Using a Natural Experiment to Evaluate the Long-Term Effects of Neighborhood Deprivation on Alzheimer's Disease and Vascular Risk Factors

摘要 NIA呼吁社会科学和社区研究，以澄清风险和保护因素， 阿尔茨海默病和相关痴呆症（ADRD），特别是在少数民族中， 不成比例地受到影响。地点，包括居住地和出生地区/州， 一直与ADRD、中风和认知功能受损相关。但目前尚不清楚， 可修改的机制解释这种关联，或者这种关联是否仅仅是由于选择 不健康的人进入贫困地区。这项研究的目标是产生第一个准实验性的 了解邻里社会经济剥夺对ADRD及其血管影响的证据 危险因素我们利用一个独特的自然实验，克服方法上的挑战， 关于ADRD的邻域效应的先前文献。从1986年到1998年，丹麦政府积极 以近乎随机（“准随机”）的方式将大约76，000名入境难民分散在全国各地 以避免在主要城市过度拥挤。这一队列包括近12，000名活到10岁的人。 在30年随访期间，丹麦至少60岁。超过90%的家庭同意参加 程序，创建一个自然的实验，其中这些人被准随机分配到 贫困程度不同的社区。我们将使用30多年来的独特数据， 丹麦的人口和临床登记，提供社会人口统计学数据，临床接触， 以及所有丹麦居民的处方。我们确定ADRD病例及其血管危险因素， 通过使用ICD编码和临床登记处处方数据的有效技术，我们 成功地将这些登记册与详细的地理编码数据源联系起来， 邻里社会经济剥夺。在目标1中，我们的目标是检验以下假设： 剥夺会增加晚年ADRD的发病率。在目标2中，我们将研究邻居的影响 剥夺ADRD的血管风险因素，包括一生中发生的高度流行的疾病 当然了在目标3中，我们将确定发生ADRD和血管风险因素的易感亚组， 不同的反应邻里剥夺，利用大样本量和完整的 登记所有科目的可用数据。我们将采用假设驱动和假设生成 统计技术，包括创新的机器学习方法，允许更复杂和更强大的 亚组识别这将使未来的干预措施能够针对最脆弱的个人。 总的来说，这项研究的预期结果是为邻里关系的影响提供严格的证据。 ADRD和血管风险因素的特征，克服了以前的方法学挑战 工作这将直接告知临床，社区和政策战略的发展，以解决 ADRD的邻里决定因素中的脆弱人群谁是最危险的。

ABSTRACT The NIA has called for social science and community-based studies to clarify risk and protective factors for Alzheimer's disease and related dementias (ADRD), particularly among racial minorities who are disproportionately affected. Place, including both neighborhood of residence and region/state of birth, has consistently been correlated with ADRD, stroke, and impaired cognitive function. Yet it is unclear whether modifiable mechanisms explain this association, or whether the association is merely due to the selection of unhealthy individuals into poor regions. The goal of this study is to produce the first quasi-experimental evidence to understand the influence of neighborhood socioeconomic deprivation on ADRD and its vascular risk factors. We take advantage of a unique natural experiment, overcoming methodological challenges in the previous literature on neighborhood effects on ADRD. From 1986 to 1998, the Danish government actively dispersed roughly 76,000 incoming refugees across the country in a nearly randomized (“quasi-random”) fashion to avoid over-crowding in major cities. This cohort includes nearly 12,000 individuals who lived until at least age 60 in Denmark during the 30-year follow-up. Over 90% of families agreed to participate in the program, creating a natural experiment in which these individuals were quasi-randomly assigned to neighborhoods with different levels of deprivation. We will employ unique data spanning over 30 years from Denmark's population and clinical registers, which provide data on sociodemographics, clinical encounters, and prescriptions for all Danish residents. We identify cases of ADRD and its vascular risk factors among this racially diverse cohort via validated techniques using ICD codes and prescription data in clinical registers. We have successfully linked these registers to detailed geocoded data sources on eight measures of neighborhood socioeconomic deprivation. In Aim 1, our goal is to test the hypothesis that neighborhood deprivation increases the incidence of ADRD later in life. In Aim 2, we will examine the effects of neighborhood deprivation on vascular risk factors for ADRD, including highly prevalent conditions that occur across the life course. In Aim 3, we will identify vulnerable subgroups whose development of ADRD and vascular risk factors differs in response to neighborhood deprivation, taking advantage of the large sample size and complete register data available on all subjects. We will employ both hypothesis-driven and hypothesis-generating statistical techniques, including innovative machine learning methods that allow for more complex and robust subgroup identification. This will enable future interventions to be tailored to the most vulnerable individuals. Overall, the expected outcome of this research is to produce rigorous evidence on the effects of neighborhood characteristics on ADRD and vascular risk factors, overcoming the methodological challenges in previous work. This will directly inform the development of clinical, community, and policy strategies to address the neighborhood determinants of ADRD among vulnerable populations who are most at-risk.