African AMERICANS Fighting Alzheimer's In Midlife

认识到阿尔茨海默病（AD）的风险是多方面的，AA-FAiM的长期目标 一个名为“非裔美国人在中年对抗阿尔茨海默氏症”的项目旨在确定中年人可改变的目标 干预为此，我们将结合联合收割机以前收集的数据，并在以下方面扩大数据收集： 威斯康星州AD研究中心（ADRC）和（2）R 01资助的威斯康星州阿尔茨海默病登记处 预防（WRAP）研究，共有约500例受试者的横断面样本，研究入组时年龄为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AD研究的主要焦点，我们将评估招募和保留策略， 生物标志物参与。我们还将研究风险和弹性因素的相互作用，预测纵向 认知的改变。我们的长期目标是建立一个独特的队列，致力于持续收集 纵向认知和生物标志物数据。假设和具体目标如下： 横断面假设：当建立良好的固定预测因素，包括遗传风险和父母 如果病史保持不变，则临床前AD病理学（从疾病标志物推断）在认知方面将更大 健康的中年非裔美国人，（1）高CVD负担（用ASCVD评分估计），（2）低CVD负担 自我效能、社会支持、PiL和外部LoC，（3）来自弱势社区， 与邻里劣势指数，以及区域发展指数（ADI）。 目的1：检查上述预测因子与受试者内变异指数（IICV）的相关性。 目的2：在AA-FAiM参与者的子集（约40%的队列）中，检查上述预测因素的相关性 采用神经影像学和CSF生物标志物：海马体积（HV）和CSF Aβ42/P-tau 181比值。 探索性目标2.1：对从参与者那里收集的访谈数据进行定性分析， 参加了生物标志物亚组研究，以及那些拒绝参加的人，以探索 研究-社区-临床（RCC）研究招募和保留模式的有效性。 探索性目标2.2：检查上述预测因子与新的 评估脑血流的神经影像学结果：相位对比-严重欠采样 各向同性投影（PC-VIPR）.5 纵向假设：当既定的固定预测因子保持不变时， 临床前AD病理学（从认知疾病标志物推断）在认知健康的人中将更大， 中年非裔美国人有更大的风险负担（如上所述）。 目标3：检查上面列出的预测因素与认知结果变化率的关联。 发展目标3.1：为纵向收集神经影像学资料奠定基础， CSF生物标志物，即，海马体积丢失（HVL）; CSF Aβ42/P-tau 181比值的变化率。

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.