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The effects of ramipril in individuals at risk for Alzheimer’s disease: results of a pilot clinical trial


Wharton, Whitney, Stein, James H., Korcarz, Claudia, Sachs, Jane, Olson, Sandra R., Zetterberg, Henrik, Dowling, Maritza, Ye, Shuyun, Gleason, Carey E., Underbakke, Gail, Jacobson, Laura E., Johnson, Sterling C., Sager, Mark A., Asthana, Sanjay, Carlsson, Cynthia M.


Journal Of Alzheimer's Disease: JAD, Volume: 32, No.: 1, Pages.: 147-156

Year of Publication



Research shows that certain antihypertensives taken during midlife confer Alzheimer’s disease (AD) related benefits in later life. We conducted a clinical trial to evaluate the extent to which the angiotensin converting enzyme inhibitor (ACE-I), ramipril, affects AD biomarkers including cerebrospinal fluid (CSF) amyloid-β (Aβ) levels and ACE activity, arterial function, and cognition in participants with a parental history of AD. This four month randomized, double-blind, placebo-controlled, pilot clinical trial evaluated the effects of ramipril, a blood-brain-barrier crossing ACE-I, in cognitively healthy individuals with mild, or Stage I hypertension. Fourteen participants were stratified by gender and apolipoprotein E ε4 (APOE ε4) status and randomized to receive 5 mg of ramipril or matching placebo daily. Participants were assessed at baseline and month 4 on measures of CSF Aβ(1-42) and ACE activity, arterial function, and cognition. Participants were middle-aged (mean 54 y) and highly educated (mean 15.4 y), and included 50% men and 50% APOE ε4 carriers. While results did not show a treatment effect on CSF Aβ(1-42) (p = 0.836), data revealed that ramipril can inhibit CSF ACE activity (p = 0.009) and improve blood pressure, however, there were no differences between groups in arterial function or cognition. In this study, ramipril therapy inhibited CSF ACE activity and improved blood pressure, but did not influence CSF Aβ1-42. While larger trials are needed to confirm our CSF Aβ results, it is possible that prior research reporting benefits of ACE-I during midlife may be attributed to alternative mechanisms including improvements in cerebral blood flow or the prevention of angiotensin II-mediated inhibition of acetylcholine.;


adult, aged, alzheimer disease, amyloid betapeptides, angiotensinconverting enzyme inhibitors, ankle brachial index, apolipoproteins e, arteries, biological markers, blood pressure, brachial artery, cerebrospinal fluid, cognition, data interpretation statistical, dementia, doubleblind method, familial, family, female, genetics, history, humans, male, middle aged, neuropsychological tests, of, peptidyldipeptidase a, physiology, physiopathology, pilot projects, prevention & control, ramipril, tau proteins, therapeutic use, ultrasonography

Countries of Study


Types of Study

Non randomised controlled trial

Type of Outcomes

Cognition, Physical Health

Type of Interventions

Risk Factor Modification

Risk Factor Modifications

At risk population

Pharmaceutical Interventions