Alzheimer's Disease In Brazil Research Articles

GWAS-Top Polymorphisms Associated With Late-Onset Alzheimer Disease in Brazil: Pointing Out Possible New Culprits Among Non-Coding RNAs.

Several genome-wide association studies (GWAS) have been carried out with late-onset Alzheimer’s disease (LOAD), mainly in European and Asian populations. Different polymorphisms were associated, but several of them without a functional explanation. GWAS are fundamental for identifying loci associated with diseases, although they often do not point to causal polymorphisms. In this sense, functional investigations are a fundamental tool for discovering causality, although the failure of this validation does not necessarily indicate a non-causality. Furthermore, the allele frequency of associated genetic variants may vary widely between populations, requiring replication of these associations in other ethnicities. In this sense, our study sought to replicate in 150 AD patients and 114 elderly controls from the South Brazilian population 18 single-nucleotide polymorphisms (SNPs) associated with AD in European GWAS, with further functional investigation using bioinformatic tools for the associated SNPs. Of the 18 SNPs investigated, only four were associated in our population: rs769449 (APOE), rs10838725 (CELF1), rs6733839, and rs744373 (BIN1–CYP27C1). We identified 54 variants in linkage disequilibrium (LD) with the associated SNPs, most of which act as expression or splicing quantitative trait loci (eQTLs/sQTLs) in genes previously associated with AD or with a possible functional role in the disease, such as CELF1, MADD, MYBPC3, NR1H3, NUP160, SPI1, and TOMM40. Interestingly, eight of these variants are located within long non-coding RNA (lncRNA) genes that have not been previously investigated regarding AD. Some of these polymorphisms can result in changes in these lncRNAs’ secondary structures, leading to either loss or gain of microRNA (miRNA)-binding sites, deregulating downstream pathways. Our pioneering work not only replicated LOAD association with polymorphisms not yet associated in the Brazilian population but also identified six possible lncRNAs that may interfere in LOAD development. The results lead us to emphasize the importance of functional exploration of associations found in large-scale association studies in different populations to base personalized and inclusive medicine in the future.

Who are the people with Alzheimer's disease in Brazil? Findings from the Brazilian Longitudinal Study of Aging.

To describe the socioeconomic, behavioral, clinical, and health-related characteristics of Brazilian older adults with Alzheimer's disease (AD). Baseline data from the Brazilian Longitudinal Study of Aging were analyzed. This nationwide survey interviewed 9,412 adults aged at least 50 years. Self-reported medical diagnosis of AD and exposure variables (sociodemographic, clinical, behavioral, and health-related) were assessed by face-to-face questionnaire-based interview. Multivariate analyses accounted for possible confounding factors, and values were reported in prevalence ratio (PR) and 95% confidence interval (95%CI). Participants with AD have important demographic differences compared with older non-AD participants such as low education level and retirement. Clinically, these patients reported more medical appointments, falls, and higher frequency and duration of hospitalizations compared with non-AD participants. These characteristics may be related to worse physical and mental health observed in this population. Indeed, two out of five older adults with AD in Brazil reported always feeling lonely, while two out of three said they felt depressed or sad much of the time. Adjusted analyses showed that patients with AD were 95% (95%CI 1.08 - 3.50) more likely to be hospitalized in a year compared with non-AD older adults. People with AD in Brazil were more likely to be diagnosed with diabetes (PR = 1.83 [95%CI 1.08 - 3.12]), depression (PR = 3.07% [95%CI 1.63 - 5.79]), Parkinson's disease (PR = 17.63 [95%CI 6.99 - 44.51]), and stroke (PR = 3.55 [95%CI 1.90 - 6.67]) compared with non-AD participants. Older adults with AD in Brazil reported impaired physical and mental health compared with the non-AD population.

Cost-effectiveness analysis of the treatment of mild and moderate Alzheimer's disease in Brazil.

Objective:To perform a cost-effectiveness analysis of donepezil and rivastigmine therapy for mild and moderate Alzheimer’s disease (AD) from the perspective of the Brazilian Unified Health System.Method:A hypothetical cohort of 1,000 individuals of both sexes, aged >65 years, and diagnosed with AD was simulated using a Markov model. The time horizon was 10 years, with 1-year cycles. A deterministic and probabilistic sensitivity analysis was performed.Results:For mild AD, the study showed an increase in quality-adjusted life years (QALYs) of 0.61 QALY/21,907.38 Brazilian reais (BRL) for patients treated with donepezil and 0.58 QALY/BRL 24,683.33 for patients treated with rivastigmine. In the moderate AD group, QALY increases of 0.05/BRL 27,414.96 were observed for patients treated with donepezil and 0.06/BRL 34,222.96 for patients treated with rivastigmine.Conclusions:The findings of this study contradict the standard of care for mild and moderate AD in Brazil, which is based on rivastigmine. A pharmacological treatment option based on current Brazilian clinical practice guidelines for AD suggests that rivastigmine is less cost-effective (0.39 QALY/BRL 32,685.77) than donepezil. Probabilistic analysis indicates that donepezil is the most cost-effective treatment for mild and moderate AD.

Alzheimer's disease diagnosis disclosure in Brazil: a survey of specialized physicians' current practice and attitudes

There is little, though growing, interest in the research area of attitudes held among physicians towards disclosing the diagnosis of dementia and Alzheimer's disease (AD), or the current practice on AD disclosure. This study aimed to investigate the practice and attitudes of specialized physicians towards AD diagnosis disclosure in Brazil. A questionnaire was devised to survey the current practice and attitudes regarding diagnosis disclosure of AD in Brazil and sent to specialized physicians (170 geriatricians, 300 neurologists and 500 psychiatrists) by electronic mail. From 970 potential respondents, 181 physicians who usually attend AD patients returned the questionnaire. There were no significant differences between the three specialties regarding the frequency with which they informed patients of their AD diagnosis (p = 0.17). The results revealed that only 44.8% of the physicians would regularly inform the patient of the diagnosis, although 85.6% of these use clear terminology. Despite their usual practice, 76.8% would want to know their diagnosis if they themselves were affected by AD. Disclosure of AD diagnosis is not common among specialized physicians in Brazil and different factors are involved. In the clinical context, discussion on advantages of diagnosis disclosure can be useful for improving the care of AD patients and their families.

Diagnóstico de doença de Alzheimer no Brasil: critérios diagnósticos e exames complementares. Recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia

This panel had the objective of recommending evidence-based guidelines for the clinical diagnosis of Alzheimer's disease (AD) in Brazil. Guidelines from other countries and papers on the diagnosis of AD in Brazil were systematically evaluated in a thorough research of PUBMED and LILACS databases. The panel concluded that dementia diagnosis should be based on the DSM criteria and AD diagnosis, on the McKhann et al. criteria (NINCDS-ADRDA). The recommended auxiliary tests are: blood cell count, blood urea nitrogen, serum levels of creatinine, free-thyroxine, thyroid-stimulant hormone, albumin, hepatic enzymes, vitamin B12 and calcium, serological tests for syphilis and, for those aged less than 60 years, serological tests for HIV. Cerebrospinal fluid examination is recommended in special situations. Computed tomography (or preferentially magnetic resonance imaging, when available) is mandatory and has the main objective of excluding other diseases. SPECT and EEG are optional diagnostic methods.

Diagnóstico de doença de Alzheimer no Brasil: avaliação cognitiva e funcional. Recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia

As heterogeneidades educacional e cultural da população brasileira condicionam características peculiares ao diagnóstico da doença de Alzheimer (DA) no Brasil. Este consenso teve o objetivo de recomendar condutas baseadas em evidências para este diagnóstico. Foram avaliados sistematicamente artigos sobre o diagnóstico de DA no Brasil disponíveis no PUBMED ou LILACS. Para a avaliação cognitiva global recomendou-se o Mini-Exame do Estado Mental; avaliação da memória: recordação tardia do CERAD ou de objetos apresentados como figuras; atenção: teste de trilhas ou extensão de dígitos; linguagem: testes de nomeação de Boston, do ADAS-Cog ou do NEUROPSI; funções executivas: fluência verbal ou desenho do relógio; conceituação e abstração: semelhanças do CAMDEX ou do NEUROPSI; habilidades construtivas: desenhos do CERAD. Para avaliação funcional recomendou-se o IQCODE , o questionário de Pfeffer ou a escala Bayer de atividades da vida diária. Recomendou-se a utilização combinada de instrumentos de avaliação cognitiva e de escalas de avaliação funcional.