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1.
Behav Brain Sci ; 42: e290, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31896351

RESUMO

Although the integrative memory model proposed by Bastin et al. is interesting, particularly for Alzheimer's disease, it may benefit from incorporating the subjective experience of recollection. We therefore offer complementary lines of interpretation to explain how recollection and familiarity in Alzheimer's disease can be dissociated based not only on accounts of their neural correlates but, critically, on the subjective experience of memory in patients.


Assuntos
Doença de Alzheimer , Humanos , Memória , Transtornos da Memória , Rememoração Mental
2.
Behav Brain Sci ; 42: e291, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31896384

RESUMO

Cognitive control constrains retrieval processing and so restricts what comes to mind as input to the attribution system. We review evidence that older adults, patients with Alzheimer's disease, and people with traumatic brain injury exert less cognitive control during retrieval, and so are susceptible to memory misattributions in the form of dramatic levels of false remembering.


Assuntos
Doença de Alzheimer , Memória , Idoso , Cognição , Humanos , Transtornos da Memória , Rememoração Mental
3.
Behav Brain Sci ; 42: e293, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31896385

RESUMO

We suggest that the inclusion of anxiety, as one relevant mood factor, could enhance the implementation of the integrative memory model in research and the clinic. The role of anxiety in Alzheimer's disease neuroanatomy, symptomology, and progression is used as an example. Customization of the integrative memory model can establish strong foundations for pathology-specific models of memory deficits, enhancing the development of precision medicine applications.


Assuntos
Doença de Alzheimer , Memória , Ansiedade , Humanos , Transtornos da Memória , Rememoração Mental
4.
Adv Exp Med Biol ; 1232: 409-414, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893438

RESUMO

Nakamura et al. examined the evidence, using a discovery and a validation database, that amyloid-ß precursor protein (APP)669-711/amyloid-ß (Aß)1-42 and Aß1-40/Aß1-42 ratios, and composites based on traditional statistics; they concluded that these may be useful as biomarkers of Alzheimer's Disease (AD). We reexamined the same datasets, each of which included cognitively normal individuals (CN), individuals with mild cognitive impairment (MCI) and individuals with AD. We used fractal self-similar analyses and reexamined their data from (1) the Japanese National Center for Geriatrics and Gerontology (NCGG) (discovery database) and (2) the Australian Imaging, Biomarker and Lifestyle Study of Ageing (AIBL) cohort (validation database). Results: Using our methods, the three groups of individuals were found to be self-similar, i.e., they could not be differentiated quantitatively, in contrast to the findings of Nakamura et al. Conclusion: Appropriate biomarkers need further study. Our results suggest that APP669-711/Aß1-42 and Aß1-40/Aß1-42 ratios and their composites may not be valid biomarkers of AD, when reexamined using fractal methods for comparing biomarkers across populations.


Assuntos
Doença de Alzheimer , Biomarcadores , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides , Humanos
5.
Bratisl Lek Listy ; 120(12): 887-893, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31855046

RESUMO

OBJECTIVE: We aimed to investigate the effects of recurrent sevoflurane anesthesia on cognitive functions in Alzheimer Disease. MATERIALS AND METHODS: Rats were divided into 4 groups as followed: control (Group C), sevoflurane (Group S), Alzheimer's (Group A) and Alzheimer's + sevoflurane (Group AS)]. Cognitive functions were evaluated with Radial Arm Maze Test (RAMT). Alzheimer model was created by administering 3 mg/kg (10 µl) STZ. Sevoflurane was administered to S and AS groups. Serum samples and hippocampus tissues were analyzed. RESULTS: In RAM test, the entry-exit data were significantly decreased in A and AS groups. After the 2nd and 3rd administration of anesthesia, the numbers were significantly decreased in Group S. Glial-fibrillary-acidic protein levels were significantly higher in AS compared to the C and S groups. The brain tissue caspase 3 activity was less than 1% in all rats in the Group C, 3 % in 2 rats and 1 % in 1 rat in the Group AS. In A and AS group, serum catalase, myeloperoxidase and ferroxidase activities were found to be higher than in the other groups and myeloperoxidase activity was higher in the AS than in the A Group. Serum native thiol, total thiol and disulfide levels were found to be significantly different in the A and AS groups. CONCLUSION: Sevoflurane anesthesia negatively affected the cognitive functions (Tab. 5, Fig. 10, Ref. 51).


Assuntos
Doença de Alzheimer/induzido quimicamente , Anestesia , Anestésicos Inalatórios , Cognição/efeitos dos fármacos , Éteres Metílicos/farmacologia , Sevoflurano/efeitos adversos , Estreptozocina/farmacologia , Animais , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos , Sevoflurano/administração & dosagem
7.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde, LIS-bvsms | ID: lis-LISBR1.1-46882

RESUMO

Aqui pode encontrar a descrição de um grupo de demências conhecido por Demências Frontotemporais, que é constituído pela Demência Frontotemporal, Afasia Progressiva não-Fluente, Demência Semântica e Doença de Pick. São, ainda, abordadas as causas, os sintomas e o diagnóstico deste tipo de Demência.


Assuntos
Doença de Alzheimer , Demência Frontotemporal , Afasia Primária Progressiva
8.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde, LIS-bvsms | ID: lis-LISBR1.1-46883

RESUMO

A Associação Alzheimer Portugal rege-se pelo princípio do Respeito Absoluto pelos Direitos Fundamentais à Liberdade e à Autodeterminação, e pelo princípio da Abordagem Centrada na Pessoa com Demência. A Doença de Alzheimer e outras formas de Demência são doenças progressivas e degenerativas com impactos profundos na pessoa e em quem a rodeia, e que determinam a perda gradual de capacidade.


Assuntos
Doença de Alzheimer , Demência , Demência Frontotemporal
9.
Adv Exp Med Biol ; 1192: 27-52, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31705489

RESUMO

Alzheimer's disease is a complex and heterogeneous, severe neurodegenerative disorder and the predominant form of dementia, characterized by cognitive disturbances, behavioral and psychotic symptoms, progressive cognitive decline, disorientation, behavioral changes, and death. Genetic background of Alzheimer's disease differs between early-onset familial Alzheimer's disease, other cases of early-onset Alzheimer's disease, and late-onset Alzheimer's disease. Rare cases of early-onset familial Alzheimer's diseases are caused by high-penetrant mutations in genes coding for amyloid precursor protein, presenilin 1, and presenilin 2. Late-onset Alzheimer's disease is multifactorial and associated with many different genetic risk loci (>20), with the apolipoprotein E ε4 allele being a major genetic risk factor for late-onset Alzheimer's disease. Genetic and genomic studies offer insight into many additional genetic risk loci involved in the genetically complex nature of late-onset Alzheimer's disease. This review highlights the contributions of individual loci to the pathogenesis of Alzheimer's disease and suggests that their exact contribution is still not clear. Therefore, the use of genetic markers of Alzheimer's disease, for monitoring development, time course, treatment response, and prognosis of Alzheimer's disease, is still far away from the clinical application, because the contribution of genetic variations to the relative risk of developing Alzheimer's disease is limited. In the light of prediction and prevention of Alzheimer's disease, a novel approach could be found in the form of additive genetic risk scores, which combine additive effects of numerous susceptibility loci.


Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença , Presenilina-1/genética , Presenilina-2/genética , Doença de Alzheimer/diagnóstico , Precursor de Proteína beta-Amiloide , Apolipoproteínas E , Marcadores Genéticos , Humanos
10.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(5): 702-708, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31699204

RESUMO

Alzheimer's disease(AD)is a central nervous system disease characterized by progressive cognitive dysfunction and memory loss.Increasing evidences suggest that ß amyloid(Aß)plays a critical role and may be a upstream molecule in AD pathogenesis involving both genetic and environmental factors.Aß accumulation and its related inflammation are considered early events preceding neurodegeneration and neuronal loss in AD brain.However,all strategies and compounds targeting Aß deposition have failed in clinical trials,implying complexity of AD pathogenesis.This article reviews Aß hypothesis and its related mechanisms,pathophysiological process,and therapeutics of AD.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides , Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/terapia , Encéfalo/fisiopatologia , Humanos
11.
Medicine (Baltimore) ; 98(45): e17824, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702636

RESUMO

The hippocampus is one of the earliest sites involved in the pathology of Alzheimer's disease (AD). Therefore, we specifically investigated the sensitivity and specificity of hippocampal volume and glucose metabolism in patients being evaluated for AD, using automated quantitative tools (NeuroQuant - magnetic resonance imaging [MRI] and Scenium - positron emission tomography [PET]) and clinical evaluation.This retrospective study included adult patients over the age of 45 years with suspected AD, who had undergone fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET-CT) and MRI. FDG-PET-CT images were analyzed both qualitatively and quantitatively. In quantitative volumetric MRI analysis, the percentage of the total intracranial volume of each brain region, as well as the total hippocampal volume, were considered in comparison to an age-adjusted percentile. The remaining brain regions were compared between groups according to the final diagnosis.Thirty-eight patients were included in this study. After a mean follow-up period of 23 ±â€Š11 months, the final diagnosis for 16 patients was AD or high-risk mild cognitive impairment (MCI). Out of the 16 patients, 8 patients were women, and the average age of all patients was 69.38 ±â€Š10.98 years. Among the remaining 22 patients enrolled in the study, 14 were women, and the average age was 67.50 ±â€Š11.60 years; a diagnosis of AD was initially excluded, but the patients may have low-risk MCI. Qualitative FDG-PET-CT analysis showed greater accuracy (0.87), sensitivity (0.76), and negative predictive value (0.77), when compared to quantitative PET analysis, hippocampal MRI volumetry, and specificity. The positive predictive value of FDG-PET-CT was similar to the MRI value.The performance of FDG-PET-CT qualitative analysis was significantly more effective compared to MRI volumetry. At least in part, this observation could corroborate the sequential hypothesis of AD pathophysiology, which posits that functional changes (synaptic dysfunction) precede structural changes (atrophy).


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Fluordesoxiglucose F18/metabolismo , Hipocampo/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Disfunção Cognitiva/metabolismo , Diagnóstico Precoce , Feminino , Glucose/metabolismo , Hipocampo/metabolismo , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Sensibilidade e Especificidade
12.
Brain Nerve ; 71(11): 1209-1214, 2019 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-31722306

RESUMO

The most common neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are known to be protein-misfolding diseases, and characterized by the presence of disease-specific protein aggregates in neuronal and glial cells. Recently, the propagation hypothesis of prion-like protein inclusions in neurodegenerative diseases has been proposed. Many studies have shown that aggregation-prone proteins such as tau, alpha-synuclein and TDP-43 can form aggregates in a seed-dependent and self-templating prion-like manner, and these aggregates can be transferred intercellularly to neighboring cells and seeded for further aggregation. Propagation of aggregated proteins in these diseases may therefore occur through mechanisms similar to those that underlie prion pathogenesis. If this hypothesis is verified in vivo, it will suggest new therapeutic strategies to block the propagation of aggregated proteins throughout the brain.


Assuntos
Doenças Neurodegenerativas/patologia , Doenças Priônicas/patologia , Príons , Doença de Alzheimer , Esclerose Amiotrófica Lateral , Proteínas de Ligação a DNA , Humanos , Doença de Parkinson , alfa-Sinucleína , Proteínas tau
14.
Adv Exp Med Biol ; 1189: 233-265, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31758537

RESUMO

Inflammation plays an important role in the onset and progression of many neurological diseases. As the central nervous system (CNS) constitutes a highly specialized environment where immune activation can be detrimental, it is crucial to understand mechanisms by which the immune system is regulated during neurological diseases. The system of co-signaling pathways provides the immune system with the means to fine-tune immune responses by turning on and off immune cell activation. Studies of co-signaling molecules in neurological diseases and their animal models have highlighted the complexities of immune regulation within the CNS and the intricacies of the interplay between the different cells of the immune system and how they interact with the resident cells of the CNS. This complexity poses challenges when targeting co-signaling pathway to treat neurological diseases and may explain why no drugs targeting these pathways have been successfully developed this far. Here, we will review the current literature on some important co-signaling pathways in multiple sclerosis (MS), Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, and ischemic stroke to understand these pathways in mediating and controlling neuroinflammation.


Assuntos
Doenças do Sistema Nervoso , Transdução de Sinais , Doença de Alzheimer , Esclerose Amiotrófica Lateral , Animais , Isquemia Encefálica , Esclerose Múltipla , Doença de Parkinson
15.
Biochemistry (Mosc) ; 84(11): 1346-1358, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31760922

RESUMO

Neprilysin (NEP) is a zinc-dependent metalloproteinase that exists in organisms in both transmembrane and soluble forms. NEP substrates are involved in regulating the cardiovascular and nervous systems. In this review, we discuss some of the biochemical characteristics and physiological functions of this enzyme with special emphasis on the use of NEP as a therapeutic target. The history and various physiological aspects of applying NEP inhibitors for treating heart failure and attempts to increase NEP activity when treating Alzheimer's disease using gene and cell therapies are described. Another important issue discussed is the role of NEP as a potential marker for predicting the risk of cardiovascular disease complications. The diagnostic and prognostic performance of soluble NEP in various types of heart failure is analyzed and presented. We also discuss the methods and approaches for measuring NEP activity for prognosis and diagnosis, as well as a possible new role of natriuretic peptides (NEP substrates) in cardiovascular diagnostics.


Assuntos
Doença de Alzheimer/diagnóstico , Neprilisina/metabolismo , Doença de Alzheimer/tratamento farmacológico , Biomarcadores/análise , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Neprilisina/análise , Neprilisina/antagonistas & inibidores , Inibidores de Proteases/uso terapêutico , Sistema Renina-Angiotensina , Yin-Yang
16.
Brain Nerve ; 71(10): 1039-1051, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31588048

RESUMO

Dementia is a leading cause of death in many countries. Late-onset Alzheimer's disease (LOAD) is the most common form of dementia, with approximately 35 million affected people. LOAD shows a high heritability (h2) of 58-79%. Clarifying the genetic architecture of LOAD could contribute to precision medicine. In recent years, large-scale genome-wide association studies (GWASs) and their meta-analyses with a large sample size have elucidated the disease-susceptible genes and disease-causing pathways. To date, meta-analyses of GWASs in the Caucasian population have successfully identified approximately 40 LOAD risk loci. The gene set and disease pathway analysis obtained from the results of GWASs suggested biological mechanisms involving brain immune function, lipid-related processes, tau binding proteins, and degradation of amyloid precursor proteins in the pathogenesis of LOAD. Furthermore, the exome sequencing analysis in Japanese individuals with LOAD also revealed a rare variant with a large effect of SHARPIN in LOAD susceptibility, and the variant protein possibly affects the immune response through aberrant cellular localization, which may result in attenuated NF-κB activity in the brain. These findings could provide biological and pharmaceutical approaches in precision medicine for LOAD.


Assuntos
Doença de Alzheimer/genética , Patrimônio Genético , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Humanos , NF-kappa B/metabolismo , Ubiquitinas/genética , Proteínas tau/metabolismo
17.
Brain Nerve ; 71(10): 1053-1060, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31588049

RESUMO

Apolipoprotein E (APOE) is reported to be a strong genetic risk factor for Alzheimer's disease (AD), broadly contributing to the AD pathologies observed in most populations. However, it is difficult to explicate these AD pathologies based only on the known functions of APOE. In this review article, we revisited the histories and functions of APOE and also reviewed its recently elucidated the pleiotropic roles in the brain.


Assuntos
Doença de Alzheimer/genética , Apolipoproteína E4/genética , Encéfalo , Humanos , Fatores de Risco
18.
Brain Nerve ; 71(10): 1071-1079, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31588051

RESUMO

Next generation sequencing (NGS) technology has dramatically influenced the field of omics studies, such as genomics and transcriptomics. It is now possible to access a significant number of previously known and novel genomic variants through NGS. Although the effective manipulation and accurate interpretation of the inordinate amount of data may pose a considerable challenge, it enables us to identify specific genes responsible for causing or influencing the susceptibility to a plethora of diseases. Alzheimer's disease (AD) is the most common etiology of dementia in the elderly (approximately 60-70%). The current research trend of AD genetics focuses on the analysis of rare variants (allelic frequency <1%) instead of common variants (allelic frequency >1%) to identify AD-associated genes/variants. A number of genes (such as TREM2, ABCA7, SORL1) that carry rare pathogenic variants have reportedly conferred susceptibility to AD with stronger genetic risk effects (odds ratio >2.0). Here, we are going to introduce a small part of the latest many attractive findings about AD genetic researches.


Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença , Transportadores de Cassetes de Ligação de ATP/genética , Alelos , Frequência do Gene , Testes Genéticos , Genômica , Humanos , Proteínas Relacionadas a Receptor de LDL/genética , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras/genética , Receptores Imunológicos/genética
19.
Brain Nerve ; 71(10): 1081-1088, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31588052

RESUMO

During the past 20 years, genome studies for Alzheimer's disease (AD) have elucidated the pathogenesis of AD including the amyloid hypothesis. However, clinical trials of the disease modifying drugs for AD developed based on the amyloid hypothesis have been largely unsuccessful. New genes associated with AD have been identified through comprehensive genome analyses such as genome-wide association studies and whole genome/exome sequencing using next-generation sequencers. With these efforts, new therapeutic targets to AD have been explored. This review summarizes the genetic make-up of AD in terms of both risk and protective factors from the viewpoint of novel therapeutic targets to AD.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Testes Genéticos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Fatores de Proteção , Fatores de Risco
20.
Medicine (Baltimore) ; 98(42): e17557, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626119

RESUMO

BACKGROUND: Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are neurodegenerative diseases associated with aging. The major clinical features of both are progressive memory loss and progressive cognitive loss. The objective of this systematic review protocol is to provide the methods for evaluating the effectiveness of acupuncture in the treatment on cognitive deficits in transgenic mouse. METHODS AND ANALYSIS: We will search the electronic databases of PubMed, Web of Science, Embase, PsycINFO, as well as the Chinese databases such as Chinese Biomedicine Literature (CBM), Chinese Medical Current Content (CMCC), Chinese Scientific Journal Database (VIP), WanFang Database and China National Knowledge Infrastructure (CNKI) from their inceptions to July 2019. RevMan 5.3 software will be used for the data synthesis and the quality of each study was assessed independently by use of the CAMARADES checklist. RESULTS: This review will provide a high-quality synthesis based on present evidence of acupuncture treatment for AD and MCI in transgenic mouse models. CONCLUSIONS: This systematic review will provide evidence for weather acupuncture is an effective intervention for AD and MCI in transgenic mouse models. ETHICS AND DISSEMINATION: Ethical approval is not necessary since this protocol is only for systematic review and does not involve privacy data or conduct an animal experiment. This protocol will be disseminated by a peer-review journal or conference presentation. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019142985. STRENGTHS AND LIMITATIONS OF THIS STUDY: This systematic review will be the first to provide new knowledge underlying the effectiveness to improve cognitive function of acupuncture treatment for AD and MCI in transgenic mouse models. The result of this systematic review may provide experimental and theoretical basis for the future clinical application of acupuncture in the treatment of AD.The limitation of this systematic review may come from language barriers, because only English and Chinese can be included. Also, this study includes various kinds of acupuncture treatments which may result in essential heterogeneity.


Assuntos
Terapia por Acupuntura/métodos , Doença de Alzheimer/terapia , Cognição/fisiologia , Disfunção Cognitiva/terapia , Doença de Alzheimer/complicações , Doença de Alzheimer/fisiopatologia , Animais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos
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