Early life social influences on Cognitive Decline and Alzheimers Disease

摘要 越来越多的科学证据表明，阿尔茨海默病和相关疾病的可改变危险因素 痴呆症(ADRD)可以追溯到早年。大脑区域的发育，如海马体 树突棘在2岁时出现，神经在5岁时发生显著的发育。这个 儿童早期环境的影响被认为是通过多个系统发挥作用的，包括通过消极的 宫内条件，被认为受到父母资源、教育、物理环境、 父母的健康行为，如吸烟和营养不良。然而，由于持续时间较长， 在暴露和结果之间，几乎没有直接证据表明这些问题的规模和性质。 联想。目前的证据在很大程度上依赖于对早期环境的回溯性测量，这些测量是 易受回忆偏差的影响，特别是在研究痴呆症时。此外，童年的各个方面 环境往往很难理清，事实上，往往被认为是一个结构(即童年的SES)。 因此，关于早期生命因素可能有助于 防范未来的ADRD风险。父母R01的总体目标，长期的健康影响 新政：对4个队列(R01 AG059791)进行80年的随访，以了解长期 通过利用New Deal的空间差异，早期生活条件对慢性病结局的影响 投资。本补充申请的总体目标是促进对 通过测试三种特定类型的早期暴露对ADRD风险的影响：1)面积增加 2)额外的教育资源，3)更好的营养环境。至 为了实现我们的目标，我们建议使用来自四个国家的关于老年认知功能和/或痴呆症风险的数据 已建立的长期队列研究。这些数据已经(或目前正在)与1940年 完整的人口普查为我们提供了有关父母参与WPA和早期生活的准确信息 地址，使我们能够检查特定新政计划对ADRD长期风险的影响。 我们的中心假设是，新政计划的好处将与较低的ADRD水平相关 社区改善的个人面临的风险：1)就业，2)教育资源，3) 营养环境。我们的具体目标是，目标1：测试新政地区层面就业对 晚年ADRD风险，目标2：测试新政地方一级增加受教育机会的效果 晚年ADRD风险的机会，目标3：测试新政地区改善营养水平的效果 环境对晚年ADRD风险的影响。我们将在所有四个数据集中测试所有这三个特定目标，并且 组合跨数据集的影响估计以增强我们的统计能力，以及检查 我们的结果涵盖了四个不同的样本，增加了这些补充提案分析的严谨性。

ABSTRACT There is emerging scientific evidence that modifiable risk factors for Alzheimer’s disease and related dementias (ADRD) can be traced back to early life. Development of brain regions such as the hippocampus and dendritic spine occur by age 2 years and dramatic neural development occurs through age 5 years. The effects of early childhood environments are thought to operate through multiple systems, including via negative in-utero conditions, which are thought to be impacted by parental resources, schooling, physical environment, and parental health behaviors like smoking and poor nutrition. However, because of the long time duration between exposure and outcome, there is little direct evidence on the magnitude and nature of these associations. Current evidence relies most heavily on retrospective measures of early environments, which are subject to recall bias, particularly when studying dementia. Moreover, various aspects of childhood environments are often difficult to untangle, and in fact, often conceived as one construct (i.e. childhood SES). There is thus a gap in knowledge regarding the specific mechanisms by which early-life factors may help to protect against later-life ADRD risk. The overarching goal of the parent R01, The long-term health effects of the New Deal: An 80 year follow-up of 4 cohorts (R01 AG059791), is to understand the extent to which long-term chronic disease outcomes are impacted by early life conditions by leveraging spatial variation in New Deal investments. The overall objective of this supplemental application is to advance the scientific understanding of early-life influence on ADRD risk through testing three specific types of early-life exposures: 1) increased area level parental employment, 2) additional educational resources, and 3) better nutritional environments. To accomplish our objective, we propose to use data on old-age cognitive function and/or dementia risk from four established, long term cohort studies. These data have already been (or are currently being) linked to the 1940 complete count census providing us with information on parental WPA participation and early life exact address which allows us to examine the impacts of specific New Deal programs on the long-term risk of ADRD. Our central hypothesis is that benefits from New Deal programs will be associated with lower levels of ADRD risk for individuals whose communities had improved: 1) employment, 2) educational resources, and 3) nutritional environments. Our specific aims are, Aim 1: Test the effect of New Deal area level employment on later-life ADRD risk, Aim 2: Test the effect of New Deal local area level increased access to educational opportunities on later-life ADRD risk, Aim 3: Test the effect of New Deal area level improved nutritional environments on later-life ADRD risk. We will test all three of these specific aims in all four datasets, and combine effect estimates across datasets to increase our statistical power, as well as examine robustness of our results across four different samples, increasing the rigor of these supplemental proposal analyses.