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

阿尔茨海默病和相关痴呆症（ADRD）引起的痴呆对种族/族裔的影响不成比例 少数民族和社会经济弱势群体。制定有效的干预措施需要 理解远端基本力量，包括社会经济背景（即“邻里劣势”） 或特定地区健康的社会决定因素），使人们处于“[更接近]风险的风险”，如 个人水平的收入、教育、健康行为和共病。先前的研究支持这种背景 缺点是可以改变的，并与生物过程相互作用，产生疾病，但很少有人知道它的 对ADRD的影响。为此，我们创建了验证量化的邻里劣势的充分 我们这一地区发展指数包括贫困、教育、住房和就业指标; 预测与生育相关的健康结果;并通过我们的公共平台（社区）免费分享 Atlas）。我们已经验证了基于调查和公共数据的住宅历史追踪方法， 对生者和死者在整个生命过程中的邻里不利暴露的剂量和时间 人士我们已经证明，即使在调整了个体风险因素后， 缺点与认知功能，MRI显示的神经退行性变和死后 AD斑块神经病理学。然而，我们目前的样本缺乏地域多样性， 规模进行更强大的多因素表型风险评估的社会-生物相互作用及其 机制;开发新的治疗干预的必要基础。该提案采用 与22个阿尔茨海默病研究中心（ADRC）及其现有的认知，神经成像 和神经病理学数据。我们承担了大量的工作，为每个ADRC创建详细的住宅历史 受试者（N~ 9，234例存活，N~ 10，469例脑库）建立一个剂量和时间邻近的缺点 在每个生命周期中暴露。假设：更大和更早地暴露于邻里劣势， 预测认知功能降低、认知功能下降更快和疾病负担更大，包括AD神经病理学 在目标样本中。目的1：确定累积剂量和邻近时间的影响 不利暴露（按ADI指数），对认知功能和随时间的变化;目标2：AD特异性 神经影像学标记物（淀粉样蛋白和tau PET）和体积MRI的次要结果;以及 目的3：探讨神经病理组织学特点及诊断。目标4：使用现有的ADRC数据和新收集的数据 调查数据，确定个人种族/民族、年龄、性别、收入、教育、共同语言和 健康行为调节这些关系。这项拟议中的项目如果得到资助，将是同类研究中规模最大的一项 在AD背景下的健康社会决定因素。成功完成将导致开发一个 为未来的社会-生物表型评估提供新的背景暴露协作基础设施， 为新疗法提供了潜在的途径，并直接响应NIA的使命。

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.