Changes in hippocampal subfield volumes (HSV) along the Alzheimer's disease (AD) continuum have been scarcely investigated to date in elderly subjects classified based on the presence of β-amyloid aggregation and signs of neurodegeneration. We classified patients (either sex) with mild dementia compatible with AD (n = 35) or amnestic mild cognitive impairment (n = 39), and cognitively unimpaired subjects (either sex; n = 26) using [ 11 C]PIB-PET to assess β-amyloid aggregation (A+) and [ 18 F]FDG-PET to account for neurodegeneration ((N)+). Magnetic resonance imaging-based automated methods were used for HSV and white matter hyperintensity (WMH) measurements. Significant HSV reductions were found in A+(N)+ subjects in the presubiculum/subiculum complex and molecular layer, related to worse memory performance. In both the A+(N)+ and A+(N)− categories, subicular volumes were inversely correlated with the degree of Aβ deposition. The A−(N)+ subgroup showed reduced HSV relative to the A−(N)− subgroup also in the subiculum/presubiculum. Combining all (N)− subjects, HSV were lower in subjects presenting significant cognitive decline irrespective of A+/A− classification (controlling for WMH load); these between-group differences were detected again in the presubiculum, but also involved the CA4 and granular layer. These findings demonstrate that differential HSV reductions are detectable both in (N)+ and (N)− categories along the AD continuum, and are directly related to the severity of cognitive deficits. HSV reductions are larger both in A+(N)+ and A+(N)− subjects in direct proportion to the degree of Aβ deposition. The meaningful HSV reductions detected in the A−(N)+ subgroup highlights the strength of biomarker-based classifications outside of the classical AD continuum.
AGRADECIMENTOSTenho poucas certezas na vida, mas uma delas é a de que muitas pessoas contribuíram para a realização deste trabalho. Serei eternamente grata a todos vocês, obrigada! À professora Sílvia Martorano Raimundo, pelas inúmeras aulas e discussões conceituais e, principalmente, pela dedicação, carinho e verdadeira amizade que sempre estiveram presentes em todos os momentos.Ao professor Marcelo Nascimento Burattini, pela orientação, pelas sugestões conceituais e apoio no processo de execução do trabalho.Ao professor Eduardo Massad, por ter me proposto o tema para este trabalho, por propiciar condições técnicas e financeiras para que ele fosse realizado e, principalmente, por ter acreditado que eu conseguiria. espalhamento de rumores levando em conta a simetria no número de contatos diretos entre "suscetíveis" e "infectados" pelo rumor e estudamos as implicações de uma campanha publicitária educativa na dinâmica do modelo.Posteriormente, propomos uma simplificação do modelo e desconsideramos o contato entre os indivíduos "suscetíveis" e "infectados" mais resistentes às novidades. Discutimos suas implicações no espalhamento do rumor e a conexão com os parâmetros que descrevem o comportamento social.
ABSTRACT Mathematical Model to study the spread of information from educative campaigns and rumorsWe have developed a deterministic mathematical model based on the mass-action principle, in analogy to the works that study the dynamics of infectious diseases in Epidemiology. We analyzed the dynamic of rumors spreading, taking into account the symmetry of contacts among "susceptible"and "infectious" individuals and studied the implications of an educative broadcasting advertising in the model.We also simulated the model eliminating the contact among opinioned "susceptible" and "infective" to simplify the model.
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