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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2020.tde-10022021-103949
Document
Author
Full name
Renata Ferreira Rosa
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2020
Supervisor
Committee
Andrade, Danieli Castro Oliveira de (President)
Appenzeller, Simone
Borba Neto, Eduardo Ferreira
Ribeiro, Ana Cristina de Medeiros
Title in Portuguese
Disfunção cognitiva e níveis séricos do fator neurotrófico derivado do cérebro (BDNF) na síndrome antifosfolípide primária
Keywords in Portuguese
Anticorpos antifosfolipídeos
Disfunção cognitiva
Doenças autoimunes
Fator neurotrófico derivado do encéfalo
Síndrome antifosfolipídica
Testes neuropsicológicos
Abstract in Portuguese
Introdução: A disfunção cognitiva (DC) é uma manifestação não trombótica do sistema nervoso central, pouco compreendida na síndrome antifosfolípide (SAF). O fator neurotrófico derivado do cérebro (BDNF) é uma neurotrofina que desempenha um papel importante na plasticidade neural e pode potencialmente ser um biomarcador de DC na SAF primária. Objetivos: Avaliar a presença de DC em pacientes com SAF primária e sua associação com os dados clínicos, anticorpos antifosfolípides e níveis séricos de BDNF. Métodos: Este estudo transversal comparou 44 pacientes com SAF primária e 20 controles saudáveis pareados por idade, gênero e escolaridade. Os pacientes com SAF primária e controles foram submetidos a uma bateria de testes neuropsicológicos (NP) padronizada e adaptada para população estudada. Características demográficas, clínicas e laboratoriais dos pacientes com SAF primária foram analisadas buscando por associações com a presença de DC. O BDNF sérico foi avaliado pela técnica ELISA sanduíche. Resultados: Quatorze (31,8%) dos 44 pacientes com SAF primária tinham DC em comparação com apenas 1 (5%) controle (p = 0,019). Pacientes com SAF primária apresentaram níveis séricos de BDNF mais baixos quando comparados aos controles (647,3 ± 271,6 vs. 863,0 ± 318,6 ng/mL; p = 0,007). A DC em pacientes com SAF primária foi associada a níveis significantemente mais baixos de BDNF sérico (p = 0,032). Na análise univariada, foi encontrada uma associação positiva entre DC e livedo reticular, trombose venosa profunda, acidente vascular cerebral (AVC), convulsão, tabagismo, bem como uma associação negativa com o Mini- Exame do Estado Mental e o BDNF sérico. De acordo com a análise multivariada, o único preditor independente de DC na SAF primária foi o AVC (OR 137,06; IC 95%, 4,73-3974,32; p = 0,004). Conclusão: A DC é comumente descrita em pacientes com SAF primária; no entanto, sua avaliação carece de testes de triagem objetivos e padronizados. Nosso estudo demonstrou que a DC pode ser identificada na SAF primária, aplicando-se uma bateria de testes NP padronizada e adaptada à população brasileira, e a associação entre DC e BDNF sérico sugere essa neurotrofina como biomarcador promissor no diagnóstico de comprometimento cognitivo na SAF primária
Title in English
Cognitive dysfunction (CD) and serum levels of brain-derived neurotrophic factor (BDNF) in primary antiphosholipid syndrome
Keywords in English
Antibodies antiphospholipid, Autoimmune diseases
Antiphospholipid syndrome
Cognitive dysfunction
Neuropsychological tests, Brain-derived neurotrophic factor
Abstract in English
Introduction: Cognitive dysfunction (CD) is a poorly understood non-stroke central neurological manifestation in antiphospholipid syndrome (APS). Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in the neural plasticity, and could potentially be a biomarker of CD in primary APS (PAPS). Objectives: The aim of the study is to assess CD in PAPS patients and to evaluate its association with clinical data, antiphospholipid antibodies and serum BDNF levels. Methods: This crosssectional study compared 44 PAPS patients and 20 healthy controls matched for age, gender and education. PAPS patients and controls underwent an adapted standardized cognitive examination to the studied population. The demographic, clinical, and laboratory characteristics of patients were analysed searching for associations with CD presence. Serum BDNF was measured by sandwich ELISA. Results: Fourteen (31.8%) of the 44 patients with PAPS had CD compared with only 1 (5%) healthy control (p=0.019). PAPS patients presented lower serum BDNF levels when compared with controls (647.3 ± 271.6 vs. 863.0 ± 318.6 ng/mL, p=0.007). Lower levels of BDNF were associated with CD in PAPS patients (p=0.032). In the univariate analysis, a positive association was found between CD and livedo reticularis, deep vein thrombosis, stroke, seizure, smoking as well as a negative association with Mini Mental State Examination and serum BDNF. According to multivariate analysis, the only independent predictor of CD in PAPS was stroke (OR 137.06; 95%CI, 4.73-3974.32; p=0.004). Conclusion: CD is commonly reported in PAPS patients; however, its assessment lacks in standards and objective screening tests. Our study demonstrated that CD can be detected in PAPS by applying a standardized NP test battery adapted to the Brazilian population, and the association between CD and serum BDNF levels suggests that this neurotrophin can be a promising biomarker in the diagnosis of PAPS cognitive impairment
 
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Publishing Date
2021-02-12
 
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