Genetic Differences in the Causal Effect of Education Quantity and Quality on Cognitive Functioning and Dementia Diagnosis Later in Life

项目摘要/摘要 预期寿命的延长和人口老龄化正在推动阿尔茨海默病和相关疾病的急剧上升 痴呆(ADRD)。在这种情况下，了解哪些因素可以改变ADRD风险和认知是至关重要的 在较年长的年龄中出现衰退。随着高等教育的蓬勃发展，教育已被确定为一个潜在的修饰物 与较低的ADRD风险相关。然而，关于这种联系在多大程度上反映了因果关系，我们知之甚少。 从教育到ADRD风险的影响，以及在多大程度上是由共同的第三方因素驱动的，如遗传因素，可能 混淆和缓和这种关系。此外，教育质量以外的因素的相关性 -特别是教育质量的重要性，因为教育质量是消除灾害风险的驱动因素，也是 教育和ADRD之间的关系--还没有被很好地理解。填补这些知识空白是至关重要的 旨在改善认知健康和减少ADRD风险差异的有效政策的设计。 在这个项目中，我们打算研究教育、认知和ADRD风险之间的关联有多大 在晚年是由于从教育数量和质量到认知/ADRD风险的因果效应。去做交易 由于不同的人自己选择不同的教育类型和数量，我们将使用两种 自然实验：一项影响教育质量(义务教育年限)的学校改革 另一个影响质量的因素(学术课程)。我们将使用构建来补充现有的数据集 关于教育程度(EA)和阿尔茨海默病(AD)的多基因指数(PGI)，并通过将 参加当地历史悠久的学校质量指标，如学生/教师比例和教师工资。这将允许 美国将研究遗传学和学校质量在缓和两所学校改革对ADRD影响方面的作用。 我们将使用来自三个大型国际老龄化队列的数据：英国Biobank(英国)、FinnGen(芬兰)和 生命线(荷兰)。这些队列使我们能够研究ADRD诊断的行政措施， ADRD危险因素和以调查为基础的认知测量。此外，这三个群体都进行了基因分型， 使我们能够探索遗传学在驱动ADRD风险中的作用以及在调节 教育和ADRD风险。 要确定教育对晚年认知和ADRD风险是否有因果关系是具有挑战性的，但 对于确定临床和政策干预措施至关重要。没有因果证据，政策制定者不知道 是教育改善了个人晚年的认知健康，还是教育-ADRD协会 反映了自我选择接受教育的个人特征的差异。此外，它同样也是 重要的是要知道教育的哪些方面会对ADRD风险产生因果影响。增加的相对收益是什么？ 是教育的数量还是质量的提高？预计将接受更多教育的人 基于他们的基因保护免受阿尔茨海默病的遗传风险？缺乏这样的知识限制了设计 旨在减少ADRD风险差异的政策。我们的项目旨在开始填补这些知识空白。

Project Summary/Abstract Gains in life expectancy and population aging are driving a sharp rise in Alzheimer's Disease and Related Dementias (ADRD). In this context, it is crucial to understand what factors can modify ADRD risk and cognitive decline in older ages. Education has been identified as one potential modifier, as higher education is robustly associated with lower ADRD risk. However, little is known about how much of this association reflects a causal effect from education to ADRD risk and how much is driven by common third factors, such as genetics, that may confound and moderate this relationship. In addition, the relevance of factors beyond the quantity of education – in particular the importance of education quality as a driver of ADRD risk, as well as a moderator in the relationship between education and ADRD – are not well understood. Filling these knowledge gaps is essential to the design of effective policies aimed at improving cognitive health and reducing disparities in ADRD risk. In this project, we propose to study how much of the association between education, cognition and ADRD risk in late-life is due to a causal effect running from education quantity and quality to cognition/ADRD risk. To deal with the fact that different people self-select into different types and quantities of schooling, we will use two natural experiments: one school reform that affected education quantity (years of compulsory schooling) and another that affected quality (academic curriculum). We will supplement existing datasets with the construction of polygenic indexes (PGIs) for educational attainment (EA) and for Alzheimer's Disease (AD), and by linking participants to local historic school quality measures such as pupil/teacher ratios and teacher pay. This will allow us to study the role of genetics and school quality in moderating the effects of both school reforms on ADRD. We will use data from three large international aging cohorts: the UK Biobank (UK), FinnGen (Finland) and Lifelines (the Netherlands). These cohorts allow us to study administrative-based measures of ADRD diagnosis, ADRD risk factors and survey-based measures of cognition. Moreover, the three cohorts were genotyped, allowing us to explore the role of genetics in driving ADRD risk as well as in moderating the relationship between education and ADRD risk. Establishing whether education has a causal effect on late-life cognition and ADRD risk is challenging but essential for identifying clinical and policy interventions. Without causal evidence, policy makers do not know whether education improves individuals' later-life cognitive health or whether the education-ADRD association reflects differences in the characteristics of individuals who self-select into education. Moreover, it is equally important to know what aspects of education causally affect ADRD risk. What is the relative benefit of increasing the quantity of education versus improving its quality? Are individuals who are predicted to get more education based on their genes protected against genetic risk of AD? The lack of such knowledge limits the design of policies aimed at reducing disparities in ADRD risk. Our project aims to start filling these knowledge gaps.