Non-Atherosclerotic Brain Arterial Remodeling and Associated Vascular Dementia Risk

非动脉粥样硬化性脑动脉重塑和相关血管性痴呆风险

基本信息

批准号：
10194703
负责人：
MELISSA C CAUGHEY
金额：
$ 45.83万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10194703
关键词：
3-Dimensional Age Aging Arterial Fatty Streak Arteries Atherosclerosis Atherosclerosis Risk in Communities Attention Autopsy Blood Pressure Blood Vessels Blood flow Brain Brain imaging Caliber Central Artery Cerebrovascular system Clinical Clinical Data Cognition Cognitive Collagen Communities Cross-Sectional Studies Data Dementia Deposition Elastin Elderly Evaluation Funding General Population Head Image Impairment Incidence Individual Internal carotid artery structure Intracranial Atherosclerotic Disease Investigation Magnetic Resonance Imaging Measures Mechanics Medial Microvascular Dysfunction Modification Monitor Neurocognitive Neurologic Examination Observational Study Outcome Participant Patients Physiologic pulse Positioning Attribute Prevalence Prospective Studies Public Health Reporting Resolution Risk Factors Risk Marker Role Sampling Series Stenosis Testing Thick Time Vascular Dementia Vascular Diseases Visit White Matter Hyperintensity arterial remodeling arterial stiffness basilar artery biracial brain parenchyma brain remodeling capillary bed cardiovascular risk factor cognitive function cognitive testing cohort cost efficient dementia risk electric impedance epidemiology study high risk hypoperfusion imaging biomarker intracranial artery macrovascular disease member middle age middle cerebral artery mild cognitive impairment population based pressure prospective rate of change research study shear stress transmission process vascular factor vascular risk factor

项目摘要

Non-Atherosclerotic Brain Arterial Remodeling and Associated Vascular Dementia Risk Non-atherosclerotic brain arterial remodeling (NABAR) of the large intracranial arteries has recently emerged as a determinant of poor cognitive outcomes. Vascular aging is associated with elastin fragmentation and collagen deposition, and may present as either outward or tortuous remodeling, both of which may occur in the absence of atherosclerosis. In cross-sectional studies, non-atherosclerotic outward remodeling of the cerebral vasculature has been reported in association with diminished cognitive function. However, the extent to which brain arterial remodeling is permanent vs. reversible, or whether it progresses with age in older individuals is unknown. Mechanistic studies suggest that arterial wall thickness is regulated by intraluminal pressure and wall tension, and that arterial lumen diameter is regulated by blood flow and shear stress. Tortuous elongation has also been associated with mechanical factors, including blood flow, blood pressure, axial tension and wall changes. It is thus plausible that brain arterial remodeling may be dynamic rather than static, even in individuals of advanced age. We propose to examine prevalence and rate of change in NABAR, quantified by luminal diameters and degree of tortuosity, in older individuals from the general population who were imaged by brain MRI at 2 time points. We aim to determine whether vascular risk factors at midlife and their trajectories since midlife associate with NABAR in late life. We will also identify putative factors which may be associated with an accelerated 5-year progression of remodeling in late life. As secondary aims, we will examine the prospective relationship between NABAR and 5-year neurocognitive outcomes (change in cognition and incidence of vascular mild cognitive impairment or vascular dementia), as well as the correlation between 5- year change in NABAR and 5-year change in cognition. We will be uniquely positioned to carry out this project in the Atherosclerosis Risk in Communities study, which has collected clinical data from cohort members over the past 30 years, including multiple assessments by brain MRI and cognitive testing. We will quantify NABAR (dilation and tortuosity) in the basilar artery, middle cerebral arteries, and internal carotid arteries, using existing MRI data (TOF MRA and 3D vessel wall imaging) from ARIC study visit 5 (2011-2013, completed) and visit 6/7 (2016-2019).

非动脉粥样硬化的脑动脉重塑和相关的血管痴呆风险大型颅内动脉的非动脉粥样硬化脑动脉重塑（NABAR）最近出现了作为差认知结果的决定因素。血管衰老与弹性蛋白碎片和胶原蛋白沉积，可能以外向或曲折的重塑形式出现，这两者都可能发生在缺乏动脉粥样硬化。在横断面研究中，大脑的非二动性外部重塑据报道，脉管系统与认知功能降低有关。但是，在多大程度上脑动脉重塑是永久性与可逆的，或者是否随着年龄的年龄的年龄发展是未知。机械研究表明，动脉壁厚度受腔内压力和壁调节张力，该动脉管腔直径受血流和剪切应力调节。有曲折的伸长还与机械因素有关，包括血流，血压，轴向张力和壁更改。因此，即使在高年龄的人。我们建议检查Nabar的患病率和变化率，由来自一般人群的老年人的腔直径和曲折程度由大脑MRI在两个时间点。我们旨在确定中年及其轨迹的血管危险因素是否由于中年与纳巴尔（Nabar）在后期与纳巴尔（Nabar）交往。我们还将确定可能关联的推定因素在后期重塑的5年进展加速了。作为次要目标，我们将研究纳巴尔与5年神经认知结果之间的潜在关系（认知和变化血管轻度认知障碍或血管性痴呆的发生率）以及5-之间的相关性 Nabar的年份变化和认知的5年变化。我们将在执行这个项目的位置独特在社区研究中的动脉粥样硬化风险中，该研究已收集了队列成员的临床数据过去30年，包括大脑MRI和认知测试的多次评估。我们将量化纳巴尔（扩张和曲折）在基底动脉，中部动脉和内部颈动脉中，使用 ARIC研究的现有MRI数据（TOF MRA和3D船墙成像）访问5（2011- 2013年，完成）和访问6/7（2016-2019）。