end of the experiment the brain tissues were fixed for assessment of A(3 deposition by immunohistochemistry, neuronal function changes by Nissl staining, neuronal morphological changes by transmission electron microscopy. Results The results showed that MSL could improve the spatial learning and memory abilitiesof AD mice by shortening latency time, prolonging time spent in target quadrant and increasing number of crossings of APP/PS1 mice. MSL could reduce partial Aβ deposition, alleviate the damage of nerve cells and improve the ultrastructural lesions of neuropil projections. Conclusion MSL could reduce Aβ deposition and protect neurons through anti-inflammatory effects, thus improving the learning and memory abilities of Alzheimer' s APP/PS1 transgenic mice.
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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)
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Humans , Heredodegenerative Disorders, Nervous System/genetics , Telomere Shortening/geneticsABSTRACT
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)
Subject(s)
Humans , Male , Female , Fish Oils , Fatty Acids, Omega-3 , Oxidative Stress , Alzheimer Disease , Cell Membrane , Chronic Disease , NeurogenesisABSTRACT
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)
Subject(s)
Humans , Cognitive Reserve , Alzheimer DiseaseABSTRACT
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.
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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.
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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.
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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.
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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.
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Epidemiology , Widowhood , Dementia , Alzheimer DiseaseABSTRACT
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.