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)

• 批准号: 10361428
• 负责人: Barbara Brigitta Bendlin
• 金额: $ 630.81万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 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/10361428
• 关键词: Address; Alzheimer' s Disease; Alzheimer' 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; Distal; Dose; Education; Employment; Ethnic Origin; Evaluation; Exposure to; Foundations; Funding; Future; Geography; Goals; Government; Health; Health behavior; Housing; Human; Impaired cognition; Income; Individual; Individual Adjustment; Industry; Infrastructure; Interdisciplinary Study; Life Cycle Stages; Link; Magnetic Resonance Imaging; Mediating; Mediator of activation protein; Methodology; Mission; National Institute on Aging; Neighborhoods; Nerve Degeneration; Outcome; Participant; Partner in relationship; Pathologic; Pathway interactions; Persons; Phenotype; 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 and ethnic; randomized trial; secondary outcome; sex; social; social health determinants; socioeconomic disadvantage; socioeconomics; sociologist; tau Proteins; theories; therapy development

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.

阿尔茨海默病和相关痴呆(ADRD)对种族/民族的影响不成比例 少数群体和社会经济上的弱势群体。有效干预措施的发展需要机械化 理解远距离基本力量，包括社会经济背景(即“邻里劣势” 或某一特定地区健康的社会决定因素)，这些因素会使人们面临[更近的]风险，例如 个人水平的收入、教育、健康行为和合并症。先前的研究支持这一背景 劣势是可以改变的，并与生物过程相互作用而产生疾病，但人们对其知之甚少。 对ADRD的影响。为此，我们创建了经过验证的社区劣势量化方法 我们。该地区贫困指数(ADI)包括贫困、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)免费分享 阿特拉斯)。我们已经验证了基于调查和公共数据的住宅历史跟踪方法，这些方法建立了 在生者和已故者的整个生命过程中邻里劣势暴露的剂量和时间 人。我们已经证明，即使在对个别风险因素进行调整后，社区 劣势与认知功能、核磁共振显示的神经变性和尸检密切相关 AD斑块神经病理学。然而，我们目前的样本缺乏地理多样性，而且不足。 规模以对社会-生物相互作用及其影响进行更有力的多因素表型风险评估 机制；开发新的治疗干预措施的必要基础。这项提案采用了 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创造详细的住宅历史 受试者(N~9,234生活，N~10,469脑库)建立邻里劣势的剂量和时机 在每一个生命过程中都有接触。假设：更大和更早的邻居劣势敞口将 预测认知功能下降，认知衰退更快，以及更大的疾病负担，包括AD神经病理 在目标样本中。目标1：确定邻里累积剂量和时间的影响 劣势暴露(以ADI为索引)，关于认知功能和随时间的变化；目标2：关于特定于AD的 神经成像标记物(淀粉样蛋白和tau-PET)和容量磁共振二次结果； 目的3：探讨神经病理组织学特点及诊断。目标4：利用现有的ADRC数据和新收集的数据 调查数据，定义个人种族/民族、年龄、性别、收入、教育程度、共病和 健康行为是这些关系的中介。拟议中的项目，如果得到资助，将是同类研究中规模最大的 关于阿尔茨海默病背景下健康的社会决定因素。成功完成将导致开发一种 为未来的社会-生物表型评估提供背景暴露的新型协作基础设施， 提供新疗法的潜在途径，并直接响应NIA的使命。