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Principal Investigator: Brittany Butts
Organization: EMORY UNIVERSITY
Fiscal Year: 2023
Award: $192,780
Funding agency: National Institute on Aging
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.
Terms: <(TNF)-α><21+ years old><ACE2><AD dementia><Adult><Adult Human><Adventitial Cell><African American><Afro American><Afroamerican><Age><Age Years><Aging><Alzheimer Type Dementia><Alzheimer beta-Protein><Alzheimer disease dementia><Alzheimer risk factor><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Amyloid beta-Protein><Alzheimer's Disease><Alzheimer's Disease Pathway><Alzheimer's amyloid><Alzheimer's biomarker><Alzheimer's disease biological marker><Alzheimer's disease patient><Alzheimer's disease risk><Alzheimer's patient><Alzheimers Dementia><Alzheimer’s biological marker><Alzheimer’s disease biomarker><Amyloid (Aβ) plaques><Amyloid Alzheimer's Dementia Amyloid Protein><Amyloid Beta-Peptide><Amyloid Plaques><Amyloid Protein A4><Amyloid beta-Protein><Amyloid β><Amyloid β-Peptide><Amyloid β-Protein><Angiotensin Converting Enzyme><Angiotensin I-Converting Enzyme><Aβ><B cell differentiation factor><B cell stimulating factor 2><B-Cell Differentiation Factor><B-Cell Differentiation Factor-2><B-Cell Stimulatory Factor-2><BBB disruption><BCDF><BSF-2><BSF2><Beta Proprotein Interleukin 1><Biological Markers><Black><Black race><Blood><Blood - brain barrier anatomy><Blood Diseases><Blood Reticuloendothelial System><Blood Vessels><Blood capillaries><Blood-Brain Barrier><C-reactive protein><CCL2><CCL2 gene><CD140b Antigens><CD143 Antigens><Cachectin><Carboxycathepsin><Cardiac><Cardiac Output><Cardiovascular><Cardiovascular Body System><Cardiovascular Diseases><Cardiovascular Organ System><Cardiovascular system><Career Development Awards><Career Development Awards and Programs><Career Development Programs K-Series><Cerebrospinal Fluid><Cerebrovascular Circulation><Chemokine, CC Motif, Ligand 2><Data><Development><Diagnosis><Dipeptidyl Peptidase A><Disease><Disease Progression><Disorder><Dysfunction><EFRAC><Ejection Fraction><Elderly><Enrollment><Essential Hypertension><Functional disorder><Future><Goals><HP40><HPGF><Health Disparities Research><Health disparities related research><Heart Vascular><Heart failure><Hemato-Encephalic Barrier><Hematologic Diseases><Hematological Disease><Hematological Disorder><Hepatocyte-Stimulating Factor><High Prevalence><Homolog of Mouse T Cell and Mast Cell Growth Factor 40><Hybridoma Growth Factor><Hypertension><IFN-beta 2><IFNB2><IL-1 beta><IL-1 β><IL-1-b><IL-1β><IL-6><IL-9><IL1-Beta><IL1-β><IL1B Protein><IL1F2><IL1β><IL6 Protein><IL9 Protein><Individual><Inflammation><Inflammatory><Interleukin 1beta><Interleukin 9 Precursor><Interleukin-1 beta><Interleukin-1β><Interleukin-6><Interleukin-9><Intervention><Intervention Strategies><K-Awards><K-Series Research Career Programs><Kininase A><Kininase II><Knowledge><LVEF><Lead><Left Ventricular Ejection Fraction><Left Ventricular Hypertrophy><Light><Link><Longitudinal Studies><MCAF><MCP-1><MCP1><MGI-2><MT-bound tau><Macrophage-Derived TNF><Measures><Memory><Monocyte Chemoattractant Protein-1><Monocyte Chemotactic Protein-1><Monocyte Chemotactic and Activating Factor><Monocyte Chemotactic and Activating Protein><Monocyte Chemotactive and Activating Factor><Monocyte Secretory Protein JE><Monocyte-Derived TNF><Morbidity><Morbidity - disease rate><Myeloid Differentiation-Inducing Protein><Neuritic Plaques><Non-Hispanic><Nonhispanic><Not Hispanic or Latino><PDGF Receptor β><PDGF beta Receptor><PDGF β Receptor><PDGFR beta><PDGFR-β><Participant><Pathogenesis><Pathologic><Pathway interactions><Pb element><Peptidyl-Dipeptidase A><Pericapillary Cell><Pericytes><Perivascular Cell><Persons><Photoradiation><Physiologic pulse><Physiopathology><Plasmacytoma Growth Factor><Platelet-Derived Growth Factor Receptor Beta Polypeptide><Platelet-Derived Growth Factor Receptor β><Platelet-Derived Growth Factor beta Receptor><Play><Population><Preinterleukin 1 Beta><Prevalence><Primary Senile Degenerative Dementia><Proteins, specific or class, C-reactive><Pulse><Race><Races><Relative Risks><Renin-Angiotensin System><Research><Research Career Program><Risk><Risk Reduction><Role><Rouget Cells><SCYA2><Sampling><Science><Senile Plaques><Small Inducible Cytokine A2><T-Cell Growth Factor P40><T-Cell/Mast Cell Growth Factor p40><TNF><TNF A><TNF Alpha><TNF gene><TNF-α><TNFA><TNFα><Testing><Time><Training><Transforming Growth Factors><Translational Research Enterprise><Tumor Growth Factors><Tumor Necrosis Factor><Tumor Necrosis Factor-alpha><Vascular Diseases><Vascular Disorder><Vascular Hypertensive Disease><Vascular Hypertensive Disorder><Visuospatial><a beta peptide><abeta><abeta accumulation><abeta aggregation><adulthood><advanced age><ages><alzheimer risk><amyloid beta><amyloid beta accumulation><amyloid beta aggregation><amyloid beta plaque><amyloid β accumulation><amyloid β aggregation><amyloid-b plaque><amyloid-b protein><angiotensin converting enzyme 2><angiotensin converting enzyme II><arterial stiffening><arterial stiffness><artery stiffening><artery stiffness><aβ accumulation><aβ aggregation><aβ plaques><beta amyloid fibril><bio-markers><biologic marker><biomarker><blood disorder><blood vessel disorder><blood-brain barrier disruption><bloodbrain barrier><bloodbrain barrier disruption><brain blood flow><capillary><cardiac failure><cardiovascular disorder><cardiovascular risk><cardiovascular risk factor><career development><cerebral blood flow><cerebral circulation><cerebral hypoperfusion><cerebral spinal fluid><cerebrocirculation><cerebrovascular blood flow><circulatory system><clinical trial implementation><cognitive function><cohort><cored plaque><cytokine><developmental><diffuse plaque><disparity in health><elders><endothelial dysfunction><enroll><enzyme activity><experience><geriatric><health disparities science><health disparity><heart output><heavy metal Pb><heavy metal lead><high blood pressure><high risk><high risk group><high risk individual><high risk people><high risk population><hyper-phosphorylated tau><hyperphosphorylated tau><hyperpiesia><hyperpiesis><hypertensive disease><hypertensive disorder><idiopathic hypertension><implementation of clinical trials><improved><interferon beta 2><interventional strategy><late life><later life><long-term study><longitudinal outcome studies><longterm study><microtubule bound tau><microtubule-bound tau><mid life><mid-life><middle age><middle aged><midlife><mortality><neurofibrillary tangle formation><neurofilament><novel><older adult><older person><p-tau><p-τ><p40 Cytokine><p40 Protein><pathophysiology><pathway><patient living with Alzheimer's disease><patient suffering from Alzheimer's disease><patient with Alzheimer's><patient with Alzheimer's disease><phospho-tau><phospho-τ><phosphorylated tau><post-translational modification of tau><posttranslational modification of tau><predictive biomarkers><predictive marker><predictive molecular biomarker><preservation><primary degenerative dementia><primary hypertension><race differences><racial><racial background><racial difference><racial diversity><racial origin><racially diverse><reduce risk><reduce risks><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><risk-reducing><senile dementia of the Alzheimer type><senior citizen><social role><soluble amyloid precursor protein><spinal fluid><tangle formation><tau><tau Proteins><tau factor><tau phosphorylation><tau posttranslational modification><tau-1><transforming growth factors Animal growth regulators><translation research enterprise><translational research program><vascular><vascular dysfunction><vascular risk factor><vasculopathy><visual spatial><τ Proteins><τ phosphorylation>