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多见于老年，可归因于高血压血管病或脑淀粉样血管病。它们与中风（尤其是脑出血）、认知障碍和痴呆的风险增加有关。它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、发病率和遗传决定因素尚不清楚。在弗雷明汉心脏研究中，我们收集了心血管危险因素的纵向数据，也有遗传、生物标志物和亚临床心血管疾病的测量。参与者进行了脑部核磁共振，并同时测量了认知表现。在拟议的拨款中，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伤的亚临床指标的关系，以及与炎症和血管功能障碍的新型循环生物标志物的关系。我们还将把CMB与脑缺血损伤、衰老和认知表现的其他MRI测量联系起来。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。目前的项目将是罗梅罗博士职业发展计划的一部分。他接受过血管神经科医生的培训，是波士顿大学医学院的神经病学助理教授。他对亚临床脑血管疾病和脑血管疾病预防有着长期的兴趣。Romero博士已经积极参与Framingham心脏研究的临床研究，现在提议获得成为该团队独立调查员所需的培训。他的短期计划是通过波士顿大学公共卫生学院的一个结构化项目来发展神经流行病学方面的专业知识，并致力于作为血管神经学临床研究者的长期职业生涯，研究CMB。本项目将在弗雷明汉心脏研究的背景下进行，利用研究资源，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。本课题的研究不仅有助于加深我们对CMB病理生理的认识，而且为进一步全面研究CMB作为脑血管疾病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.