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Master's Dissertation
DOI
https://doi.org/10.11606/D.5.2024.tde-28062024-150045
Document
Author
Full name
Maristella Yahagi Estevam
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2024
Supervisor
Committee
Suemoto, Claudia Kimie (President)
Pasqualucci, Carlos Augusto Goncalves
Porto, Fabio Henrique de Gobbi
Yamaguchi, Ayumi Aurea Miyakawa
Title in Portuguese
Associação entre aterosclerose coronariana com comprometimento cognitivo e doença de Alzheimer: um estudo clinico-patológico
Keywords in Portuguese
Aterosclerose
Demência
Doença da artéria coronariana
Doença de Alzheimer
Emaranhados neurofibrilares
Placa neurítica
Abstract in Portuguese
Introdução: O envelhecimento populacional tem um profundo impacto no aumento da prevalência de demência, que tem a aterosclerose coronariana como um dos seus fatores de risco. Estudos clínicos mostraram associação entre aterosclerose coronariana e comprometimento cognitivo, porém os estudos baseados em autópsia mostraram resultados controversos. Objetivos: Investigar a associação da aterosclerose em artérias coronárias com comprometimento cognitivo e doença de Alzheimer, avaliada por critérios clínicos e neuropatológicos. Método: Este estudo observacional transversal foi conduzido em amostras coletadas pelo Biobanco para Estudos em Envelhecimento. Foram avaliadas a associação entre medidas morfométricas de estenose coronária e comprometimento cognitivo definido por critérios clínicos, e a associação entre componentes da placa aterosclerótica e neuropatologia da doença de Alzheimer, caracterizada por placas neuríticas e emaranhados neurofibrilares. Resultados: Na publicação The potential role of selection bias in the association between coronary atherosclerosis and cognitive impairment não houve associação entre estenose coronária e comprometimento cognitivo. Para explorar o papel dos fatores de seleção, dividimos os indivíduos em nascidos antes de 1936 e estratificamos por causa de morte cardiovascular. Em indivíduos que nasceram antes de 1936 e sem doença cardiovascular como causa de morte, maior estenose foi associada a maiores chances de comprometimento cognitivo e pior função cognitiva. Por outro lado, em indivíduos que morreram por causas cardiovasculares, a maior estenose foi relacionada à melhor função cognitiva tanto na amostra total quanto na restrita aos nascidos antes de 1936. O viés de seleção pode ser uma questão importante ao investigar fatores de risco para doenças crônico-degenerativas em indivíduos mais velhos usando amostras de autópsia. No manuscrito Association of atherosclerotic plaque components with Alzheimer's disease pathology o aumento da calcificação foi associado à diminuição do depósito de placas neuríticas e o aumento de vasa vasorum foi associado ao aumento do diagnóstico de Alzheimer. Hipotetizamos que componentes ligados à estabilidade da placa aterosclerótica estariam associados a neuropatologia de Alzheimer, visto que é uma doença de início tardio e decorrente de mudanças crônicas. Porém, estabelecer uma ligação clara entre aterosclerose e a doença de Alzheimer é um desafio, principalmente devido à complexidade da progressão da placa aterosclerótica
Title in English
Association between coronary atherosclerosis with cognitive impairment and Alzheimer's disease: a clinicopathological study
Keywords in English
Alzheimer disease
Atherosclerosis
Coronary artery disease
Dementia
Neuritic plaque
Neurofibrillary tangles
Abstract in English
Introduction: Population aging has a profound impact on the increased prevalence of dementia, which has coronary atherosclerosis as one of its risk factors. Clinical studies have shown an association between coronary atherosclerosis and cognitive impairment, but autopsy-based studies have shown controversial results. Objectives: To investigate the association of atherosclerosis in coronary arteries with cognitive impairment and Alzheimer's disease, assessed by clinical and neuropathological criteria. Method: This cross-sectional observational study was conducted on samples collected by the Biobank for Studies in Aging. The association between morphometric measurements of coronary stenosis and cognitive impairment defined by clinical criteria and the association between atherosclerotic plaque components and the neuropathology of Alzheimer's disease, characterized by neuritic plaques and neurofibrillary tangles, were evaluated. Results: In the publication The potential role of selection bias in the association between coronary atherosclerosis and cognitive impairment there was no association between coronary stenosis and cognitive impairment. To explore the role of selection factors, we divided individuals into those born before 1936 and stratified by cause of cardiovascular death. In individuals born before 1936 and without cardiovascular disease as a cause of death, greater stenosis was associated with greater odds of cognitive impairment and worse cognitive function. On the other hand, in individuals who died from cardiovascular causes, greater stenosis was related to better cognitive function both in the total sample and in the sample restricted to those born before 1936. Selection bias can be an important issue when investigating risk factors for diseases chronic degenerative diseases in older individuals using autopsy samples. In the manuscript Association of atherosclerotic plaque components with Alzheimer's disease pathology, increased calcification was associated with a decrease in the deposition of neuritic plaques and an increase in vasa vasorum was associated with an increase in the diagnosis of Alzheimer's. We hypothesized that components linked to the stability of the atherosclerotic plaque would be associated with Alzheimer's neuropathology, as it is a late-onset disease resulting from chronic changes. However, establishing a clear link between atherosclerosis and Alzheimers disease is challenging, mainly due to the complexity of atherosclerotic plaque progression
 
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Publishing Date
2024-07-10
 
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