A prospective, double-blind, community-controlled comparison of three doses of galantamine in the treatment of mild to moderate Alzheimer's disease in a Korean population.

摘要

BACKGROUND: With the Korean population rapidly aging and the number of Koreans with Alzheimer's disease(AD) steadily growing, treatment of AD is becoming an increasing concern. Galantamine hydrobromide, a dual acetylcholinesterase inhibitor and allosteric modulator of nicotinic receptors, is being studied in the treatment of the disease. OBJECTIVE: This study compared the efficacy and tolerability of 3 doses of galantamine in a Korean population with mild to moderate AD. METHODS: In this prospective, multicenter, double-blind, community-controlled, comparative study, patients with mild to moderate AD were randomized to receive galantamine 8, 16, or 24 mg/d; patients were evaluated at baseline (week 0) and after 4, 8, and 16 weeks of treatment. A 4-week dose-titration schedule was used in the 16-and 24-mg/d groups. Also included were patients with AD from a community control group who were untreated and assessed at baseline and week 16. The primary efficacy outcome was change in cognitive function, as measured with the Korean version of the AD Assessment Scale-11-item cognitive subscale (ADAS-cog/11-K); secondary efficacy measures included changes in functional capacity, behavioral symptoms, and global impression (clinical response), as measured with the Korean versions of the Disability Assessment for Dementia Scale (DAD-K), Behavior Pathology in AD Rating Scale (BEHAVE-AD-K), and Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus-K). RESULTS: A total of 300 patients (228 women, 72 men) were enrolled (76, 78, 80, and 66 patients in the 8-, 16-,24-mg/d and community control groups, respectively). Significant differences in demographic characteristics were found between the galantamine and community control groups for age, sex, and duration of formal education (P = 0.042, P = 0.049, and P < 0.001, respectively). Results demonstrated a robust dose-response relationship between ADAS-cog/11-K and galantamine dosage compared with baseline and controls at 16 weeks. Mean (SE) improvements ranged from 3.7 (0.8) to 5.6 (0.8) points in the galantamine groups, whereas the control group deteriorated by 4.7 (0.5) points (P < 0.001). Similarly, significant improvements in all 3 treatment groups were observed in mean DAD-K, BEHAVE-AD-K, and CIBIC-plus-K scores (P < 0.001, P < 0.005, and P < 0.001, respectively). Galantamine was relatively well tolerated. CONCLUSIONS: This study found that galantamine effected significant benefits on the cognitive, functional, and behavioral symptoms of mild to moderate AD in this population of Korean patients. The tolerability results suggest that galantamine is well tolerated in these patients. Inc.