Lifetime stressors and Alzheimer's Disease genetic variants and biomarkers in relation to cognitive decline among Black Women'sHealth Study participants. - ABSTRACT Older Black Americans have higher rates of cognitive impairment and Alzheimer’s disease (AD) than their White counterparts, a disparity that is greater for Black women. Given the lack of effective therapies to slow disease progression and symptoms, effective prevention is needed. Most knowledge of risk factors for cognitive decline, the hallmark feature of AD, comes from studies of White populations and the contribution of racially/socially-patterned risk factors among Black adults remains under-studied. We propose to study 2,500 Black women ages 55 and older from the Black Women’s Health Study (BWHS), a follow-up study of 59,000 Black women from across the US. Our goal is to identify social factors that, together with biomarkers of AD, influence cognitive decline. The BWHS provides a unique opportunity to accomplish this goal. Over 27 years, the BWHS has collected data through biennial questionnaires from participants on socioeconomic, psychological, and physical stressors occurring at various times of life (e.g., low parental education, childhood sexual/physical abuse, interpersonal racism), as well as information on many potential risk factors for AD and cognitive decline (e.g., demographics, body size, behavioral factors (e.g., exercise, diet, smoking), medical history, reproductive history, medication use, health care). The BWHS has collected and stored blood from a large subsample of participants who agreed to wide sharing, such as GWAS results with other investigators and public databases. After enrollment of 2,500 such participants with already-collected blood samples from the BWHS, we propose to administer a validated telephone cognitive battery annually to measure cognition. We will also measure a panel of AT(N) plasma biomarkers and conduct GWAS in order to examine the associations of plasma biomarkers and genetic variants with cognitive decline. Based on the collected data and the results from biomarker assessments, we will assess the joint effects of the stressors and biomarkers on cognitive decline. A feasibility study demonstrated the willingness of BWHS participants to complete the cognitive test battery over the telephone and indicated that enough BWHS participants will participate to reach a study size of ~2,500 participants. The investigators have the experience and expertise to enroll participants; measure cognition with a validated telephone cognitive battery; measure AT(N) biomarkers in stored plasma and conduct GWAS; and with these data, to assess their separate and joint effects on cognitive decline. The proposed study provides an unparalleled opportunity to leverage a large national sample of older Black women on which comprehensive data on many factors that affect cognition have been collected to identify life-course risk factors for cognitive decline. The findings will have important translational implications for efforts to prevent cognitive decline in all populations, but especially in Black women who are disproportionately burdened.
