Risk Factors, Genetics and Cognition in Cerebral Microbleeds: Framingham Study

描述(申请人提供)：脑MRI检测到的脑微出血(CMB)越来越被认为是亚临床脑血管疾病的重要标志。CMB多见于高龄人群，多见于高血压血管病或淀粉样脑血管病。它们与中风(尤其是脑出血)、认知障碍和痴呆症的风险增加有关。他们的存在使缺血性中风和阿尔茨海默病的预防和治疗工作复杂化。然而，CMB的潜在病理生理学、发病率和遗传决定因素尚不清楚。在弗雷明翰心脏研究中，我们收集了关于心血管危险因素的纵向数据，还收集了遗传、生物标记物和亚临床心血管疾病指标。参与者接受了脑部核磁共振检查，并同时测量了认知能力。在建议的拨款中，我们假设CMB的患病率和发病率随着年龄的增长而增加，并与心血管危险因素有关。我们将研究CMB与动脉粥样硬化和高血压器官损害的亚临床指标的关系，以及与炎症和血管功能障碍的新的循环生物标志物的关系。我们还将把CMB与脑缺血损伤和衰老以及认知能力的其他MRI指标联系起来。最后，我们将利用已有的全基因组关联数据研究CMB的遗传决定因素。本项目将是罗梅罗博士职业发展计划的一部分。他接受过血管神经学家的培训，是波士顿大学医学院的神经学助理教授。他长期以来一直对亚临床脑血管疾病和脑血管疾病预防感兴趣。罗梅罗博士已经积极参与了弗雷明翰心脏研究的临床研究，现在他提议接受成为该团队独立研究员所需的培训。他的短期计划是通过波士顿大学公共卫生学院的结构化项目发展神经流行病学方面的专业知识，并致力于长期担任血管神经病学的临床研究员，研究CMB。本项目将在弗雷明翰心脏研究的背景下进行，利用该研究的资源，并涉及一组国际公认的神经流行病学、生物统计学、神经放射学和遗传流行病学专家的指导。这项研究不仅将加深我们对CMB的病理生理学的认识，也将为进一步全面研究CMB作为脑血管疾病的亚临床标志物奠定基础。

DESCRIPTION (provided by applicant): Cerebral microhemorrhages (CMB) detected using brain MRI are increasingly recognized as important markers of subclinical cerebrovascular disease. CMB are more frequent in advanced age, and are attributed to hypertensive vasculopathy or cerebral amyloid angiopathy. They have been related to an increased risk of stroke (especially brain hemorrhage) cognitive impairment and dementia. Their presence complicates prevention and treatment efforts for ischemic stroke and Alzheimer's disease. However the underlying pathophysiology, incidence and genetic determinants of CMB are not well understood. In the Framingham Heart Study, we have collected longitudinal data on cardiovascular risk factors, and also have genetic, biomarker and subclinical cardiovascular disease measures. Participants have had brain MRI, and simultaneous measures of cognitive performance. In the proposed grant we hypothesize that the prevalence and incidence of CMB increase with age, and relate to cardiovascular risk factors. We will investigate the relation of CMB to subclinical measures of atherosclerosis and hypertensive organ damage, and to novel circulating biomarkers of inflammation and vascular dysfunction. We will also relate CMB to other MRI measures of brain ischemic damage and aging, and cognitive performance. Finally we will study genetic determinants of CMB using already available genome-wide association data. The present project will be part of a career advancement program for Dr. Romero. He has training as a Vascular Neurologist and is an Assistant professor of Neurology at the Boston University Medical Campus. He has a long-standing interest in subclinical cerebrovascular disease, and in cerebrovascular disease prevention. Dr. Romero has already been actively involved in clinical research at the Framingham Heart Study and now proposes to obtain the training required to become an independent investigator in this team. He has short term plans to develop expertise in Neuroepidemiology through a structured program at the Boston University School of Public Health and is committed to a long term career as a clinical investigator in Vascular Neurology, studying CMB. The present project is to be conducted in the context of the Framingham Heart Study, using the resources of the study and involving the mentorship of a group of internationally recognized experts in Neuroepidemiology, Biostatistics, Neuroradiology, and Genetic Epidemiology. The proposed research project will not only advance our understanding of the pathophysiology of CMB, but also serve as the basis for further comprehensive studies of CMB as subclinical markers of cerebrovascular disease.