Midlife Vascular Risk Factors for Alzheimer's Disease in Persons with HFpEF

ABSTRACT
The purpose of this study is to determine the extent to which vascular risk factors are associated with
biomarkers of Alzheimer’s disease (AD) risk over time in middle aged adults with heart failure with preserved
ejection fraction (HFpEF). Mid-life cardiovascular risk factors contribute to the development of AD in later life
and to AD progression. Pathophysiologic mechanisms in HFpEF share mechanistic pathways implicated in AD
development, such as cerebral hypoperfusion, blood brain barrier (BBB) disruption, systemic and central
inflammation, and neurohormonal dysregulation. These AD pathways lead to accumulation of AD biomarkers
in cerebral spinal fluid (CSF) and blood. This study will enroll persons with HFpEF to elucidate vascular risk
factors specific to this understudied population with pathophysiologic drivers of vascular dysfunction associated
with AD risk. The proposed longitudinal study will test the hypothesis that midlife vascular risk factors predict
biomarkers of AD risk in persons with HFpEF. We will test the following Specific Aims in a high-risk cohort of
80 non-Hispanic White (n=40) and Black/African American (n=40) individuals during middle age (45-65yrs)
who have a diagnosis of HFpEF over 2 years: 1) assess the association of vascular risks with CSF biomarkers
of AD risk over two years in middle aged adults with HFpEF, 2) assess the association of vascular risks with
blood biomarkers of AD risk over two years in middle aged adults with HFpEF, and 3) assess the association
of vascular risks with cognitive function over two years in middle aged adults with HFpEF. This career
development award builds on previously developed strengths in studying mechanisms in cardiovascular
disease pathophysiology and aims to fill the gap related to Alzheimer’s disease research in the applicant’s
training. Specific career development goal included in this plan are: 1) gain expertise in the science of AD and
AD biomarkers, including collecting and analyzing AD biomarkers from blood and cerebrospinal fluid and
vascular function measures, 2) gain advanced training and experience in cognitive function measures, 3) gain
expertise in clinical trial implementation, 4) refine knowledge in health disparities research, and 5) transition to
independence and prepare for the next stage of my translational research program. Findings from this study
will lead to the identification of pathways that might be amenable to interventions that improve vascular
function for persons with HFpEF, with the goal of decreasing AD risk in this high morbidity population.

Grant Number: 5K23AG076977-03
NIH Institute/Center: NIH
Principal Investigator: Brittany Butts