PMID- 28786987
OWN - NLM
STAT- MEDLINE
DCOM- 20171004
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 8
DP  - 2017
TI  - 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.
PG  - e0182123
LID - 10.1371/journal.pone.0182123 [doi]
LID - e0182123
AB  - 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.
FAU - Park, Kyung Won
AU  - Park KW
AUID- ORCID: 0000-0002-4180-8626
AD  - Department of Neurology, Cognitive Disorders and Dementia Center, Dong-A 
      University College of Medicine and Institute of Convergence Bio-Health, Busan, 
      South Korea.
FAU - Kim, Eun-Joo
AU  - Kim EJ
AD  - Department of Neurology, Pusan National University Hospital and Biomedical 
      Research Institute, Pusan National University School of Medicine, Busan, South 
      Korea.
FAU - Han, Hyun Jeong
AU  - Han HJ
AD  - Department of Neurology, Seonam University College of Medicine, Myongji Hospital, 
      Goyang, South Korea.
FAU - Shim, Yong S
AU  - Shim YS
AD  - Department of Neurology, Holy Family Hospital, The Catholic University of Korea, 
      School of Medicine, Bucheon, South Korea.
FAU - Kwon, Jae C
AU  - Kwon JC
AD  - Department of Neurology, Changwon Fatima Hospital, Changwon, South Korea.
FAU - Ku, Bon D
AU  - Ku BD
AD  - Department of Neurology, Catholic Kwandong University College of Medicine, 
      Gangneung, South Korea.
FAU - Park, Kee Hyung
AU  - Park KH
AD  - Department of Neurology, Gachon University Gil Hospital, Incheon, South Korea.
FAU - Yi, Hyon-Ah
AU  - Yi HA
AD  - Department of Neurology, Keimyung University College of Medicine, Daegu, South 
      Korea.
FAU - Kim, Kwang K
AU  - Kim KK
AD  - Department of Neurology, Dongguk University College of Medicine, Seoul, South 
      Korea.
FAU - Yang, Dong Won
AU  - Yang DW
AD  - Department of Neurology, The Catholic University of Korea, School of Medicine, 
      Seoul, South Korea.
FAU - Lee, Ho-Won
AU  - Lee HW
AD  - Department of Neurology, Kyungpook National University School of Medicine, Daegu, 
      South Korea.
FAU - Kang, Heeyoung
AU  - Kang H
AD  - Department of Neurology, Gyeongsang National University College of Medicine, 
      Jinju, South Korea.
FAU - Kwon, Oh Dae
AU  - Kwon OD
AD  - Department of Neurology, Catholic University of Daegu School of Medicine, Daegu, 
      South Korea.
FAU - Kim, SangYun
AU  - Kim S
AD  - Department of Neurology, Seoul National University College of Medicine, Seoul 
      National University Bundang Hospital, Seongnam, South Korea.
FAU - Lee, Jae-Hyeok
AU  - Lee JH
AD  - Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, 
      South Korea.
FAU - Chung, Eun Joo
AU  - Chung EJ
AD  - Department of Neurology, Busan Paik Hospital, Inje University College of 
      Medicine, Busan, South Korea.
FAU - Park, Sang-Won
AU  - Park SW
AD  - Department of Neurology, Daegu Fatima Hospital, Daegu, South Korea.
FAU - Park, Mee Young
AU  - Park MY
AD  - Department of Neurology, Yeungnam University College of Medicine, Daegu, South 
      Korea.
FAU - Yoon, Bora
AU  - Yoon B
AD  - Department of Neurology, Konyang University College of Medicine, Daejeon, South 
      Korea.
FAU - Kim, Byeong C
AU  - Kim BC
AD  - Department of Neurology, Chonnam National University School of Medicine, Gwangju, 
      South Korea.
FAU - Seo, Sang Won
AU  - Seo SW
AD  - Department of Neurology, Samsung Medical Center, Sungkyunkwan University School 
      of Medicine, Seoul, South Korea.
FAU - Choi, Seong Hye
AU  - Choi SH
AD  - Department of Neurology, Inha University School of Medicine, Incheon, South 
      Korea.
LA  - eng
SI  - ClinicalTrials.gov/NCT01380288
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
DEP - 20170807
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - PKI06M3IW0 (Rivastigmine)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*diagnostic imaging/*drug therapy
MH  - Brain/diagnostic imaging/drug effects
MH  - Cholinesterase Inhibitors/*administration & dosage/adverse effects
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neuroprotective Agents/*administration & dosage/adverse effects
MH  - Republic of Korea
MH  - Rivastigmine/*administration & dosage/adverse effects
MH  - Severity of Illness Index
MH  - Transdermal Patch
MH  - Treatment Outcome
MH  - White Matter/diagnostic imaging/drug effects
PMC - PMC5546604
COIS- Competing Interests: KWP received funding from Novartis for this study. This does 
      not alter the authors' adherence to all the PLOS ONE policies on sharing data and 
      materials. There are no patents, products in development or marketed products to 
      declare.
EDAT- 2017/08/09 06:00
MHDA- 2017/10/05 06:00
PMCR- 2017/08/07
CRDT- 2017/08/09 06:00
PHST- 2017/02/03 00:00 [received]
PHST- 2017/07/12 00:00 [accepted]
PHST- 2017/08/09 06:00 [entrez]
PHST- 2017/08/09 06:00 [pubmed]
PHST- 2017/10/05 06:00 [medline]
PHST- 2017/08/07 00:00 [pmc-release]
AID - PONE-D-17-03421 [pii]
AID - 10.1371/journal.pone.0182123 [doi]
PST - epublish
SO  - PLoS One. 2017 Aug 7;12(8):e0182123. doi: 10.1371/journal.pone.0182123. 
      eCollection 2017.