Challenges in the diagnosis of dementia: insights from the United Kingdom-Brazil Dementia Workshop.

In July 2019, a group of multidisciplinary dementia researchers from Brazil and the United Kingdom (UK) met in the city of Belo Horizonte, Minas Gerais, Brazil, to discuss and propose solutions to current challenges faced in the diagnosis, public perception and care of dementia. Here we summarize the outcomes from the workshop addressing challenges in diagnosis. Brazil faces a major problem in dementia underdiagnosis, particularly involving the population in an adverse socioeconomic context. There is poor availability of resources and specialists, and the knowledge of general practitioners and other healthcare professionals is far from satisfactory. Low education level is a further obstacle in diagnosing dementia, as the most commonly used screening tests are not designed to evaluate this population. Patients and their families must overcome the stigma of a diagnosis of dementia, which is still prevalent in Brazil and increases the burden of this condition. Whilst the UK has greater resources, dedicated memory services and a National Dementia Strategy plan, the National Health Service (NHS) has limited funding. Therefore, some challenges regarding diagnosis are common across both countries. The authors suggest possible solutions to confront these, with the goal of improving assessment and recognition of dementia and reducing misdiagnosis.

Em julho de 2019, um grupo multidisciplinar de pesquisadores em demência do Brasil e do Reino Unido se reuniu em Belo Horizonte para discutir e propor soluções para os desafios no diagnóstico, percepção pública e tratamento dessa condição. Neste artigo, sintetizamos as conclusões do workshop sobre os desafios no diagnóstico de demência. O Brasil enfrenta um grande problema no subdiagnóstico de demência, principalmente entre a população em condições socioeconômicas adversas. Há pouca disponibilidade de recursos e de especialistas e o conhecimento de médicos generalistas e de outros profissionais de saúde é pouco abrangente. Baixa escolaridade é também um obstáculo no diagnóstico de demência, uma vez que os testes de rastreio mais utilizados na prática clínica não são estruturados para avaliar a população com esse perfil. Os pacientes com demência e suas famílias ainda têm que superar o estigma do diagnóstico, que é ainda muito prevalente no Brasil e colabora para a piora da qualidade de vida. O Reino Unido, por outro lado, dispõe de mais recursos financeiros e de pessoal, possui serviços dedicados à avaliação de problemas de memória e um plano estratégico nacional para demência. Contudo, o National Health Service (NHS) tem verbas limitadas, o que faz com que alguns dos desafios no diagnóstico de demência sejam comuns aos dois países. Os autores sugerem possíveis soluções para enfrentá-los, com o objetivo de melhorar a avaliação e o reconhecimento da demência e reduzir os erros de diagnóstico.

Challenges in the diagnosis of dementia: insights from the United Kingdom-Brazil Dementia Workshop / Desafios no diagnóstico de demência: conclusões do Workshop de Demência Reino Unido-Brasil

ABSTRACT. In July 2019, a group of multidisciplinary dementia researchers from Brazil and the United Kingdom (UK) met in the city of Belo Horizonte, Minas Gerais, Brazil, to discuss and propose solutions to current challenges faced in the diagnosis, public perception and care of dementia. Here we summarize the outcomes from the workshop addressing challenges in diagnosis. Brazil faces a major problem in dementia underdiagnosis, particularly involving the population in an adverse socioeconomic context. There is poor availability of resources and specialists, and the knowledge of general practitioners and other healthcare professionals is far from satisfactory. Low education level is a further obstacle in diagnosing dementia, as the most commonly used screening tests are not designed to evaluate this population. Patients and their families must overcome the stigma of a diagnosis of dementia, which is still prevalent in Brazil and increases the burden of this condition. Whilst the UK has greater resources, dedicated memory services and a National Dementia Strategy plan, the National Health Service (NHS) has limited funding. Therefore, some challenges regarding diagnosis are common across both countries. The authors suggest possible solutions to confront these, with the goal of improving assessment and recognition of dementia and reducing misdiagnosis.

RESUMO. Em julho de 2019, um grupo multidisciplinar de pesquisadores em demência do Brasil e do Reino Unido se reuniu em Belo Horizonte para discutir e propor soluções para os desafios no diagnóstico, percepção pública e tratamento dessa condição. Neste artigo, sintetizamos as conclusões do workshop sobre os desafios no diagnóstico de demência. O Brasil enfrenta um grande problema no subdiagnóstico de demência, principalmente entre a população em condições socioeconômicas adversas. Há pouca disponibilidade de recursos e de especialistas e o conhecimento de médicos generalistas e de outros profissionais de saúde é pouco abrangente. Baixa escolaridade é também um obstáculo no diagnóstico de demência, uma vez que os testes de rastreio mais utilizados na prática clínica não são estruturados para avaliar a população com esse perfil. Os pacientes com demência e suas famílias ainda têm que superar o estigma do diagnóstico, que é ainda muito prevalente no Brasil e colabora para a piora da qualidade de vida. O Reino Unido, por outro lado, dispõe de mais recursos financeiros e de pessoal, possui serviços dedicados à avaliação de problemas de memória e um plano estratégico nacional para demência. Contudo, o National Health Service (NHS) tem verbas limitadas, o que faz com que alguns dos desafios no diagnóstico de demência sejam comuns aos dois países. Os autores sugerem possíveis soluções para enfrentá-los, com o objetivo de melhorar a avaliação e o reconhecimento da demência e reduzir os erros de diagnóstico.

Protein levels of ADAM10, BACE1, and PSEN1 in platelets and leukocytes of Alzheimer's disease patients.

The clinical diagnosis of Alzheimer's disease (AD) is a probabilistic formulation that may lack accuracy particularly at early stages of the dementing process. Abnormalities in amyloid-beta precursor protein (APP) metabolism and in the level of APP secretases have been demonstrated in platelets, and to a lesser extent in leukocytes, of AD patients, with conflicting results. The aim of the present study was to compare the protein level of the APP secretases A-disintegrin and metalloprotease 10 (ADAM10), Beta-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PSEN1) in platelets and leukocytes from 20 non-medicated older adults with AD and 20 healthy elders, and to determine the potential use of these biomarkers to discriminate cases of AD from controls. The protein levels of all APP secretases were significantly higher in platelets compared to leukocytes. We found statistically a significant decrease in ADAM10 (52.5%, p < 0.0001) and PSEN1 (32%, p = 0.02) in platelets from AD patients compared to controls, but not in leukocytes. Combining all three secretases to generate receiver-operating characteristic (ROC) curves, we found a good discriminatory effect (AD vs. controls) when using platelets (the area under the curve-AUC-0.90, sensitivity 88.9%, specificity 66.7%, p = 0.003), but not in leukocytes (AUC 0.65, sensitivity 77.8%, specificity 50.0%, p = 0.2). Our findings indicate that platelets represent a better biological matrix than leukocytes to address the peripheral level of APP secretases. In addition, combining the protein level of ADAM10, BACE1, and PSEN1 in platelets, yielded a good accuracy to discriminate AD from controls.

Protein Expression of BACE1 is Downregulated by Donepezil in Alzheimer's Disease Platelets.

BACKGROUND: Abnormal amyloid-ß protein precursor (AßPP) metabolism is a key feature of Alzheimer's disease (AD). Platelets contain most of the enzymatic machinery required for AßPP processing, and correlates of intracerebral abnormalities have been demonstrated in platelets of patients with AD. Thus, AßPP-related molecules in platelets may be regarded as peripheral markers of AD. OBJECTIVE: We sought to determine the protein expression of the AßPP secretases (ADAM10, BACE1, and PSEN1) and AßPP ratio in platelets of patients with mild or moderate AD compared to healthy controls. We further determined whether the protein expression of these markers might be modified by chronic treatment with donepezil. METHODS: Platelet samples were obtained from patients and controls at baseline and after 3 and 6 months of continuous treatment with therapeutic doses of donepezil. The protein expression of platelet markers was determined by western blotting. RESULTS: AD patients had a significant decrease in AßPP ratio, ADAM10, and PSEN1 compared to controls at baseline, but these differences were not modified by the treatment. Nonetheless, a significant reduction in the protein expression of BACE1 was observed in patients treated with donepezil for 6 months. CONCLUSION: Our results corroborate previous findings from our group and others of decreased AßPP ratio and protein expression of ADAM10 in AD. We further show that PSEN1 is decreased in AD platelets, and that the protein expression of BACE1 is downregulated by chronic treatment with donepezil. This effect may be interpreted as evidence of disease modification.

ADAM10 as a biomarker for Alzheimer's disease: a study with Brazilian elderly.

Alzheimer's disease (AD) is the most common cause of dementia in people above age 65. Platelet studies with ADAM10 have shown that its expression is reduced in AD patients. The aim of this research was to compare the platelet levels of ADAM10 protein in two Brazilian elderly groups, considering the stages of the disease. The SDS-PAGE technique followed by Western blotting was used. Data were analyzed using comparison, correlation and association statistical methods. The results showed reduced platelet ADAM10 levels in AD elderly compared to non-AD subjects. The disease progression intensified this reduction. ADAM10 was the only statistically significant variable (p = 0.01) to increase the AD occurrence probability. The cutoff value of 0.4212 in the receiver operating characteristic curve captured sensitivity and specificity of 70 and 80.77%, respectively. Together with other clinical criteria, ADAM10 seems to be a relevant biomarker tool for early and accurate AD diagnosis.