Efficacy and tolerability of rivastigmine patch therapy in patients with mild-to-moderate Alzheimer's dementia associated with minimal and moderate ischemic white matter hyperintensities: A multicenter prospective open-label clinical trial

PLoS One. 2017 Aug 7;12(8):e0182123. doi: 10.1371/journal.pone.0182123. eCollection 2017.

Abstract

Background and objective: Studies investigating the impact of white matter hyperintensities (WMHs) on the response of acetylcholinesterase inhibitors in patients with Alzheimer's disease (AD) have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs.

Methods: Three hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog) from the baseline to the end of the study.

Results: Of the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 136; group 2, n = 46) during the 24-week study period. Demographic factors did not differ between group 1 and group 2. There were no significant differences in change in ADAS-cog between group 1 (-0.62±5.70) and group 2 (-0.23±5.98) after the 24-week rivastigmine patch therapy (p = 0.378). The patients in group 1 had a 0.63-point improvement from baseline on the Frontal Assessment Battery, while group 2 had a 0.16-point decline compared to baseline at the end of the study (p = 0.037). The rates of adverse events (AEs) (42.6 vs. 40.3%) and discontinuation due to AEs (10.3% vs. 4.3%) did not differ between the groups.

Conclusions: Although the efficacy and tolerability of rivastigmine patch therapy were not associated with WMH severity in patients with AD, some improvement in frontal function was observed in those with minimal WMHs.

Trial registration: ClinicalTrials.gov NCT01380288.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / drug therapy*
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Cholinesterase Inhibitors / administration & dosage*
  • Cholinesterase Inhibitors / adverse effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuroprotective Agents / administration & dosage*
  • Neuroprotective Agents / adverse effects
  • Republic of Korea
  • Rivastigmine / administration & dosage*
  • Rivastigmine / adverse effects
  • Severity of Illness Index
  • Transdermal Patch
  • Treatment Outcome
  • White Matter / diagnostic imaging
  • White Matter / drug effects

Substances

  • Cholinesterase Inhibitors
  • Neuroprotective Agents
  • Rivastigmine

Associated data

  • ClinicalTrials.gov/NCT01380288

Grants and funding

This study was supported by Novartis and the funding was received by KWP. This study was also supported by the Original Technology Research Program for Brain Science through the National Research Foundation of Korea (NRF), which is funded by the Korean government (Ministry of Science, ICT and Future Planning; No. 2014M3C7A1064752); this funding was received by SHC. The financial sponsors had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.