Cummings_2004_Am.J.Psychiatry_161_532

OBJECTIVE: Alzheimer's disease pathology includes both histologic changes and neurotransmitter deficits. The cholinergic deficit contributes to both cognitive and behavioral disturbances, and cholinesterase inhibitors may improve behavior in Alzheimer's disease patients. This analysis was conducted to assess the impact of galantamine, a cholinesterase inhibitor with nicotinic-receptor-modulating properties, on the pattern and evolution of behavioral disturbances in patients with Alzheimer's disease and on caregiver distress related to patients' behavior. METHOD: Data from 978 patients with mild to moderate Alzheimer's disease who were randomly assigned to placebo or galantamine (8, 16, or 24 mg/day) were analyzed. Behavioral changes were assessed with the Neuropsychiatric Inventory, and alterations in caregiver distress were measured by the Neuropsychiatric Inventory distress scale. Data collected at baseline and 12 and 21 weeks postbaseline were analyzed.
RESULTS: Neuropsychiatric Inventory scores worsened with placebo, whereas patients treated with 16 or 24 mg/day of galantamine had no change in total Neuropsychiatric Inventory scores. Treated patients, asymptomatic or symptomatic at baseline, had better Neuropsychiatric Inventory subscale scores than did patients receiving placebo. Behavioral improvement in patients symptomatic at baseline ranged from 29% to 48%. Changes were evident in patients receiving 16 or 24 mg/day of galantamine. High-dose galantamine was associated with a significant reduction in caregiver distress.
CONCLUSIONS: Galantamine therapy was associated with reduced emergence of behavioral disturbances and improvement in existing behavioral problems in patients with mild to moderate Alzheimer's disease, with a concomitant reduction in reported caregiver distress.