title: The effects of ramipril in individuals at risk for Alzheimer's disease: results of a pilot clinical trial.
abstract: 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.
authors: Alzheimer's Disease Research Center, University of Wisconsin, Madison, WI 53705, USA. wlwharto@medicine.wisc.edu
authors: Whitney
authors: W
authors: Wharton
authors: James H
authors: JH
authors: Stein
authors: Claudia
authors: C
authors: Korcarz
authors: Jane
authors: J
authors: Sachs
authors: Sandra R
authors: SR
authors: Olson
authors: Henrik
authors: H
authors: Zetterberg
authors: Maritza
authors: M
authors: Dowling
authors: Shuyun
authors: S
authors: Ye
authors: Carey E
authors: CE
authors: Gleason
authors: Gail
authors: G
authors: Underbakke
authors: Laura E
authors: LE
authors: Jacobson
authors: Sterling C
authors: SC
authors: Johnson
authors: Mark A
authors: MA
authors: Sager
authors: Sanjay
authors: S
authors: Asthana
authors: Cynthia M
authors: CM
authors: Carlsson
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D055109:Ankle Brachial Index; D001057:Apolipoproteins E / Q000235:genetics; D001158:Arteries / Q000503:physiopathology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001794:Blood Pressure / Q000502:physiology; D001916:Brachial Artery / Q000000981:diagnostic imaging; D003071:Cognition / Q000502:physiology; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D007703:Peptidyl-Dipeptidase A / Q000134:cerebrospinal fluid; D010865:Pilot Projects; D017257:Ramipril / Q000627:therapeutic use*; D014463:Ultrasonography; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D000806:Angiotensin-Converting Enzyme Inhibitors; D001057:Apolipoproteins E; D015415:Biomarkers; D016875:tau Proteins; D007703:Peptidyl-Dipeptidase A; D017257:Ramipril