MRI markers of brain aging and risk factors for cognitive decline in older African Americans

摘要 老龄化研究界已经确定了与各种疾病相关的许多风险因素 认知包括轻度认知障碍和阿尔茨海默病(AD)，并且有更多的理解 潜在的大脑机制。不幸的是，绝大多数知识都来自于对 主要是非西班牙裔白人。尽管非裔美国人背负着不成比例的阿尔茨海默氏症负担 疾病(AD)和认知障碍，这些差异背后的神经生物学机制仍然 难以捉摸。这项拟议研究的总体目标是调查潜在的神经生物学 文化相关的心理社会风险因素与认知功能减退和AD风险之间的联系机制 年长的非裔美国人。现有的关于老年非裔美国人核磁共振数据的文献几乎集中在 仅关于认知或AD事件的横截面关联，并检查了传统风险 各种因素。很少有对非裔美国人的研究反复检查与文化相关的风险因素 随时间推移测量认知功能和大脑完整性，以测试潜在的神经生物机制 将风险因素与认知能力下降和阿尔茨海默病风险联系起来。我们建议审问结构性和结构性的变化 作为关键神经生物学基础的MRI功能完整性将这些社会相关风险因素与 非裔美国人认知功能减退与AD风险。利用基础设施完善的 少数民族老龄化研究(MARS)，包括关于风险因素的现有数据，以及重复测量 认知功能，我们将使用一种多模式神经成像方法来获取400例生前MRI扫描 并量化一些脑部核磁共振指数的变化，以解决具体目标。目标1 将研究脑部MRI指标的变化与认知功能减退率和AD风险之间的关系 老年非裔美国人；目标2将检查早年和中年文化风险因素与 老年非裔美国人的结构和功能脑MRI指数；Aim 3将确定 脑MRI指标影响早、中年危险因素与AD下降率和风险之间的关系 年长的非裔美国人；并利用在No. 来自快速记忆和老龄化项目(MAP)的成本，目标4将确定种族差异与 脑部MRI结构和功能完整性改变为认知功能减退。与认知障碍相关的 老龄化是一个巨大的、日益严重的公共卫生问题，给非裔美国人带来了不成比例的负担。 将危险因素与认知能力下降联系起来的神经生物学途径的知识最终将提供靶子 用于今后的预防/干预研究，并将对实地产生强大和持续的影响。

ABSTRACT The aging research community has identified numerous risk factors associated with the full spectrum of cognition including mild cognitive impairment and Alzheimer’s disease (AD), and there is greater understanding of the underlying brain mechanisms. Unfortunately, the vast majority of knowledge comes from studies of primarily non-Hispanic Whites. Although African Americans bear a disproportionate burden of Alzheimer’s disease (AD) and cognitive impairment, the neurobiologic mechanisms underlying these disparities remain elusive. The overall goal of the proposed study is to investigate the underlying neurobiologic mechanisms linking culturally-relevant psychosocial risk factors to cognitive decline and risk of AD in older African Americans. Existing literature with MRI data in older African Americans has focused almost exclusively on cross-sectional associations of cognition or incident AD, and has examined traditional risk factors. Very few studies of African Americans have examined culturally relevant risk factors with repeated measures of cognitive function and brain integrity over time to test the underlying neurobiologic mechanisms linking risk factors to cognitive decline and risk of AD. We propose to interrogate changes in structural and functional integrity on MRI as key neurobiologic substrates linking these socially relevant risk factors to cognitive decline and risk of AD in African Americans. Leveraging the well-established infrastructure of the Minority Aging Research Study (MARS), including available data on risk factors, and repeated measures of cognitive function, we will use a multi-modal neuroimaging approach to acquire antemortem MRI scans on 400 African Americans and quantify change in a number of brain MRI indices to address the Specific Aims. Aim 1 will examine the relation of change in brain MRI indices with rate of cognitive decline and risk of AD among older African Americans; Aim 2 will examine the relation of early and mid-life cultural risk factors with change in structural and functional brain MRI indices among older African Americans; Aim 3 will determine if change in brain MRI indices affects the relation of early- and mid-life risk factors to rate of decline and risk of AD among older African Americans; and taking advantage of neuroimaging and cognitive function data available at no cost from the Rush Memory and Aging Project (MAP), Aim 4 will identify racial differences in the relation of change in MRI structural and functional brain integrity to cognitive decline. Cognitive impairment associated with aging is a large and growing public health problem that disproportionately burdens African Americans. Knowledge of the neurobiologic pathways linking risk factors to cognitive decline will ultimately provide targets for future prevention/intervention studies, and will have a strong and sustained impact on the field.