Risk Factors for Cognitive Decline in African-Americans

描述(申请人提供)：与衰老和阿尔茨海默病(AD)相关的认知衰退是最常见和最令人衰弱的疾病之一，并构成一个巨大的且日益严重的公共卫生问题。预测表明，与老龄化有关的慢性病的流行率预计在未来十年将大幅增加。少数族裔尤其如此，尤其是年长的非裔美国人，他们的增长速度甚至比年长的白人更快。少数民族老龄化研究(MARS)是一项纵向队列研究，对350多名没有痴呆的老年非裔美国人进行了研究，他们同意进行年度临床评估。在之前的项目期间，我们确定了非裔美国人认知能力下降的几个风险因素。拟议继续的总体目标是量化三个常见的神经病理指标，包括火星参与者的阿尔茨海默病病理、脑梗塞和路易小体，并检查它们与认知功能和临床风险因素的关系。此外，为了增强力量并检查这些相关性中的种族差异，我们建议使用来自Rush的另外两项正在进行的队列研究中关于白人的现有纵向临床和神经病理学数据。我们的具体目标是：1)检查三个死后神经病理指数与1a：全球认知水平和五种认知能力的关系，1b：全球认知和五种认知能力的变化；2)检查神经病理与认知功能水平和变化之间的种族差异；3)测试假设，即APOE e4等位基因与AD病理水平的增加有关，而52等位基因与非裔美国人的AD病理水平较低有关；以及4)检查BMI与神经病理学的关系，并测试BMI与AD病理的相关性在白人中比在非裔美国人中更强的假设。关于非裔美国人认知障碍的神经病理基础的数据有限。将死后指标整合到对增长最快的少数群体之一认知能力下降的风险因素的研究中是非常有创新性的，并有可能极大地提高对风险因素与神经病理相互作用影响认知能力和认知测试成绩种族差异的方式的理解。此外，这些发现可能对治疗干预和疾病预防具有重要意义。 公共卫生相关性：该项目将研究阿尔茨海默病病理和其他常见神经病理指标与风险因素和老年非裔美国人认知功能随时间变化的关系。这项研究的一个重要优势是，它将利用先前项目期有关认知功能以及感兴趣的生物和临床风险因素的详细信息，并对100多名非裔美国人进行量化尸检。这项研究的结果有望更好地了解神经病理指标在多大程度上导致非裔美国人的认知障碍，以及病理可能如何与重要的风险因素相互作用，影响认知功能的种族差异。

DESCRIPTION (provided by applicant): Cognitive decline associated with aging and Alzheimer's disease (AD) is among the most common and debilitating conditions, and poses a large and increasing public health problem. Projections indicate that the prevalence of aging-related chronic conditions is expected to increase substantially in the next decade. This will be particularly true for minority populations, especially the older African American population, which is growing at an even more rapid pace than the older White population. The Minority Aging Research Study (MARS) is a longitudinal cohort study of more than 350 older African Americans without dementia who agreed to annual clinical evaluations. During the previous project period we identified several risk factors for cognitive decline in African Americans. The overall goal of the proposed continuation is to quantify three common neuropathologic indices including Alzheimer's disease pathology, cerebral infarctions, and Lewy bodies in MARS participants, and examine their associations to cognitive function and clinical risk factors. In addition, to increase power and examine racial differences in these associations, we propose to use existing longitudinal clinical and neuropathologic data on Whites from two other ongoing cohort studies at Rush. Our Specific Aims are to: 1) examine the association of the three post-mortem neuropathologic indices to 1a: level of global cognition and five cognitive abilities, 1b: change in global cognition and five cognitive abilities; 2) examine racial differences in the associations of neuropathology to level of and change in cognitive function; 3) test the hypothesis that the APOE e4 allele is associated with increased levels of AD pathology, and the 52 allele is associated with a lower level of AD pathology in African Americans; and 4) examine the relationship of BMI to neuropathology, and test the hypothesis that BMI is more strongly associated with AD pathology in Whites than in African Americans. There is limited data on the neuropathologic basis of cognitive impairment in African Americans. Integrating post-mortem indices into a study of risk factors for cognitive decline in one of the fastest growing minority groups is highly innovative and has the potential to greatly increase understanding of the ways in which risk factors interact with neuropathology to influence cognition and racial disparities in cognitive test performance. Further, the findings could have important implications for therapeutic intervention and disease prevention. PUBLIC HEALTH RELEVANCE: This project will examine the association of Alzheimer disease pathology and other common neuropathologic indices on risk factors and change in cognitive function over time in older African Americans. An important strength of the study is that it will take advantage of the availability of detailed information on cognitive function and biological and clinical risk factors of interest from the prior project period and supplement it with quantitative postmortem measurements on more than 100 African Americans. Findings from this study are expected to provide a better understanding of the extent to which neuropathologic indices contribute to cognitive impairment in African Americans, and how pathology may interact with important risk factors to effect racial differences in cognitive function.