Akira Homma

Brief screening tool for mild cognitive impairment in older Japanese: Validation of the Japanese version of the Montreal Cognitive Assessment

Aim:  The Montreal Cognitive Assessment (MoCA), developed by Dr Nasreddine (Nasreddine et al. 2005), is a brief cognitive screening tool for detecting older people with mild cognitive impairment (MCI). We examined the reliability and validity of the Japanese version of the MoCA (MoCA‐J) in older Japanese subjects.

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-cm2 (9-mg loading dose; 4.6 mg/24 h delivery rate) and 10-cm2 (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-cm2 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.

Efficacy and safety of memantine in patients with moderate-to-severe Alzheimer's disease: results of a pooled analysis of two randomized, double-blind, placebo-controlled trials in Japan

Background: With the increase in the aging population, there is a pressing need to provide effective treatment options for individuals with Alzheimers disease (AD). Memantine is an N-methyl-D-aspartate receptor antagonist used to treat AD in > 80 countries worldwide, and studies in the USA and Europe have shown it to be effective in improving language deficits; however, there are currently no data on language improvements in Japanese patients treated with memantine. Objectives: To clarify the efficacy and safety of memantine in Japanese outpatients with moderate to severe AD, using a pooled analysis of two multicenter randomized placebo-controlled trials, a phase 2 dose-finding study and a phase 3 study. Results: The final analysis comprised 633 patients (318 receiving memantine and 315 placebo). Memantine produced better outcomes in terms of Severe Impairment Battery-Japanese version, Clinicians Interview-Based Impression of Change plus-Japanese version, Behavioral Pathology in AD Rating Scale, and language scores, versus placebo. The overall incidence of adverse events and adverse reactions was similar between groups. Conclusion: In this pooled analysis of Japanese patients, memantine achieved better outcomes than placebo in terms of cognition, including attention, praxis, visuospatial ability and language, and behavioral and psychological symptoms, including activity disturbances and aggressiveness.

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.

Reliability Study on the Japanese Version of the Clinician’s Interview-Based Impression of Change

The Japanese version of the Clinician’s Interview-Based Impression of Change (CIBIC-plus J) is a semistructured interview format including a 7-point Likert type scale for the Clinician’s Global Impression of Change. It comprises subscales of DAD for ADL, Behave-AD for behavioral and psychiatric symptoms and MENFIS for cognitive and emotional impairment. DAD and Behave-AD are used for caregivers and MENFIS for both caregivers and patients. The objective of this study was to examine the interrater reliability of the CIBIC-plus J by the videotape method. Twenty videotaped patients including 13 real and 7 virtual patients were independently assessed by 11 raters. The kappa coefficient from the full set of data of 20 patients and 11 raters was 0.453, and from the limited data of 13 real patients, 0.383. By permitting one-point disagreements on the 7-point scale or by collapsing it into the 3-point scale (improved, no change, or worsened), kappa improved to 0.894 and 0.731, or 0.734 and 0.504, respectively. From these results, it was concluded that the reliability of a 7-point Clinician’s Global Impression of Change was halfway, i.e., neither sufficient nor insufficient. However, if one-point disagreements or collapsing into 3-point scale are allowable, the CIBIC-plus J will be sufficiently reliable.

Cognitive Function in Japanese Centenarians according to the Mini-Mental State Examination

Background/Aims: We examined the effect of aging on cognitive function at the limit of human life expectancy by characterizing state of cognition in centenarians without clinical cognitive impairment. Methods: Participants were 68 centenarians without cognitive impairment (Clinical Dementia Rating (CDR) 0), 96 controls 60 to 74 years old, and 46 controls 75 to 89 years old. We visited the places where centenarians were living and administered the Mini-Mental State Examination (MMSE) individually. Control subjects came to the assembly hall within their dwelling area, to be administered the MMSE. Results: Mean total scores of centenarians (22.3) were lower than for either 60–74 (27.2) or 75–89 (26.2). Comparison of scores in each of five cognitive domains measured by MMSE showed a significant age-group effect upon orientation, memory, and attention. Centenarians’ scores were lower than for younger groups in every domain except for the language and praxis, concentration, and for repetition. Conclusion: The centenarians’ scores in memory and orientation declined as in earlier studies of normal aging. Centenarians’ scores for attention and concentration differed from those in previous studies. The present result suggests that even primary memory is influenced by advanced age in centenarians, while ability to store information declines, ability to process is maintained.

Early Onset Alzheimer Type Dementia More Rapidly Deteriorates than Late Onset Type : A Follow-up Study on MMSE Scores in Japanese Patients

Background:Cognitive function in patients with Alzheimer type dementia (ATD) changes over time, and the rate of progression varies according to reports. An aim of the study is to examine the rate of progression in patients with ATD by the onset of the disease.

Reliability of a Rating Scale to Assess Post-stroke Psychiatric Symptoms

Background: Various rating scales for post‐stroke psychiatric symptoms such as cognitive impairment have long been used in drug efficacy trials in Japan. However, their reliability has not been established. The purpose of the present study was to examine the inter‐rater and intra‐rater reliability of a rating scale, which has been conventionally used in Japan.

Does the Use of Nursing-Care Services Reduce the Information about Dementia Patients Provided by Their Caregivers?

Background: The rate of use of nursing-care services has been increasing dramatically in recent years with the upgrading of the public long-term care insurance system in Japan. We addressed how the increased use of the nursing-care services might affect the information on the patients provided by their caregivers. Methods: A questionnaire survey of 531 family caregivers caring for dementia patients at home was carried out to investigate how the use of these services might affect the information about the patients provided by the caregivers. The survey revealed that the use of the nursing-care services reduced the burden (quality, quantity, time of nursing care, and feeling) on the caregivers. Results: According to the observation provided by the caregivers, the patients’ behaviors and activities at home tended to decrease. These results indicated that the use of the nursing-care services resulted in a reduction in the opportunity for and the time spent on observation of the patients by the caregivers, making it more difficult for the caregiver to provide an appropriate assessment of the patient’s condition. Conclusions: We discussed the impact of the use of the nursing-care services on the Clinician’s Interview-Based Impression of Change plus (CIBIC-plus) rating. Due to the reduction in the time spent on nursing care and in the opportunity for observation of the patient’s activities of daily living by the caregiver resulting from the use of the nursing-care services, it is difficult to obtain an accurate picture of the patient’s clinical condition using the CIBIC-plus, probably leading to an inappropriate CIBIC-plus rating.

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

PLACEBO-CONTROLLED STUDY TO EVALUATE THEEFFICACY, SAFETY, ANDTOLERABILITYOF THE RIVASTIGMINE PATCH IN JAPANESE PATIENTS WITH ALZHEIMER’S DISEASE Yu Nakamura, Yukimichi Imai, Masahiro Shigeta, Ana Graf, Toru Shirahase, Hyosung Kim, Akifumi Fujii, Joji Mori, Akira Homma, Kagawa University, Osaka, Japan; Japan College of Social Work, Tokyo, Japan; Tokyo Metropolitan University, Tokyo, Japan; 4 Novartis Pharma AG, Basel, Switzerland; 5 Novartis Pharma K.K., Tokyo, Japan; 6 Ono Pharmaceutical Co. Ltd., Osaka, Japan; 7 Ono Pharmaceutical Co. Ltd, Osaka, Japan; Dementia Care Research and Training Center, Tokyo, Japan.