CIBIC Plus-J Assessment Using a Videotaped Method in Alzheimer's Disease Patients.

BACKGROUND/AIMS: CIBIC plus-J is the Japanese language version equivalent to CIBIC plus. Variability of CIBIC plus-J arises among raters in accordance with their experience and their memories of patients' conditions at baseline. Therefore, in a multicenter trial of Alzheimer's disease, CIBIC plus-J interviews with Alzheimer's disease patients were videotaped, and the tapes were assessed by central raters as a means to improve the reliability of CIBIC plus-J assessment. METHODS: Two of eight central raters were randomly selected and independently assessed the CIBIC plus-J of each patient. RESULTS: CIBIC plus-J of 41 patients was assessed. The agreement rate between the two raters was 46.3% (19/41), when two raters assessed the CIBIC plus-J of the same patient. However, when considering disagreement between adjacent points as 'agree', the agreement rate was 97.6% (40/41). Although the kappa coefficients contained coincidence, simple and quadratic weighted kappa coefficients [95% confidential interval (CI)] were 0.226 (0.066-0.386) and 0.633 (0.507-0.759), respectively, and when considering disagreement between adjacent points as 'agree', the agreement kappa was 0.896 (0.752-1.041). The interclass coefficient from the two-way layout model was 0.639. CONCLUSION: The reliability of the CIBIC plus-J assessment with the videotaped method was acceptable.

A 24-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety and tolerability of the rivastigmine patch in Japanese patients with Alzheimer's disease.

BACKGROUND: As of 2010, the rivastigmine patch was licensed for the treatment of Alzheimer's disease (AD) in 64 countries. METHODS: This 24-week, multicenter, randomized, double-blind, placebo-controlled study evaluated the efficacy, safety and tolerability of the 5-cm(2) (9-mg loading dose; 4.6 mg/24 h delivery rate) and 10-cm(2) (18-mg loading dose; 9.5 mg/24 h delivery rate) rivastigmine patch in Japanese patients with AD. RESULTS: In the primary analysis population (intent-to-treat last observation carried forward) at week 24, delayed deterioration was seen with the 10-cm(2) patch versus placebo on the Japanese version of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-J cog; p = 0.005) and the Japanese version of the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC plus-J; p = 0.067). Participants receiving the rivastigmine patch showed numerically less decline versus placebo at week 24 on the CIBIC plus-J, although this did not reach statistical significance. Statistical significance for the CIBIC plus-J was met following adjustment for body weight and baseline Mini-Mental State Examination score as dynamic allocation factors (p = 0.042) and on the Disability Assessment for Dementia (DAD; p = 0.024) and Mental Function Impairment (MENFIS; p = 0.016) subscales. Serious adverse events were rare and were consistent with the known safety profile of the rivastigmine patch. CONCLUSION: The rivastigmine patch has a favorable efficacy and tolerability profile in Japanese patients with AD.

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.

Validation of the 7-Minute Screen for the detection of early-stage Alzheimer's disease.

BACKGROUND/AIMS: The 7-Minute Screen (7MS) is a screening battery to identify individuals with a high probability of Alzheimer's disease (AD). The 7MS consists of four subtests (Temporal Orientation, Enhanced Cued Recall, Clock Drawing, and Verbal Fluency), each measuring a different aspect of cognition. The present study is designed to examine the predictive validity of the 7MS to distinguish between patients with early-stage AD and healthy control subjects. METHODS: Sixty-three patients who were diagnosed as having probable or possible AD and 91 community-dwelling elderly individuals of comparable age, sex distribution, and education were administered the 7MS (paper-and-pencil version) and other screening batteries. All patients were rated Clinical Dementia Rating (CDR) 0.5-1, categorized as early-stage AD, and all participants obtained a score of less than 6 for the Geriatric Depression Scale (15-item version). RESULTS: Mean scores for patients and controls on all the four subtests were significantly different. When using the total score of the 7MS, which was calculated by the original logistic regression formula based on all of the four subtests, the sensitivity for early-stage AD was 90.5% with a specificity of 92.3%. Correlation analysis indicated high concurrent validity between the 7MS and existing standard cognitive screening batteries (e.g., MMSE, HDS-R). In correlation analysis and multiple regression analysis, demographic effects (age, sex, and education) were not significantly associated with the total score of the 7MS in controls. CONCLUSIONS: The results showed that the 7MS had a high level of sensitivity and specificity. We also found that the 7MS was not affected by demographic characteristics. These findings demonstrated that the 7MS is a useful screening tool for discriminating patients with early-stage AD from intact individuals.