Long-term safety and efficacy of donepezil in patients with severe Alzheimer's disease: results from a 52-week, open-label, multicenter, extension study in Japan.

BACKGROUND/AIMS: A 6-month, randomized, double-blind, placebo-controlled study was extended to evaluate long-term safety and efficacy of donepezil in community-dwelling Japanese patients with severe Alzheimer's disease (AD). METHODS: 189 patients were enrolled from the double-blind study into a 52-week, open-label extension study. After a 2- to 8-week washout, donepezil was escalated within 6 weeks to 10 mg/day. Main outcomes were Severe Impairment Battery (SIB), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale for severe AD (ADCS-ADL-sev) and Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). Safety parameters were monitored throughout. RESULTS: Overall, mean change from extension study baseline in SIB scores improved until week 24; however, scores were influenced by prior treatment during the double-blind study and by length of washout. Patients treated with donepezil retained some treatment benefits after a washout of 2-4 weeks but lost all treatment benefits after a washout of 4-8 weeks. There was no change in ADCS-ADL-sev or BEHAVE-AD scores. Adverse events were consistent with the known donepezil safety profile. CONCLUSION: Donepezil is effective and safe for symptomatic treatment of severe AD for at least 1 year. Patients who receive donepezil 10 mg daily with little or no interruption achieve the best long-term outcome.

Donepezil treatment of patients with severe Alzheimer's disease in a Japanese population: results from a 24-week, double-blind, placebo-controlled, randomized trial.

BACKGROUND/AIMS: A 24-week, randomized, parallel-group, double-blind placebo-controlled study was conducted to evaluate the efficacy and tolerability of donepezil in severe Alzheimer's disease (AD). METHODS: Patients with severe AD (Mini-Mental State Examination score 1-12; modified Hachinski Ischemic Score < or =6; Functional Assessment Staging > or =6) were enrolled in this study in Japan. A total of 325 patients were randomized to donepezil 5 mg/day (n = 110), donepezil 10 mg/day (n = 103) or placebo (n = 112). Primary outcome measures were change from baseline to endpoint in the Severe Impairment Battery (SIB) and Clinician's Interview-Based Impression of Change-plus caregiver input (CIBIC-plus) at the endpoint visit. RESULTS: Donepezil 5 mg/day and 10 mg/day were significantly superior to placebo on the SIB, with a least-squares mean treatment difference of 6.7 and 9.0, respectively (p < 0.001 compared with placebo). CIBIC-plus analyses showed significant differences in favor of donepezil 10 mg/day over placebo at endpoint (p = 0.003). A statistically significant dose-response relationship was demonstrated with the SIB and CIBIC-plus. Donepezil was well tolerated. CONCLUSION: This study confirmed the effectiveness of donepezil 10 mg/day in patients with severe AD and demonstrated a significant dose-response relationship. Donepezil at dosages of both 5 mg/day and 10 mg/day is safe and well tolerated in Japanese patients with severe AD.

Development of a simplified Short-Term Memory recall Test (STMT) and its clinical evaluation.

BACKGROUND AND AIMS: The early detection and prevention of dementia is attracting attention. We therefore developed an easily performed protocol to identify patients with memory impairment which may progress to dementia, and evaluated its validity. METHODS: We focused on short-term memory impairment alone, and named the test, consisting of 3 tasks, the simplified Short-Term Memory recall Test (STMT; with a maximum score of 8). Patients were classified into a memory impairment group of 26 subjects and a control group of 23 subjects. At the first examination, subjects underwent the STMT, MMSE and ADAS-Jcog. as cognitive function tests. Follow-up observations were performed for 2 years at 6-month intervals. RESULTS: There were significant differences in the mean scores for all tests, except for MMSE memory items between the 2 groups. When the cut-off value of STMT was established as 4 points, and scores lower than this value were defined as memory impairment, the sensitivity and specificity were highest, 73.1% and 82.6%, respectively. Sensitivity and specificity also rose to 92.3% and 95.7%, respectively, when STMT scores were added together with those of ADAS-Jcog. Results of logistic regression analysis indicated that development into Alzheimer's disease 2 years later was significantly correlated with STMT scores at first examination. The incidence of progression to Alzheimer's disease in patients with scores < or =4 (cut-off value) was about 5 times higher than that of patients with scores > or =5. CONCLUSIONS: This study suggests the usefulness of the STMT for identifying memory impairment as a pre-dementia state.