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的长期目标是 该项目(非洲裔美国人在中年与阿尔茨海默氏症作斗争)是为中年确定可修改的目标 干预。为此，我们将结合以前收集的数据，并在以下方面扩大数据收集：(1) 威斯康星州AD研究中心(ADRC)和(2)R01资助的威斯康星州阿尔茨海默氏症注册中心 预防(WRAP)研究共抽样调查约500名受试者，研究开始时年龄在45-65岁之间。 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 生物标记物数据是AD研究的主要焦点，我们将评估招聘和保留战略 生物标记物的参与。我们还将研究风险和弹性因素的相互作用，预测纵向 认知上的变化。我们的长期目标是建立一支独特的队伍，致力于继续收集 纵向认知和生物标记物数据。假设和具体目标如下： 横截面假设：当确定的固定预测因素，包括遗传风险和父母 病史保持不变，临床前AD病理(从疾病标记物推断)在认知上将更大 健康的中年非裔美国人，有(1)高心血管负担(用ASCVD评分估计)，(2)低心血管负担 自我效能感、社会支持、PIL和外部LOC，(3)来自弱势社区 用邻里劣势指数和面积剥夺指数(ADI)。4 目标1：检查上面列出的预测因素与受试者内变异性指数IICV之间的联系。 目标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关联 神经影像和脑脊液生物标志物：海马体积(HV)和脑脊液Aβ42/P-tau181的比值。 试探性目标2.1：对从以下参与者收集的访谈数据进行定性分析 参加了Biomarker的子研究，以及那些拒绝参加的人，以便探索 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：检验上述预测因素与一部小说的横截面关联 评估脑血流的神经影像结果：相位对比-样本严重不足 各向同性投影(PC-VIPR)。5 纵向假设：当公认的固定预测因子保持不变时， 临床前AD病理(从认知疾病标记物推断)将在认知健康的人中更严重， 风险负担较大的中年非裔美国人(如上所述)。 目的3：检验上述预测因素与认知结果变化率之间的关系。 发展目标3.1：为收集纵向收集的神经成像和 脑脊液生物标志物，即海马区体积损失和脑脊液Aβ42/P-tau181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.