Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.543
Filtrar
1.
J Alzheimers Dis ; 77(4): 1805-1813, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32986671

RESUMO

BACKGROUND: The COVID-19 pandemic has brought great disruption to health systems worldwide. This affected ongoing clinical research, particularly among those most vulnerable to the pandemic, like dementia patients. Fundació ACE is a research center and memory clinic based in Barcelona, Spain, one of the hardest-hit countries. OBJECTIVE: To describe the ad-hoc strategic plan developed to cope with this crisis and to share its outcomes. METHODS: We describe participants' clinical and demographic features. Additionally, we explain our strategic plan aimed at minimizing the impact on clinical trial research activities, which included SARS-CoV-2 RT-PCR and IgG serological tests to all participants and personnel. The outcomes of the plan are described in terms of observed safety events and drop-outs during the study period. RESULTS: A total of 130 patients were participating in 16 active clinical trials in Fundació ACE when the lockdown was established. During the confinement, we performed 1018 calls to the participants, which led to identify adverse events in 26 and COVID-19 symptoms in 6. A total of 83 patients (64%) could restart on-site visits as early as May 11, 2020. All SARS-CoV-2 RT-PCR diagnostic tests performed before on-site visits were negative and only three IgG serological tests were positive. Throughout the study period, we only observed one drop-out, due to an adverse event unrelated to COVID-19. DISCUSSION: The plan implemented by Fundació ACE was able to preserve safety and integrity of ongoing clinical trials. We must use the lessons learned from the pandemic and design crisis-proof protocols for clinical trials.


Assuntos
Doença de Alzheimer/terapia , Ensaios Clínicos como Assunto , Infecções por Coronavirus , Pandemias , Assistência ao Paciente , Pneumonia Viral , Idoso , Instituições de Assistência Ambulatorial , Betacoronavirus , Técnicas de Laboratório Clínico , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/organização & administração , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Feminino , Humanos , Masculino , Pandemias/prevenção & controle , Assistência ao Paciente/métodos , Assistência ao Paciente/tendências , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Espanha/epidemiologia , Telemedicina/métodos , Terapias em Estudo/métodos
2.
Zhen Ci Yan Jiu ; 45(9): 689-95, 2020 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-32959549

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture at "Baihui"(GV20) and "Shenshu"(BL23) on the expression of autophagy-related proteins in the hippocampus of rats with Alzheimer's disease (AD),so as to explore its underlying mechanisms on improvement of AD. METHODS: Forty-eight male SD rats were randomly divided into blank control group, model group, electroacupuncture group and sham electroacupuncture group, with 12 rats in each group. The AD rat model was establish by intraperitoneal injection of D-galactose for 6 weeks. Rats in the electroacupuncture group received electroacupuncture (50 Hz, 1 mA)at GV20 and BL23 for 20 min each time after daily intraperitoneal injection. Rats in the sham electroacupuncture group received acupuncture at the local skin of GV20 and BL23 without electricity. After the intervention, Morris water maze and open field test were used to evaluate the learning and cognitive ability of rats in each group. The transmission electron microscope was used to observe the numerical density of synaptic in hippocampus, and the immunohistochemical staining was used to observe the paired helical filament protein-1 (PHF-1) in the hippocampus. Western blot was used to detected the expression of autophagy-related proteins phosphoinositide-3-kinase (PI3K), protein kinase B (AKT), phosphorylated AKT (p-AKT), mammalian target of rapamycin (mTOR) in the hippocampus. RESULTS: Compared with the blank control group, the escape latency of the rats in the model group increased from day 2 to day 5 (P<0.01), and the ratio of the time through the quadrant of the original platform reduced (P<0.01), in the open field test the distance of exercise, the number of uprights and the rate of exercise time in the central area decreased (P<0.01), meanwhile the density of hippocampus synapses decreased (P<0.01), the positive expression of PHF-1 and the relative expression of PI3K, AKT, p-AKT, and mTOR all increased (P<0.01). Compared with the model group, the escape latency of rats in the electroacupuncture group was shortened from day 2 to day 5 (P<0.01), and the ratio of the time through the quadrant of the original platform meanwhile, the distance of the open field test, the number of uprights, and the rate of central area exercise time up-regulated (P<0.01), the numerical density of hippocampus synatic increased (P<0.01), the positive expression of PHF-1 and the relative expression of PI3K, AKT, p-AKT, and mTOR all down-regulated (P<0.01). Compared with the model group, the expression of PI3K in the sham electroacupuncture group decreased (P<0.05). CONCLUSION: Electroacupuncture can improve learning and memory and cognitive impairment in AD rats, which may be associated with its effects in regulation of hippocampal autophagy and removal of neurofibrillary tangles by suppressing PI3K/AKT/mTOR signaling pathway.


Assuntos
Doença de Alzheimer , Autofagia , Eletroacupuntura , Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Animais , Cognição , Galactose , Hipocampo , Masculino , Fosfatidilinositol 3-Quinases , Ratos , Ratos Sprague-Dawley
3.
Medicine (Baltimore) ; 99(38): e22385, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957420

RESUMO

INTRODUCTION: Reduced bone mineral density and increased risk of falls are related with Alzheimer disease, and these increase likelihood of bone osteoporotic fractures causing serious complications such as disability, fear of falling, loss autonomy, decreased quality of life, and anticipated mortality in elderly patients. Gait and balance disturb are 2 factors to favor falls in elderly, and in patients with cognitive impairment, the risk of falls increases to double. Exercise and Mediterranean diet produce beneficial effects for aging, cognitive decline, and are widely recommended to reduce the effects of osteoporosis, fall risk, and related fragility fractures. The primary objective of this study is to evaluate the short and medium-term effects during 6 months, of a multicomponent physical exercise program with a Mediterranean diet on bone mineral density, fall risk, balance, and gait by a controlled clinical trial in patients with Alzheimer disease. METHODS: The study is a 6-month, randomized controlled parallel-group, single-blinded clinical trial. Institutionalized patients with Alzheimer disease will be included. The intervention group will perform a multicomponent physical exercise program in reduced groups, with a frequency of 3 sessions per week, associated with a Mediterranean diet. This program includes strength, balance, and aerobic resistance exercises, and in the main part of the session, also ludic exercises to improve agility, coordination, and balance. The control group will receive usual care. The outcomes to assess are the change of physical functions, such as gait and balance, and the change of bone mineral density by calcaneal quantitative ultrasound, during the study follow-up at 1, 3, and 6 months. This clinical trial will generate more and new evidence on the effects of a multicomponent physical exercise program and Mediterranean diet in patients with Alzheimer disease on risk of falls and osteoporotic fractures, the relation of these with bone mineral density, gait and balance, and the correlations between them. ETHICS AND DISSEMINATION: This study protocol has been approved by the Ethics Committee of the University of Salamanca. The results will be published in peer-reviewed journals and disseminated in national and international conferences, to the participants and their families, and the general public through the associations of people with AD. TRIAL REGISTRATION ID: ClínicalTrials.gov ID: NCT04439097.


Assuntos
Doença de Alzheimer/terapia , Densidade Óssea , Dieta Mediterrânea , Terapia por Exercício/métodos , Acidentes por Quedas/prevenção & controle , Feminino , Marcha , Humanos , Masculino , Equilíbrio Postural , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Artigo em Inglês | MEDLINE | ID: mdl-32784777

RESUMO

Dementia is one of the main causes of disability among elderly people. It is a progressive neurodegenerative disease that affects elderly people's ability to perform daily living activities. Alzheimer's disease is the main subtype of dementia and causes declining memory, reasoning, and communication skills. They also have behavioural and psychological symptoms, such as depression and aggression. It is essential for them to maintain good oral health, as oral health is an important and integral part of their general health. Neglecting oral health allows dental diseases to develop, and these diseases are difficult and costly to treat. However, dental diseases can be treated with ambulatory care rather than hospitalisation and emergency care. Elderly people should establish daily oral hygiene care routines during the early stages of Alzheimer's disease. They should have regular dental examinations and early minimal interventions to prevent the need for extensive and complicated procedures. Maintaining oral health becomes challenging, however, when Alzheimer's disease progresses to the middle and late stages. Because elderly people might forget or lose interest in keeping their teeth healthy, caretakers and community health workers may need to take over this task. Dentists should provide guidance on the maintenance of oral health, as the techniques used to provide this support vary depending on the elderly people concerned. The purpose of this paper is to provide an overview of oral health and the importance of oral care for elderly people with Alzheimer's disease. The paper also discusses appropriate dental interventions and techniques for maintaining good oral health and helping people with Alzheimer's to enjoy a satisfactory quality of life.


Assuntos
Doença de Alzheimer/epidemiologia , Saúde Bucal/estatística & dados numéricos , Higiene Bucal , Idoso , Doença de Alzheimer/terapia , Humanos , Higiene Bucal/métodos , Qualidade de Vida/psicologia
5.
J Rehabil Med ; 52(9): jrm00106, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32778901

RESUMO

OBJECTIVE: To compare the costs and monetary benefits of non-pharmacological interventions for patients with Alzheimer's disease in real-world settings. METHODS: A systematic review was performed to determine the most effective treatment strategies for being able to stay at home for patients with Alzheimer's disease. Care-management, family support, and multidisciplinary rehabilitation were identified as effective interventions applicable in the Finnish healthcare setting. Data on medical and social service costs, and the costs of residential care for all patients newly diagnosed with Alzheimer's disease in 2 major cities in Finland were analysed in a 4-year follow-up study. The potential cost savings of the different treatment strategies were assessed. RESULTS: The annual cost increased from €9,481 to €28,400 (mean per patient) during the 4-year follow-up. Cost savings were achieved in care-management, family support programmes, and rehabil-itative cognitive and social activation if the patients' transition to long-term care was delayed by 2.8, 1.8 and 43.0 days, respectively. CONCLUSION: Care-management and informal caregiver support for patients with Alzheimer's disease may benefit patients and result in concurrent cost savings. Delaying the decline in cognitive and social functioning through rehabilitation is indicated for more severe phases of Alzheimer's disease, and the costs appear to be compensated by savings in the cost of long-term care.


Assuntos
Doença de Alzheimer/economia , Doença de Alzheimer/terapia , Redução de Custos/métodos , Idoso de 80 Anos ou mais , Feminino , Finlândia , Humanos , Masculino , Resultado do Tratamento
6.
Science ; 369(6507)2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32855309

RESUMO

Neuronal synapses undergo structural and functional changes throughout life, which are essential for nervous system physiology. However, these changes may also perturb the excitatory-inhibitory neurotransmission balance and trigger neuropsychiatric and neurological disorders. Molecular tools to restore this balance are highly desirable. Here, we designed and characterized CPTX, a synthetic synaptic organizer combining structural elements from cerebellin-1 and neuronal pentraxin-1. CPTX can interact with presynaptic neurexins and postsynaptic AMPA-type ionotropic glutamate receptors and induced the formation of excitatory synapses both in vitro and in vivo. CPTX restored synaptic functions, motor coordination, spatial and contextual memories, and locomotion in mouse models for cerebellar ataxia, Alzheimer's disease, and spinal cord injury, respectively. Thus, CPTX represents a prototype for structure-guided biologics that can efficiently repair or remodel neuronal circuits.


Assuntos
Proteína C-Reativa/farmacologia , Proteínas do Tecido Nervoso/farmacologia , Vias Neurais/efeitos dos fármacos , Precursores de Proteínas/farmacologia , Receptores de AMPA/metabolismo , Proteínas Recombinantes/farmacologia , Sinapses/efeitos dos fármacos , Doença de Alzheimer/terapia , Animais , Proteína C-Reativa/química , Proteína C-Reativa/uso terapêutico , Ataxia Cerebelar/terapia , Modelos Animais de Doenças , Células HEK293 , Hipocampo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/uso terapêutico , Domínios Proteicos , Precursores de Proteínas/química , Precursores de Proteínas/uso terapêutico , Receptores de Glutamato/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/uso terapêutico , Coluna Vertebral/efeitos dos fármacos , Coluna Vertebral/fisiologia
7.
PLoS One ; 15(8): e0235691, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857763

RESUMO

Exercise exerts a beneficial effect on the major pathological and clinical symptoms associated with Alzheimer's disease in humans and mouse models of the disease. While numerous mechanisms for such benefits from exercise have been proposed, a clear understanding of the causal links remains elusive. Recent studies also suggest that cerebral blood flow in the brain of both Alzheimer's patients and mouse models of the disease is decreased and that the cognitive symptoms can be improved when blood flow is restored. We therefore hypothesized that the mitigating effect of exercise on the development and progression of Alzheimer's disease may be mediated through an increase in the otherwise reduced brain blood flow. To test this idea, we performed a pilot study to examine the impact of three months of voluntary wheel running in a small cohort of ~1-year-old APP/PS1 mice on short-term memory function, brain inflammation, amyloid deposition, and baseline cerebral blood flow. Our findings that exercise led to a trend toward improved spatial short-term memory, reduced brain inflammation, markedly increased neurogenesis in the dentate gyrus, and a reduction in hippocampal amyloid-beta deposits are consistent with other reports on the impact of exercise on the progression of Alzheimer's related symptoms in mouse models. Notably, we did not observe any impact of wheel running on overall baseline blood flow nor on the incidence of non-flowing capillaries, a mechanism we recently identified as one contributing factor to cerebral blood flow deficits in mouse models of Alzheimer's disease. Overall, our findings add to the emerging picture of differential effects of exercise on cognition and blood flow in Alzheimer's disease pathology by showing that capillary stalling is not decreased following exercise.


Assuntos
Doença de Alzheimer/fisiopatologia , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/irrigação sanguínea , Terapia por Exercício , Presenilina-1/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/terapia , Precursor de Proteína beta-Amiloide/genética , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Circulação Cerebrovascular , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Mutação , Neurogênese , Condicionamento Físico Animal , Projetos Piloto , Presenilina-1/genética , Transgenes
8.
J Alzheimers Dis ; 77(1): 113-125, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804145

RESUMO

BACKGROUND: A system of photosensitive retinal ganglion cells provides 'non-visual' information on the circadian sequences of light to the suprachiasmatic nucleus (SCN), which, as the 'master clock', synchronizes the chronobiological mechanisms of all the biological clocks. Damage to SCN structure alters circadian behavioral and hormonal rhythms and interferes with a regular sleep-wake pattern. Several studies have shown that, in aging and in Alzheimer's disease (AD), circadian rhythms change their synchronization with the environment and behavior loses sync with light. OBJECTIVE: The current overview aims to examine research studies showing the effect of bright light therapy (BLT) on sleep disorders and sleep-wake patterns in AD. METHODS: A literature search was conducted, taking into consideration the relevant studies over the last 20 years. Fifteen studies have been thorough: seven followed an environmental-architectural approach and eight followed a treatment devices approach. RESULTS: Studies agree in considering BLT as a promising non-pharmacological intervention to compensate for circadian rhythm alterations and they support the need for standardized protocols that allow a comparison between multicenter studies. CONCLUSION: Interestingly, in an attempt to contain the spread of the COVID-19 pandemic, health authorities have forced the population to stay home. Therefore, AD people are not currently able to enjoy exposure to sunlight. It is predictable that they may experience an exacerbation of circadian disturbances and that the BLT can be an effective response to prevent such exacerbation.


Assuntos
Doença de Alzheimer/terapia , Fototerapia/métodos , Transtornos do Sono-Vigília/terapia , Doença de Alzheimer/complicações , Doença de Alzheimer/fisiopatologia , Infecções por Coronavirus , Humanos , Pandemias , Pneumonia Viral , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/fisiopatologia , Luz Solar , Núcleo Supraquiasmático
9.
PLoS Biol ; 18(8): e3000851, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32822389

RESUMO

High levels of the amyloid-beta (Aß) peptide have been shown to disrupt neuronal function and induce hyperexcitability, but it is unclear what effects Aß-associated hyperexcitability may have on tauopathy pathogenesis or propagation in vivo. Using a novel transgenic mouse line to model the impact of human APP (hAPP)/Aß accumulation on tauopathy in the entorhinal cortex-hippocampal (EC-HIPP) network, we demonstrate that hAPP overexpression aggravates EC-Tau aggregation and accelerates pathological tau spread into the hippocampus. In vivo recordings revealed a strong role for hAPP/Aß, but not tau, in the emergence of EC neuronal hyperactivity and impaired theta rhythmicity. Chronic chemogenetic attenuation of EC neuronal hyperactivity led to reduced hAPP/Aß accumulation and reduced pathological tau spread into downstream hippocampus. These data strongly support the hypothesis that in Alzheimer's disease (AD), Aß-associated hyperactivity accelerates the progression of pathological tau along vulnerable neuronal circuits, and demonstrates the utility of chronic, neuromodulatory approaches in ameliorating AD pathology in vivo.


Assuntos
Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Córtex Entorrinal/metabolismo , Tauopatias/genética , Proteínas tau/genética , Potenciais de Ação/fisiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/terapia , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Dependovirus/genética , Dependovirus/metabolismo , Modelos Animais de Doenças , Eletrodos Implantados , Córtex Entorrinal/patologia , Feminino , Regulação da Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/metabolismo , Neurônios/patologia , Agregados Proteicos , Técnicas Estereotáxicas , Tauopatias/metabolismo , Tauopatias/patologia , Tauopatias/terapia , Ritmo Teta/fisiologia , Transdução Genética , Transgenes , Proteínas tau/metabolismo
10.
Zhen Ci Yan Jiu ; 45(6): 508-2, 2020 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-32643890

RESUMO

Alzheimer's disease is a neurodegenerative disease closely related to age, which is characterized by cognitive and memory impairment. Extensive studies have confirmed that Wnt/ß-catenin signal pathway is involved in the occurrence and development of Alzheimer's disease. With the characteristics of holistic concept and syndrome differentiation, acupuncture is widely used in clinic. Acupuncture plays a role in the treatment of Alzheimer's disease through the regulation of each target and the whole of the pathway. The author reviewed and combed the research on acupuncture treatment of Alzheimer's disease in recent years, and reviewed the regulatory effects of acupuncture on the important components of Wnt/ß-catenin signal pathway (Wnt protein, ß-catenin, glycogen synthase kinase-3ß) and whole, ATP-binding cassette subfamily B member 1 (ABCB1), low density lipoprotein receptor associated protein-1 (LRP-1)..


Assuntos
Terapia por Acupuntura , Doença de Alzheimer , Doença de Alzheimer/terapia , Humanos , Via de Sinalização Wnt , beta Catenina
11.
Lancet Neurol ; 19(9): 758-766, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32730766

RESUMO

Insulin is a peptide secreted by the pancreas and plays an important role in the regulation of glucose metabolism in peripheral tissues. Although the role of insulin in the periphery is well understood, less is known about its multifactorial role in the brain. However, emerging evidence from human and animal studies indicate that insulin influences cerebral bioenergetics, enhances synaptic viability and dendritic spine formation, and increases turnover of neurotransmitters, such as dopamine. Insulin also has a role in proteostasis, influencing clearance of the amyloid ß peptide and phosphorylation of tau, which are hallmarks of Alzheimer's disease. Insulin also modulates vascular function through effects on vasoreactivity, lipid metabolism, and inflammation. Through these multiple pathways, insulin dysregulation could contribute to neurodegeneration. Thus, new approaches to restore cerebral insulin function that could offer therapeutic benefit to adults with Alzheimer's disease, vascular cognitive impairment, or related disorders are being investigated.


Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/terapia , Encéfalo/metabolismo , Resistência à Insulina/fisiologia , Comportamento de Redução do Risco , Animais , Encéfalo/efeitos dos fármacos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Insulina/farmacologia , Insulina/uso terapêutico
12.
Clin Ter ; 171(4): e357-e368, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614371

RESUMO

BACKGROUND: Alzheimer's disease is the most widespread senile dementia in the world and diagnoses are on the rise due to the aging of the world's population and this is causing a significant increase in health spending on the care of the disease. Current studies highlight the need for rapid diagnosis in order to prevent the therapeutic approach from being ineffective, and a comprehensive management of the disease, both with pharmacological and integrative therapies (safety of the environment, music therapy, diet, physical activity, recreational activities, etc.). Regarding the care provided by caregivers, the need to educate these figures is fundamental, to support them economically and psycho-socially (especially during the most difficult stages of the disease) and to provide them with technical skills to effectively and safely address the patient's care. OBJECTIVES: Aim of this study was to investigate the current evidence from scientific literature about the early stage of Alzheimer's disease in order to educate and support caregivers with specific technical and practical skills. MATERIAL AND METHODS: A systematic review of the scientific literature of the last 10 years, has been conducted in September 2019 through Medline (PubMed), Scopus and Cinahl databases, in accordance with the criteria of PRISMA Statement guideline (Preferred Reporting Items for Systematic reviews and Meta-Analyses). The included studies were related to Alzheimer's disease and patients' management. RESULTS: Thirty-six articles met the inclusion criteria but only for 26 of these it was possible to retrieve and access the full text. CONCLUSIONS: The evidences from this study provide information on how to effectively address Alzheimer's disease. The studies address different aspects of the disease, with different methodologies, thus providing heterogeneous evidence. Future studies with reproducible methodologies should be undertaken in order to achieve robustness in results.


Assuntos
Doença de Alzheimer/terapia , Intervenção Médica Precoce , Cuidadores , Progressão da Doença , Humanos
13.
Life Sci ; 257: 118020, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32603820

RESUMO

Alzheimer's disease (AD) is the most common form of dementia worldwide. ß-amyloid peptide (Aß) is currently assumed to be the main cause of synaptic dysfunction and cognitive impairments in AD, but the molecular signaling pathways underlying its neurotoxic consequences have not yet been completely explored. Additional investigations regarding these pathways will contribute to development of new therapeutic targets. In context, developing evidence suggest that Aß decreases brain-derived neurotrophic factor (BDNF) mostly by lowering phosphorylated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) protein. In fact, it has been observed that brain or serum levels of BDNF appear to be beneficial markers for cognitive condition. In addition, the participation of transcription mediated by CREB has been widely analyzed in the memory process and AD development. Designing pharmacologic or genetic therapeutic approaches based on the targeting of CREB-BDNF signaling could be a promising treatment potential for AD. In this review, we summarize data demonstrating the role of CREB-BDNF signaling pathway in cognitive status and mediation of Aß toxicity in AD. Finally, we also focus on the developing intervention methods for improvement of cognitive decline in AD based on targeting of CREB-BDNF pathway.


Assuntos
Doença de Alzheimer/terapia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Cognição/fisiologia , Transtornos Cognitivos/metabolismo , Disfunção Cognitiva/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/fisiologia , Modelos Animais de Doenças , Humanos , Memória/fisiologia , Neurônios/metabolismo , Fosforilação , Transdução de Sinais
15.
Health Qual Life Outcomes ; 18(1): 255, 2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32727503

RESUMO

BACKGROUND: It is essential to better understand the caregiving burden and its determinants to support caregivers. The aim of this study was to test the validity and reliability (internal consistency) of the caregiver burden inventory (CBI) in Iranian caregivers of elderly patients with Alzheimer. METHODS: A cross sectional study was conducted to translate and validate the CBI in Iran. The structural validity of the scale was evaluated by exploratory factor analysis. The concurrent validity was tested correlating the CBI scores with the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI) scores. The internal consistency reliability was assessed using the Cronbach's alpha coefficient. RESULTS: In total, we enrolled 315 caregivers of elderly patients with Alzheimer disease (79% women, mean age 56.5 ± 13.9). The structural validity of the CBI as assessed by exploratory factor analysis indicated three factors (emotional/psychological, time-dependence and physical burden) that jointly explained 45.21% of the total variance observed. The Pearson correlation coefficient for the relationship between the scores obtained on the Caregiver Burden Inventory and the BAI and the BDI were 0.69 and 0.49 respectively, confirming the concurrent validity. The Cronbach's alpha for the CBI was 0.91 ranging from 0.78 to 0.92 for its subscales. CONCLUSION: Used in clinical practice and research, the CBI was verified to be a proper multidimensional instrument for evaluating the burden in caregivers of elderly patients with Alzheimer disease.


Assuntos
Doença de Alzheimer/terapia , Cuidadores/psicologia , Inquéritos e Questionários/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Reprodutibilidade dos Testes , Traduções
16.
Medicine (Baltimore) ; 99(21): e20244, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481301

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the fifth-leading cause of death in people more than 65 years old. Acupuncture therapy has been traditionally used to treat various kinds of health problems including AD. This protocol aims to summarize the available evidence from current systematic reviews (SRs) for the efficacy of acupuncture therapy for AD. METHODS: Seven databases will be searched: PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chongqing VIP (CQVIP), and Chinese Biomedical Literature Database (CBM). SRs/meta-analyses (MAs) of acupuncture therapy for AD which were reported in Chinese or English will be included. Study selection, data extraction, and assessment of the study quality will be performed independently by 2 or more reviewers. And the methodological quality, report quality and evidence quality will be evaluated by Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) tool, Preferred Reporting Items for Systematic Reviews and Meta Analyses Statement (PRISMA) checklist and Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, respectively. RESULTS: The article in this overview will be submitted for publication in a peer-reviewed journal. CONCLUSION: We expect to compile evidence from multiple systematic reviews of acupuncture therapy in AD patients in an accessible and useful document.Registration number: INPLASY202040035.


Assuntos
Terapia por Acupuntura/métodos , Doença de Alzheimer/mortalidade , Doença de Alzheimer/terapia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Lista de Checagem/métodos , China/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Editoração/provisão & distribução , Pesquisa Qualitativa , Resultado do Tratamento
17.
Medicine (Baltimore) ; 99(21): e20128, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481282

RESUMO

INTRODUCTION: In China, the over 60 population is estimated to grow from 12% in 2010 to 33% of the overall population by 2050. The escalation in the aging population is projected to result in an Alzheimer's disease prevalence of 27.7 million people in China by 2050 causing substantial health and economic burden. While there are some published studies on multicomponent, non-pharmacological interventions for people with dementia, we have found no published community-based approach to care that encompasses personalized selection of non-pharmacological interventions, active social participation, and dementia education. PATIENT CONCERNS: An elderly female living at home alone in urban Beijing presented with significant short-term memory impairment, episodes of confusion, difficulty with language skills, and episodes of wandering. She had become reclusive and disengaged from her previous social networks, and no longer attended any community activities or events. The patient had no significant past medical or psychiatric history. DIAGNOSIS: The patient was diagnosed with Alzheimer's disease by a local physician based on clinical features of impaired communication, disorientation, confusion, poor judgement, behavioral changes, and difficulty speaking. Depression was considered a differential diagnosis but is also both a risk factor and symptom of dementia. INTERVENTIONS: A novel, community-based, multicomponent social care program for dementia was used to facilitate implementation of non-pharmacological interventions, gradual socialization and provide supportive carer and community education. Non-pharmacological interventions included a combination of validation therapy, music therapy, art therapy, reminiscence therapy, talking therapy, reality orientation, cognitive training, smell therapy, food therapy, sensory stimulation, garden therapy, and physiotherapy. OUTCOMES: Improvements in the patient's Geriatric Depression Scale and Mini Mental State Examination scores were noted in association with increased social participation in the community. CONCLUSION: The community-based, multicomponent dementia social care program described in this case report has enabled a socially isolated patient with Alzheimer's disease to reduce her social isolation with an associated improvement in her mood and prevention of cognitive decline. Educating the community was an essential part of re-integrating the patient into the social setting. Reducing social isolation and increasing community engagement were essential to maintaining the patient's independence in her own home.


Assuntos
Doença de Alzheimer/terapia , Disfunção Cognitiva/terapia , Apoio Social , Atividades Cotidianas , Idoso , Doença de Alzheimer/complicações , Pequim , Cuidadores/educação , Disfunção Cognitiva/etiologia , Progressão da Doença , Feminino , Humanos , Testes de Estado Mental e Demência , Determinação de Necessidades de Cuidados de Saúde , Qualidade de Vida
18.
J Oleo Sci ; 69(7): 771-782, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32522946

RESUMO

The role of fish oil, primrose oil and their mixture in ameliorating the changes in Alzheimer's like model was evaluated in rats. Primrose oil and primrose/fish oil mixture fatty acids composition was assessed by gas chromatography. The rat experiment consisted of 5 groups; the first fed on balanced diet as control normal (CN); the other four groups treated with intraperitoneal aluminum lactate and consumed dyslipidemic diet; one group served as control Alzheimer's like disease (CA) while the other three groups (test groups) received daily oral dose from primrose oil, fish oil and primrose/fish oil mixture separately for 5 weeks. Results showed primrose oil and primrose/ fish oil mixture to contain gamma linolenic acid as 9.15 and 4.3% of total fatty acids, respectively. Eicosapentaenoic and docosahexaenoic were present as 10.9 and 6.5 %, respectively in the oil mixture. Dyslipidemia and increased erythrocyte sedimentation rate (ESR), plasma butyrylcholinesterase (BChE), brain malondialdehyde (MDA) and NO with decrease in plasma magnesium, brain catalase, reduced glutathione, body weight gain and brain weight were demonstrated in CA compared to CN. Brain histopathology and immuno-histochemistry showed neuronal degeneration and neurofibrillary tangles with elevated myeloperoxidase and nuclear factor-kappa B in CA compared to CN. The tested oils demonstrated neuro-protection reflected in the variable significant improvement of biochemical parameters, immuno-histochemistry and brain histopathology. Primrose/fish oil mixture was superior in reducing ESR, brain MDA, plasma activity of BChE and brain histopathological changes along with elevating plasma magnesium. Primrose/fish oil mixture and fish oil were more promising in improving plasma high density lipoprotein cholesterol (HDL-C) than primrose. Fish oil was the most efficient in improving plasma total cholesterol (T-C), low density lipoprotein cholesterol and T-C /HDL-C. Primrose/fish oil mixture and primrose oil were superior in elevating brain catalase compared to fish oil. Other parameters were equally improved by the different oil treatments. Primrose oil, fish oil and their mixture reduced the progression of Alzheimer's disease in rats with superiority to primrose/fish oil mixture.


Assuntos
Compostos de Alumínio/efeitos adversos , Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/terapia , Óleos de Peixe/administração & dosagem , Lactatos/efeitos adversos , Óleos Vegetais/administração & dosagem , Primula , Ácido gama-Linolênico/análise , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/metabolismo , Animais , Encéfalo/metabolismo , Butirilcolinesterase/metabolismo , Catalase/metabolismo , Colesterol/sangue , Modelos Animais de Doenças , Progressão da Doença , Ácidos Docosa-Hexaenoicos/análise , Ácido Eicosapentaenoico/análise , Óleos de Peixe/química , Masculino , Malondialdeído/metabolismo , Óleos Vegetais/química , Ratos , Ratos Endogâmicos
19.
JAMA Netw Open ; 3(6): e207559, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32525547

RESUMO

Importance: Social determinants of health, such as income, education, housing quality, and employment, are associated with disparities in Alzheimer disease and health generally, yet these determinants are rarely incorporated within neuropathology research. Objective: To establish the feasibility of linking neuropathology data to social determinants of health exposures using neighborhood disadvantage metrics (the validated Area Deprivation Index) and to evaluate the association between neighborhood disadvantage and Alzheimer disease-related neuropathology. Design, Setting, and Participants: This cross-sectional study consisted of decedents with a known home address who donated their brains to 1 of 2 Alzheimer disease research center brain banks in California and Wisconsin between January 1, 1990, and December 31, 2016. Neither site had preexisting social metrics available for their decedents. Neuropathologic features were obtained from each site for data collected using the standardized Neuropathology Data Set form and from autopsy reports. Data were analyzed from June 7 to October 10, 2019. Exposures: Geocoded decedent addresses linked to neighborhood disadvantage as measured by the Area Deprivation Index calculated for the year of death. Main Outcomes and Measures: Presence of Alzheimer disease neuropathology. The association between neighborhood disadvantage and Alzheimer disease neuropathology was evaluated via logistic regression, adjusting for age, sex, and year of death. Results: The sample consisted of 447 decedents (249 men [56%]; mean [SD] age, 80.3 [9.5] years; median year of death, 2011) spanning 24 years of donation. Fewer decedents (n = 24 [5.4%]) originated from the top 20% most disadvantaged neighborhood contexts. Increasing neighborhood disadvantage was associated with an 8.1% increase in the odds of Alzheimer disease neuropathology for every decile change on the Area Deprivation Index (adjusted odds ratio, 1.08; 95% CI, 1.07-1.09). As such, living in the most disadvantaged neighborhood decile was associated with a 2.18 increased odds of Alzheimer disease neuropathology (adjusted odds ratio, 2.18; 95% CI, 1.99-2.39). Conclusions and Relevance: The findings of this cross-sectional study suggest that social determinants of health data can be linked to preexisting autopsy samples as a means to study sociobiological mechanisms involved in neuropathology. This novel technique has the potential to be applied to any brain bank within the United States. To our knowledge, this is the first time Alzheimer disease neuropathology has been associated with neighborhood disadvantage.


Assuntos
Doença de Alzheimer , Área Programática de Saúde/estatística & dados numéricos , Determinantes Sociais da Saúde/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/patologia , Doença de Alzheimer/terapia , Pesquisa Biomédica , Encéfalo/patologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Bancos de Tecidos
20.
J Pharmacol Sci ; 143(4): 290-299, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32507685

RESUMO

The pathophysiological roles of astrocytes in the reactive state are thought to have important significance in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). However, the detailed mechanisms underlying the transition of astrocytes from the resting state to the reactive state during neurodegenerative disease largely remain to be defined. Here, we investigated the pathways involved in activating astrocytes from the resting state to the reactive state in primary cultured astrocytes treated with oligomeric Aß and in the hippocampus of 5XFAD mice. Treatment with oligomeric Aß induced an increase in reactive astrocytes, as assessed by the protein level of glial fibrillary acidic protein (GFAP) and this increase was caused by STAT3 phosphorylation in primary cultured astrocytes. The administration of Stattic, an inhibitor of STAT3, rescued the activation of astrocytes in primary cultured astrocytes and in the hippocampus of 6-month-old 5XFAD mice as well as impairments in learning and memory. Collectively, these results demonstrated that reactive astrocytes in the AD brain are induced via STAT3 and the impairments in learning and memory observed in 5XFAD mice are rescued by STAT3 inhibition, suggesting that the inhibition of STAT3 phosphorylation in astrocytes may be a novel therapeutic target for cognitive impairment in AD.


Assuntos
Doença de Alzheimer/genética , Inativação Gênica , Fator de Transcrição STAT3 , Doença de Alzheimer/terapia , Animais , Astrócitos/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Camundongos Transgênicos , Terapia de Alvo Molecular , Fosforilação
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA