Donepezil preserves cognition and global function in patients with severe Alzheimer disease

Neurology. 2007 Jul 31;69(5):459-69. doi: 10.1212/01.wnl.0000266627.96040.5a.


Objective: To evaluate the efficacy and safety of donepezil for severe Alzheimer disease (AD).

Methods: Patients with severe AD (Mini-Mental State Examination [MMSE] scores 1 to 12 and Functional Assessment Staging [FAST] scores > or =6) were enrolled in this multinational, double-blind, placebo-controlled trial at 98 sites. Patients were randomized to donepezil 10 mg daily or placebo for 24 weeks. Primary endpoints were the Severe Impairment Battery (SIB) and Clinician's Interview-Based Impression of Change-Plus caregiver input (CIBIC-Plus). Secondary endpoints included the MMSE, the Alzheimer Disease Cooperative Study-Activities of Daily Living-severe version (ADCS-ADL-sev), the Neuropsychiatric Inventory (NPI), the Caregiver Burden Questionnaire (CBQ), and the Resource Utilization for Severe Alzheimer Disease Patients (RUSP). Efficacy analyses were performed in the intent-to-treat (ITT) population using last post-baseline observation carried forward (LOCF). Safety assessments were performed for patients receiving > or =1 dose of donepezil or placebo.

Results: Patients were randomized to donepezil (n = 176) or placebo (n = 167). Donepezil was superior to placebo on SIB score change from baseline to endpoint (least squares mean difference 5.32; p = 0.0001). CIBIC-Plus and MMSE scores favored donepezil at endpoint (p = 0.0473 and p = 0.0267). Donepezil was not significantly different from placebo on the ADCS-ADL-sev, NPI, CBQ, or RUSP. Adverse events reported were consistent with the known cholinergic effects of donepezil and with the safety profile in patients with mild to moderate AD.

Conclusion: Patients with severe AD demonstrated greater efficacy compared to placebo on measures of cognition and global function.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activities of Daily Living
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Alzheimer Disease / psychology
  • Caregivers / statistics & numerical data
  • Cholinesterase Inhibitors / administration & dosage
  • Cholinesterase Inhibitors / adverse effects
  • Cognition / drug effects
  • Cognition / physiology
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology
  • Cognition Disorders / physiopathology
  • Disease Progression
  • Donepezil
  • Double-Blind Method
  • Female
  • Humans
  • Indans / administration & dosage*
  • Indans / adverse effects
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Piperidines / administration & dosage*
  • Piperidines / adverse effects
  • Placebos
  • Recovery of Function / drug effects*
  • Recovery of Function / physiology
  • Severity of Illness Index
  • Surveys and Questionnaires
  • Treatment Outcome


  • Cholinesterase Inhibitors
  • Indans
  • Piperidines
  • Placebos
  • Donepezil