Risk Factors for Cognitive Decline in African-Americans

描述（由申请人提供）：与衰老和阿尔茨海默病（AD）相关的认知能力下降是最常见和使人衰弱的疾病之一，并构成了一个巨大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疾病的患病率预计将在未来十年大幅增加。对于少数民族人口来说尤其如此，尤其是老年非洲裔美国人，他们的增长速度甚至比老年白人人口还要快。少数民族老龄化研究（MARS）是一项纵向队列研究，对350多名没有痴呆症的非裔美国老年人进行研究，他们同意每年进行临床评估。在上一个项目期间，我们确定了非洲裔美国人认知能力下降的几个风险因素。拟议继续研究的总体目标是量化MARS参与者的三个常见神经病理学指标，包括阿尔茨海默病病理学、脑梗死和路易小体，并检查它们与认知功能和临床危险因素的关系。此外，为了增强这些关联的力量并检验种族差异，我们建议使用拉什大学另外两项正在进行的队列研究中现有的白人纵向临床和神经病理学数据。我们的具体目的是：1)研究三种死后神经病理学指标与1a：全局认知水平和五种认知能力，1b：全局认知和五种认知能力的变化的关系；2)研究神经病理学与认知功能水平和变化之间的种族差异；3)验证APOE e4等位基因与非裔美国人AD病理水平升高有关，52等位基因与AD病理水平降低有关的假设；4)研究BMI与神经病理的关系，并验证白人的BMI与AD病理的关系比非裔美国人更强的假设。关于非裔美国人认知障碍的神经病理学基础数据有限。将死后指数整合到对一个增长最快的少数群体的认知能力下降的风险因素的研究中是非常具有创新性的，并且有可能大大增加对风险因素与神经病理学相互作用的方式的理解，从而影响认知和认知测试表现中的种族差异。此外，这些发现可能对治疗干预和疾病预防具有重要意义。

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.