Galantamine in Alzheimer's Disease: 
A 6-month randomized, placebo-controlled trial 
with a 6-month extension. 
The Galantamine USA-1 Study Group.

Raskind MA, Peskind ER, Wessel T, Yuan W.

Veteran Affairs Puget Sound Health Care System
  and the Department of Psychiatry and Behavioral Sciences
University of Washington, Seattle, WA 98108, USA.


BACKGROUND: Galantamine is a reversible, competitive cholinesterase inhibitor that also allosterically modulates nicotinic acetylcholine receptors.  These mechanisms of action provided the rationale for a therapeutic trial of galantamine in AD. 

METHODS: A 6-month, multicenter, double-blind trial was undertaken in 636 patients with mild to moderate AD.  Patients were randomly assigned to placebo or galantamine and escalated to maintenance doses of 24 or 32 mg/d.  Eligible patients then entered a 6-month, open-label study of the 24 mg/d dose. Primary efficacy measures were the 11-item AD Assessment Scale cognitive subscale (ADAS-cog/11) and the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). The Disability Assessment for Dementia (DAD) scale was a secondary efficacy variable. 

RESULTS: Galantamine significantly improved cognitive function relative to placebo; the treatment effects were 3.9 points (lower dose) and 3.8 points (higher dose) on the ADAS-cog/11 scale at month 6 (p < 0.001 in both cases). Both doses of galantamine produced a better outcome on CIBIC-plus than placebo (p < 0.05). Therapeutic response to galantamine was not affected by APOE genotype. At 12 months, mean ADAS-cog/11 and DAD scores had not significantly changed from baseline for patients who received galantamine 24 mg/d throughout the 12 months. The most common adverse events, which were predominantly gastrointestinal, decreased in frequency during long-term treatment. There was no evidence of hepatotoxicity. 

CONCLUSIONS: Galantamine is effective and safe in AD. At 6 months, galantamine significantly improved cognition and global function. Moreover, cognitive and daily function were maintained for 12 months with the 24 mg/d dose.

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Research abstracts
  Galantamine: its use in Alzheimer's
  Galantamine: in Alzheimer's patients
acetylcholinesterase inhibition
  Galantamine: therapeutic effects beyond cognition
  Galantamine: benefits to Alzheimer's patients
nicotinic receptors modulation in Alzheimer's
  Galantamine: a study in Alzheimer's  
  Galantamine: its effects on Alzheimer's  
  Galantamine: a new treatment for Alzheimer's
  Galantamine: effect on nicotinic receptor binding
  Galantamine: an allosterically potentiating ligand
  Galantamine: nicotinic modulation in an animal model
  Galantamine: memory & nicotinic receptors effect in rats  
  Galantamine: a 6 month study