title: Efficacy of higher-dose 13.3 mg/24 h (15 cm2) rivastigmine patch on the Alzheimer's Disease Assessment Scale-cognitive subscale: domain and individual item analysis.
abstract: OBJECTIVE
  Rivastigmine displays dose-dependent efficacy on cognition in patients with Alzheimer's disease (AD), as measured by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Subanalysis of the OPTIMA (OPtimising Transdermal Exelon In Mild-to-moderate Alzheimer's disease) study aimed to define ADAS-cog domains by factor analysis of individual items. Efficacy of 13.3 mg/24 h versus 9.5 mg/24 h rivastigmine patch on individual items and newly derived domains was assessed.
  
  
  METHODS
  OPTIMA was a 48-week, double-blind (DB) study in patients with mild-to-moderate AD. Patients meeting pre-defined decline criteria during open-label treatment with 9.5 mg/24 h patch were randomized in the DB phase to 13.3 mg/24 h (n = 280) or 9.5 mg/24 h (n = 287) patch. ADAS-cog change from baseline was a co-primary outcome measure. Factor analysis categorized ADAS-cog items into newly derived domains. Change from DB-baseline was calculated for domains and individual items.
  
  
  RESULTS
  Numerically, less decline was displayed with 13.3 mg/24 h versus 9.5 mg/24 h patch in the total ADAS-cog score at all time points (significant at Week 24, p = 0.027). Factor analysis identified two domains: memory and language. Significantly, less decline was observed on the memory domain with 13.3 mg/24 h versus 9.5 mg/24 h patch at Weeks 12, 24, and 48 (p < 0.05; observed cases). Three items (following commands, orientation, and word recognition) displayed numerically less decline with 13.3 mg/24 h versus 9.5 mg/24 h patch at all time points. No significant between-group differences were observed on the language domain.
  
  
  CONCLUSIONS
  Results suggest that the greater cognitive efficacy of 13.3 mg/24 h versus 9.5 mg/24 h rivastigmine patch is driven primarily by effects on memory, particularly in the areas of following commands, orientation, and word recognition.
authors.affiliation: ATP Clinical Research, Costa Mesa, CA, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Alva
authors.forename: Richard
authors.initials: R
authors.lastname: Isaacson
authors.forename: Carl
authors.initials: C
authors.lastname: Sadowsky
authors.forename: George
authors.initials: G
authors.lastname: Grossberg
authors.forename: Xiangyi
authors.initials: X
authors.lastname: Meng
authors.forename: Monique
authors.initials: M
authors.lastname: Somogyi
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D010054:Brief Psychiatric Rating Scale; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D003071:Cognition / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005163:Factor Analysis, Statistical; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D048448:Phenylcarbamates / Q000008:administration & dosage*; D000068836:Rivastigmine; D012720:Severity of Illness Index; D057968:Transdermal Patch
chemical_list: D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D048448:Phenylcarbamates; D000068836:Rivastigmine
keywords: Alzheimer's disease; clinical trial; cognitive function; rivastigmine