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

翻译后摘要：有一个强大的共识，最近由2017年柳叶刀委员会阐述， 痴呆症的根源以及预防痴呆症的可能性可以追溯到早期生活。然而， 生命早期对痴呆风险的影响，以及可以抵消这种风险的成年行为， 仍然知之甚少。缺乏具有丰富特征的完整生命历程的纵向研究 遗传、认知、地理、社会经济、教育和行为因素的测量。扎根生活 当然流行病学，这个项目旨在帮助澄清生物和行为过程，跨操作 影响痴呆风险的生命历程。这个框架的关键是早期生活的关键影响。结果 这项研究提供的证据可能会对公共政策和公共卫生产生重要影响， 特别是，早期的社会经济条件和成年后可改变的行为如何改变 AD/ADRD。因此，本研究的目的如下：目的1：跟踪痴呆症的进展， 认知表型（正常，AD痴呆，非AD痴呆），包括使用严格的AD诊断 方案，在威斯康星州纵向研究（WLS）中，一项60年的纵向研究。与会者将在他们的 基线时70多岁目的2：测试早期生活劣势/优势对后期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， 功能和生活在农村社区会影响晚年AD/ADRD的风险。现有措施 在WLS中捕捉这些早期生命因素在现有的痴呆症研究中是无与伦比的。目标3：测试 早期生活中的不利因素是否可以被成年后的行为保护因素所抵消。可随后 教育程度，即使在30多岁和40多岁时获得，以及参与健康行为（例如， 不吸烟，保持正常体重，参加锻炼），抵消了早期生活的不利因素， 认知功能水平较低，在社会经济上处于不利地位？兄弟姐妹模特，a 这些数据的独特特征，将提供一种机制，以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年人的行为是如何调解性与性之间的关系的 AD/ADRD。目的4：测试青少年的智商和教育程度是否会降低遗传风险， AD/ADRD。目标5：我们将创造一种公共产品：一种可以促进尖端痴呆症的数据资源 research.所有的研究人员-通过我们的网站-将有机会获得所有的数据WLS所提供的-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.