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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2022.tde-24112022-133221
Document
Author
Full name
Breno José Alencar Pires Barbosa
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2022
Supervisor
Committee
Brucki, Sônia Maria Dozzi (President)
Takada, Leonel Tadao
Bromberg, Elke
Nitrini, Ricardo
Title in Portuguese
Avaliação dos marcadores de estresse crônico em indivíduos do estudo brasileiro de memória e envelhecimento
Keywords in Portuguese
Alostase
Disfunção cognitiva
Doença de Alzheimer
Envelhecimento
Estresse fisiológico
Síndrome metabólica
Abstract in Portuguese
Introdução: Diversos estudos sugerem que o estresse crônico e níveis persistentemente elevados de cortisol estão relacionados a disfunção cognitiva e processos neurodegenerativos. O estudo brasileiro de memória e envelhecimento (Brazilian Memory and Aging Study BRAMS) é uma iniciativa de pesquisa para acompanhamento longitudinal de indivíduos em ambulatório especializado em cognição. Objetivos: investigar a relação entre marcadores de estresse crônico e status cognitivo no BRAMS, realizando comparações entre os grupos classificados como controle, declínio cognitivo subjetivo (DCS) e comprometimento cognitivo leve (CCL) (amnéstico, não amnéstico, único domínio ou múltiplos domínios). Secundariamente correlacionar os marcadores quanto ao status amiloide dos participantes. Metodologia: estudo observacional do tipo recorte transversal de subgrupo do BRAMS, em que indivíduos de idade > 60 anos que tiveram acesso à avaliação médica, neuropsicológica e PET amiloide. A presente análise busca aferir o índice de carga alostática (ICA), uma medida global de estresse crônico que engloba marcadores antropométricos, endocrinológicos, cardiovasculares, metabólicos e inflamatórios, correlacionando as variáveis com status cognitivo e status amiloide. Resultados: Entre os anos de 2018 e 2021, 77 participantes foram avaliados no presente protocolo, sendo que, destes, 65 preencheram critério de inclusão. A média de idade foi de 70,2 (+ 6,01) anos, sendo 72% do sexo feminino e escolaridade média de 11 anos (intervalo interquartil 7 15). Houve 42 indivíduos classificados como CCL, 15 como DCS e 8 como controles. Houve diferença significativa entre as medidas de HDL (high-density lipoprotein) (55,6 no grupo CCL vs. 66 no grupo DCS vs. 69 no grupo controle, p = 0,04), relação cintura/quadril (0,94 no grupo CCL vs. 0,88 no grupo DCS, p = 0.03) e também para a medida do ICA em valor percentual considerando os extremos de cortisol (ICA % cortisol p<12,5 ou p>87,5) (36,9% no grupo CCL vs. 27,2% no grupo DCS, p = 0,04). Corrigindo-se para fatores de confusão através da análise multivariável, maior escolaridade foi associada a risco reduzido de CCL. Maior escolaridade e classe econômica (ABEP) também foram associadas de forma independente a menor chance de DCS. Conclusão: o presente trabalho representa provavelmente uma das primeiras iniciativas de pesquisa a abordar as medidas de estresse crônico para além do cortisol em uma população com os diagnósticos de DCS e CCL, com marcadores aumentados no grupo CCL. Pela natureza transversal do estudo, as associações encontradas não permitem inferir causalidade entre as medidas, mas poderão ser melhor exploradas em seguimento longitudinal dos participantes no médio e longo prazo
Title in English
Evaluation of chronic stress markers in individuals from the Brazilian aging and memory study
Keywords in English
Aging
Allostasis
Alzheimer's disease
Cognitive dysfunction
Metabolic syndrome
Physiological stress
Abstract in English
Introduction: Several studies suggest that chronic stress and persistently high levels of cortisol are related to cognitive dysfunction and neurodegeneration. The Brazilian Memory and Aging Study (BRAMS) is a research initiative for the longitudinal follow-up of individuals in a tertiary center specialized memory outpatient clinic. Objectives: to investigate the relationship between markers of chronic stress and cognitive status in BRAMS, making comparisons between participants classified as controls, subjective cognitive decline (SCD) and mild cognitive impairment (MCI) (amnestic, non-amnestic, single domain or multiple domains). Secondarily to correlate the markers with the amyloid status of the participants. Methodology: observational study of the cross-sectional type with a subgroup analysis of the BRAMS cohort, in which individuals aged > 60 years who had access to medical, neuropsychological and amyloid PET assessment. The present analysis seeks to measure the allostatic load index (ALI), a global measure of chronic stress through anthropometric, endocrinological, cardiovascular, metabolic and inflammatory markers, correlating the variables with cognitive status and amyloid status. Results: Between the years 2018 and 2021, 77 participants were evaluated in the present protocol, of which 65 met the inclusion criteria. The mean age was 70.2 (+ 6.01) years, with 72% being female and 11 years of schooling (interquartile range 7 15). There were 42 subjects classified as MCI, 15 as SCD and 8 as controls. There was a significant difference between HDL (high-density lipoprotein) measurements (55.6 in the MCI group vs. 66 in the SCD group vs. 69 in the control group, p = 0.04), waist/hip ratio (0.94 in the MCI group vs. 0, 88 in the SCD group, p = 0.03) and also for the measurement of the ALI in percentage value considering the extremes of cortisol (ALI % cortisol p<12.5 or p>87.5) (36.9% in the MCI group vs. 27.2% in the SCD group, p = 0.04). Correcting for confounders through multivariate analysis, higher education was associated with reduced risk of MCI. Higher education and economic class were also independently associated with a lower chance of SCD. Conclusion: The present work probably represents one of the first research initiatives to address measures of chronic stress beyond cortisol in elderly participants diagnosed with SCD and MCI, with increased markers in the MCI group. Due to the cross-sectional nature of the study, the associations found do not allow inferring causality between the measures, but they can be better explored in the longitudinal follow-up of the participants
 
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Publishing Date
2022-11-30
 
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