African AMERICANS Fighting Alzheimer's In Midlife

非裔美国人在中年时期与阿尔茨海默氏症作斗争

• 批准号: 9913432
• 负责人: CAREY E GLEASON
• 金额: $ 75.39万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9913432
• 关键词: Address; African American; Age; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-42; Area; Attenuated; Biological Markers; Cardiovascular Diseases; Cerebrum; Clinical; Cognition; Cognition Disorders; Cognitive; Cohort Studies; Collection; Communities; Data; Data Collection; Dementia; Development; Diagnosis; Disease; Disease Marker; Emotions; Fibrinogen; Foundations; Funding; Genetic Diseases; Genetic Risk; Goals; Hippocampus (Brain); Human; Image; Individual; Infrastructure; Intervention; Interview; Liquid substance; Measures; Methods; Modeling; Outcome; Participant; Phase; Positioning Attribute; Psychological Factors; Race; Recording of previous events; Recovery; Registries; Research; Resources; Risk; Risk Factors; Sampling; Self Efficacy; Social support; Symptoms; Underrepresented Groups; United States National Institutes of Health; Well in self; Wisconsin; Work; base; cognitive change; cohort; comorbidity; deprivation; disorder risk; economic cost; fighting; genetic variant; indexing; middle age; modifiable risk; neighborhood disadvantage; neuroimaging; novel; pre-clinical; rate of change; recruit; resilience; retention rate; socioeconomics; white matter

Recognizing that risk for Alzheimer's disease (AD) is multidimensional, the long-term goal of the AA-FAiM project (African Americans Fighting Alzheimer's in Midlife) is to identify modifiable targets for midlife intervention. Toward this, we will combine previously collected data and expand data collection in: (1) the Wisconsin AD Research Center (ADRC) and (2) the R01-funded Wisconsin Registry for Alzheimer's Prevention (WRAP) study for a total cross-sectional sample of ~500 subjects, age 45–65 at study entry. Additionally, we will collect optional biomarker data from no less than 40% of the cohort (n~200). Because biomarker data are a major focus of AD research, we will evaluate a recruitment and retention strategy for biomarker participation. We will also examine the interplay of risk and resilience factors, predicting longitudinal change in cognition. Our long-term goal is to build a unique cohort committed to the continued collection of longitudinal cognitive and biomarker data. Hypotheses and Specific Aims are as follows: Cross-sectional Hypothesis: When well-established fixed predictors, including genetic risks and parental history are held constant, preclinical AD pathology (inferred from disease markers) will be greater in cognitively healthy, middle-aged African Americans with (1) high CVD burden (estimated with ASCVD score), (2) with low self efficacy, social support, PiL, and an external LoC, (3) from disadvantaged neighborhoods, as measured with an index of neighborhood disadvantage, and the Area Deprivation Index (ADI).4 Aim 1: Examine the association of predictors listed above with an index of within subject variability, IICV. Aim 2: In a sub-set of AA-FAiM participants (~40% of cohort), examine the association of above predictors with neuroimaging and CSF biomarkers: hippocampal volume (HV) and the ratio of CSF Aβ42/P-tau181. Exploratory Aim 2.1: Conduct qualitative analysis of interview data gathered from participants who have participated in Biomarker substudies, as well as those who declined to participate, in order to explore efficacy of a Research – Community – Clinical (RCC) model of research recruitment and retention. Exploratory Aim 2.2: Examine the cross-sectional association of the above predictors with a novel neuroimaging outcome assessing cerebral blow flow: Phase Contrast – Vastly undersampled Isotropic Projection (PC-VIPR).5 Longitudinal Hypothesis: When well-established fixed predictors are held constant, longitudinal change in preclinical AD pathology (inferred from a cognitive disease marker) will be greater in cognitively healthy, middle-aged African Americans with a greater risk burden (described above). Aim 3: Examine the association of predictors listed above with rate of change in cognitive outcomes. Developmental Aim 3.1: Lay foundation for collection of longitudinal collection of neuroimaging and CSF biomarkers, i.e., hippocampal volume loss (HVL); and rate of change in the ratio of CSF Aβ42/P-tau181.

认识到阿尔茨海默氏病（AD）的风险是多维的，这是AA-FAIM的长期目标 项目（非洲裔美国人在中年与阿尔茨海默氏症战斗）是确定中年的可修改目标 干涉。在此方面，我们将结合先前收集的数据并扩展数据收集：（1） 威斯康星州广告研究中心（ADRC）和（2）阿尔茨海默氏症的R01资助的威斯康星州注册中心 预防（WRAP）研究〜500名受试者的总横断面样本，年龄45-65岁。 此外，我们将从不少于40％的队列（n〜200）中收集可选的生物标志物数据。因为 生物标志物数据是广告研究的主要重点，我们将评估招聘和保留策略 生物标志物参与。我们还将检查风险和弹性因素的相互作用，预测纵向 认知变化。我们的长期目标是建立一个独特的队列，致力于继续收集 纵向认知和生物标志物数据。假设和特定目的如下： 横断面假设：当建立良好的固定预测因子（包括遗传风险和父母）时 在认知上，历史保持恒定，临床前AD病理（从疾病标记中推断）将更大 健康的中年非裔美国人（1）高CVD Burnen（估计为ASCVD得分），（2），低 如测量 带有邻里灾难的指数，以及区域剥夺指数（ADI）。4 AIM 1：检查上面列出的预测因子的关联与主体变异性内部索引，IICV。 AIM 2：在AA-FAIM参与者的子集中（约占队列的40％），检查上述预测变量的关联 神经影像学和CSF生物标志物：海马体积（HV）和CSFAβ42/p-TAU181的比率。 探索目的2.1：对从参与者收集的访谈数据进行定性分析 参加了生物标志物的物种以及拒绝参加的生物标志物 研究招募和保留的研究的功效 - 社区 - 临床（RCC）模型。 探索性目标2.2：检查上述预测因子与新型预测因子的横截面关联 神经影像学评估大脑吹流的结果：相比 - 大量采样 各向同性投影（PC-VIPR）.5 纵向假设：当稳定的固定预测因子保持恒定时，纵向变化 临床前AD病理（从认知疾病标记中推断）在认知健康中会更大， 伯恩（Burnen）风险更大的中年非裔美国人（如上所述）。 AIM 3：检查上述预测变量与认知结果变化率的关联。 发展目的3.1：收集神经影像纵向的基础 CSF生物标志物，即海马体积损失（HVL）； CSFAβ42/p-TAU181的比率变化速率。