Rationale and Design of the Mechanistic Potential of Antihypertensives in Preclinical Alzheimer's (HEART) Trial

Whitney Wharton, Patrick Kehoe, Felicia C Goldstein, Malu G Tansey

Research output: Contribution to journalArticle (Academic Journal)

8 Citations (Scopus)
292 Downloads (Pure)

Abstract

Research indicates that certain antihypertensive medications alter Alzheimer’s disease (AD) biomarkers in Caucasians. The renin angiotensin system (RAS) regulates blood pressure (BP) in the body and the brain and may directly influence AD biomarkers, including amyloid-β (Aβ) neuropathology, cerebral blood flow (CBF), and inflammatory markers. This hypothesis is supported by studies, including ours, showing that antihypertensives targeting the RAS reduce the risk and slow the progression of AD in Caucasians. While mounting evidence supports a protective role of RAS medications in Caucasians, this mechanism has not been explored in African Americans. To assess the mechanism by which RAS medications modify the brain RAS, cerebrospinal fluid (CSF) Aβ, CBF, and inflammatory markers in African Americans, we are conducting an eight month, Phase Ib randomized, placebo controlled trial, enrolling 60 middle-aged (45–70 years), non-demented individuals, at risk for AD by virtue of a parental history. Participants include normotensive and treated hypertensives that have never been exposed to a RAS medication. Participants are randomized (1 : 1:1) by gender and BP medication use (yes/no) to one of three groups: placebo, or 20 mg, or 40 mg telmisartan (Micardis), to determine the dose required to penetrate the CNS. Our overarching hypothesis is that, compared to placebo, both doses of telmisartan will penetrate the CNS and produce salutary, dose dependent effects on the brain RAS as well as CSF Aβ, CBF, and CSF inflammatory markers in African Americans, over eight months. This manuscript describes the trial rationale and design.
Original languageEnglish
Pages (from-to)815-824
Number of pages10
JournalJournal of Alzheimer's Disease
Volume61
Issue number2
Early online date19 Dec 2017
DOIs
Publication statusPublished - Jun 2018

Keywords

  • Alzheimer’s disease
  • clinical trial
  • hypertension,
  • parental history
  • renin angiotensin system
  • vascular risk

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