Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.174
Filtrar
1.
Nutrients ; 13(2)2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546262

RESUMO

African Americans have higher incidence of, and mortality from, many health-related problems than European Americans. They also have a 15 to 20-fold higher prevalence of severe vitamin D deficiency. Here we summarize evidence that: (i) this health disparity is partly due to insufficient vitamin D production, caused by melanin in the skin blocking the UVB solar radiation necessary for its synthesis; (ii) the vitamin D insufficiency is exacerbated at high latitudes because of the combination of dark skin color with lower UVB radiation levels; and (iii) the health of individuals with dark skin can be markedly improved by correcting deficiency and achieving an optimal vitamin D status, as could be obtained by supplementation and/or fortification. Moderate-to-strong evidence exists that high 25-hydroxyvitamin D levels and/or vitamin D supplementation reduces risk for many adverse health outcomes including all-cause mortality rate, adverse pregnancy and birth outcomes, cancer, diabetes mellitus, Alzheimer's disease and dementia, multiple sclerosis, acute respiratory tract infections, COVID-19, asthma exacerbations, rickets, and osteomalacia. We suggest that people with low vitamin D status, which would include most people with dark skin living at high latitudes, along with their health care provider, consider taking vitamin D3 supplements to raise serum 25-hydroxyvitamin D levels to 30 ng/mL (75 nmol/L) or possibly higher.


Assuntos
/etiologia , Colecalciferol/administração & dosagem , Suplementos Nutricionais , Disparidades nos Níveis de Saúde , Deficiência de Vitamina D/etnologia , Deficiência de Vitamina D/epidemiologia , Afro-Americanos , Doença de Alzheimer/etiologia , Doença de Alzheimer/prevenção & controle , Antígenos de Neoplasias , Demência/etiologia , Demência/prevenção & controle , Diabetes Mellitus/etiologia , Diabetes Mellitus/prevenção & controle , Feminino , Humanos , Masculino , Prevalência , Estado Asmático/etiologia , Estado Asmático/prevenção & controle , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/complicações
3.
J Urol ; 205(1): 60-67, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32856962

RESUMO

PURPOSE: Androgen deprivation therapy is a standard therapy for some patients with localized and almost all patients with metastatic prostate cancer. Although several clinical cohort studies have identified an impact of androgen deprivation therapy on cognitive function, the previous reviews were not able to perform a well designed quantitative synthesis to summarize the risk of dementia and/or Alzheimer disease. Consequently there is still a lack of systematic review and meta-analysis regarding the impact of this risk including more recent studies. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of the literature assessing the differential incidence of dementia and/or Alzheimer disease as outcomes in patients with prostate cancer who did vs did not receive androgen deprivation therapy. We queried PubMed® and Web of Science™ databases from January 1 to 3, 2020. We used random or fixed effects meta-analytic models in the presence or absence of heterogeneity per the I2 statistic. We performed 6 meta-analyses for all cause dementia, Alzheimer disease and all cause dementia or Alzheimer disease according to the duration of androgen deprivation therapy (up to 12 or more than 12 months). RESULTS: A total of 14 studies were selected after considering inclusion and exclusion criteria. Nine of them reported all cause dementia (ie all types of dementia including Alzheimer disease), with 8 reporting Alzheimer disease. Five studies assessed these outcomes according to the duration of androgen deprivation therapy. The risk of new onset dementia (all cause) and Alzheimer disease was higher in patients with prostate cancer who received androgen deprivation therapy compared to those who did not (HR 1.21, 95% CI 1.11-1.33 and HR 1.16, 95% CI 1.09-1.24). The risk of dementia (all cause) was higher in patients with prostate cancer who received androgen deprivation therapy for more than 12 months (HR 1.36, 95% CI 1.07-1.72); however, for those who had less than 12 months of androgen deprivation therapy exposure the difference was not statistically significant 1.06 (95% CI 0.77-1.28). There was no association between the androgen deprivation therapy duration and the risk of Alzheimer disease (HR 1.21, 95% CI 0.97-1.51 for exposure up to 12 months and HR 1.39, 95% CI 0.69-2.79 for exposure greater than 12 months). CONCLUSIONS: Men who receive androgen deprivation therapy for prostate cancer have an increased risk of dementia and/or Alzheimer disease compared to men who do not receive androgen deprivation therapy; this was more pronounced when androgen deprivation therapy was given longer than 12 months.


Assuntos
Doença de Alzheimer/epidemiologia , Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Demência/epidemiologia , Neoplasias da Próstata/tratamento farmacológico , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/prevenção & controle , Antagonistas de Androgênios/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Cognição/efeitos dos fármacos , Demência/induzido quimicamente , Demência/prevenção & controle , Esquema de Medicação , Humanos , Masculino , Neoplasias da Próstata/patologia , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Fatores de Tempo
4.
PLoS One ; 15(12): e0237622, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382689

RESUMO

STUDY OBJECTIVES: While poor sleep quality has been related to increased risk of Alzheimer's disease, long-time shift workers (maritime pilots) did not manifest evidence of early Alzheimer's disease in a recent study. We explored two hypotheses of possible compensatory mechanisms for sleep disruption: Increased efficiency in generating deep sleep during workweeks (model 1) and rebound sleep during rest weeks (model 2). METHODS: We used data from ten male maritime pilots (mean age: 51.6±2.4 years) with a history of approximately 18 years of irregular shift work. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). A single lead EEG-device was used to investigate sleep in the home/work environment, quantifying total sleep time (TST), deep sleep time (DST), and deep sleep time percentage (DST%). Using multilevel models, we studied the sleep architecture of maritime pilots over time, at the transition of a workweek to a rest week. RESULTS: Maritime pilots reported worse sleep quality in workweeks compared to rest weeks (PSQI = 8.2±2.2 vs. 3.9±2.0; p<0.001). Model 1 showed a trend towards an increase in DST% of 0.6% per day during the workweek (p = 0.08). Model 2 did not display an increase in DST% in the rest week (p = 0.87). CONCLUSIONS: Our findings indicated that increased efficiency in generating deep sleep during workweeks is a more likely compensatory mechanism for sleep disruption in the maritime pilot cohort than rebound sleep during rest weeks. Compensatory mechanisms for poor sleep quality might mitigate sleep disruption-related risk of developing Alzheimer's disease. These results should be used as a starting point for future studies including larger, more diverse populations of shift workers.


Assuntos
Adaptação Fisiológica , Pilotos/psicologia , Privação do Sono/fisiopatologia , Transtornos do Sono do Ritmo Circadiano/fisiopatologia , Sono/fisiologia , Tolerância ao Trabalho Programado/psicologia , Doença de Alzheimer/prevenção & controle , Estudos de Coortes , Eletroencefalografia , Humanos , Masculino , Pessoa de Meia-Idade , Privação do Sono/diagnóstico , Transtornos do Sono do Ritmo Circadiano/diagnóstico , Inquéritos e Questionários , Tolerância ao Trabalho Programado/fisiologia
5.
Med Sci Monit ; 26: e930340, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33323916

RESUMO

Alterations in complex behavioral patterns during the extended period of the COVID-19 pandemic are predicted to promote a variety of psychiatric disease symptoms due to enforced social isolation and self-quarantine. Accordingly, multifaceted mental health problems will continue to increase, thereby creating a challenge for society and the health care system in general. Recent studies show that COVID-19 can directly or indirectly influence the central nervous system, potentially causing neurological pathologies such as Alzheimer disease and Parkinson disease. Thus, chronic COVID-19-related disease processes have the potential to cause serious mental illnesses, including depression, anxiety, and sleep disorders. Importantly, mental health problems can foster systemic changes in functionally-linked neuroendocrine conditions that heighten a person's susceptibility to COVID-19 infection. These altered defense mechanisms may include compromised "self-control" and "self-care", as well as a "lack of insight" into the danger posed by the virus. These consequences may have serious social impacts on the future of COVID-19 survivors. Compounding the functionally related issues of altered mental health parameters and viral susceptibility are the potential effects of compromised immunity on the establishment of functional herd immunity. Within this context, mental health takes on added importance, particularly in terms of the need to increase support for mental health research and community-based initiatives. Thus, COVID-19 infections continue to reveal mental health targets, a process we must now be prepared to deal with.


Assuntos
/complicações , Saúde Mental , Sobreviventes/psicologia , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/virologia , Ansiedade/epidemiologia , Ansiedade/prevenção & controle , Ansiedade/psicologia , /psicologia , Depressão/epidemiologia , Depressão/prevenção & controle , Depressão/psicologia , Suscetibilidade a Doenças/psicologia , Humanos , Pandemias , Doença de Parkinson/epidemiologia , Doença de Parkinson/prevenção & controle , Doença de Parkinson/virologia , Autocuidado/psicologia , Autocontrole/psicologia , Isolamento Social/psicologia
6.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(10. Vyp. 2): 31-38, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33205928

RESUMO

OBJECTIVE: To assess the delayed effect of course therapy with cerebrolysin on the cognitive functioning of the first degree relatives of patients with Alzheimer's disease (AD), including, depending on the ApoE4 genotype. MATERIAL AND METHODS: A cohort of 72 blood relatives of patients with AD, including 46 with objectively confirmed clinical and neuropsychological examination signs of mild cognitive dysfunction (group 1) and 26 (group 2) with cognitive impairment that meets the diagnostic criteria of mild cognitive impairment (ICD-10 F06.7), was studied. The dynamics of the initial (0 day) indicators of cognitive functioning was compared immediately after a four-week course of treatment with cerebrolysin infusions, as well as 1 and 2 months after its completion, depending on the presence of ApoE4(+) or ApoE4(-) genotype. Clinical, psychopathological, psychometric, follow-up, molecular-genetic and statistical methods were used. RESULTS: A positive prolonged effect of course therapy with cerebrolysin on cognitive functioning of the first degree relatives of patients with AD was established in both groups. A significant negative effect of the ApoE4(+) genotype on the immediate and delayed effects of cerebrolysin treatment has been proven. CONCLUSION: The results can form the basis for the development of therapeutic measures aimed at preventing the progression of cognitive impairment and the development of dementia in the first degree relatives of patients with AD as those with the highest risk of dementia.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/prevenção & controle , Aminoácidos , Apolipoproteínas E/genética , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/genética , Disfunção Cognitiva/prevenção & controle , Progressão da Doença , Genótipo , Humanos , Testes Neuropsicológicos
7.
Yakugaku Zasshi ; 140(11): 1351-1363, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33132271

RESUMO

Epidemiological studies have shown that coffee consumption may be associated with a lower risk of developing several chronic disorders. To elucidate the molecular mechanism of the effects of coffee, we analyzed molecular response upon exposure to coffee extract using cellular and animal models of these diseases. As obesity is recognized as a major risk factor for these chronic diseases, we investigated the effect of coffee on adipogenesis using mouse preadipocyte 3T3-L1 cells. We found that coffee induced proteasomal degradation of IRS-1, leading to reduction of PPARγ expression, a master transcription factor for adipogenesis. Reduction in weight as well as in IRS-1 expression was detected in the fat tissues of the high fat-diet-fed mice when reared with 60% coffee for 7 weeks. As for Alzheimer's disease, we analyzed the effect of coffee on amyloid ß (Aß) production in human neuronal SH-SY5Y cells. We found a 20% reduction in Aß production when treated with 2.5% coffee for 2 d. This reduction was due to proteasomal degradation of BACE1 (ß-secretase), which was activated by protein kinase A. In addition, coffee ameliorates LPS-induced inflammatory responses in RAW264.7 macrophages by reducing NFκB activity and Nrf2 activation. Roasted coffee prevents selenite-induced cataractogenesis by ameliorating antioxidant loss. Pyrocatechol, a component of roasted coffee, also reduced Aß production and exhibits anti-inflammatory effects by a similar mechanism as coffee. Our results suggest that roasting coffee beans to generate pyrocatechol is necessary for the preventive effects of coffee intake on the chronic diseases.


Assuntos
Doença de Alzheimer/prevenção & controle , Catarata/prevenção & controle , Doença Crônica/prevenção & controle , Café , Ingestão de Líquidos/fisiologia , Adipogenia , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Catecóis , Células Cultivadas , Café/química , Modelos Animais de Doenças , Manipulação de Alimentos , Temperatura Alta , Humanos , Proteínas Substratos do Receptor de Insulina/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , PPAR gama/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Células RAW 264.7
8.
Rev. neurol. (Ed. impr.) ; 71(10): 353-364, 16 nov., 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-198070

RESUMO

INTRODUCCIÓN: La enfermedad de Alzheimer (EA) es el tipo de demencia más prevalente en la actualidad, con una incidencia estimada del 30% de la población mayor de 85 años, lo que representa un problema de salud en la sociedad actual. OBJETIVO: Conocer si el bilingüismo puede actuar como factor de protección de la EA, incrementando así la reserva cognitiva. Sujetos y métodos: Se realizó la búsqueda de estudios en las bases de datos PsychInfo, Pubmed, Psicodoc, Medline y PubPsych, a partir de la combinación de diversos términos relacionados con las palabras clave. Finalmente se incluyeron 10 estudios. RESULTADOS: Siete de los 10 estudios seleccionados sugieren una relación significativamente positiva entre bilingüismo y EA, aunque dos de los estudios restantes encuentran una relación parcial, sólo en unas circunstancias muy concretas (en uno se da una relación positiva cuando hay un nivel bajo de educación, mientras que en el otro sólo se encuentra relación cuando se hablan más de dos lenguas). Únicamente un estudio no halla una relación significativa entre bilingüismo y EA. CONCLUSIONES: Los citados estudios encontraron un retraso en el momento del diagnóstico o en el inicio de la sintomatología clínicamente significativa de entre 4,5 y 7 años; así pues, el bilingüismo se podría considerar un factor contribuidor de la reserva cognitiva y, en consecuencia, un probable factor de protección para prevenir o retrasar la aparición de la EA y su posterior progresión


INTRODUCTION: Alzheimer's disease (AD) is the most prevalent type of dementia today, with an incidence estimated at 30% of the population over 85 years of age, which is why it represents a health problem in today's society. AIM: To know if bilingualism can act as a protection factor for AD, thus increasing cognitive reserve. SUBJECTS AND METHODS: We searched for studies in the PsychInfo, Pubmed, Psicodoc, Medline and PubPych databases, based on the combination of various terms related to the keywords. Finally, ten studies were included. RESULTS: Seven of the ten selected studies suggest a significantly positive relationship between bilingualism and AD, although on the contrary two of the remaining studies find a partial relationship, where there is only a relationship in very specific circumstances (in the first one there is only one positive relationship when there is a low level of education, while in the second one there is only a relationship when more than two languages are spoken); only one of the studies found no significant relationship between bilingualism and AD. CONCLUSIONS: The aforementioned studies have found a delay at the time of diagnosis or at the onset of clinically significant symptoms, between 4.5 years and 7 years; thus, bilingualism could be considered a contributing factor of the cognitive reserve and as a consequence a probable protection factor to prevent or slow the onset of AD and its subsequent progression


Assuntos
Humanos , Doença de Alzheimer/prevenção & controle , Multilinguismo , Doença de Alzheimer/fisiopatologia , Escalas de Graduação Psiquiátrica , Psicometria , Fatores de Proteção , Reserva Cognitiva
9.
Science ; 370(6512): 61-66, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33004512

RESUMO

To provide better prevention and treatment, we need to understand the environmental and genetic risks of Alzheimer's disease (AD). However, the definition of AD has been confounded with dementia in many studies. Thus, overinterpretation of genetic findings with regard to mechanisms and drug targets may explain, in part, controversies in the field. Here, we analyze the different forms of genetic risk of AD and how these can be used to model disease. We stress the importance of studying gene variants in the right cell types and in the right pathological context. The lack of mechanistic understanding of genetic variation has become the major bottleneck in the search for new drug targets for AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Desenvolvimento de Medicamentos , Predisposição Genética para Doença , Pesquisa Médica Translacional , Doença de Alzheimer/prevenção & controle , Animais , Modelos Animais de Doenças , Variação Genética , Humanos , Camundongos , Camundongos Transgênicos , Terapia de Alvo Molecular , Risco
10.
Maturitas ; 141: 39-45, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33036701

RESUMO

OBJECTIVES: To investigate the effect of omega-3 (ω-3) polyunsaturated fatty acid supplementation and a multidomain intervention (MI) (physical activity counselling, cognitive training and nutritional advice) among community-dwelling older adults on levels of intrinsic capacity (IC), a construct recently proposed by the World Health Organization. STUDY DESIGN: Secondary analysis from the factorial-design 3-year Multidomain Alzheimer Preventive Trial (MAPT) with 1445 subjects (64.2 % female, mean age 75.3 years, SD = 4.4) randomized to one group of MI plus ω-3 (800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid/day); MI plus placebo; ω-3 supplementation alone; or placebo alone. Data collection was held between 2008 and 2014. MAIN OUTCOME MEASURES: IC domains were examined with the Geriatric Depression Scale (psychological); Short Physical Performance Battery (mobility); Z-score combining four tests (cognitive function); and handgrip strength (vitality). All domains were combined into a composite IC Z-score. RESULTS: After 3 years, IC Z-score decreased among all groups when time was considered continuous (MI plus ω-3: -0.16, 95 %CI: -0.22 to -0.10; MI alone: -0.13, 95 %CI: -0.19 to -0.07; ω-3 alone: -0.19, 95 %CI: -0.25 to -0.10; placebo: -0.20, 95 %CI: -0.26 to -0.14; all p < 0.0001). There were no significant differences between groups. In a sensitivity analysis with categorical time, significant within-group declines were first identified at 24 months for all groups. CONCLUSIONS: This trial designed to improve cognitive function was unable to find effects of the intervention on the composite IC Z-score. Further investigations are needed, especially trials providing stronger interventions (such as exercise training and a controlled diet) and also embracing the sensorial domain of IC.


Assuntos
Doença de Alzheimer/prevenção & controle , Cognição/efeitos dos fármacos , Ácidos Graxos Ômega-3/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico/análogos & derivados , Exercício Físico , Ácidos Graxos Ômega-3/farmacologia , Feminino , Avaliação Geriátrica , Força da Mão , Estilo de Vida Saudável , Humanos , Vida Independente , Estilo de Vida , Estudos Longitudinais , Masculino , Amplitude de Movimento Articular/efeitos dos fármacos
12.
Yakugaku Zasshi ; 140(9): 1129-1139, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32879245

RESUMO

The medical information and communication technology "Kibitan Health Net" was introduced as a part of the medical reconstruction assistance national project in Fukushima. However, its effect on the performance of the pharmacists has not yet been validated in community pharmacy. In this study, we investigated the usefulness of acquisition and utilization of precise medical information from diabetic patients using Kibitan Health Net. The subjects of this study were 18 patients having type 2 diabetes mellitus with a mean HbA1c level of 7.4±1.0 (%). We compared the HbA1c level captured by the pharmacists from the patients (total 72 times) with that updated on Kibitan Health Net (41 times correctly captured by the pharmacists). We next compared the HbA1c levels between the "group that could listen to accurate laboratory data" and the "group that could not listen to accurate laboratory data" using intergroup analysis. After factor analysis between the two groups, we demonstrated that the proportion of patients who could not precisely communicate laboratory results was significantly higher among the elderly population (p<0.05). Recent studies have reported that elderly diabetic patients have a higher risk of cognitive decline and Alzheimer-type dementia resulting in higher brain dysfunction. The utilization of Kibitan Health Net enabled the capturing of precise patient information. These data could make it possible to provide instruction for proper compliance and guidance for recuperation among the elderly diabetic patients, and prevent their cognitive decline due to poor glycemic control, as well as set future therapeutic goals and improve adherence.


Assuntos
Diabetes Mellitus/diagnóstico , Hemoglobina A Glicada/análise , Tecnologia da Informação , Farmacêuticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/etiologia , Doença de Alzheimer/prevenção & controle , Biomarcadores/sangue , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Complicações do Diabetes/etiologia , Complicações do Diabetes/prevenção & controle , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Farmácias , Encaminhamento e Consulta , Adulto Jovem
13.
J Prev Alzheimers Dis ; 7(4): 294-298, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32920634

RESUMO

Individuals experiencing brain aging, cognitive decline, and dementia are currently confronted with several more complex challenges due to the current Sars-Cov-2 pandemic as compared to younger and cognitively healthy people. During the first six months of the pandemic, we are experiencing critical issues related to the management of mild cognitive impairment (MCI) and dementia. The evolving, highly contagious global viral spread has created a pressure test of unprecedented proportions for the existing brain health care infrastructure and related services for management, diagnosis, treatment, and prevention. Social distancing and lock-down measures are catalyzing and accelerating a technological paradigm shift, away from a traditional model of brain healthcare focused on late symptomatic disease stages and towards optimized preventive strategies to slow brain aging and increase resilience at preclinical asymptomatic stages. Digital technologies transform global healthcare for accessible equality of opportunities in order to generate better outcomes for brain aging aligned with the paradigm of preventive medicine.


Assuntos
Doença de Alzheimer/prevenção & controle , Disfunção Cognitiva/prevenção & controle , Infecções por Coronavirus , Relações Interpessoais , Pandemias , Pneumonia Viral , Isolamento Social/psicologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Doença de Alzheimer/psicologia , Betacoronavirus , Disfunção Cognitiva/psicologia , Progressão da Doença , Humanos , Masculino , Quarentena/psicologia , Fatores de Risco , Tecnologia
14.
PLoS One ; 15(7): e0235979, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32706773

RESUMO

Alzheimer's disease (AD) is proposed to be induced by abnormal aggregation of amyloidß in the brain. Here, we designed a brain-permeable peptide nanofiber drug from a fragment of heat shock protein to suppress aggregation of the pathogenic proteins. To facilitate delivery of the nanofiber into the brain, a protein transduction domain from Drosophila Antennapedia was incorporated into the peptide sequence. The resulting nanofiber efficiently suppressed the cytotoxicity of amyloid ßby trapping amyloid ß onto its hydrophobic nanofiber surface. Moreover, the intravenously or intranasally injected nanofiber was delivered into the mouse brain, and improved the cognitive function of an Alzheimer transgenic mouse model. These results demonstrate the potential therapeutic utility of nanofibers for the treatment of AD.


Assuntos
Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/administração & dosagem , Encéfalo/metabolismo , Modelos Animais de Doenças , Transtornos da Memória/prevenção & controle , Nanofibras/administração & dosagem , Placa Amiloide/prevenção & controle , Administração Intranasal , Doença de Alzheimer/etiologia , Doença de Alzheimer/patologia , Animais , Encéfalo/efeitos dos fármacos , Feminino , Transtornos da Memória/etiologia , Transtornos da Memória/patologia , Camundongos , Camundongos Transgênicos , Nanofibras/química , Placa Amiloide/etiologia , Placa Amiloide/patologia
15.
Neurology ; 95(16): e2305-e2313, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-32665410

RESUMO

OBJECTIVE: Alzheimer disease (AD) risk factors are present throughout the lifespan. This randomized controlled trial evaluated the effectiveness of various online education strategies concerning AD risk reduction and brain health in younger populations. METHOD: High school and college students were recruited via social media (Facebook and Instagram) to join AlzU.org, an evidence-based education portal, and were randomized to 1 of 4 courses: highly interactive webinar lessons narrated by actor Seth Rogen (celebrity webinar) or a physician (doctor webinar), minimally interactive video lessons with Seth Rogen (celebrity video), or minimally interactive video lessons (control). Surveys were administered at baseline and postcourse. The primary outcome was change in knowledge of AD risk reduction assessed by pre vs post lesson quiz scores. Secondary outcomes included change in awareness of AD research, hopefulness about AD, interest in pursuing health care, willingness to volunteer, and likelihood of recommending AlzU.org. RESULT: A total of 721 participants joined. A total of 281 (38.9%) completed the course. Among college students, quiz score improvements were greater in celebrity webinar and celebrity video vs doctor webinar and control. Among high school students, no differences were found in quiz scores. In both groups, celebrity webinar, celebrity video, and doctor webinar resulted in greater improvements in awareness that nutrition and exercise may reduce AD risk vs controls. Among college students, celebrity webinar and celebrity video group participants felt more hopeful about the future of AD and more likely to recommend AlzU.org vs doctor webinar and control participants. Among college students, celebrity webinar, celebrity video, and doctor webinar participants were more willing to volunteer for AD causes and pursue health care careers vs controls. CONCLUSION: Online education involving a celebrity may be an effective strategy for educating college students about AD risk reduction strategies. Further studies are warranted in high school students.


Assuntos
Doença de Alzheimer/prevenção & controle , Educação a Distância/métodos , Educação em Saúde/métodos , Promoção da Saúde/métodos , Estudantes/psicologia , Adolescente , Adulto , Pessoas Famosas , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Internet , Masculino , Comportamento de Redução do Risco , Adulto Jovem
16.
Am J Geriatr Psychiatry ; 28(9): 913-920, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32507686

RESUMO

Advances in treating and preventing Alzheimer disease and other neurocognitive disorders of aging arise from rigorous preclinical and clinical research, with randomized controlled treatment trials as the last and definitive test. The COVID-19 pandemic has greatly disrupted ongoing interventional studies and researchers are scrambling to find ways to safely continue this critical work amidst rapidly shifting guidelines from sponsors, institutions, and state and federal guidelines. Here the authors describe novel approaches and work-flow adaptations to study visits, drug delivery and interim and endpoint safety and outcomes assessments to avoid sacrificing years of preparation and substantial financial investments, to work in the best interest of participants and their caregivers, and to continue on the path toward discovering disease-modifying treatments for the millions of individuals impacted by major neurocognitive disorders.


Assuntos
Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Infecções por Coronavirus/prevenção & controle , Transtornos Neurocognitivos/tratamento farmacológico , Transtornos Neurocognitivos/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Idoso , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/prevenção & controle , Betacoronavirus , Guias como Assunto , Humanos
17.
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
18.
Cochrane Database Syst Rev ; 4: CD011459, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32352165

RESUMO

BACKGROUND: Dementia is a worldwide concern. Its global prevalence is increasing. At present, there is no medication licensed to prevent or delay the onset of dementia. Inflammation has been suggested as a key factor in dementia pathogenesis. Therefore, medications with anti-inflammatory properties could be beneficial for dementia prevention. OBJECTIVES: To evaluate the effectiveness and adverse effects of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) for the primary or secondary prevention of dementia. SEARCH METHODS: We searched ALOIS, the specialised register of the Cochrane Dementia and Cognitive Improvement Group up to 9 January 2020. ALOIS contains records of clinical trials identified from monthly searches of several major healthcare databases, trial registries and grey literature sources. We ran additional searches across MEDLINE (OvidSP), Embase (OvidSP) and six other databases to ensure that the searches were as comprehensive and up-to-date as possible. We also reviewed citations of reference lists of included studies. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing aspirin or other NSAIDs with placebo for the primary or secondary prevention of dementia. We included trials with cognitively healthy participants (primary prevention) or participants with mild cognitive impairment (MCI) or cognitive complaints (secondary prevention). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the strength of evidence for each outcome using the GRADE approach. MAIN RESULTS: We included four RCTs with 23,187 participants. Because of the diversity of these trials, we did not combine data to give summary estimates, but presented a narrative description of the evidence. We identified one trial (19,114 participants) comparing low-dose aspirin (100 mg once daily) to placebo. Participants were aged 70 years or older with no history of dementia, cardiovascular disease or physical disability. Interim analysis indicated no significant treatment effect and the trial was terminated slightly early after a median of 4.7 years' follow-up. There was no evidence of a difference in incidence of dementia between aspirin and placebo groups (risk ratio (RR) 0.98, 95% CI 0.83 to 1.15; high-certainty evidence). Participants allocated aspirin had higher rates of major bleeding (RR 1.37, 95% CI 1.17 to 1.60, high-certainty evidence) and slightly higher mortality (RR 1.14, 95% CI 1.01 to 1.28; high-certainty evidence). There was no evidence of a difference in activities of daily living between groups (RR 0.84, 95% CI 0.70 to 1.02; high-certainty evidence). We identified three trials comparing non-aspirin NSAIDs to placebo. All three trials were terminated early due to adverse events associated with NSAIDs reported in other trials. One trial (2528 participants) investigated the cyclo-oxygenase-2 (COX-2) inhibitor celecoxib (200 mg twice daily) and the non-selective NSAID naproxen (220 mg twice daily) for preventing dementia in cognitively healthy older adults with a family history of Alzheimer's disease (AD). Median follow-up was 734 days. Combining both NSAID treatment arms, there was no evidence of a difference in the incidence of AD between participants allocated NSAIDs and those allocated placebo (RR 1.91, 95% CI 0.89 to 4.10; moderate-certainty evidence). There was also no evidence of a difference in rates of myocardial infarction (RR 1.21, 95% CI 0.61 to 2.40), stroke (RR 1.82, 95% CI 0.76 to 4.37) or mortality (RR 1.37, 95% CI 0.78 to 2.43) between treatment groups (all moderate-certainty evidence). One trial (88 participants) assessed the effectiveness of celecoxib (200 mg or 400 mg daily) in delaying cognitive decline in participants aged 40 to 81 years with mild age-related memory loss but normal memory performance scores. Mean duration of follow-up was 17.6 months in the celecoxib group and 18.1 months in the placebo group. There was no evidence of a difference between groups in test scores in any of six cognitive domains. Participants allocated celecoxib experienced more gastrointestinal adverse events than those allocated placebo (RR 2.66, 95% CI 1.05 to 6.75; low-certainty evidence). One trial (1457 participants) assessed the effectiveness of the COX-2 inhibitor rofecoxib (25 mg once daily) in delaying or preventing a diagnosis of AD in participants with MCI. Median duration of study participation was 115 weeks in the rofecoxib group and 130 weeks in the placebo group. There was a higher incidence of AD in the rofecoxib than the placebo group (RR 1.32, 95% CI 1.01 to 1.72; moderate-certainty evidence). There was no evidence of a difference between groups in cardiovascular adverse events (RR 1.07, 95% CI 0.68 to 1.66; moderate-certainty evidence) or mortality (RR 1.62, 95% CI 0.85 to 3.05; moderate-certainty evidence). Participants allocated rofecoxib had more upper gastrointestinal adverse events (RR 3.53, 95% CI 1.17 to 10.68; moderate-certainty evidence). Reported annual mean difference scores showed no evidence of a difference between groups in activities of daily living (year 1: no data available; year 2: 0.0, 95% CI -0.1 to 0.2; year 3: 0.1, 95% CI -0.1 to 0.3; year 4: 0.1, 95% CI -0.1 to 0.4; moderate-certainty evidence). AUTHORS' CONCLUSIONS: There is no evidence to support the use of low-dose aspirin or other NSAIDs of any class (celecoxib, rofecoxib or naproxen) for the prevention of dementia, but there was evidence of harm. Although there were limitations in the available evidence, it seems unlikely that there is any need for further trials of low-dose aspirin for dementia prevention. If future studies of NSAIDs for dementia prevention are planned, they will need to be cognisant of the safety concerns arising from the existing studies.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Demência/prevenção & controle , Atividades Cotidianas , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/prevenção & controle , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Celecoxib/administração & dosagem , Celecoxib/efeitos adversos , Celecoxib/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Demência/epidemiologia , Demência/mortalidade , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Incidência , Lactonas/uso terapêutico , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Naproxeno/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/epidemiologia , Sulfonas/uso terapêutico
19.
Neurobiol Aging ; 92: 114-134, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32417748

RESUMO

Evidence suggests that changes in intestinal microbiota may affect the central nervous system. However, it is unclear whether alteration of intestinal microbiota affects progression of Alzheimer's disease (AD). To understand this, wild-type control (C57BL/6) mice were compared with the AppNL-G-F model of disease. We used probiotic supplementation to manipulate the gut microbiota. Fecal samples were collected for microbiota profiling. To study brain and intestinal inflammation, biochemical and histological analyses were performed. Altered metabolic pathways were examined by quantifying eicosanoid and bile acid profiles in the brain and serum using ultraperformance liquid chromatography-tandem mass spectrometry. We observed that brain pathology was associated with intestinal dysbiosis and increased intestinal inflammation and leakiness in AppNL-G-F mice. Probiotic supplementation significantly decreased intestinal inflammation and gut permeability with minimal effect on amyloid-ß, cytokine, or gliosis levels in the brain. Concentrations of several bile acids and prostaglandins were altered in the serum and brain because of AD or probiotic supplementation. Our study characterizes intestinal dysfunction in an AD mouse model and the potential of probiotic intervention to ameliorate this condition.


Assuntos
Doença de Alzheimer/etiologia , Doença de Alzheimer/microbiologia , Encéfalo/metabolismo , Encéfalo/patologia , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/administração & dosagem , Probióticos/farmacologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Eicosanoides/metabolismo , Feminino , Gliose , Inflamação , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
20.
PLoS One ; 15(4): e0221985, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32324741

RESUMO

BACKGROUND: Studies have suggested associations between self-reported engagement in health behaviors and reduced risk of cognitive decline. Most studies explore these relationships using one health behavior, often cross-sectionally or with dementia as the outcome. In this study, we explored whether several individual self-reported health behaviors were associated with cognitive decline when considered simultaneously, using data from the Wisconsin Registry for Alzheimer's Prevention (WRAP), an Alzheimer's disease risk-enriched cohort who were non-demented and in late midlife at baseline. METHOD: We analyzed longitudinal cognitive data from 828 participants in WRAP, with a mean age at baseline cognitive assessment of 57 (range = 36-78, sd = 6.8) and an average of 6.3 years (standard deviation = 1.9, range = 2-10) of follow-up. The primary outcome was a multi-domain cognitive composite, and secondary outcomes were immediate/delayed memory and executive function composites. Predictors of interest were self-reported measures of physical activity, cognitive activity, adherence to a Mediterranean-style diet (MIND), and interactions with each other and age. We conducted linear mixed effects analyses within an Information-theoretic (IT) model averaging (MA) approach on a set of models including covariates and combinations of these 2- and 3-way interactions. The IT approach was selected due to the large number of interactions of interest and to avoid pitfalls of traditional model selection approaches. RESULTS: Model-averaged results identified no significant self-reported health behavior*age interactions in relationship to the primary composite outcome. In secondary outcomes, higher MIND diet scores associated with slower decline in executive function. Men showed faster decline than women on delayed memory, independent of health behaviors. There were no other significant interactions among any other health behaviors and cognitive trajectories. CONCLUSIONS: When multiple covariates and health behaviors were considered simultaneously, there were limited weak associations with cognitive decline in this age range. These results may be explained alone or in combination by three alternative explanations: 1) the range of cognitive decline is in middle age is too small to observe relationships with health behaviors, 2) the putative associations of these health behaviors on cognition may not be robust in this age range, or 3) the self-reported measures of the health behaviors may not be optimal for predicting cognitive decline. More study may be needed that incorporates sensitive measures of health behaviors, AD biomarker profiles, and/or other disease comorbidities.


Assuntos
Doença de Alzheimer/epidemiologia , Cognição , Adulto , Idoso , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/prevenção & controle , Função Executiva , Exercício Físico , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Autorrelato , Wisconsin/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...