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1.
Cochrane Database Syst Rev ; 2: CD013306, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33704781

RESUMO

BACKGROUND: Vascular cognitive impairment (VCI) describes a broad spectrum of cognitive impairments caused by cerebrovascular disease, ranging from mild cognitive impairment to dementia. There are currently no pharmacological treatments recommended for improving either cognition or function in people with VCI. Three cholinesterase inhibitors (donepezil, galantamine, and rivastigmine) are licenced for the treatment of dementia due to Alzheimer's disease. They are thought to work by compensating for reduced cholinergic neurotransmission, which is also a feature of VCI. Through pairwise comparisons with placebo and a network meta-analysis, we sought to determine whether these medications are effective in VCI and whether there are differences between them with regard to efficacy or adverse events. OBJECTIVES: (1) To assess the efficacy and safety of cholinesterase inhibitors in the treatment of adults with vascular dementia and other VCI. (2) To compare the effects of different cholinesterase inhibitors on cognition and adverse events, using network meta-analysis. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 19 August 2020. SELECTION CRITERIA: We included randomised controlled trials in which donepezil, galantamine, or rivastigmine was compared with placebo or in which the drugs were compared with each other in adults with vascular dementia or other VCI (excluding cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)). We included all drug doses and routes of administration. DATA COLLECTION AND ANALYSIS: Two review authors independently identified eligible trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the certainty of the evidence. The primary outcomes were cognition, clinical global impression, function (performance of activities of daily living), and adverse events. Secondary outcomes were serious adverse events, incidence of development of new dementia, behavioural disturbance, carer burden, institutionalisation, quality of life and death. For the pairwise analyses, we pooled outcome data at similar time points using random-effects methods. We also performed a network meta-analysis using Bayesian methods. MAIN RESULTS: We included eight trials (4373 participants) in the review. Three trials studied donepezil 5 mg or 10 mg daily (n= 2193); three trials studied rivastigmine at a maximum daily dose of 3 to 12 mg (n= 800); and two trials studied galantamine at a maximum daily dose of 16 to 24 mg (n= 1380). The trials included participants with possible or probable vascular dementia or cognitive impairment following stroke. Mean ages were between 72.2 and 73.9 years. All of the trials were at low or unclear risk of bias in all domains, and the evidence ranged from very low to high level of certainty. For cognition, the results showed that donepezil 5 mg improves cognition slightly, although the size of the effect is unlikely to be clinically important (mean difference (MD) -0.92 Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) points (range 0 to 70), 95% confidence interval (CI) -1.44 to -0.40; high-certainty evidence). Donepezil 10 mg (MD -2.21 ADAS-Cog points, 95% CI -3.07 to -1.35; moderate-certainty evidence) and galantamine 16 to 24 mg (MD -2.01 ADAS-Cog point, 95%CI -3.18 to -0.85; moderate-certainty evidence) probably also improve cognition, although the larger effect estimates still may not be clinically important. With low certainty, there may be little to no effect of rivastigmine 3 to 12 mg daily on cognition (MD 0.03 ADAS-Cog points, 95% CI -3.04 to 3.10; low-certainty evidence). Adverse events reported in the studies included nausea and/or vomiting, diarrhoea, dizziness, headache, and hypertension. The results showed that there was probably little to no difference between donepezil 5 mg and placebo in the number of adverse events (odds ratio (OR) 1.22, 95% CI 0.94 to 1.58; moderate-certainty evidence), but there were slightly more adverse events with donepezil 10 mg than with placebo (OR 1.95, 95% CI 1.20 to 3.15; high-certainty evidence). The effect of rivastigmine 3 to 12 mg on adverse events was very uncertain (OR 3.21, 95% CI 0.36 to 28.88; very low-certainty evidence). Galantamine 16 to 24 mg is probably associated with a slight excess of adverse events over placebo (OR 1.57, 95% CI 1.02 to 2.43; moderate-certainty evidence). In the network meta-analysis (NMA), we included cognition to represent benefit, and adverse events to represent harm. All drugs ranked above placebo for cognition and below placebo for adverse events. We found donepezil 10 mg to rank first in terms of benefit, but third in terms of harms, when considering the network estimates and quality of evidence. Galantamine was ranked second in terms of both benefit and harm. Rivastigmine had the lowest ranking of the cholinesterase inhibitors in both benefit and harm NMA estimates, but this may reflect possibly inadequate doses received by some trial participants and small trial sample sizes. AUTHORS' CONCLUSIONS: We found moderate- to high-certainty evidence that donepezil 5 mg, donepezil 10 mg, and galantamine have a slight beneficial effect on cognition in people with VCI, although the size of the change is unlikely to be clinically important. Donepezil 10 mg and galantamine 16 to 24 mg are probably associated with more adverse events than placebo. The evidence for rivastigmine was less certain. The data suggest that donepezil 10 mg has the greatest effect on cognition, but at the cost of adverse effects. The effect is modest, but in the absence of any other treatments, people living with VCI may still wish to consider the use of these agents. Further research into rivastigmine is needed, including the use of transdermal patches.


Assuntos
Inibidores da Colinesterase/administração & dosagem , Demência Vascular/tratamento farmacológico , Donepezila/administração & dosagem , Galantamina/administração & dosagem , Metanálise em Rede , Rivastigmina/administração & dosagem , Atividades Cotidianas , Viés , Inibidores da Colinesterase/efeitos adversos , Cognição/efeitos dos fármacos , Donepezila/efeitos adversos , Galantamina/efeitos adversos , Humanos , Nootrópicos/administração & dosagem , Nootrópicos/efeitos adversos , Desempenho Físico Funcional , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rivastigmina/efeitos adversos
2.
Artigo em Russo | MEDLINE | ID: mdl-33580760

RESUMO

OBJECTIVE: The aim of the study was to study the effect of the drug recognan (citicoline) on the neurodynamic characteristics of mental activity in patients with mild cognitive impairment. MATERIAL AND METHODS: A survey of 58 subjects (17 of them male and 41 female) aged 18-45 years (average age 27.2±12.5 years) was conducted. Clinical diagnosis according to ICD-10 «Mild cognitive impairment¼ (F06.7). The main subgroup included29 people received oral recognan therapy (in solution, 100 mg in 1 ml) for 30 days, with a daily dosage of 500 mg (5 ml of solution). In the control group (29 people) drug therapy was not performed. Tests were used: «Graphic sample¼, the sample on the reciprocal coordination of the hands (Ozeretsky test), test for the compression of fingers, the test «number series¼. The follow-up period was 30 days. All subjects were examined three times (initially, in the middle of the study - on day 15, at the end of the study - on day 30). RESULTS AND CONCLUSION: The results obtained showed that the use of the drug recognan (citicoline) has a positive effect on the indicators of visual-motor coordination and spatial representations, neurodynamic characteristics of movement, and cognitive functions. After a 2-week treatment with recognan improved graphical sample, 84% of patients, with reliable improvement according to the Wilcoxon (p=0.0002), the sample in the compression of the fingers 60%, as well as coordination 60%, the accounting functions in 44%. After a month (30 day) treatment course recomanem there was an increase in indices of samples for the compression of fingers in 71.4% of patients, with significant improvement (p=0.0499) and run the graphical samples of 71.4%, coordination at 46.4%, counting functions - 48% patients.


Assuntos
Disfunção Cognitiva , Nootrópicos , Preparações Farmacêuticas , Adolescente , Adulto , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/tratamento farmacológico , Citidina Difosfato Colina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nootrópicos/uso terapêutico , Adulto Jovem
3.
Nat Commun ; 12(1): 1033, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589615

RESUMO

Clinical trials of novel therapeutics for Alzheimer's Disease (AD) have consumed a large amount of time and resources with largely negative results. Repurposing drugs already approved by the Food and Drug Administration (FDA) for another indication is a more rapid and less expensive option. We present DRIAD (Drug Repurposing In AD), a machine learning framework that quantifies potential associations between the pathology of AD severity (the Braak stage) and molecular mechanisms as encoded in lists of gene names. DRIAD is applied to lists of genes arising from perturbations in differentiated human neural cell cultures by 80 FDA-approved and clinically tested drugs, producing a ranked list of possible repurposing candidates. Top-scoring drugs are inspected for common trends among their targets. We propose that the DRIAD method can be used to nominate drugs that, after additional validation and identification of relevant pharmacodynamic biomarker(s), could be readily evaluated in a clinical trial.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Drogas em Investigação/farmacologia , Aprendizado de Máquina , Proteínas do Tecido Nervoso/genética , Fármacos Neuroprotetores/farmacologia , Nootrópicos/farmacologia , Medicamentos sob Prescrição/farmacologia , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Reposicionamento de Medicamentos , Drogas em Investigação/química , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ensaios de Triagem em Larga Escala , Humanos , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/química , Nootrópicos/química , Farmacogenética/métodos , Farmacogenética/estatística & dados numéricos , Polifarmacologia , Medicamentos sob Prescrição/química , Cultura Primária de Células , Índice de Gravidade de Doença
4.
J Med Chem ; 64(4): 1844-1855, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-33570950

RESUMO

The acetylcholinesterase (AChE) inhibitors remain key therapeutic drugs for the treatment of Alzheimer's disease (AD). However, the low-safety window limits their maximum therapeutic benefits. Here, a novel kinetics-driven drug design strategy was employed to discover new-generation AChE inhibitors that possess a longer drug-target residence time and exhibit a larger safety window. After detailed investigations, compound 12 was identified as a highly potent, highly selective, orally bioavailable, and brain preferentially distributed AChE inhibitor. Moreover, it significantly ameliorated cognitive impairments in different mouse models with a lower effective dose than donepezil. The X-ray structure of the cocrystal complex provided a precise binding mode between 12 and AChE. Besides, the data from the phase I trials demonstrated that 12 had good safety, tolerance, and pharmacokinetic profiles at all preset doses in healthy volunteers, providing a solid basis for its further investigation in phase II trials for the treatment of AD.


Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/uso terapêutico , Indanos/uso terapêutico , Nootrópicos/uso terapêutico , Piperidinas/uso terapêutico , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Animais , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/metabolismo , Cristalografia por Raios X , Cães , Desenho de Fármacos , Feminino , Humanos , Indanos/síntese química , Indanos/metabolismo , Cinética , Masculino , Camundongos Endogâmicos ICR , Estrutura Molecular , Nootrópicos/síntese química , Nootrópicos/metabolismo , Piperidinas/síntese química , Piperidinas/metabolismo , Ligação Proteica , Ratos Sprague-Dawley , Escopolamina , Relação Estrutura-Atividade
5.
Biomed Pharmacother ; 133: 111088, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378982

RESUMO

Alzheimer's disease (AD) is a neurodegenerative condition mostly communal in people of advanced years accompanying various dysfunctionalities especially cognitive impairments. A number of cellular damages, such as amyloid-beta aggregation, tau protein hyperphosphorylation, some neurotransmitter imbalances, apoptosis, oxidative stress, and inflammatory responses are responsible for AD incidence. As a reason for inadequate efficacy, side effects, and pharmacokinetic problems of conventional drugs used for AD, the discovery of novel therapeutic agents with multi-targeted potential is desirable. Protective properties of phytochemicals combat numerous diseases and their vast acceptance and demand in human beings encouraged scientists to assess their effective activities. Zingiber officinale, gingerol, shogaol, and borneol were evaluated against memory impairments. Online databases including; Web of Science, Scopus, Embase, Pubmed, ProQuest, ScienceDirect, and Cochrane Library were searched until 3th February 2020. In vitro, in vivo, and clinical studies are included after screening their eligibility. Mostly interventive mechanisms such as; oxidative stress, neuroinflammation, and apoptosis are described. Correlation between the pathogenesis of AD and signaling pathways is explicated. Results and scores of cognition measurements are clarified due to in vivo studies and clinical trials. Some traditional aspects of consuming ginger in AD are also mentioned in the present review. In accumulation ginger and its components possess great potency for improving and abrogating memory dysfunctions but conducting further studies to evaluate their pharmacological and pharmaceutical aspects is required.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Gengibre , Memória/efeitos dos fármacos , Nootrópicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Animais , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Disfunção Cognitiva/patologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Modelos Animais de Doenças , Gengibre/química , Humanos , Mediadores da Inflamação/metabolismo , Nootrópicos/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação
6.
Neurosci Lett ; 743: 135566, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33352289

RESUMO

Smokers have a higher incidence of chronic pain than non-smokers, but the neural mechanism is not yet fully understood. Nicotine is the main component of tobacco and acts as an agonist for nicotinic cholinergic receptors (nAChRs) in the nervous system. This study was approved by the IACUC of UM. The effects of chronic nicotine administration on mechanical sensitivity were studied using a rat model. The changes in the expression levels of the α7 isoform of nAChR (α7-nAChR), inflammatory cytokines TNFα and COX-2, as well as the density of neuro-immune cells (astrocytes and microglia) were measured concurrently. The results indicate that long-term nicotine administration induces hypersensitivity to mechanical stimuli, as demonstrated by a significant reduction in the pain perception threshold. In response to nicotine, the expression levels of α7-nAChR increased in the periaqueductal gray matter (PAG) and decreased in the spinal cord. Acute administration of the selective α7-nAChR agonist CDP-Choline reversed this hypersensitivity. Chronic nicotine administration led to an increase of microglial cells in the dorsal horn of the spinal cord and increased expression levels of the cytokines TNFα and COX-2. This study suggests that decreased α7-nAChR expression in the spinal cord, as a result of long-term exposure to nicotine, may be causatively linked to chronic pain. Simultaneously, the increase of neuro-immune factors in the spinal cord is also a potential factor leading to chronic pain.


Assuntos
Modelos Animais de Doenças , Hiperalgesia/metabolismo , Nicotina/toxicidade , Medula Espinal/metabolismo , Tato/fisiologia , Receptor Nicotínico de Acetilcolina alfa7/biossíntese , Animais , Dor Crônica/induzido quimicamente , Dor Crônica/tratamento farmacológico , Dor Crônica/metabolismo , Citidina Difosfato Colina/farmacologia , Citidina Difosfato Colina/uso terapêutico , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Masculino , Nicotina/administração & dosagem , Nicotina/agonistas , Nootrópicos/farmacologia , Nootrópicos/uso terapêutico , Ratos , Ratos Sprague-Dawley , Medula Espinal/efeitos dos fármacos , Receptor Nicotínico de Acetilcolina alfa7/genética
7.
Int J Mol Sci ; 21(24)2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339351

RESUMO

Alzheimer's disease (AD) is the most common cause of dementia, typically showing progressive neurodegeneration in aging brains. The key signatures of the AD progression are the deposition of amyloid-beta (Aß) peptides, the formation of tau tangles, and the induction of detrimental neuroinflammation leading to neuronal loss. However, conventional pharmacotherapeutic options are merely relying on the alleviation of symptoms that are limited to mild to moderate AD patients. Moreover, some of these medicines discontinued to use due to either the insignificant effectiveness in improving the cognitive impairment or the adverse side effects worsening essential bodily functions. One of the reasons for the failure is the lack of knowledge on the underlying mechanisms that can accurately explain the major causes of the AD progression correlating to the severity of AD. Therefore, there is an urgent need for the better understanding of AD pathogenesis and the development of the disease-modifying treatments, particularly for severe and late-onset AD, which have not been covered thoroughly. Here, we review the underlying mechanisms of AD progression, which have been employed for the currently established therapeutic strategies. We believe this will further spur the discovery of a novel disease-modifying treatment for mild to severe, as well as early- to late-onset, AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Humanos , Fatores de Crescimento Neural/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Nootrópicos/uso terapêutico , Proteínas tau/metabolismo
8.
Artigo em Russo | MEDLINE | ID: mdl-33244956

RESUMO

OBJECTIVE: To study the therapeutic efficacy of two treatment modes of peptidergic nootropic medication cortexin in children with developmental dysphasia aged 3-4 years. MATERIAL AND METHODS: Ninety-four children with developmental dysphasia were divided into three groups. In group 1 (27 patients), cortexin was administered once a day intramuscularly for 10 days. After this course, the children were not prescribed drug therapy, a second examination was carried out 2 months after the start of treatment. In group 2 (40 patients), two courses of cortexin were administered at 1-month intervals, and the children were also followed up for two months. Control group 3 (27 patients) did not receive medication, but was also followed up for two months. All the parents were provided with recommendations for the stimulation of speech development in children. Before the study and two months later, speech development was assessed with special scales and questionnaires for parents. RESULTS: The increase ratio of the active vocabulary volume by 2 times or more was observed in group 2 (two courses of cortexin treatment) in 80.0% of patients (significant differences with groups 1 and 3, p<0.001), in 44.4% of group 1 (one course of cortexin), in 22.2% of the control group. Over a two-month period, the increase ratio in the active vocabulary and the number of uttered phrases in group 2 was 2.8 and 4.2 times, in group 1 2.3 and 3.6 times, respectively, in the control group it was only 1.4 and 1.5 times. Furthermore, the volume of active vocabulary in group 2 (42.4±3.6) became significantly larger (p=0.01) than in group 1 (31.7±5.6), although its initial values in group 1 (13.7±1.8) and group 2 (14.9±1.7) were similar. CONCLUSION: The results of the study confirm the higher effectiveness of two courses of the peptidergic nootropic medication cortexin in the pharmacotherapy of developmental dysphasia in children, aged 3-4 years, conducted over two months, compared with the indication of one treatment course.


Assuntos
Afasia , Nootrópicos , Afasia/tratamento farmacológico , Criança , Pré-Escolar , Humanos , Injeções Intramusculares , Nootrópicos/uso terapêutico , Pais , Inquéritos e Questionários
9.
Yakugaku Zasshi ; 140(11): 1397-1403, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33132276

RESUMO

Pharmacological cognitive enhancement (PCE) usually refers to the use of medical substances by healthy individuals to improve mental performance. Given that certain substances have been frequently used for years, the long-term effectiveness and safety are essential to know but particularly difficult and costly to determine. Although PCE is a widespread and frequent phenomenon among university students in other countries, PCE prevalence in Japan has not been elucidated. The present study aimed to investigate the prevalence of and the attitude toward PCE among Japanese undergraduates over 3 years (2017-2019). Almost no student had ever used prescription drugs for cognitive enhancement. When asked, "Would you like to use drugs to enhance your cognitive performance?" 68.6-72.0% of the students answered, "No," 25.4-26.7% answered, "I couldn't say," and 2.5-4.8% answered, "Yes." These answers were associated with sex (2017-2018) and stress sensitivity (2019) but not with drinking, smoking, or stress of academic performance. Half of the students had used energy drinks for neural enhancement prior to an examination, which is similar to Western usage. The users of soft enhancers, such as energy drinks, are more likely to use other drugs. Given that caffeine can be a gateway for cognitive enhancement, future education addressing PCE among students should emphasize the side effects of prescription drugs as well as health risks of caffeine products.


Assuntos
Atitude Frente a Saúde , Conscientização , Nootrópicos , Estudantes de Farmácia/psicologia , Inquéritos e Questionários , Adolescente , Adulto , Cafeína , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Japão , Masculino , Nootrópicos/efeitos adversos , Prevalência , Fatores de Tempo , Adulto Jovem
10.
BMC Psychol ; 8(1): 119, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33160397

RESUMO

BACKGROUND: Cognitive enhancement (CE) refers to the voluntary improvement of human cognitive capabilities. Few studies have examined the general attitude of the public towards CE. Such studies have suggested that the use of CE is considered largely unacceptable by the public. In parallel, past research indicates that individuals scoring high on the Dark Triad of personality (Machiavellianism, narcissism, and psychopathy) and competitiveness have atypical views of ethical questions. In this study, we examined (a) whether attitudes towards CE are associated with individual differences in the Dark Triad of personality as well as in trait and contextual competitiveness and (b) whether the Dark Triad moderates the effect of trait and contextual competitiveness on attitudes towards CE. METHOD: US employees (N = 326) were recruited using Mechanical Turk. Participants completed a web survey. Data were analyzed by means of (robust) hierarchical regression and (robust) ANCOVAs. RESULTS: The Dark Triad of personality and one of its subscales, Machiavellianism, predicted positive attitudes towards CE. Neither trait competitiveness nor contextual competitiveness were linked to general attitudes towards CE, but the DT was a positive moderator of the association between contextual competitiveness and positive attitudes. CONCLUSION: Our findings extend the incipient knowledge about the factors relating to favourable views of CE by highlighting the role of dark personality traits in shaping such views. Our study further shows contextual factors can play a differentiated role with respect to such attitudes depending upon dark personality traits. Implications for policy-making are discussed.


Assuntos
Transtorno da Personalidade Antissocial/psicologia , Atitude , Maquiavelismo , Narcisismo , Nootrópicos , Cognição/efeitos dos fármacos , Comportamento Competitivo , Humanos , Nootrópicos/farmacologia
11.
Medicine (Baltimore) ; 99(33): e21242, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871984

RESUMO

Currently there is no effective treatment for vascular dementia (VaD). Pharmacological treatment often lead to severe complications and require drug dosage adjustment. This study investigated the effect of scalp electroacupuncture combined with Memantine in VaD. The safety and antioxidative effect of scalp electroacupuncture were also explored.A retrospective study was conducted and data of inpatients of Linyi Central Hospital with VaD between June 2017 and May 2018 were collected and sorted. The patients were divided into scalp electroacupuncture-medication (A), scalp electroacupuncture (B) and medication (control) (C) groups, in which Memantine was prescribed as medication. Cognitive function, activities of daily living and quality of life assessed by Montreal Cognitive Assessment (MoCA), Barthel index and dementia quality of life questionnaire; the contents of superoxide dismutase, lipid peroxide and nitric oxide in blood samples; and adverse reaction were compared.Data from a total of 150 patients were collected (Group A, n = 55; Group B, n = 50; Group C, n = 45). The post-treatment/follow-up Montreal Cognitive Assessment, Barthel index and dementia quality of life questionnaire scores were significantly improved in all groups compared to pre-treatment (groups A and B, P<.01; group C, P<.05). The improvements were significant for groups A vs C, B vs C (P<0.01, both), and group A vs B (P<.05). The post-treatment/follow-up levels of lipid peroxide and nitric oxide decreased significantly while superoxide dismutase increased significantly in groups A and B compared to pre-treatment (P<.01, both). The differences were significant for groups A vs C, and B vs C (P < .01, both), but not significant between groups A and B (P > .05). There were no significant adverse events occurred during the study and follow-up.In combined treatment, scalp electroacupuncture works in parallel with Memantine and significantly increase the therapeutic effect in VaD with no significant adverse events. Scalp electroacupuncture may have the potential to serve as an option or alternative treatment for VaD. Scalp electroacupuncture may alleviate VaD symptoms through its antioxidative mechanism.


Assuntos
Demência Vascular/terapia , Eletroacupuntura , Memantina/uso terapêutico , Nootrópicos/uso terapêutico , Atividades Cotidianas , Idoso , Biomarcadores/sangue , Cognição/efeitos dos fármacos , Terapia Combinada , Demência Vascular/sangue , Eletroacupuntura/efeitos adversos , Eletroacupuntura/métodos , Feminino , Seguimentos , Humanos , Peróxidos Lipídicos/sangue , Masculino , Memantina/efeitos adversos , Óxido Nítrico/sangue , Nootrópicos/efeitos adversos , Qualidade de Vida , Estudos Retrospectivos , Couro Cabeludo , Superóxido Dismutase/sangue , Resultado do Tratamento
12.
Cochrane Database Syst Rev ; 8: CD013066, 2020 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-32860632

RESUMO

BACKGROUND: Stroke is one of the leading causes of long-lasting disability and mortality and its global burden has increased in the past two decades. Several therapies have been proposed for the recovery from, and treatment of, ischemic stroke. One of them is citicoline. This review assessed the benefits and harms of citicoline for treating patients with acute ischemic stroke. OBJECTIVES: To assess the clinical benefits and harms of citicoline compared with placebo or any other control for treating people with acute ischemic stroke. SEARCH METHODS: We searched in the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS until 29 January 2020. We searched the World Health Organization Clinical Trials Search Portal and ClinicalTrials.gov. Additionally, we also reviewed reference lists of the retrieved publications and review articles, and searched the websites of the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). SELECTION CRITERIA: We included randomized controlled trials (RCTs) in any setting including participants with acute ischemic stroke. Trials were eligible for inclusion if they compared citicoline versus placebo or no intervention. DATA COLLECTION AND ANALYSIS: We selected RCTs, assessed the risk of bias in seven domains, and extracted data by duplicate. Our primary outcomes of interest were all-cause mortality and the degree of disability or dependence in daily activities at 90 days. We estimated risk ratios (RRs) for dichotomous outcomes. We measured statistical heterogeneity using the I² statistic. We conducted our analyses using the fixed-effect and random-effects model meta-analyses. We assessed the overall quality of evidence for six pre-specified outcomes using the GRADE approach. MAIN RESULTS: We identified 10 RCTs including 4281 participants. In all these trials, citicoline was given either orally, intravenously, or a combination of both compared with placebo or standard care therapy. Citicoline doses ranged between 500 mg and 2000 mg per day. We assessed all the included trials as having high risk of bias. Drug companies sponsored six trials. A pooled analysis of eight trials indicates there may be little or no difference in all-cause mortality comparing citicoline with placebo (17.3% versus 18.5%; RR 0.94, 95% CI 0.83 to 1.07; I² = 0%; low-quality evidence due to risk of bias). Four trials found no difference in the proportion of patients with disability or dependence in daily activities according to the Rankin scale comparing citicoline with placebo (21.72% versus 19.23%; RR 1.11, 95% CI 0.97 to 1.26; I² = 1%; low-quality evidence due to risk of bias). Meta-analysis of three trials indicates there may be little or no difference in serious cardiovascular adverse events comparing citicoline with placebo (8.83% versus 7.77%; RR 1.04, 95% CI 0.84 to 1.29; I² = 0%; low-quality evidence due to risk of bias). Overall, either serious or non-serious adverse events - central nervous system, gastrointestinal, musculoskeletal, etc. - were poorly reported and harms may have been underestimated. Four trials assessing functional recovery with the Barthel Index at a cut-off point of 95 points or more did not find differences comparing citicoline with placebo (32.78% versus 30.70%; RR 1.03, 95% CI 0.94 to 1.13; I² = 24%; low-quality evidence due to risk of bias). There were no differences in neurological function (National Institutes of Health Stroke Scale at a cut-off point of ≤ 1 points) comparing citicoline with placebo according to five trials (24.31% versus 22.44%; RR 1.08, 95% CI 0.96 to 1.21; I² = 27%, low-quality evidence due to risk of bias). A pre-planned Trial Sequential Analysis suggested that no more trials may be needed for the primary outcomes but no trial provided information on quality of life. AUTHORS' CONCLUSIONS: This review assessed the clinical benefits and harms of citicoline compared with placebo or any other standard treatment for people with acute ischemic stroke. The findings of the review suggest there may be little to no difference between citicoline and its controls regarding all-cause mortality, disability or dependence in daily activities, severe adverse events, functional recovery and the assessment of the neurological function, based on low-certainty evidence. None of the included trials assessed quality of life and the safety profile of citicoline remains unknown. The available evidence is of low quality due to either limitations in the design or execution of the trials.


Assuntos
Citidina Difosfato Colina/uso terapêutico , Nootrópicos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Atividades Cotidianas , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Viés , Isquemia Encefálica/complicações , Causas de Morte , Citidina Difosfato Colina/efeitos adversos , Humanos , Pessoa de Meia-Idade , Nootrópicos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade
13.
Artigo em Russo | MEDLINE | ID: mdl-32678562

RESUMO

The analysis of mechanisms of the neuroprotective effect of choline precursors reveals the primary effects of citicoline on the processes of repair of neuronal membranes, a decrease in the degeneration of free fatty acids, and choline alfoscerate, an increase in the production of the neurotransmitter acetylcholine. Although citicoline has a lesser effect on choline secretion than choline alfoscerate, the combination of choline and cytidine in its composition is a universal tool to reduce symptoms of cerebral ischemia, to stabilize cognitive status, superior to the standard benefits of choline. Various mechanisms of the action of citicoline enable to recommend it as a drug effective both in the acute phase of the disease and in the delayed period, giving it the status of a universal nootropic compound.


Assuntos
Colina/farmacologia , Isquemia Encefálica , Citidina Difosfato Colina , Humanos , Fármacos Neuroprotetores , Nootrópicos
14.
Biomed Khim ; 66(3): 257-264, 2020 May.
Artigo em Russo | MEDLINE | ID: mdl-32588832

RESUMO

Physicochemical properties of the original pharmaceutical substance TST-9 based on the 3,7-diazabicyclo[3.3.1]nonane derivative with the chemical name IUPAC 6-[4methoxy-3-(1H-pyrazol-1-ylmethyl) benzyl]-1,11-dimethyl-3,6,9-triazatricyclo[7.3.1.1]tetradecane-4,8,12-trion, were studied. TST-9 is used as an active substance for the development of the composition and technology for the preparation of an innovative oral drug. The pharmaceutical substance TST-9 is an amorphous white powder, odorless, soluble in chloroform, acetonitrile, methylene chloride, acetone, dimethyl sulfoxide, dimethylformamide and alcohol, sparingly soluble in diethyl ether, dioxane and is very slightly soluble in water, hexane, and heptane. The melting point ranged from 94°C to 96°C without visible decomposition of the substance. The microbiological purity corresponds to category 2.2. Residual organic solvents in the form of chloroform did not exceed 0.006%. The amount of impurities was not more than 0.15%. The loss in mass upon drying was not more than 0.5%. The "identity" was confirmed using nuclear magnetic resonance spectroscopy and HPLC with UV detection. The data obtained in the study will contribute to the further development of the dosage form, the choice of the route of administration and the dosage regimen, as well as the selection of analytical methods for analyzing the quality of the finished dosage form and the effective, high-precision determination of the content of the active substance and its likely decay products.


Assuntos
Nootrópicos , Cromatografia Líquida de Alta Pressão , Nootrópicos/química , Solventes
15.
Value Health ; 23(6): 710-718, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32540228

RESUMO

OBJECTIVES: Decision-analytic models for Alzheimer's disease (AD) have been advanced to a discrete-event simulation (DES), in which individual-level modeling of disease progression across continuous severity spectra become feasible. This study aimed to apply DES to perform cost-effectiveness analysis of AD treatment in Thailand. METHODS: A data set of Thai AD patients, representing unique demographic and clinical characteristics, was bootstrapped to generate a baseline cohort of 50 000 patients. Each patient was cloned and assigned to donepezil, galantamine, rivastigmine, memantine, or no treatment. Correlated changes in cognitive and behavioral status over time were developed using patient-level data. Treatment effects were obtained from the most recent network meta-analysis. Treatment persistence; mortality; and predictive equations for functional status, costs (Thai baht in 2017), and quality-adjusted life-year (QALY) were derived from country-specific real-world data. RESULTS: From a societal perspective, only the prescription of donepezil to AD patients with all disease-severity levels was found to be cost-effective (incremental cost-effectiveness ratio): 138 524 Thai baht/QALY ($4062/QALY)]. Regardless of whether the treatment-stopping rule when the mini-mental state examination score <10 was introduced, providing early treatment with donepezil to mild AD patients further reduced the incremental cost-effectiveness ratio. Extensive sensitivity analyses indicated robust simulation findings. CONCLUSIONS: Discrete-event simulation greatly enhances the real-world representativeness of decision-analytic models for AD. Donepezil is the most cost-effective treatment option for AD in Thailand and is worth being considered for universal financial coverage. Application of DES in heath technology assessment should be encouraged, especially when the validity of the model is questionable with classical modeling methods.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Nootrópicos/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida , Avaliação da Tecnologia Biomédica , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/economia , Estudos de Coortes , Simulação por Computador , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nootrópicos/economia , Estudos Retrospectivos , Tailândia , Resultado do Tratamento
16.
Clin Interv Aging ; 15: 691-693, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32546987

RESUMO

Chemobrain is one of the problems that may arise during or after treatment and there is currently no specific treatment for this condition. Our case was a 76-year-old female patient who presented to our clinic with complaints of forgetfulness that did not affect daily living activities for the last year. Breast cancer was diagnosed in 2013 and she has been receiving anastrozole treatment for 6 years after local mass excision surgery and radiotherapy. After a comprehensive geriatric evaluation, cognitive impairment due to systemic cancer therapy was detected and treatment was started with Theracurmin 90 mg twice a day therapy. After 3-months of Theracurmin therapy, she had no cognitive improvement during the follow-up. This case report demonstrated that Theracurmin treatment may be a new option for chemobrain.


Assuntos
Anastrozol , Neoplasias da Mama/terapia , Transtornos Cognitivos , Cognição/efeitos dos fármacos , Curcumina/administração & dosagem , Radioterapia , Idoso , Anastrozol/administração & dosagem , Anastrozol/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/patologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Feminino , Avaliação Geriátrica/métodos , Humanos , Mastectomia Segmentar/métodos , Nootrópicos/administração & dosagem , Radioterapia/efeitos adversos , Radioterapia/métodos , Resultado do Tratamento
17.
Clin Interv Aging ; 15: 743-754, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32546992

RESUMO

Background: Preventative measures have recently been taken to reduce the incidence of Alzheimer's disease worldwide. We previously showed that Met-Lys-Pro (MKP), a casein-derived angiotensin-converting enzyme inhibitory peptide with the potential to cross the blood-brain barrier, attenuated cognitive decline in a mouse model of Alzheimer's disease. However, the effect of MKP on cognitive function improvement in humans remains unknown. This exploratory study sought to investigate whether MKP intake could improve cognitive function in adults without dementia. Methods: A total of 268 community-dwelling adults without dementia participated in this 24-week randomized controlled trial. Participants were randomly allocated to the MKP (n = 134) or placebo (n = 134) group. The MKP group received four tablets daily, each containing 50 µg MKP, while the placebo group received four dextrin tablets containing no detectable MKP for 24 weeks. Scores on the Japanese version of the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog) were used as the primary outcome to compare cognitive function between the MKP and placebo groups. The study products were also evaluated for safety. Results: The intention-to-treat analysis showed that there was no significant difference between the groups in terms of the ADAS-cog total score. Orientation, as measured by the respective ADAS-cog subscale, was significantly improved compared to placebo at 24 weeks post-MKP administration (P = 0.022). No serious adverse events due to MKP intake were observed. Conclusion: To the best of our knowledge, this is the first study to report the effects of MKP on human cognition. These preliminary results suggested the safety of daily MKP intake and its potential to improve orientation in adults without dementia. Further clinical studies are needed to confirm the present findings and the benefits of MKP on cognitive function.


Assuntos
Caseínas/farmacologia , Cognição/efeitos dos fármacos , Disfunção Cognitiva , Oligopeptídeos/administração & dosagem , Administração Oral , Idoso , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/prevenção & controle , Método Duplo-Cego , Feminino , Humanos , Vida Independente , Masculino , Testes Neuropsicológicos , Nootrópicos/administração & dosagem , Comprimidos , Resultado do Tratamento
18.
J Glaucoma ; 29(7): 513-520, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32541370

RESUMO

PRECIS: Citicoline eyedrops in patients with progressing glaucoma. PURPOSE: This study aimed to test whether the additional therapy with citicoline eyedrops to intraocular pressure (IOP)-lowering treatment could slow glaucoma progression in patients with worsening of damage and IOP 18 mm Hg or less. DESIGN: This was a randomized, double-masked, placebo-controlled, multicenter 3-year study. OUTCOMES: The outcomes studied were difference in the visual field (mean deviation, MD, of 24-2; MD of 10-2) rates of progression and difference in retinal nerve fiber layer (RNFL) thickness change between the 2 study groups at 3 years. METHODS: Patients with mild to moderate open-angle glaucoma (OAG) showing damage progression of at least -0.5 dB/y in the 2 years before enrollment despite IOP ≤18 mm Hg were randomized to receive citicoline eyedrops or placebo 3 times daily for 3 years. Patients were followed every 3 months and underwent a visual field examination with 24-2 and 10-2 strategies and RNFL assessment. Analysis of variance and linear models were used to test the differences between groups. RESULTS: Eighty patients were randomized in the trial. The mean 3-year rates of progression were -1.03 (2.14) dB in the citicoline group and -1.92 (2.23) dB in the placebo group (P=0.07) for 24-2 MD and -0.41 (3.45) dB in the citicoline group and -2.22 (3.63) dB in the placebo group (P=0.02) for 10-2 MD. On average, patients receiving citicoline eyedrops lost 1.86 µm of RNFL in 3 years, versus 2.99 µm in the placebo group (P=0.02). CONCLUSIONS: Additional treatment with citicoline eyedrops to IOP-lowering treatment might reduce disease progression in patients with progressing glaucoma despite IOP ≤18 mm Hg.


Assuntos
Citidina Difosfato Colina/uso terapêutico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Nootrópicos/uso terapêutico , Administração Oftálmica , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Método Duplo-Cego , Feminino , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Soluções Oftálmicas , Células Ganglionares da Retina/patologia , Tonometria Ocular , Campos Visuais/fisiologia
19.
J Psychiatr Res ; 128: 1-4, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32474140

RESUMO

Prenatal COVID-19 infection is anticipated by the U.S. Centers for Disease Control to affect fetal development similarly to other common respiratory coronaviruses through effects of the maternal inflammatory response on the fetus and placenta. Plasma choline levels were measured at 16 weeks gestation in 43 mothers who had contracted common respiratory viruses during the first 6-16 weeks of pregnancy and 53 mothers who had not. When their infants reached 3 months of age, mothers completed the Infant Behavior Questionnaire-Revised (IBQ-R), which assesses their infants' level of activity (Surgency), their fearfulness and sadness (Negativity), and their ability to maintain attention and bond to their parents and caretakers (Regulation). Infants of mothers who had contracted a moderately severe respiratory virus infection and had higher gestational choline serum levels (≥7.5 mM consistent with U.S. Food and Drug Administration dietary recommendations) had significantly increased development of their ability to maintain attention and to bond with their parents (Regulation), compared to infants whose mothers had contracted an infection but had lower choline levels (<7.5 mM). For infants of mothers with choline levels ≥7.5 µM, there was no effect of viral infection on infant IBQ-R Regulation, compared to infants of mothers who were not infected. Higher choline levels obtained through diet or supplements may protect fetal development and support infant early behavioral development even if the mother contracts a viral infection in early gestation when the brain is first being formed.


Assuntos
Betacoronavirus/patogenicidade , Encéfalo , Desenvolvimento Infantil , Colina , Desenvolvimento Fetal , Comportamento do Lactente , Complicações Infecciosas na Gravidez , Adulto , Atenção , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Desenvolvimento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/fisiologia , Colina/administração & dosagem , Colina/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Suplementos Nutricionais , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Desenvolvimento Fetal/fisiologia , Idade Gestacional , Humanos , Lactente , Comportamento do Lactente/fisiologia , Comportamento do Lactente/psicologia , Masculino , Nootrópicos/administração & dosagem , Nootrópicos/sangue , Apego ao Objeto , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/virologia , Cuidado Pré-Natal/métodos
20.
Toxicol Appl Pharmacol ; 398: 115028, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32360636

RESUMO

NADPH oxidase (NOX) has been identified as a crucial contender of oxidative damage in Alzheimer's disease (AD). However, the capability of diapocynin, a NOX inhibitor, to offer neuroprotection in AD models is still a matter of debate. Hence, the current work is dedicated to investigate the influence of diapocynin on cognitive impairment prompted by ovariectomy combined with D-galactose injection in rats (an AD animal model), and to elucidate the signaling mechanisms regulating diapocynin-induced effects. Female rats were exposed to ovariectomy or sham operation. Ovariectomized rats were injected intraperitoneally with D-galactose (150 mg/kg/day) for 70 days and, on day 43, they were orally treated with diapocynin (10 mg/kg/day) for 28 days. Diapocynin amended cognitive functions as confirmed using novel object recognition and Morris water maze tests along with histopathological improvement. It caused a prominent decrement in ß-secretase, p-tau, and amyloid ß, contrary to α-secretase elevation in hippocampus and hampered neuroinflammation and oxidative stress, manifested by declined levels of NOX1, tumor necrosis factor-α, and nuclear factor-kappa B p65. In addition, diapocynin augmented synaptophysin, brain-derived neurotrophic factor, and phospho-cAMP response element binding protein and enhanced protein expression of phosphorylated forms of phosphoinositide 3-kinase (PI3K), glycogen synthase kinase-3ß (GSK-3ß), protein kinase B (Akt), extracellular signal-regulated kinase (ERK) 1/2, ERK kinase kinase (Raf-1), and ERK kinase (MEK) 1/2, while inhibiting those of c-Jun and c-Jun N-terminal kinase (JNK). In conclusion, diapocynin attenuated memory impairment and AD-like anomalies via activating Raf-1/MEK/ERK and PI3K/Akt/GSK-3ß, while inhibiting JNK/c-Jun signaling cascades.


Assuntos
Acetofenonas/farmacologia , Doença de Alzheimer/tratamento farmacológico , Compostos de Bifenilo/farmacologia , Cognição/efeitos dos fármacos , Galactose/metabolismo , Nootrópicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Doença de Alzheimer/metabolismo , Animais , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Memória/efeitos dos fármacos , Ratos , Ratos Wistar
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