The Neighborhoods Study: Contextual Disadvantage and Alzheimer’s Disease and Related Dementias (ADRD)

社区研究：环境劣势与阿尔茨海默病及相关痴呆症 (ADRD)

基本信息

批准号：
10803585
负责人：
Barbara Brigitta Bendlin
金额：
$ 349.4万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-01 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10803585
关键词：
Address Age Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Amyloid Animal Model Area Atlases Autopsy Back Behavior Biological Biological Process Biological Specimen Banks Brain California Clinical Code Cognitive Collaborations Consent Data Dementia Development Diagnosis Disadvantaged Disease Disparity Distal Dose Education Employment Ethnic Origin Evaluation Exposure to Foundations Funding Future Geography Goals Health Health behavior Housing Human Impaired cognition Income Individual Individual Adjustment Industry Infrastructure Interdisciplinary Study Life Cycle Stages Link Magnetic Resonance Imaging Mediating Mediator Methodology Mission National Institute on Aging Neighborhoods Nerve Degeneration Outcome Participant Partner in relationship Pathologic Pathway interactions Persons Phenotype Populations at Risk Positron-Emission Tomography Poverty Prevalence Race Recording of previous events Research Research Design Research Support Risk Risk Assessment Risk Factors Sampling Science Standardization Surveys Time Tissues Universities Wisconsin Work burden of illness cognitive change cognitive function comorbidity deprivation dosage effective intervention ethnic minority improved indexing mortality neighborhood association neighborhood disadvantage neuroimaging neuropathology neurophysiology novel novel therapeutic intervention novel therapeutics prospective public database racial minority randomized trial secondary outcome sex social social health determinants socioeconomic disadvantage socioeconomics sociologist tau Proteins theories therapy development

项目摘要

Dementia due to Alzheimer’s disease and related dementias (ADRD) disproportionately impacts racial/ethnic minorities and the socioeconomically disadvantaged. Development of effective interventions require mechanistic understanding of distal fundamental forces, including socioeconomic context (i.e. “neighborhood disadvantage” or the social determinants of health of a given area), that put people at “risk for [more proximal] risks” such as individual-level income, education, health behaviors and comorbidity. Prior research supports that contextual disadvantage is modifiable and interacts with biological processes to produce disease, yet little is known of its impact on ADRD. Towards this, we created validated quantifications of neighborhood disadvantage for the full US. This Area Deprivation Index (ADI) incorporates poverty, education, housing and employment indicators; predicts disparity-related health outcomes; and is freely shared through our public platform (the Neighborhood Atlas). We have validated survey and public data-based residential history tracing methodologies that establish dosage and timing of neighborhood disadvantage exposure across a life-course for both living and deceased persons. We have demonstrated that even after adjustment for individual risk factors, neighborhood disadvantage is strongly associated with cognitive function, neurodegeneration shown on MRI, and post-mortem AD plaque neuropathology. However, our current sample is lacking in geographic diversity and is of insufficient size to conduct a more robust multi-factor phenotypic risk assessment of social-biological interactions and their mechanisms; a necessary foundation towards developing new therapeutic intervention. This proposal employs collaboration with 22 Alzheimer’s Disease Research Centers (ADRC) and their existing cognitive, neuroimaging and neuropathology data. We take on the substantial work to create detailed residential histories for each ADRC subject (N~9,234 living, N~10,469 brain bank) to establish a dosage and timing of neighborhood disadvantage exposure across each life-course. Hypothesis: Larger and earlier exposures to neighborhood disadvantage will predict lower cognitive function, faster cognitive decline and greater disease burden including AD neuropathology among the targeted sample. Aim 1: Determine the impact of the cumulative dose and timing of neighborhood disadvantage exposure (indexed by ADI), on cognitive function and change over time; Aim 2: on AD-specific markers indexed by neuroimaging (amyloid and tau PET) and the secondary outcome of volumetric MRI; and Aim 3: on neuropathologic tissue features and diagnosis. Aim 4: Using existing ADRC data and newly collected survey data, define the extent to which individual race/ethnicity, age, sex, income, education, comorbidity and health-behaviors mediate these relationships. The proposed project, if funded, will be the largest study of its kind on social determinants of health in the context of AD. Successful completion will result in the development of a novel collaborative infrastructure of contextual exposure for future social-biological phenotypic evaluation, providing a potential pathway to new therapeutics, and directly responsive to the NIA mission.

由于阿尔茨海默氏病和相关痴呆症（ADRD）导致的痴呆症对种族/种族的影响不成比例少数民族和社会经济处于不利地位。开发有效干预需要机械了解远端基本力量，包括社会经济背景（即“邻里灾难”）或给定地区健康的社会决定者），使人们处于“有[更近端]风险的风险”，例如个人级别的收入，教育，健康行为和合并症。先前的研究支持这种背景劣势是可修改的，并且与生物学过程相互作用以产生疾病，但知之甚少对ADRD的影响。为此，我们创建了对邻里灾难的经过验证的量化我们。该地区剥夺指数（ADI）纳入了贫困，教育，住房和就业指标；预测与差异相关的健康结果；并通过我们的公共平台（社区）自由共享地图集）。我们已经验证了建立的调查和基于公共数据的居民历史记录追踪方法生命和死者的生命过程中邻里灾难暴露的剂量和时机人。我们已经证明，即使调整了个人风险因素，社区缺点与认知功能，MRI上显示的神经退行性和验尸密切相关 AD斑块神经病理学。但是，我们目前的样本缺乏地理多样性，并且不足进行更强大的多因素表型风险评估社会生物互动及其的大小机制；发展新的治疗干预措施的必要基础。该提案员工与22个阿尔茨海默氏病研究中心（ADRC）及其现有的认知，神经影像合作和神经病理学数据。我们从事大量工作，为每个ADRC创建详细的居民历史主题（N〜9,234 Living，N〜10,469 Brain Bank）建立剂量和邻里灾难时机每个生命过程中的暴露。假设：对邻里灾难的更大和更早的暴露将预测较低的认知功能，更快的认知能力下降和更大的疾病燃烧包括AD神经病理在目标样本中。目标1：确定累积剂量和邻里时间的影响缺点暴露（由ADI索引），关于认知功能和随着时间的变化； AIM 2：在广告中由神经成像（淀粉样蛋白和Tau PET）和体积MRI的次要结果索引的标记；和目标3：对神经病理组织特征和诊断。 AIM 4：使用现有的ADRC数据并新收集调查数据，定义个人种族/种族，年龄，性别，收入，教育，合并症的程度健康行为调解了这些关系。拟议的项目（如果资助）将是同类项目的最大研究关于在AD背景下健康的社会决定者。成功完成将导致发展对未来社会生物表型评估的上下文暴露的新型协作基础设施，提供了通往新疗法的潜在途径，并直接响应了NIA任务。