Utility of the Japanese version of the Clinical Dementia Rating® plus National Alzheimer's Coordinating Centre Behaviour and Language Domains for sporadic cases of frontotemporal dementia in Japan.

BACKGROUND: We aimed to validate the Clinical Dementia Rating (CDR®) dementia staging instrument plus the National Alzheimer's Coordinating Centre Behaviour and Language Domains (CDR® plus NACC FTLD) for use in clinical settings in Japan and in the Japanese language. METHODS: This prospective observational study enrolled 29 patients with frontotemporal dementia (FTD) and 21 patients with Alzheimer's disease (AD) dementia from the Departments of Psychiatry at Osaka University Hospital and Asakayama General Hospital and the Brain Function Centre at Nippon Life Hospital. CDR® plus NACC FTLD, CDR®, Mini-Mental State Examination (MMSE), Western Aphasia Battery (WAB), Neuropsychiatric Inventory-plus (NPI-plus), Stereotypy Rating Inventory (SRI), and frontal behavioural symptom scores obtained from items of NPI-plus and SRI, were conducted to assess inter- and intra-rater reliability, validity, and responsiveness. We performed receiver operating characteristic (ROC) curve analysis to evaluate the discriminating power of the Behaviour/Comportment/Personality (BEHAV) and Language (LANG) domains of the CDR® plus NACC FTLD and the MEMORY domain of the CDR® in patients AD dementia and FTD. RESULTS: The CDR® plus NACC FTLD showed good inter- and intra-rater reliabilities. In patients with FTD, the BEHAV domain of the CDR® plus NACC FTLD was significantly correlated with all clinical measures except for the SRI total score, while the LANG domain of the CDR® plus NACC FTLD was significantly correlated with the MMSE and the WAB-Aphasia quotient. In addition, the CDR® plus NACC FTLD sum of boxes significantly changed after 6 months and after 1 year. ROC curve analysis showed that the BEHAV and LANG domains of the CDR® plus NACC FTLD distinguished between patients with AD dementia and FTD better than the MEMORY domain of the CDR®. CONCLUSIONS: This study validated the Japanese version of the CDR® plus NACC FTLD with good reliability, validity, and responsiveness.

Communication-related experiences of individuals in the early phase of semantic dementia and their families: an interview study.

BACKGROUND: Semantic dementia (SD), a subtype of frontotemporal dementia, manifests as verbal symptoms, including social and behavioural deficits, associated with focal atrophy of the frontotemporal lobes. This study aimed to clarify the experiences of individuals with early-onset SD receiving speech and language rehabilitation (hereafter referred to as 'rehabilitation'), with the intent of making it routine, as well as the experiences of their families. METHODS: Individual interviews were conducted with nine families with members who had adopted rehabilitation. Verbatim transcripts were used as data, and analyzed inductively according to the content analysis process. RESULTS: The family members realised the changes in the personality and behaviour of the individual with SD early, to the extent that they thought the individual with SD was different from before and were distressed by the loss of verbal communication. Nevertheless, the family members found a way to communicate by maintaining residual functions through rehabilitation and utilising their unique relationship with the individual with SD. CONCLUSIONS: It is important to carefully explain the characteristics of the disease and the long-term significance of rehabilitation to individuals with SD and their families in the early stages of the disease.

An autopsy case of Alzheimer's disease with amygdala-predominant Lewy pathology presenting with frontotemporal dementia-like psychiatric symptoms.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are progressive neurodegenerative diseases associated with several cognitive and behavioral symptoms. It is sometimes difficult to distinguish AD from FTD in a patient because both of them can exhibit clinical overlap. In the present study, we report a case of a patient who showed sychiatric symptoms mimicking the behavioral variant of FTD (bvFTD) and combined AD amygdala-predominant Lewy pathologies on autopsy. The patient was a Japanese man who developed personality changes in his late 50s, presenting with obsessive-compulsive stereotypical behavior, stereotypy of speech, behavioral disinhibition, inertia, loss of empathy or sympathy, change in eating habits, and stimulus-bound behavior. He also frequently left during medical examinations. Eventually, he was clinically diagnosed as having possible bvFTD, according to the International Consensus Criteria for bvFTD. The patient died of systemic metastasis of gastric cancer at 69 years of age. Postmortem neuropathological examination revealed severe AD pathology (Braak Amyloid stage C, Consortium to Establish a Registry for Alzheimer's Disease [CERAD] stage C, Thal phase 5, and Braak AT8 stage IV) along with Lewy pathology and argyrophilic grains, predominantly in the amygdala. Furthermore, no transactivation response DNA-binding protein of 43 kDa (TDP-43) pathology was observed. Our results suggest that a combination of these pathologies causes bvFTD-like cognitive and behavioral symptoms. This case is very insightful when considering the lesions responsible for the psychiatric symptoms characteristic of bvFTD.

Factors influencing the quality of life in patients with severe dementia.

BACKGROUND: A comprehensive understanding of the relevant factors involved in improving quality of life (QoL) is essential in patients with severe dementia; however, rating scales used in previous studies may not adequately reflect the factors that affect these patients. The purpose of this study was to identify factors that contribute to QoL using an evaluation scale suitable for patients with severe dementia. METHODS: The current cross-sectional study was conducted at a hospital for recuperation in Hyogo prefecture in Japan. The measurement scales included the QoL in Late-Stage Dementia Japanese version (QUALID-J), Cognitive Test for Severe Dementia, Neuropsychiatric Inventory-Nursing Home (NPI-NH), Physical Self-Maintenance Scale (PSMS), Pain Assessment in Advanced Dementia (PAINAD), and Special Care Unit Environment Quality Scale (SCUEQS). Multiple regression analyses were performed. RESULTS: We assessed a total of 105 patients with severe dementia (80 women; aged 87.3 ± 6.3 years). Multiple regression demonstrated that the QUALID-J total score was significantly affected by the NPI-NH and PAINAD scores. Factors 1 (expression of comfort) and 2 (expression of discomfort) of the QUALID-J were significantly affected by the PSMS and PAINAD, and the NPI-NH and PAINAD scores, respectively. CONCLUSION: Our results indicate that behavioural and psychological symptoms of dementia and pain are important factors in influencing the QoL of patients with severe dementia.

Decline of gustatory sensitivity with the progression of Alzheimer's disease.

BACKGROUND: Patients with Alzheimer's disease (AD) manifest various impairments in eating behavior. However, few previous studies have directly investigated the gustatory function of AD patients, and results have been inconsistent. METHODS: Thirty-two AD patients (Clinical Dementia Rating (CDR) 0.5/1/2, respectively 11/15/6 patients) and 22 normal control participants were examined to measure detection and recognition thresholds of the four elemental tastes (sweet, salty, sour, and bitter), and their ability to discriminate between tastes. Effects of demographic and clinical factors (age, sex, histories of alcohol and tobacco consumption, and CDR grade) on gustatory threshold were examined using ordinal logistic regression analysis. Performance was compared between AD and control groups. RESULTS: Total threshold values (the sum of threshold grades for the four tastes) for detection and recognition of tastes were significantly higher in the AD group. Detection thresholds for sweet, salty, and bitter, and recognition thresholds for sweet and sour, were also significantly higher in the AD group. Ordinal logistic regression analysis revealed that CDR grade was the only factor that significantly affected both total threshold values. Regarding taste discrimination, there were no significant differences between the AD group and control group. CONCLUSIONS: These findings suggest that progression of dementia severity accompanies gustatory decline. Although it seemingly paradoxical, weight loss and preference for sweet tastes are frequently, often simultaneously, observed in AD. Gustatory dysfunction may be partially involved in these symptoms. Thus, the nutritional care of patients with AD could be improved by making the taste of meals stronger, while controlling calorie and mineral intake.

Classifying eating-related problems among institutionalized people with dementia.

AIMS: Various eating-related problems are commonly observed among people with dementia, and these problems place a huge burden on the caregivers. An appropriate classification of these problems is important in order to understand their underlying mechanisms and to develop a therapeutic approach for managing them. The aim of this study was to develop a possible classification of eating-related problems and to reveal the background factors affecting each of these problems across various conditions causing dementia. METHODS: The participants were 208 institutionalized patients with a diagnosis of dementia. Care staff were asked to report all kinds of eating-related problems that they observed. After the nurses' responses were analyzed, 24 items relating to eating-related problems were extracted. A factor analysis of these 24 items was conducted, followed by a logistic regression analysis to investigate the independent variables that most affected each of the eating-related factors. RESULTS: Four factors were obtained. Factor 1 was overeating, factor 2 was swallowing problems, factor 3 was decrease in appetite, and factor 4 was obsession with food. Each factor was associated with different background variables, including Mini-Mental State Examination scores, Clinical Dementia Ratings, and neuropsychiatric symptoms. CONCLUSIONS: This study suggests that eating-related problems are common across conditions causing dementia and should be separately considered in order to understand their underlying mechanisms.

Assessment and care of visuospatial disorientation in a mixed dementia patient: a case study using objective measurements.

We present a case of a mixed dementia patient with visuospatial disorientation and a developmental disability. The patient was a 69-year-old man who was hospitalized for resistance to care, wandering, and a sleep disorder. He was in the advanced stages of dementia and had severe visual impairment due to cataracts. We used an integrated circuit monitoring system and Actiwatch to measure the distance moved per day and sleep-rest cycle, respectively. We administered a coloured paper test to assess the colour most easily recognized by the patient, which was red. We found that displaying his name in large red letters by his door enabled the patient to read his name. We also moved him to a private room next to the day room. The distance moved per day decreased significantly after the implementation of the care plan. However, after the room change, large urine spills were often observed in the bathroom, indicating visuospatial problems. We placed red adhesive tape onto the toilet bowl to make it more visible, which solved the urine spill problem. This case study demonstrates the efficacy of using simple assessment techniques to identify the remaining abilities of a dementia patient and taking simple steps to address the behavioural and psychological symptoms of dementia.

Caring for early-onset dementia with excessive wandering of over 30 kilometres per day: a case report.

Excessive wandering in people in dementia is associated with a severe care burden. However, the quantification of excessive wandering has not been described, and its cause and treatment have not been evaluated with objective measurements to date. The purpose of this study was to evaluate pharmacological treatments and non-pharmacological interventions to reduce excessive wandering in an early-onset Alzheimer disease patient with objective indicators. Wandering was quantified using an integrated circuit monitoring system that measured the distance moved and the location of the patient. Monitoring was conducted in the dementia ward of a general hospital in 2012. Sleep quality was measured by non-wear actigraphy. The study was approved by the ethics committees of the Osaka University School of Allied Health Science, and of the study hospital. The case involved a 62-year-old woman diagnosed with early-onset Alzheimer disease and hospitalized in 2012 because of irritability and agitation; her Mini-Mental State Examination score was 5/30 and her Clinical Dementia Rating score was 3. When olanzapine (2.5 mg) was prescribed, she developed insomnia, and her wandering movements increased from 10 to 20 km/day. On some days, it exceeded 30 km/day, and she walked most of the night. She did not experience weight loss or physical exhaustion, but she sustained a minor injury in her left sole. Olanzapine was increased to 7.5 mg, but these problems persisted. Nursing staff discovered triggers for wandering and insomnia, including high sensitivity to odour and noise in the living room or her room. When the environment was changed to meet her needs, the distance moved per day decreased to <15 km and the sleep disturbances disappeared. This case demonstrated the difficulty in assessing the degree of ambulation and sleep disorder. Objective indicators are essential in evaluating the effectiveness of pharmacological and non-pharmacological interventions.

Predictors of prolonged hospital stay for the treatment of severe neuropsychiatric symptoms in patients with dementia: a cohort study in multiple hospitals.

BACKGROUND: Long hospitalization is often needed to treat severe behavioral and psychological symptoms of dementia (BPSD), which places heavy demands on hospital resources. Consequently, patients with severe BPSD usually wait for a long time to be admitted. There is a need to identify factors related to long hospitalization to better manage resources of a psychiatric hospital. METHODS: We surveyed 150 consecutive patients hospitalized in the neuropsychiatric units of three hospitals for treatment of BPSD from 11 May 2009 to 30 November 2010. Only patients with reliable relatives were included in the study. We evaluated data of the patients (demographics, cognitive impairment, activities of daily living, causal disease for dementia, dementia severity, and the amount of pension), their primary caregivers (demographics and care burden), and their doctors' years of experience in treating dementia. We followed up to 180 days and assessed the effect of these factors on the length of stay. RESULTS: Of the 150 patients, 104 were discharged within 180 days and 46 were hospitalized for more than 180 days. Average length of stay for patients was 110.4 ± 58.1 days. In both univariate and multivariate Cox proportional hazard analyses, length of stay was longer for patients with smaller pensions and patients whose doctors had fewer years of experience in treating dementia. Length of stay was not found to be associated with any of the other variables. CONCLUSIONS: Patients with smaller pensions and whose doctors had less experience in treating dementia tended to require longer hospitalization.

Degree of ambulation and factors associated with the median distance moved per day in Alzheimer's disease patients.

The Integrated Circuit tag monitoring system became available to measure wandering in terms of the distance moved by dementia patients. The purposes of the study were to describe degree of ambulation in patients with Alzheimer's disease (AD) and to examine factors associated with the distance moved. AD patients were recruited at a dementia care unit in Asakayama Hospital, Osaka, Japan. The monitoring system generated the distance moved per day. Demographic and clinical data were abstracted from medical records. Mini-Mental State Examination was used to measure cognitive function. A multiple linear regression was used to predict the distance moved per day. The research was approved by the ethics committee of the university and the hospital, and written informed consent was obtained from the patients' proxies. Majority of the AD subjects monitored had moderate to advance stage of dementia. Patients' age and cognitive function were predictors of the median distance moved/day, and these two variables explained almost half of the variance. Older age and lower cognitive function were associated with reduced median distance moved per day in AD patients.

Discrepancy between subjective and objective assessments of wandering behaviours in dementia as measured by the Algase Wandering Scale and the Integrated Circuit tag monitoring system.

AIM: Although wandering is one of the major research focuses of the behavioural psychological symptoms of dementia, assessment of wandering has mostly relied on caregiver-administered questionnaires. The purpose of this study was to compare staff-administered Algase Wandering Scale outcomes with objective temporal and spatial movement indicators obtained from the Integrated Circuit (IC) tag monitoring system. METHODS: Patients with dementia were recruited from a dementia care unit in Osaka, Japan in 2007. Primary nurses administered the Algase Wandering Scale, and the temporal and spatial movements of the subjects were monitored by the IC tag. Written informed consent was obtained from each subject's proxies. RESULTS: Nurses' assessments of wandering were in agreement with the IC tag outcomes only during the day shift. Spatial movements assessed by the staff did not reflect those measured by the IC tag. CONCLUSION: This objective measurement of wandering showed the limitations in the assessment of spatial and temporal movement by the staff.

A heterozygous splicing variant IVS9-7A > T in intron 9 of the MAPT gene in a patient with right-temporal variant frontotemporal dementia with atypical 4 repeat tauopathy.

Right temporal variant frontotemporal dementia, also called right-predominant semantic dementia, often has an unclear position within the framework of the updated diagnostic criteria for behavioral variant frontotemporal dementia or primary progressive aphasia. Recent studies have suggested that this population may be clinically, neuropathologically, and genetically distinct from those with behavioral variant frontotemporal dementia or left-predominant typical semantic variant primary progressive aphasia. Here we describe a Japanese case of right temporal variant frontotemporal dementia with novel heterozygous MAPT mutation Adenine to Thymidine in intervening sequence (IVS) 9 at position -7 from 3' splicing site of intron 9/exon 10 boundary (MAPT IVS9-7A > T). Postmortem neuropathological analysis revealed a predominant accumulation of 4 repeat tau, especially in the temporal lobe, amygdala, and substantia nigra, but lacked astrocytic plaques or tufted astrocytes. Immunoelectron microscopy of the tau filaments extracted from the brain revealed a ribbon-like structure. Moreover, a cellular MAPT splicing assay confirmed that this novel variant promoted the inclusion of exon 10, resulting in the predominant production of 4 repeat tau. These data strongly suggest that the MAPT IVS9-7 A > T variant found in our case is a novel mutation that stimulates the inclusion of exon 10 through alternative splicing of MAPT transcript and causes predominant 4 repeat tauopathy which clinically presents as right temporal variant frontotemporal dementia.

[Difference in sundowning of wandering behavior in patients with Alzheimer disease and frontotemporal dementia].

OBJECTIVES: To delineate the difference in sundowning of wandering behavior between patient with Alzheimer Disease (AD) and frontotemporal dementia (FTD). METHODS: The study was conducted in a dementia care unit at A hospital in Osaka, Japan from September 2008 to September 2009. Twenty-four-hour movements of 27 ambulatory inpatients with AD and 7 with FTD were coded consecutively by the IC tag monitoring system. RESULTS: Repeated measures ANOVA after the adjustment of Huynh-Feldt Epsilon (H-F) showed no significant difference in 24 h standardized activity level between two groups (F = 3.74, P = 0.06), and there was no interaction between diagnosis and time (F = 1.42, P > 0.05). The standardized activity levels gradually increased from late afternoon to evening and then reached the highest point at 18:00 in AD group and 19:00 in FTD group. Test of within-subjects contrasts for order 17 was significant (F = 5.24, P < 0.05) and for order 9 was a tendency of significant (F = 4.26; P = 0.05) between two groups. AD group was significant greater active at 5:00, 6:00 and 7:00 (0.75 ± 0.08 vs 0.35 ± 0.16, F = 4.91; 1.13 ± 0.13 vs 0.49 ± 0.26, F = 5.06; 1.24 ± 0.15 vs 0.56 ± 0.28, F = 4.47 respectively, P < 0.05), and less active at 16:00 (1.65 ± 0.11 vs 2.22 ± 0.22, P < 0.05) comparing to FTD group by Bonferroni's multiple comparison test. Meanwhile, the time of peak value of hourly distance moved per day (PV-time) was delayed in FTD group comparing to AD by circular χ² test (14:12 ± 5:12 vs 15:47 ± 4:19, χ² = 87.31, P < 0.01). CONCLUSIONS: The study suggests great possibility of sundowning of wandering behavior in both two subtypes with different temporal pattern of wandering behavior. Comparing to FTD patients, AD patients showed an advanced PV-time and prolonged active phase.

Comparing dementia patients' nighttime objective movement indicators with staff observations.

BACKGROUND: Pharmacological and non-pharmacological approaches are commonly used to treat patients' institutionalised for nighttime wandering. Actigraphy and other scales have been used to evaluate the efficacy of these treatments. However, in clinical settings, nursing records are often the sole source of daily observation of nighttime wandering. Thus, physicians rely on nursing records to evaluate pharmacological and non-pharmacological treatments. This study examined nighttime movements of patients with dementia, comparing the results of integrated circuit tag monitoring with hourly nighttime nursing records. We tested which factors were associated with agreement rates between the two data sources. METHODS: The study hospital was a general hospital in Osaka, Japan. Monitoring was conducted in a closed 60-bed dementia care unit. An integrated circuit tag monitoring system was used to monitor the movement of institutionalised dementia patients for over half a year. The distance moved per hour by subjects was measured using the monitoring system, and the data were compared with hourly nighttime nursing records. Agreement rates were calculated between the two data sources. RESULTS: Thirty-five patients were monitored. Between 10-30% of subjects moved at any given hour during the night. The overall agreement rate between sources of movement data was 39%. Agreement rates were significantly correlated with the interquartile of the distance moved, changes in medication, physical conditions, and behavioural and psychological symptoms of dementia measured during the day. CONCLUSIONS: Although the agreement rate was low, staff appeared to pay more attention to patients associated with notable events during the day and patients exhibiting variability in distance moved.

Changes in activity patterns after the oral administration of brotizolam in institutionalized elderly patients with dementia.

BACKGROUND: Little is known about the side effects of sedative-hypnotic agents in elderly dementia patients with sleep disorders. The present study describes activity pattern changes after a single dose of brotizolam in elderly patients with dementia. METHODS: We conducted retrospective analysis of prospectively collected data from a case series at Asakayama Hospital (Osaka, Japan) between September 2008 and September 2009. Around-the-clock movements of dementia patients who were administered a single dose of brotizolam were recorded by the integrated circuit tag monitoring system during a 4-week baseline and 7-day peri-administration period. Diurnal and nocturnal activity levels and the onset times of the least-active and most-active phases were then measured. RESULTS: Seven patients (four men, three women; age range 59-85 years) were analyzed. All seven patients had disturbed activity patterns during the peri-administration period. Compared with the pre-administration period, the incidence of reversed rest-activity pattern increased significantly in the post-administration period, as measured by the distance moved per hour (P < 0.000). Patients with advanced stages of dementia had prolonged and delayed activity responses. CONCLUSIONS: Findings showed changes in activity levels and reversed active/resting phases after a single dose of brotizolam in elderly patients with dementia. Use of brotizolam in elderly patients with dementia, especially in advanced stages, calls for closer attention and longer observation periods.

Using a Non-Wearable Actigraphy in Nursing Care for Dementia With Lewy Bodies.

People who have dementia with Lewy bodies often have sleep disorders. We used non-wearable devices to record and categorize the sleep patterns of patients with Lewy body dementia. Individual sleep data at a dementia-care unit in Japan were recorded using non-wearables. One week's worth of data from 18 patients was analyzed. Median metrics for all participants were the following: sleep efficiency, 68% (23-89); sleep duration at night, 6.8 hours (1.6-11.1); times getting out of bed at night, 3.5 (0-13). We identified three types of abnormal sleep: extremely short sleep duration, excessive sleep duration at night, and excessive number of times getting out of bed at night. Sleep disturbances in Lewy body dementia patients are treated using various practices; staff must choose the most effective plan for each patient's situation. Monitoring patient sleep using non-wearable provides more objective data that can help staff better personalize nursing care.

A prospective multicenter validation study of a machine learning algorithm classifier on quantitative electroencephalogram for differentiating between dementia with Lewy bodies and Alzheimer's dementia.

BACKGROUND AND PURPOSE: An early and accurate diagnosis of Dementia with Lewy bodies (DLB) is critical because treatments and prognosis of DLB are different from Alzheimer's disease (AD). This study was carried out in Japan to validate an Electroencephalography (EEG)-derived machine learning algorithm for discriminating DLB from AD which developed based on a database of EEG records from two different European countries. METHODS: In a prospective multicenter study, patients with probable DLB or with probable AD were enrolled in a 1:1 ratio. A continuous EEG segment of 150 seconds was recorded, and the EEG data was processed using MC-004, the EEG-based machine learning algorithm, with all clinical information blinded except for age and gender. RESULTS: Eighteen patients with probable DLB and 21 patients with probable AD were the included for the analysis. The performance of MC-004 differentiating probable DLB from probable AD was 72.2% (95% CI 46.5-90.3%) for sensitivity, 85.7% (63.7-97.0%) for specificity, and 79.5% (63.5-90.7%) for accuracy. When limiting to subjects taking ≤5 mg donepezil, the sensitivity was 83.3% (95% CI 51.6-97.9), the specificity 89.5% (66.9-98.7), and the accuracy 87.1% (70.2-96.4). CONCLUSIONS: MC-004, the EEG-based machine learning algorithm, was able to discriminate between DLB and AD with fairly high accuracy. MC-004 is a promising biomarker for DLB, and has the potential to improve the detection of DLB in a diagnostic process.

Clinical profiles of people with dementia exhibiting with neuropsychiatric symptoms admitted to mental hospitals: A multicenter prospective survey in Japan.

AIMS: Patients with severe behavioral and psychological symptoms of dementia (BPSD) are often admitted to mental hospitals, while, inpatient care could also lead to prolonged hospital stay. The present study aims to survey clinical profiles of patients who required inpatient treatment for BPSD, and then establish the criteria for introducing inpatient treatment through assessment by certified psychiatrists. METHODS: We performed a prospective survey about clinical characteristics of people with dementia who required treatment of BPSD at 12 mental medical institutions. All patients were assessed by certified psychiatrists to determine the optimal treatment settings: outpatient or inpatient. The multivariate logistic regression analysis was performed to specify factors contributed to the judgement of clinicians. Subsequently, the receiver operating characteristic curve analysis was conducted to explore a score derived from the Neuropsychiatric Inventory to divide patients into outpatient or inpatient groups. RESULTS: The present study included 386 patients, of which 242 were admitted to mental hospitals. BPSD were classified into four domains, and aggressive BPSD was significantly associated with assessment for inpatient treatment; the adjusted odds ratio was approximately 2 regardless of dementia severity. Furthermore, the composite score of agitation, irritability and aberrant behavior showed the highest area under the curve value (=0.706), which differentiated inpatients from outpatients with a sensitivity of 76% and a specificity of 54%. CONCLUSIONS: Aggressive BPSD was the risk factor for inpatient treatment. The composite score of the Neuropsychiatric Inventory subdomain-related aggressive BPSD could be a screening tool to introduce inpatient treatment for BPSD. Geriatr Gerontol Int 2021; 21: 825-829.

Repurposing bromocriptine for Aß metabolism in Alzheimer's disease (REBRAnD) study: randomised placebo-controlled double-blind comparative trial and open-label extension trial to investigate the safety and efficacy of bromocriptine in Alzheimer's disease with presenilin 1 (PSEN1) mutations.

INTRODUCTION: Alzheimer's disease (AD) is one of the most common causes of dementia. Pathogenic variants in the presenilin 1 (PSEN1) gene are the most frequent cause of early-onset AD. Medications for patients with AD bearing PSEN1 mutation (PSEN1-AD) are limited to symptomatic therapies and no established radical treatments are available. Induced pluripotent stem cell (iPSC)-based drug repurposing identified bromocriptine as a therapeutic candidate for PSEN1-AD. In this study, we used an enrichment strategy with iPSCs to select the study population, and we will investigate the safety and efficacy of an orally administered dose of bromocriptine in patients with PSEN1-AD. METHODS AND ANALYSIS: This is a multicentre, randomised, placebo-controlled trial. AD patients with PSEN1 mutations and a Mini Mental State Examination-Japanese score of ≤25 will be randomly assigned, at a 2:1 ratio, to the trial drug or placebo group (≥4 patients in TW-012R and ≥2 patients in placebo). This clinical trial consists of a screening period, double-blind phase (9 months) and extension phase (3 months). The double-blind phase for evaluating the efficacy and safety is composed of the low-dose maintenance period (10 mg/day), high-dose maintenance period (22.5 mg/day) and tapering period of the trial drug. Additionally, there is an open-labelled active drug extension period for evaluating long-term safety. Primary outcomes are safety and efficacy in cognitive and psychological function. Also, exploratory investigations for the efficacy of bromocriptine by neurological scores and biomarkers will be conducted. ETHICS AND DISSEMINATION: The proposed trial is conducted according to the Declaration of Helsinki, and was approved by the Institutional Review Board (K070). The study results are expected to be disseminated at international or national conferences and published in international journals following the peer-review process. TRIAL REGISTRATION NUMBER: jRCT2041200008, NCT04413344.

High frequency of getting out of bed in patients with Alzheimer's disease monitored by non-wearable actigraphy.

AIM: Sleep disturbances in patients with Alzheimer's disease have not been systematically evaluated, because sleep monitoring has proved difficult. Our goal was to quantitatively characterize sleep disturbances in patients with Alzheimer's disease. METHODS: The present study was a cross-sectional descriptive study, carried out in dementia care units in Japan. Participants were 63 patients with Alzheimer's disease (mean age 77.6 ± 8.0 years) with severe behavioral and psychological symptoms of dementia. A non-wearable actigraphy device placed under patient mattresses was used to measure sleep parameters: sleep time, time in bed, number of wakings and number of times they left the bed. Cut-off points for sleep parameters were based on the interquartile range of the data. RESULTS: Median nocturnal sleep time was 6.2 h (interquartile range 2.7 h). Median frequency of waking was eight times (5)/night. Median frequency of leaving the bed was five times (6), with a maximum of 31/night. We identified three types of sleep disturbance: frequent bed leaving, short sleep time and excessive sleep time. Multiple linear regression showed that duration of dementia was a significant predictor of frequent bed leaving at night (P = 0.042). CONCLUSIONS: Frequent bed leaving at night reflects severe sleep deprivation in patients with mild-to-severe Alzheimer's disease. Safety measures are required to prevent accidents related to sleep disturbances, regardless of dementia severity. Geriatr Gerontol Int 2019; 19: 130-134.