PROJECT SUMMARY/ABSTRACT
Black Americans experience a disproportionate burden of cardiovascular disease (CVD) risk factors and
Alzheimer's disease and related dementias (ADRD). Studies have identified midlife (~ ages 45-65)
dyslipidemia as a risk factor for ADRD. Black Americans have more favorable lipid profiles compared to Whites
or Latinos, but their incidence of dyslipidemia in midlife is higher. This seemingly paradoxical relationship
between favorable midlife lipid profiles yet high incidence of midlife dyslipidemia and high risk of ADRD among
Black Americans has been severely understudied. Lipids play a vital role in neurodegenerative disease, and
epidemiologic and metabolomic studies have identified commonly tested lipids (total cholesterol, HDL
cholesterol, LDL cholesterol, and triglycerides) as well as sphingolipids (ceramides) as predictors of cognitive
aging. Prior work has largely overlooked the contributions of lipids to ADRD risk in Black Americans and few
studies have examined the relationship of ceramides with cognitive aging and ADRD in this high-risk group.
This project will leverage over 40 years of longitudinal data from two NIH/NIA funded cohort studies, the Kaiser
Healthy Aging and Diverse Life Experiences (KHANDLE) Study and the Study of Health Aging in African
Americans (STAR), to better understand the role of lipids in cognitive aging and ADRD among Black
Americans. The scientific objective of this research plan is to characterize the relationship of early adulthood (~
age 30) total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides as well as the novel lipid
biomarker, ceramides, with late life cognitive decline, ADRD, and MRI markers of neurodegeneration and
vascular brain injury in an all-Black cohort of older adults. The proposed research seeks to: 1) define the role of
early adulthood lipids in cognitive aging and ADRD; 2) examine genetic (APOE) and psychosocial (racism)
factors as potential effect modifiers; and 3) determine whether the relationship of early adulthood lipid levels
with late life cognitive decline and ADRD is partially mediated by midlife (~ ages 45-65) cardiometabolic
disease (hypertension, diabetes, obesity, and dyslipidemia). For aging Black Americans with high prevalence
of CVD risk factors and at disproportionate risk of dementia, prevention of ADRD has enormous health and
economic consequences. This research will be complimented by a detailed training plan based at the
University of California, Davis, with guidance from an exceptional mentorship team of nationally and
internationally recognized ADRD, lipids, dementia, and cognitive aging researchers. The training will build upon
the applicant's background in CVD and dementia epidemiology by incorporating specialized training in
lifecourse theory and modern causal inference methods, biology of lipids, psychometric testing, and
measurement and modeling of neuroimaging biomarkers. The combined research and training will prepare the
applicant to successfully transition to an independent researcher of disparities in vascular contributions to
ADRD.