Early life social influences on Cognitive Decline and Alzheimers Disease

早期生活社会对认知衰退和阿尔茨海默病的影响

• 批准号: 10289562
• 负责人: Sepideh Modrek
• 金额: $ 38.11万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10289562
• 关键词: 2 year old; 5 year old; Accounting; Address; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; American; Area; Back; Brain; Brain region; Censuses; Child; Child Development; Childhood; Chronic Disease; Communities; Data; Data Linkages; Data Set; Dementia; Dendritic Spines; Development; Disease Outcome; Elderly; Emergency Situation; Employment; Environment; Generations; Goals; Health; Health and Retirement Study; Health behavior; Hippocampus (Brain); Impaired cognition; Individual; Investments; Knowledge; Lead; Life; Life Cycle Stages; Link; Longitudinal Studies; Longitudinal cohort study; Measures; Nature; Nutritional; Observational Study; Outcome; Parents; Pathway interactions; Physical environment; Policies; Prevention strategy; Resolution; Resources; Risk Factors; Sampling; Schools; Scientific Advances and Accomplishments; Shapes; Smoking; Specificity; System; Testing; Time; United States; Variant; Wisconsin; Woman; Women' s Health; burden of illness; cognitive function; cohort; cost effective; data infrastructure; dementia risk; disorder risk; early childhood; early life exposure; education resources; follow-up; human old age (65+); improved; in utero; men; modifiable risk; neurodevelopment; nutrition; older women; panel study of income dynamics; prevent; programs; social; treatment strategy

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.

摘要 有新的科学证据表明，阿尔茨海默病及相关疾病的可改变的风险因素 痴呆症（ADRD）可以追溯到早期生活。海马体等大脑区域的发育 和树突棘发生在2岁时，戏剧性的神经发育发生在5岁时。的 儿童早期环境的影响被认为是通过多个系统运作的，包括通过消极的 子宫内的条件，这被认为是受父母的资源，学校教育，物理环境， 以及父母的健康行为，如吸烟和营养不良。然而，由于时间跨度长， 在暴露和结果之间，几乎没有直接证据表明这些影响的程度和性质 协会.目前的证据主要依赖于对早期环境的回顾性测量， 尤其是在研究痴呆症时。此外，童年的各个方面 环境往往很难解开，事实上，往往被视为一个结构（即儿童社会经济地位）。 因此，关于生命早期因素可能有助于 预防晚年ADRD风险。父R 01的总体目标， 新政：对4个队列进行80年随访（R 01 AG 059791），以了解长期 通过利用新政中的空间变化，慢性病的结果受到早期生活条件的影响 投资.本补充申请的总体目标是促进对以下问题的科学理解： 通过测试三种特定类型的早期生活暴露来研究早期生活对ADRD风险的影响：1）增加的区域 提高父母就业水平，2）增加教育资源，3）改善营养环境。到 为了实现我们的目标，我们建议使用来自四个国家的老年认知功能和/或痴呆症风险数据。 长期的队列研究。这些数据已经（或正在）与1940年的 完整的人口普查为我们提供了有关父母WPA参与和早期生活的信息 这使我们能够研究具体的新政计划对ADRD长期风险的影响。 我们的中心假设是，从新政计划的好处将与较低水平的ADRD 社区得到改善的个人的风险：1）就业，2）教育资源，3） 营养环境。我们的具体目标是，目标1：测试新政地区一级就业的影响， 晚年ADRD风险，目标2：测试新政局部地区水平增加教育机会的影响 机会对晚年ADRD风险，目的3：测试新政地区水平改善营养的影响 晚期ADRD风险的环境。我们将在所有四个数据集中测试这三个具体目标， 联合收割机对数据集的影响估计，以提高我们的统计能力，并检查 我们的结果在四个不同的样本，增加了这些补充建议书分析的严谨性。