Oregon Brain Aging Study

描述(由申请人提供)： 俄勒冈州脑老化研究(OBAS)是对年龄最大(85岁)、人口增长最快和痴呆症风险最高的人群中与健康大脑老化相关的因素进行的纵向研究。在过去的20年里，OBA研究了脑体积、临床特征、遗传学和脑病理等一系列指标的衰老变化轨迹和意义，确定了个人在发展为坦率的痴呆症之前似乎患有症状前疾病的潜伏期为十年或更长时间。在这一潜伏期内导致认知能力下降的因素中，与血管疾病有关的因素尤为突出。这种与衰老相关的血管疾病的一个显著标志通常出现在脑部的磁共振成像(MRI)上，表现为白质高信号(WMH)。这些WMH对大脑功能有重要的影响，因为白质包含协调大脑功能的关键途径。这些通路的中断与严重的认知和运动障碍有关。了解导致WMHs和相关白质破坏的机制对于最终治疗或预防与脑血管疾病相关的认知和功能衰退是至关重要的。因此，在这项应用中，我们建议通过使用新的高场磁共振技术评估脑血流(CBF)和相关的脑内微结构白质破坏，来研究导致这种高度普遍的白质变化的最古老的潜在机制。为了实现这一目标，我们将追求三个密切相关的研究目标。首先，我们建议确定无创性动脉自旋标记(ASL)MRI测量的CBF变化在WMH发生发展中的作用，以确定在已存在WMH的老年患者的正常脑白质中是否存在CBF变化，如果随着时间的推移，CBF变化先于病理性白质变化的形成。其次，我们计划通过检查弥散张量成像(DTI)MRI所见的脑白质微结构破坏的程度来表征与脑血管疾病标志物如低CBF和高WMH相关的白质破坏的程度。最后，我们计划确定最能预测临床(认知和运动)衰退率的MRI标志物(CBF、WMH体积、大脑完整性)，以及与这些生命中的这些变化最密切相关的死后大脑病理。该项目将与100多名OBA老年志愿者一起进行，他们将接受年度标准化的临床和核磁共振评估。核磁共振成像将需要使用3特斯拉和特殊的7特斯拉核磁共振仪器，以提供随时间推移的脑血流(ASL)和微结构(DTI)损伤的高分辨率图像。考虑到队列的性质，相当多的人已经并将捐赠他们的大脑进行研究，以便在死后识别MRI和生前观察到的其他临床变化，从而最好地索引尸检发现的神经病理。作为这项工作的一部分，100多名OBA参与者贡献的独特数据将被用来检查他们一生中WMH的体积积累，以及这种变化与他们的大脑尸检中看到的主要年龄相关病理(血管和阿尔茨海默病损害)的关系。

DESCRIPTION (provided by applicant): The Oregon Brain Aging Study (OBAS) is a longitudinal study of factors related to healthy brain aging in the oldest old (those e age 85), the fastest growing segment of the population and those at highest risk for dementia. During the past 20 years the OBAS has examined the trajectory and meaning of aging change across a range of markers such as brain volumes, clinical profiles, genetics and brain pathology, identifying a latent period of a decade or more when individuals appear to have presymptomatic disease prior to developing frank dementia. Among factors leading to cognitive decline in this latent period, those related to vascular disease stand out. A prominent marker of this vascular disease associated with aging is commonly seen on magnetic resonance imaging (MRI) of the brain and appears as white matter hyperintensities (WMHs). These WMHs have important implications for brain function since the white matter contains critical pathways for coordinated brain function. Disruption of these pathways is associated with significant cognitive and motor impairments. Understanding the mechanisms that lead to WMHs and related disruption of the white matter is fundamental to ultimately treating or preventing cognitive and functional decline associated with cerebrovascular disease. Accordingly, in this application we propose to examine in the oldest old, underlying mechanisms leading to this highly prevalent white matter change by assessing cerebral blood flow (CBF) and related microstructural white matter disruption in the brain using new high field MRI techniques. To achieve this goal we will pursue three tightly related research aims. First, we propose to determine the role of changes in CBF measured with non-invasive arterial spin labeling (ASL) MRI on the development of WMHs to determine if altered CBF is present in normal appearing white matter in elderly with WMHs already present in their brain, and if over time, altered CBF precedes the formation of pathologic white matter change. Second, we plan to characterize the extent of white matter disruption related to cerebrovascular disease markers such as low CBF and high volumes of WMH by examining the extent of microstructural white matter disruption seen with diffusion tensor imaging (DTI) MRI. Finally, we plan to Identify MRI markers (CBF, WMH volume, brain integrity) that best predict rates of clinical (cognitive and motor) decline and the post mortem brain pathologies that are most closely tied to these changes during life. The project will be conducted with over 100 OBAS oldest old volunteers who will have annual standardized clinical and MRI assessments. MRI will entail the use of both 3 Tesla and a special 7 Tesla MRI instrument to provide high-resolution images of CBF (ASL) and microstructural (DTI) damage over time. Given the nature of the cohort a significant number have and will donate their brain for study allowing for post mortem identification of MRI and other clinical changes observed during life that best index the neuropathologies found on autopsy. As part of this effort, unique data contributed by over 100 OBAS participants who had annual MRI scans and died during the prior 20 years will be used to examine WMH volume accumulation during their lives and how this change relates to the major age-associated pathologies (vascular as well as Alzheimer's disease lesions) seen at post mortem examination of their brain.