Apolipoprotein E genotype-specific short-term cognitive benefits of treatment with the antihypertensive nilvadipine in Alzheimer's patients--an open-label trial

Int J Geriatr Psychiatry. 2012 Apr;27(4):415-22. doi: 10.1002/gps.2735. Epub 2011 May 10.


Background: Evidence suggests that dihydropyridine calcium channel blockers may be useful in preventing and treating Alzheimer's disease (AD).

Objective: In an open-label trial of safety and tolerability of nilvadipine in patients with AD, we examined cognition and executive function over a short time period to determine an influence of nilvadipine on these outcomes.

Method: We investigated change in cognition using the Mini mental state examination and in executive function using the EXIT25 in 55 patients with AD who received nilvadipine 8 mg daily for 6 weeks compared with 30 non-treated subjects with AD. Apolipoprotein E genotyping was performed, and the study team and caregivers were kept blinded to APOE ε4 status during the trial.

Results: Aside from differences in gender and education, both the treatment and the control groups were similar in general demographics and on baseline cognition status. After correction for potential confounders, APOE ε4 status, and use of other antihypertensive medications, a significant impact of study intervention was observed on MMSE (F = 8.67, p < 0.01) and EXIT (F = 8.77, p < 0.03) scores. An interaction between APOE ε4 carrier status and treatment (p ≤ 0.05) was observed for both outcome measures.

Conclusion: In this open-label trial, among APOE ε4 non-carriers, we observed stabilization of cognition and improvement in executive function among treated individuals compared with non-treated individuals. Among APOE ε4 carriers, cognitive stabilization was evident for treated individuals whereas a cognitive decline was observed in non-treated individuals. These findings provide additional evidence for potential therapeutic efficacy of nilvadipine in treating AD and warrant further investigation.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / psychology
  • Antihypertensive Agents / therapeutic use*
  • Apolipoprotein E4 / genetics*
  • Cognition / drug effects*
  • Cohort Studies
  • Executive Function / drug effects
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Nifedipine / analogs & derivatives*
  • Nifedipine / therapeutic use


  • Antihypertensive Agents
  • Apolipoprotein E4
  • nilvadipine
  • Nifedipine