Determinants of Midlife & Longitudinal Change in Cognitive Function: CARDIA Study

描述（由申请人提供）：几乎没有人知道在生命早期暴露于关键风险因素如何影响认知功能及其在生命后期的下降。有证据表明，导致痴呆，特别是阿尔茨海默病和血管性痴呆的神经病理过程，在临床特征变得明显之前几十年就开始了。最近的研究令人信服地表明，中年危险因素，特别是与心血管疾病和生活方式因素有关的因素，对晚年认知有重大影响。然而，对早期（例如年轻人）的风险因素及其对中年和晚年认知的影响知之甚少。我们建议通过对正在进行的CARDIA研究进行一项创新性辅助研究来解决这一差距。CARDIA是一项多中心前瞻性研究，研究对象为5,115名黑人和白色成年人，基线年龄为18-30岁（1985-86年），他们最近完成了第七次（25年）随访，其中测量了认知测试和脑部MRI，并将在2015-16年参加30年检查。我们建议对估计3100名参与者重复并增强30年访视的认知测试。在美国的第一项此类研究中，我们建议估计关键血管，代谢和生活方式因素的30年轨迹，并通过MRI量化大脑区域体积，以评估它们与成年后认知水平和变化的关系。此外，我们将使用已经收集的全基因组遗传数据来研究已知影响这些风险因素和大脑MRI结果的遗传变异与认知的关联。科学目标的完成将有助于确定认知变化何时开始开始发生在中年，使用生命过程方法将使我们能够研究从生命早期开始的长期暴露，希望研究风险因素修改的潜在影响。该提案具有很大的

DESCRIPTION (provided by applicant): Almost nothing is known about how exposure to key risk factors in early life influences cognitive function and its decline later in life. Evidence suggests that the neuropathologic process leading to dementia, especially Alzheimer disease and vascular dementia, begins decades before clinical features become apparent. Recent research has convincingly demonstrated that mid-life risk factors, especially those related to cardiovascular disease and lifestyle factors, have a substantial impact on later life cognition. However, much less is known about earlier, e.g. young adult, risk factors and their effect on cognition in mid-life and later. We propose to address this gap by conducting an innovative ancillary study to the ongoing CARDIA study. CARDIA is a multisite prospective study of 5,115 black and white adults, aged 18-30 years at baseline (1985-86), who recently completed their seventh (year 25) follow-up in which cognitive testing and brain MRIs were measured and who will be participating in a year 30 exam in 2015-16. We propose to repeat and augment the cognitive testing for the year 30 visit on an estimated 3100 participants. In the first study of it kind in the United States, we propose to estimate 30-year trajectories of key vascular, metabolic and lifestyle factors, and quantify brain region volumes by MRI to assess their relationship to level and change in cognition in adulthood. In addition, we will use already collected genome-wide genetic data to investigate the association of genetic variants, which are known to influence these risk factors and brain MRI outcomes, with cognition. Completion of the scientific aims will help determine when cognitive changes begin to occur in mid-life and the use of a life course approach will allows us to study long-term exposure, from early life onward, in hopes of studying the potential effect of risk factor modification. The proposal has great