African AMERICANS Fighting Alzheimer's In Midlife

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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.