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A identificação de biomarcadores específicos para doenças neurodegenerativas do tipo demências, é um dos principais objetivos da investigação clínica atual, sobretudo porque estes são cruciais no diagnóstico precoce, diferencial e monitorização da doença. Este trabalho tem como objetivo geral avaliar e identificar a relação entre os biomarcadores de sangue (e.g., IL- 1B, TNF- α, AB1-40, AB 1-42) e o perfil neuropsicológico (e.g., memória, atenção, linguagem, funções executivas) nas demências. A melhor compreensão desta relação, poderá contribuir para um diagnóstico precoce e monitorização de progressão da demência. No presente estudo, foi realizado uma revisão sistemática da literatura utilizando as bases de dados PubMED, LILACS, EmBASE, BMC, CINAHL, World Wide Science e Google Scholar. Para a recolha de dados, seguiu-se as diretrizes do PRISMA. As palavras chaves utilizadas para a pesquisa e seleção dos artigos foram: “blood-based biomarkers” OR “plasma biomarkers” OR “dementia” OR “alzheimer” OR “neuropsychological” OR “neuropsychological evaluation” OR “peripherical biomarkers” OR “TNF-α” OR “IL-1B” OR “Aβ 1-40” OR “Aβ 1-42”. Os termos de pesquisa foram aplicados em diferentes combinações. Antes da leitura e avaliação qualitativa dos artigos, foi aplicado um método de seleção baseado nos critérios de inclusão/exclusão. Nos critérios de inclusão integraram trabalhos de investigação e casos clínicos em inglês. Por outro lado, foram excluídos artigos incompletos, dissertações, teses e artigos que não fossem compatíveis com o tema abordado. Neste sentido, encontraram-se 10 artigos elegíveis, essencialmente, experimentais que possuíam a recolha e análise de dados relativos a um ou mais biomarcadores periféricos e medidas neuropsicológicas. Nos artigos selecionados, 80% deles apresentaram algum tipo de associação ou relação entre as variáveis cognitivas e os biomarcadores analisados. As proteínas β-amiloide (Aβ) foram associadas ao Declínio Cognitivo Geral (DCG) (30%), à memória (20%), à cognição e à função executiva (10%). A Luz de neurofilamento (NfL) foi associado ao DCG (10%), à memória e ao domínio da linguagem (10%). A P-tau foi associada à memória (20%), cognição global, atenção, capacidade; e ao domínio da linguagem e DCG (10%). O biomarcador PTX3 foi associado à mudança na cognição, ao declínio na velocidade psicomotora e à função executiva (10%). A IL-2 e IL-8 foram associadas à memória e linguagem (10%). A ET-1 foi associada ao declínio da linguagem e velocidade psicomotora (10%). Além disso, verificou-se que o método de avaliação “Composto Cognitivo Pré-clínico de Alzheimer (CCPA) ” é melhor em relação ao MEEM para verificar associações com o DCG e as Aβ42/Aβ40. Por fim, conclui-se que os biomarcadores plasmáticos amiloides, tau patologia, NfL, PTX3, IL-2 e IL-8 associados à avaliação do DCG, memória e à linguagem podem ser indicativos para identificação precoce para doenças demenciais. Esta pesquisa apresentou limitações principalmente na interpretação da relação entre biomarcadores neuropsicológicos e biomarcadores. Na análise dos diferentes estudos observou-se que o tamanho amostral, a idade, as raças podem interferir nos resultados, não permitindo generalizar para toda população os resultados que foram obtidos pelos autores em seus estudos. Por outro lado, e de acordo com o salientado por vários autores, a heterogeneidade da amostra e falta de dados como: passado cognitivo, estilo de vida e características premorbidas dos participantes constitui um dos principais problemas para a possibilidade de generalizar os resultados.
The identification of specific biomarkers for neurodegenerative diseases such as dementia is one of the main objectives of current clinical research, mainly because these are crucial in the early, differential diagnosis and monitoring of the disease. This study aims to evaluate and identify the relationship between blood biomarkers (e.g., IL-1B, TNF-α, AB1-40, AB 1-42) and the neuropsychological profile (e.g., memory, attention, language, executive) in dementias. A better understanding of this relationship may contribute to an early diagnosis and monitoring of the progression of dementia. In the present study, a systematic literature review was performed using PubMED, LILACS, EmBASE, BMC, CINAHL, World Wide Science e Google Scholar databases. For data collection, the PRISMA guidelines were followed. The keywords used for the research and selection of articles were: “blood-based biomarkers” OR “plasma biomarkers” OR “dementia” OR “alzheimer” OR “neuropsychological” OR “neuropsychological evaluation” OR “peripherical biomarkers” OR “TNF- α” OR “IL-1B” OR “Aβ 1-40” OR “Aβ 1-42”. Search terms were applied in different combinations. Before reading and qualitatively evaluating the articles, a selection method based on inclusion/exclusion criteria was applied. The inclusion criteria included research works and clinical cases in English. On the other hand, incomplete articles, dissertations, theses and articles that were not compatible with the topic addressed were excluded. In this sense, 10 eligible articles were found, essentially experimental, which had the collection and analysis of data related to one or more peripheral biomarkers and neuropsychological measures. In the selected articles, 80% of them showed some type of association or relationship between the cognitive variables and the analyzed biomarkers. β- amyloid (Aβ) proteins were associated with General Cognitive Decline (GCD) (30%), memory (20%), cognition and executive function (10%). Neurofilament lumen (NfL) was associated with GCD (10%), memory and language mastery (10%). P-tau was associated with memory (20%), global cognition, attention, ability; and to the domain of language and DCG (10%). The PTX3 biomarker was associated with change in cognition, decline in psychomotor speed and executive function (10%). IL-2 and IL-8 were associated with memory and language (10%). ET-1 was associated with language decline and psychomotor speed (10%). Furthermore, the assessment method “Cognitive Preclinical Alzheimer's Compound (CCPA)” was found to be better over the MMSE to verify associations with DCG and Aβ42/Aβ40. Finally, it is concluded that plasma amyloid biomarkers, tau pathology, NfL, PTX3, IL-2 and IL-8 associated with the assessment of GCD, memory and language may be indicative for early identification of dementia diseases. This research presented limitations mainly in the interpretation of the relationship between neuropsychological biomarkers and biomarkers. In the analysis of the different studies, it was observed that the sample size, age, race can interfere in the results, not allowing to generalize to the entire population the results that were obtained by the authors in their studies. On the other hand, and as highlighted by several authors, the heterogeneity of the sample and lack of data such as: cognitive background, lifestyle and premorbid characteristics of the participants constitutes one of the main problems for the possibility of generalizing the results.
The identification of specific biomarkers for neurodegenerative diseases such as dementia is one of the main objectives of current clinical research, mainly because these are crucial in the early, differential diagnosis and monitoring of the disease. This study aims to evaluate and identify the relationship between blood biomarkers (e.g., IL-1B, TNF-α, AB1-40, AB 1-42) and the neuropsychological profile (e.g., memory, attention, language, executive) in dementias. A better understanding of this relationship may contribute to an early diagnosis and monitoring of the progression of dementia. In the present study, a systematic literature review was performed using PubMED, LILACS, EmBASE, BMC, CINAHL, World Wide Science e Google Scholar databases. For data collection, the PRISMA guidelines were followed. The keywords used for the research and selection of articles were: “blood-based biomarkers” OR “plasma biomarkers” OR “dementia” OR “alzheimer” OR “neuropsychological” OR “neuropsychological evaluation” OR “peripherical biomarkers” OR “TNF- α” OR “IL-1B” OR “Aβ 1-40” OR “Aβ 1-42”. Search terms were applied in different combinations. Before reading and qualitatively evaluating the articles, a selection method based on inclusion/exclusion criteria was applied. The inclusion criteria included research works and clinical cases in English. On the other hand, incomplete articles, dissertations, theses and articles that were not compatible with the topic addressed were excluded. In this sense, 10 eligible articles were found, essentially experimental, which had the collection and analysis of data related to one or more peripheral biomarkers and neuropsychological measures. In the selected articles, 80% of them showed some type of association or relationship between the cognitive variables and the analyzed biomarkers. β- amyloid (Aβ) proteins were associated with General Cognitive Decline (GCD) (30%), memory (20%), cognition and executive function (10%). Neurofilament lumen (NfL) was associated with GCD (10%), memory and language mastery (10%). P-tau was associated with memory (20%), global cognition, attention, ability; and to the domain of language and DCG (10%). The PTX3 biomarker was associated with change in cognition, decline in psychomotor speed and executive function (10%). IL-2 and IL-8 were associated with memory and language (10%). ET-1 was associated with language decline and psychomotor speed (10%). Furthermore, the assessment method “Cognitive Preclinical Alzheimer's Compound (CCPA)” was found to be better over the MMSE to verify associations with DCG and Aβ42/Aβ40. Finally, it is concluded that plasma amyloid biomarkers, tau pathology, NfL, PTX3, IL-2 and IL-8 associated with the assessment of GCD, memory and language may be indicative for early identification of dementia diseases. This research presented limitations mainly in the interpretation of the relationship between neuropsychological biomarkers and biomarkers. In the analysis of the different studies, it was observed that the sample size, age, race can interfere in the results, not allowing to generalize to the entire population the results that were obtained by the authors in their studies. On the other hand, and as highlighted by several authors, the heterogeneity of the sample and lack of data such as: cognitive background, lifestyle and premorbid characteristics of the participants constitutes one of the main problems for the possibility of generalizing the results.
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Keywords
Biomarcadores periféricos Demência Perfil neuropsicológico Revisão sistemática da literatura Peripheral biomarkers Dementia Neuropsychological profile Systematic literature review