Healthy Heart, Healthy Brain? A Pooled Life-course Cohort for Dementia Risk Assessment

摘要 导致痴呆症，特别是阿尔茨海默病的神经退化过程早在临床之前就开始了 特征变得明显，有几条证据表明，心血管危险因素的减少可能 是修改临床前阶段病程的最可行的策略之一。暴露于心血管疾病 风险因素开始于生命早期，并持续到成年期，性别和种族/民族明显 心血管疾病暴露发生的年龄差异。例如，黑人可能会在更早的时候显示， 与白人相比，暴露在心血管风险中的时间更长、更严重。然而，目前关于 这些暴露的时间和对认知老化和阿尔茨海默病的影响是有争议的，支持 需要一种终生的方法。例如，高血压的影响可能在中年更为不利。 而不是晚年生活。此外，越来越多的人达成共识，认为种族/族裔和性别差异存在风险。 阿尔茨海默病和认知功能可能存在。这些差异可能部分源于 患病率和累积心血管风险以及它们与阿尔茨海默氏症相关性的差异 疾病和认知。然而，缺乏针对这些关联的纵向研究 生命历程框架。这项研究将以一种新颖的方式使用已公布的统计方法来汇集多个数据和 创建一个集合队列，以便提供更好的特定年龄暴露于心血管疾病的估计 阿尔茨海默病生命过程中的风险因素和与衰老相关的认知结果。我们会 与四个共同跨越成人生活过程的双亲预期队列一起工作，并使用兼容的数据 主要心血管危险因素、中老年认知和痴呆症结局：冠状动脉 青年风险发展(CARDIA)，动脉粥样硬化的多种族研究(MESA)，心血管 健康研究(CHS)和健康、衰老和身体成分研究(Health ABC)。这个两极阵营将 使我们能够1)估计一生中暴露于心血管危险因素的风险，特别是对于患有 在生活的后期开始跟踪，然后2)确定影响认知的暴露类型和时间 阿尔茨海默病和其他痴呆症的下降和风险，以及3)这些暴露的修改如何 减少认知衰退和阿尔茨海默病以及种族和性别差异的负担。 了解这些暴露的修改如何可以减轻认知衰退的负担和 阿尔茨海默病对公共健康至关重要。

ABSTRACT Neurodegenerative processes leading to dementia, especially Alzheimer disease, begin long before clinical features become apparent, and several lines of evidence suggest that cardiovascular risk factor reduction may be one of the most viable strategies to modify the course of the preclinical phase. Exposure to cardiovascular risk factors begins early in life and continues throughout adulthood with pronounced gender and racial/ethnic differences in the age at which cardiovascular exposures develop. For example, Blacks may show earlier, longer and more severe exposure to cardiovascular risk than whites. However, current evidence about the timing and influence of these exposures on cognitive aging and Alzheimer disease is controversial, supporting the need for a life-course approach. For example, the effects of hypertension may be more adverse in mid-life than late-life. Furthermore, there is growing consensus that racial/ethnic and gender disparities in risk of Alzheimer disease and cognitive function may exist. These disparities may partly stem from differences in prevalence and cumulative cardiovascular risks, as well as differences in their association with Alzheimer disease and cognition. Yet, there is a paucity of longitudinal research addressing these associations within a life-course framework. This study will use published statistical methods in a novel way to pool multiple data and to create a pooled cohort in order to provide improved estimates of age-specific exposures to cardiovascular risk factors over the life-course on Alzheimer disease and cognitive outcomes associated with aging. We will work with four biracial prospective cohorts which together span the adult life-course, and with compatible data on major cardiovascular risk factors, mid and late life cognition and dementia outcomes: the Coronary Artery Risk Development in Young Adults (CARDIA), Multi Ethnic Study of Atherosclerosis (MESA), Cardiovascular Health Study (CHS), and Health, Aging and Body Composition Study (Health ABC). This poled cohort will enable us to 1) estimate life-course exposures to cardiovascular risk factors, in particular for participants with follow-up starting later in life, then 2) determine the type and timing of exposures that influence cognitive decline and risk of Alzheimer disease and other dementia, and 3) how modifications of these exposures may reduce the burden of cognitive decline and Alzheimer disease, as well as racial and gender disparities. Understanding how modifications of these exposures may reduce the burden of cognitive decline and Alzheimer disease is critical for public health.