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).

非动脉粥样硬化性脑动脉重塑和相关血管性痴呆风险颅内大动脉的非动脉粥样硬化性脑动脉重塑（NABAR）最近出现作为不良认知结果的决定因素。血管老化与弹性蛋白断裂有关胶原沉积，并可能表现为向外或曲折的重塑，这两种情况都可能发生在没有动脉粥样硬化。在横断面研究中，大脑的非动脉粥样硬化向外重塑据报道，脉管系统与认知功能减弱有关。然而，在多大程度上脑动脉重塑是永久性的还是可逆的，或者在老年人中脑动脉重塑是否随着年龄的增长而进展未知。机制研究表明动脉壁厚度受腔内压力和壁的调节张力，动脉管腔直径受血流和剪切应力调节。曲折伸长有也与机械因素有关，包括血流、血压、轴向张力和壁变化。因此，脑动脉重塑可能是动态的而不是静态的，即使在高龄人士。我们建议检查 NABAR 的患病率和变化率，量化为接受成像的一般人群中的老年人的管腔直径和弯曲程度在 2 个时间点进行脑部 MRI 检查。我们的目标是确定中年时的血管危险因素及其轨迹自中年起与晚年的NABAR联系在一起。我们还将确定可能相关的推定因素晚年的重塑加速了 5 年的进程。作为次要目标，我们将研究 NABAR 与 5 年神经认知结果（认知和认知变化）之间的前瞻性关系血管性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 的一年变化和认知的 5 年变化。我们将拥有独特的优势来开展这个项目在社区动脉粥样硬化风险研究中，该研究收集了队列成员的临床数据过去 30 年，包括通过脑部 MRI 和认知测试进行的多项评估。我们将量化NABAR （扩张和迂曲）在基底动脉、大脑中动脉和颈内动脉中，使用来自 ARIC 第 5 次研究访问（2011-2013 年，已完成）的现有 MRI 数据（TOF MRA 和 3D 血管壁成像）以及请访问 6/7（2016-2019）。