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许多与全谱衰老相关的风险因素。 包括轻度认知障碍和阿尔茨海默病（AD）在内的认知障碍， 潜在的大脑机制。不幸的是，绝大多数的知识来自于对 主要是非西班牙裔白人。尽管非裔美国人在老年痴呆症中所占比例 疾病（AD）和认知障碍，这些差异背后的神经生物学机制仍然存在 难以捉摸这项研究的总体目标是调查潜在的神经生物学 将文化相关的心理社会风险因素与认知能力下降和AD风险联系起来的机制 年长的非裔美国人现有文献中的老年非裔美国人的MRI数据几乎集中在 专门研究认知或AD事件的横截面关联，并研究了传统的风险 因素很少有关于非裔美国人的研究检查了与文化相关的风险因素， 随着时间的推移测量认知功能和大脑完整性，以测试潜在的神经生物学机制 将风险因素与认知能力下降和AD风险联系起来。我们建议询问结构和 MRI上的功能完整性作为关键的神经生物学基质，将这些社会相关风险因素与 非裔美国人的认知能力下降和AD风险。利用完善的基础设施， 少数民族老龄化研究（MARS），包括有关风险因素的现有数据，以及 认知功能，我们将使用多模态神经成像方法获得死前MRI扫描400 非裔美国人和量化的变化，在一些脑MRI指数，以解决具体目标。要求1 将研究脑MRI指标变化与认知能力下降率和AD风险之间的关系， 老年非裔美国人;目标2将研究早期和中年文化风险因素与 老年非裔美国人的结构和功能性脑MRI指数;目标3将确定 脑MRI指数影响早期和中年危险因素与AD下降率和风险的关系， 老年非裔美国人;并利用神经成像和认知功能数据， 从拉什记忆和衰老项目（MAP）的成本，目标4将确定种族差异的关系， MRI结构和功能性大脑完整性的变化导致认知能力下降。相关的认知缺损 老龄化是一个巨大且日益严重的公共卫生问题，给非洲裔美国人带来了不成比例的负担。 神经生物学通路的知识将危险因素与认知能力下降联系起来， 为今后的预防/干预研究，并将在该领域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.