A putative amyloid-lowering agent, the blood pressure drug nilvadipine has proven ineffective in people with mild to moderate Alzheimer’s disease in a Phase 3 trial. In the September 24 PLoS Medicine, researchers led by Brian Lawlor at St. James’ Hospital, Dublin, reported that 18 months of treatment did not slow cognitive decline on the primary endpoints, the ADAS-Cog12 and the CDR sum of boxes. Biomarker analyses have not yet been published, so it is unclear if the drug hit its biologic targets.

  • Nilvadipine did not slow cognitive decline in mild to moderate AD.
  • Researchers are still analyzing biomarkers of target engagement.

Although nilvadipine lowers blood pressure by blocking calcium channels, this is thought to be unrelated to amyloid plaque reduction. In cell and animal models, nilvadipine suppresses Aβ production and boosts clearance of the peptide across the blood-brain barrier (Jul 2011 news). Mouse studies also indicate that nilvadipine inhibits the spleen tyrosine kinase (SYK), which activates the tau kinase GSK-3β, hence the drug potentially reduces tau phosphorylation, as well. In that same study, researchers reported that a known SYK inhibitor mimicked the effects of nilvadipine on amyloid and tau (Paris et al., 2014). Whether the purported amyloid and tau effects are related is unknown. 

In the Phase 3 trial, which began in 2013, researchers used a dose of nilvadipine, 8 mg once daily, that has minimal effects on blood pressure. Researchers recruited 511 participants from nine European countries, with 253 of them randomized to take nilvadipine, the rest placebo. Treatment and placebo groups were well-matched overall, although the treatment group had about twice as many diabetics. Participants had an average age of 73 and MMSE of 20 and met NINCDS-ADRDA criteria for Alzheimer’s, but the diagnosis was not confirmed with biomarkers.