Wisconsin Longitudinal Study - Initial Lifetime's Impact on Alzheimer's Disease and Related Dementias (WLS-ILIAD Study)

摘要：2017年柳叶刀委员会最近发表了一项强有力的共识，即 痴呆症的根源--因此预防痴呆症的可能性--可以追溯到早年。然而， 早期生命周期对痴呆症风险的影响，以及可以抵消这种风险的成人行为， 人们对此仍然知之甚少。缺乏对完整生命历程的纵向研究。 衡量遗传、认知、地理、社会经济、教育和行为因素。植根于生活 课程流行病学，这个项目的目的是帮助阐明生物和行为过程 影响痴呆症风险的生命过程。这一框架的关键是早期生活的关键影响。发现 这项研究可能会对公共政策和公共卫生产生重要影响，因为它提供了以下证据 尤其是，早期生活的社会经济条件和成人的可改变的行为如何改变患癌症的风险 AD/ADRD。因此，这项研究的目标如下：目标1：追踪老年痴呆症的进展 认知表型(正常、阿尔茨海默病、非阿尔茨海默病)，包括使用严格的阿尔茨海默病诊断 方案，在威斯康星州纵向研究(WLS)，一项为期60年的纵向研究。参与者将在他们的 基准线为70年代末。目标2：测试早期生活劣势/优势对晚期AD/ADRD风险的作用 生活。特别是，我们将测试儿童时期持续的社会经济劣势，认知水平较低 功能障碍和生活在农村社区会影响AD/ADRD在晚年生活的风险。可用的措施 在WLS中捕捉这些早期生活因素在现有的痴呆症研究中是无与伦比的。目标3：测试 早期的生活劣势是否可以被成人的行为保护因素所抵消。可以后续 教育程度，即使是在30多岁和40多岁时获得的，以及对健康行为的参与(例如 不吸烟，保持正常体重，参加锻炼)，抵消了早年的不利因素，如 认知功能水平较低，在成长过程中处于社会经济劣势？兄弟姐妹模型，一个 这些数据的独特特征，将提供一种机制，部分解决潜在的遗传和家族 环境混杂因素。我们还将测试这些成人行为如何调停性与性之间的关系 和AD/ADRD。目标4：测试青少年智商和教育程度是否存在中等的遗传风险 AD/ADRD。目标5：我们将创造一个公共产品：一个可以促进新锐痴呆症的数据资源 研究。所有研究人员-通过我们的网站-将可以访问WLS提供的所有数据-这包括所有 表型和遗传数据。

Abstract: There is a robust consensus, most recently articulated by the 2017 Lancet Commission, that the roots of dementia—and thus the possibility for prevention of dementia—can be traced back to early life. Yet, the influence of the early life period on dementia risk, as well as adult behaviors that can offset that risk, remains poorly understood. There is a lack of longitudinal studies with richly characterized full life course measures of genetic, cognitive, geographic, socioeconomic, educational and behavioral factors. Rooted in life course epidemiology, this project aims to help clarify biological and behavioral processes that operate across the life course to influence dementia risk. Key to this framework is the critical influence of early life. Findings from this study could have important public policy and public health implications by providing evidence as to how, especially, early life socioeconomic conditions and adult modifiable behaviors can alter the risk for AD/ADRD. Consequently, the study aims are as follows: Aim 1: Track the progression of dementia across cognitive phenotypes (normal, AD dementia, non-AD dementia), including the use of rigorous AD diagnostic protocols, in the Wisconsin Longitudinal Study (WLS), a 60 year longitudinal study. Participants will be in their late 70s at baseline. Aim 2: Test the role of early life disadvantage/advantage on the risk for AD/ADRD in later life. In particular, we will test how persistent socioeconomic disadvantage in childhood, lower levels of cognitive functioning, and living in rural communities influence the risk for AD/ADRD in later life. The measures available in the WLS to capture these early life factors are unparalleled in existing dementia studies. Aim 3: Test whether early life disadvantage may be offset by adult behavioral protective factors. Can subsequent educational attainment, even when gained in ones 30s and 40s, and engagement in healthy behaviors (e.g. not smoking, maintaining a normal weight, and engaging in exercise), offset early life disadvantages such as lower levels of cognitive functioning and growing up socioeconomically disadvantaged? Sibling models, a unique feature of these data, will provide a mechanism to partially address potential genetic and familial environment confounders. We will also test how these adult behaviors mediate the relationship between sex and AD/ADRD. Aim 4: Test whether adolescent IQ and educational attainment moderate genetic risk for AD/ADRD. Aim 5: We will create a public good: a data resource that can facilitate cutting edge dementia research. All researchers-via our website- will have access to all the data WLS has to offer—this includes all phenotypic and genetic data.