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.