While evidence linking the RAS and AD continues to mount, there are no therapeutic strategies targeting the RAS to prevent or delay AD. This Phase Ib RCT is the first step in understanding the potential of RAS acting medications in regard to CNS penetration and AD biomarkers with the future goal of repurposing an existing, inexpensive, safe drug. African Americans are not generally prescribed RAS medications, but when they are, doses higher than those prescribed to Caucasians are required to achieve BP control. It is unknown how these high doses alter systemic RAS levels or what dose is adequate to penetrate the CNS and alter brain RAS levels in African Americans. The dose is likely to be LOWER than the dose needed to alter BP, which is the case in Caucasians. Targeting individuals at high risk will help prevent and slow AD progression in as many people as possible, as fast as possible. Toward this goal, we must first understand the mechanistic potential of these medications in regard to the dose required to achieve CNS permeability, while safely controlling BP levels.

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​While African Americans represent only 13% of the U.S. population; they comprise 1/3 of the cost incurred from AD, half of which is concentrated in the South. African Americans comprise 61.4% of the population of Atlanta and 28.7% of the Georgia population. Thus, this trial has a unique opportunity to examine the influence of RAS medications in this high risk group. Emory is located in the “Stroke Belt” which has a high incidence of morbidity and mortality from cerebrovascular disease. In addition to having a two-fold risk for AD, African Americans are at increased risk for a host of vascular disorders. By characterizing the brain RAS, and its response to RAS medications in African Americans, we stand to glean invaluable information that could be used for prevention and treatment of vascular disease as well as AD and vascular dementia.