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

脑微出血的危险因素、遗传学和认知：弗雷明汉研究

• 批准号: 8189062
• 负责人: Jose Rafael Romero
• 金额: $ 12.87万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8189062
• 关键词: Adult; Age; Aging; Alzheimer' s Disease; Amyloid; Atherosclerosis; Biological Markers; Biometry; Blood Vessels; Boston; Brain; Brain Injuries; Brain Ischemia; Brain hemorrhage; C-reactive protein; Cardiovascular Diseases; Carotid Stenosis; Cerebral Amyloid Angiopathy; Cerebrovascular Disorders; Cerebrovascular Trauma; Cerebrum; Characteristics; Cholesterol; Clinical; Clinical Investigator; Clinical Research; Cognition; Cognitive; Cognitive aging; Cognitive deficits; Commit; Communities; Data; Dementia; Diabetes Mellitus; Elderly; Enrollment; Epidemiology; Evaluation; Extracellular Matrix; Framingham Heart Study; Functional disorder; Future; Generations; Genes; Genetic; Genetic Determinism; Genetic Variation; Genomics; Genotype; Grant; Heart; Heart Diseases; Hemorrhage; Heritability; Hippocampus (Brain); Hypertension; Image; Impaired cognition; Incidence; Infarction; Inflammation; Injury; Ischemic Brain Injury; Ischemic Stroke; Knowledge; Laboratories; Left Ventricular Mass; Location; Magnetic Resonance Imaging; Matrix Metalloproteinases; Measures; Medial; Medical; Memory; Mentorship; N,N-dimethylarginine; Neurologist; Neurology; Organ; Outcome; Participant; Pathology; Pattern; Performance; Persons; Prevalence; Prevalence Study; Prevention; Preventive Intervention; Process; Public Health Schools; Research; Research Personnel; Research Project Grants; Resources; Risk; Risk Factors; Risk Marker; Role; Sampling; Serum; Severities; Smoking; Speed; Stenosis; Stroke; Stroke prevention; Structure; Symptoms; Testing; Thick; Training; Universities; Vascular Diseases; age related; aged; aging brain; base; brain volume; cardiovascular risk factor; career; cognitive function; cohort; disorder prevention; executive function; genetic epidemiology; genetic risk factor; genome wide association study; interest; men; middle age; neuropsychological; novel; performance tests; professor; programs; trait; vascular inflammation; white matter; Adult; Age; Aging; Alzheimer' s Disease; Amyloid; Atherosclerosis; Biological Markers; Biometry; Blood Vessels; Boston; Brain; Brain Injuries; Brain Ischemia; Brain hemorrhage; C-reactive protein; Cardiovascular Diseases; Carotid Stenosis; Cerebral Amyloid Angiopathy; Cerebrovascular Disorders; Cerebrovascular Trauma; Cerebrum; Characteristics; Cholesterol; Clinical; Clinical Investigator; Clinical Research; Cognition; Cognitive; Cognitive aging; Cognitive deficits; Commit; Communities; Data; Dementia; Diabetes Mellitus; Elderly; Enrollment; Epidemiology; Evaluation; Extracellular Matrix; Framingham Heart Study; Functional disorder; Future; Generations; Genes; Genetic; Genetic Determinism; Genetic Variation; Genomics; Genotype; Grant; Heart; Heart Diseases; Hemorrhage; Heritability; Hippocampus (Brain); Hypertension; Image; Impaired cognition; Incidence; Infarction; Inflammation; Injury; Ischemic Brain Injury; Ischemic Stroke; Knowledge; Laboratories; Left Ventricular Mass; Location; Magnetic Resonance Imaging; Matrix Metalloproteinases; Measures; Medial; Medical; Memory; Mentorship; N,N-dimethylarginine; Neurologist; Neurology; Organ; Outcome; Participant; Pathology; Pattern; Performance; Persons; Prevalence; Prevalence Study; Prevention; Preventive Intervention; Process; Public Health Schools; Research; Research Personnel; Research Project Grants; Resources; Risk; Risk Factors; Risk Marker; Role; Sampling; Serum; Severities; Smoking; Speed; Stenosis; Stroke; Stroke prevention; Structure; Symptoms; Testing; Thick; Training; Universities; Vascular Diseases; age related; aged; aging brain; base; brain volume; cardiovascular risk factor; career; cognitive function; cohort; disorder prevention; executive function; genetic epidemiology; genetic risk factor; genome wide association study; interest; men; middle age; neuropsychological; novel; performance tests; professor; programs; trait; vascular inflammation; white matter

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. PUBLIC HEALTH RELEVANCE: Small hemorrhages that are seen on a brain MRI but typically cause no obvious symptoms when they happen are called cerebral microbleeds (CMB); they are more frequent in older persons and have been associated with an increased risk of ischemic stroke and of brain hemorrhage, especially in persons being treated for ischemic stroke. They have also been associated with poor cognitive performance and Alzheimer's dementia. We propose to study the prevalence, incidence and characteristics of CMB in the middle-aged, community-based Framingham Heart Study. We will relate these data to cardiovascular and genetic risk factors, markers of carotid and heart disease and to novel serum biomarkers. We will also study how CMB are related to other MRI measures of aging and brain ischemia, and to cognitive function. Understanding the pathophysiology of CMB could help prevent stroke and dementia.

描述（由申请人提供）：使用脑MRI检测到的脑微毛（CMB）越来越被认为是亚临床脑血管疾病的重要标志。 CMB在高级时代更为频繁，归因于高血压的血管病或脑淀粉样血管病。它们与中风（尤其是脑出血）认知障碍和痴呆症的风险增加有关。它们的存在使预防和治疗工作复杂化，治疗障碍性中风和阿尔茨海默氏病。但是，CMB的基本病理生理学，发病率和遗传决定因素尚不清楚。在Framingham心脏研究中，我们收集了有关心血管危险因素的纵向数据，并且还具有遗传，生物标志物和亚临床心血管疾病措施。参与者拥有脑部MRI，并同时衡量认知表现。在拟议的授予中，我们假设CMB的患病率和发生率随着年龄的增长而增加，并且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测量的关系，以及新型的炎症和血管功能障碍的生物标志物。我们还将将CMB与其他脑缺血损伤和衰老以及认知性能的MRI指标联系起来。最后，我们将使用已经可用的全基因组关联数据研究CMB的遗传决定因素。 本项目将成为罗梅罗博士的职业发展计划的一部分。他接受过血管神经科医生的培训，并且是波士顿大学医学校园的神经病学助理教授。他对亚临床脑血管疾病和预防脑血管疾病一直具有长期的兴趣。罗梅罗博士已经在弗雷明汉心脏研究中积极参与临床研究，现在建议获得成为该团队独立研究人员所需的培训。他有短期计划通过波士顿大学公共卫生学院的一项结构化计划来开发神经性ePidemiology的专业知识，并致力于从事CMB的血管神经病学临床研究者的长期职业。本项目将在弗雷明汉心脏研究的背景下进行研究，并使用研究资源，并涉及一组国际认可的神经性疾病学，生物统计学，神经放射学和遗传流行病学方面的国际认可的专家。 拟议的研究项目不仅将提高我们对CMB病理生理学的理解，而且还可以作为将CMB作为脑血管疾病的亚临床标志物进行进一步全面研究的基础。 公共卫生相关性：在大脑MRI上看到的小出血，但通常不会引起明显的症状，称为脑微粒（CMB）；它们在老年人中更为常见，并且与缺血性中风和脑出血的风险增加有关，尤其是在接受缺血性中风治疗的人时。他们还与认知表现不佳和阿尔茨海默氏症的痴呆症有关。我们建议研究CMB在中年，基于社区的Framingham心脏研究中的患病率，发病率和特征。我们将将这些数据与心血管和遗传危险因素，颈动脉和心脏病的标志以及新型血清生物标志物联系起来。我们还将研究CMB与其他MRI衰老和脑缺血以及认知功能的关系。了解CMB的病理生理可以帮助预防中风和痴呆。