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

教育数量和质量对晚年认知功能和痴呆症诊断的因果影响的遗传差异

• 批准号: 10512946
• 负责人: Silvia Helena Barcellos
• 金额: $ 81.79万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10512946
• 关键词: Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Automobile Driving; Behavioral; Body mass index; Cessation of life; Characteristics; Childhood; Clinical; Cognition; Cognitive; Conceptions; Data; Data Set; Dementia; Diagnosis; Education; Educational Curriculum; Elderly; Family; Finland; Genes; Genetic; Genetic Databases; Genetic Risk; Genotype; Geography; Health; Hospitalization; Impaired cognition; Individual; Intelligence; International; Intervention; Knowledge; Life; Life Expectancy; Link; Liquid substance; Measures; Natural experiment; Netherlands; Outcome; Parents; Participant; Persons; Policies; Policy Maker; Prevalence; Primary Health Care; Process; Pupil; Registries; Research; Respondent; Risk Factors; Role; Running; Sampling; Schools; Smoking; Source; Student Selections; Students; Surveys; Variant; Visit; aging population; base; biobank; cognitive function; cognitive testing; cohort; conditioning; dementia risk; design; disparity reduction; family genetics; genetic analysis; health disparity; health record; higher education; improved; indexing; processing speed; prospective memory; residence; teacher; visual memory

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.

项目摘要/摘要 预期寿命和人口衰老的增长正在促使阿尔茨海默氏病急剧上升和相关 痴呆症（ADRD）。在这种情况下，重要的是要了解哪些因素可以改变ADRD风险和认知能力 年龄较大的年龄下降。教育已被确定为一个潜在的修饰符，因为高等教育是强大的 与较低的ADRD风险相关。但是，对于该关联的多少，知之甚少 从教育到ADRD风险的影响以及可能由遗传学等常见的第三个因素驱动的，可能 混淆并缓和这种关系。此外，超出教育数量的因素的相关性 - 特别是教育质量作为ADRD风险的驱动力的重要性，以及 教育与ADRD之间的关系 - 不太了解。填补这些知识空白是必不可少的 设计有效政策，旨在改善认知健康并降低ADRD风险的差异。 在这个项目中，我们建议研究教育，认知和ADRD风险之间的关联 在后期，是由于因果关系从教育数量和质量到认知/ADRD风险的因果影响。交易 以不同的人自选为不同类型和数量的教育的事实，我们将使用两个 自然实验：一项影响教育数量的学校改革（强制性教育）和 另一个影响质量的（学术课程）。我们将通过构造补充现有数据集 多基因指数（PGI）用于教育程度（EA）和阿尔茨海默氏病（AD），并通过联系 参与当地历史悠久的学校质量措施，例如学生/教师比例和教师薪水。这将允许 美国研究遗传学和学校质量在调节两项改革对ADRD的影响方面的作用。 我们将使用来自三个大型国际老年人群的数据：英国生物库（英国），芬兰（芬兰）和 生命线（荷兰）。这些队列使我们能够研究基于行政的ADRD诊断措施， ADRD风险因素和基于调查的认知措施。此外，这三个队列是基因型的， 允许我们探索遗传学在驱动ADRD风险中的作用，以及调节之间的关系 教育和ADRD风险。 确定教育是否对晚期认知和ADRD风险有因果影响是具有挑战性的，但是 确定临床和政策干预措施至关重要。没有因果证据，决策者不知道 教育是改善个人的后期认知健康还是教育协会是 反映了自我选择为教育的个体的特征的差异。而且，它同样是 重要的是要了解教育的哪些方面因果关系影响ADRD风险。增加的相对好处是什么 教育的数量与提高质量的数量？被预测获得更多教育的人是 基于它们的基因保护AD的遗传风险？缺乏这样的知识限制了 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。