Post‐marketing survey of donepezil hydrochloride in Japanese patients with Alzheimer's disease with behavioral and psychological symptoms of dementia (BPSD)

Background: To investigate the efficacy and safety of donepezil hydrochloride (Aricept^®; Eisai Co., Ltd, Tokyo, Japan), we conducted a post‐marketing survey in Japanese patients with Alzheimer's disease (AD) who also had behavioral and psychological symptoms of dementia (BPSD), such as hallucinations/delusions, wandering, and aggression, which cause the greatest burden on caregivers. Methods: A prospective, centrally registered investigation was conducted through regular clinical settings with patients diagnosed as mild to moderate AD presenting with hallucinations/delusions, wandering, and/or aggression. The treatment period was 12 weeks and no restrictions were placed on concomitant medications. Results: The BPSD improvement rates at last‐observation‐carried‐forward (LOCF) were 60.1% for hallucinations/delusions, 59.6% for wandering, and 65.6% for aggression. For all symptoms, improvement rates increased with the duration of the treatment period. The BPSD deterioration rates at LOCF were 1.3% for hallucinations/delusions, 3.4% for wandering, and 1.6% for aggression. Assessment of cognitive function with both the revised Hasegawa Dementia Scale (HDS‐R) and Mini‐Mental State Examination (MMSE) indicated significant improvements after treatment. There were significant differences in the changes in HDS‐R scores between patients whose hallucinations/delusions or wandering were improved and patients whose symptoms were not improved. Moreover, the data suggested a possible correlation between changes in hallucinations/delusions and HDS‐R scores, changes in hallucinations/delusions and MMSE scores, and changes in wandering and MMSE scores. Patients in whom BPSD improved also demonstrated a greater improvement in cognitive function compared with patients in whom no improvement in BPSD was noted. Nursing burden on caregivers at LOCF showed 3.6% for ‘No burden’, 54.1% for ‘Burden decreased’, and 4.5% for ‘Burden increased.’ There was an increase in the combined ratio of ‘No burden’ and ‘Burden decreased’ in proportion with prolonged treatment period. Patients with improved BPSD had a significantly greater ratio (88.5–94.4%) of ‘No burden’ plus ‘Burden decreased’ than those patients in whom no improvement in BPSD was noted. Conclusions: These results suggest that donepezil not only improves the cognitive dysfunction of AD patients, but may also relieve BPSD in these patients. Treatment with donepezil was also found to alleviate the burden of caregivers for approximately 60% of patients. Moreover, the results indicate that donepezil is unlikely to trigger potential risks of excessive deterioration of BPSD, which would result in a heavier burden of nursing care.     

The cost of behavioral and psychological symptoms of dementia (BPSD) in community dwelling Alzheimer's disease patients

INTRODUCTION: Behavioral and psychological symptoms of dementia (BPSD) are highly prevalent in Alzheimer's disease (AD) patients. They are a source of distress for the caregivers and one of the main reasons for nursing home placement, which is the major component of the cost of Alzheimer's disease. The aim of the present study was to assess the direct and indirect cost related to the care of BPSD within a prospective study examining the overall cost of AD in Israel. METHODS: Seventy-one community dwelling AD patients were interviewed. Interviews covered information about the number of caregivers' hours invested in caring for the patient and amount of expenditure such as in-house paid help and payments for day care. Effort devoted to BPSD was defined as the number of hours spent by primary and secondary caregivers in a typical week dealing with BPSD (managing aggression, pacing, attempts to leave the house under inappropriate circumstances, or comforting a hallucinating, depressed or anxious patient). RESULTS: The annual indirect cost for management of BPSD in an AD patient was approximately 2665 dollars -over 25% of the total annual indirect cost of care ($10 520). The annual direct cost of BPSD of an AD patient was approximately 1450 dollars -over 35% of the total annual direct cost of care (3900 dollars). CONCLUSIONS: Approximately 30% (4115 dollars) of the total annual cost of AD (14420 dollars) is invested in the direct management of BPSD. Given the importance of BPSD as one of the main components of the cost of AD, future cost studies should be designed to measure the cost of specific components of BPSD and verify which are the most costly aspects of the disease. Despite the considerable methodological difficulties in disentangling the costs of the specific symptoms of AD, cost effectiveness studies of different interventions should be conducted in order to determine the optimal intervention with relation to cost.     

Behavioral and psychological symptoms of dementia (BPSD) in dementia with Lewy bodies

Behavioral and psychological symptoms of dementia (BPSD) bother patients with dementia with Lewy bodies (DLB) and their families so frequently that early diagnosis of DLB before the appearance of prominent cognitive impairment is important. Because BPSD in DLB can be reduced or improved by early intervention, medical intervention is important. Of BPSD in DLB, vivid visual hallucinations and delusions are most important. Other visual cognitive impairments and sleep disturbances, including disorders in rapid eye movement (REM) sleep, are also frequently seen. Cholinesterase inhibitors, including donepezil chloride, are the first choice for the therapy of BPSD; Yokukansan (a type of Kanpo (traditional Chinese herbal) medicine) is the second choice. When neither treatment is effective, atypical antipsychotics, such as quetiapine, risperidone, and aripiprazol, may be used.     

Characteristics of behavioral and psychological symptoms of dementia in untreated oldest old Alzheimer's disease*

Background: The proportion of the population aged 85 years and older has increased rapidly in Japan, reaching 2.5 million (1.99%) in 2002. Under these circumstances, the number of dementia patients increases annually. However, few studies have focused on Alzheimer's disease (AD) with an age at onset older than 85 years (oldest old AD). The aims of the present study were to determine the prevalence of the behavioral and psychological symptoms of dementia (BPSD) in patients with oldest old AD compared with those with young old AD. Methods: Fifty‐eight untreated AD patients were divided into two groups: young old AD patients (age at onset between 65 and 70 years; n = 28) and oldest old AD patients (age at onset 85 years or older; n = 30). Then, BPSD were compared between the two groups. Results: There were significant differences in the frequencies of hallucinations (χ² = 7.43; P = 0.011) and delusional misidentification syndrome (DMS; χ² = 7.26; P = 0.011) between the two groups. Conclusions: The results of the present study suggest that aging may play a part in the occurrence of hallucinations and DMS in oldest old AD patients.     

How to treat behavioral and psychological symptoms of dementia (BPSD): Do not treat patients exhibiting symptoms like BPSD with neuroleptics from the beginning

The present report details the case of three patients who had symptoms like behavioral and psychological symptoms of dementia (BPSD). In all three cases, other factors contributing to the disease were hidden behind the symptoms resembling BPSD. These cases exhibited symptoms like BPSD following acute or subacute onset. Before starting medication with antipsychotic drugs, the underlying causes of the symptoms, especially those with an acute or subacute onset, should be considered.     

Role of the home visit medical service for patients with behavioral and psychological symptoms of dementia (BPSD) living in the community

Background: It is important for patients with behavioral and psychological symptoms of dementia (BPSD) in the community, who refuse to go to clinics, to be medically served by means of home visits. However, there are a few clinics in Japan that are specialized in home visits for BPSD. Methods: The home visit medical service provided to several patients with BPSD was reviewed and the strategy for the treatment of BPSD was analyzed. Results: It was found that the medical approach of home visits for patients with BPSD needed to be based on daily life information as well as medical information. Conclusions: The medical service alone is not enough to provide appropriate care for patients with BPSD who are living in the community. Using the case studies presented herein, we have demonstrated the importance of ‘daily life information’ for medical intervention. Issues relating to the exacerbation of BPSD and the cooperation of caregivers in the drug monitoring system at home are also considered.     

Comparison of behavioral and psychological symptoms in early-onset and late-onset Alzheimer's disease

BACKGROUND: When comparing with early-onset Alzheimer's disease (EO-AD) and late-onset Alzheimer's disease (LO-AD), some symptomatological differences in clinical features can be seen between them. Rapid progression, more severe language problems or visuospatial dysfunction occur more often in EO-AD patients. However, there have been very few reports about the differences in behavioral and psychological symptoms between these two groups. AIM: The aim of this study was to demonstrate the differences in behavioral symptoms between EO-AD and LO-AD groups. METHOD: Three hundred and seven consecutive outpatients with AD were put into an EO-AD group (46 patients) or a LO-AD group (261 patients). Comprehensive assessment batteries, including the Neuropsychiatric Inventory (NPI), were administered at the first medical assessment. RESULTS: Significant differences were found between the EO-AD and LO-AD groups in terms of NPI total score (EO-AD: 10.3 +/- 10.9, LO-AD: 17.8 +/- 17.0, p = 0.004) and number of patients who experienced each NPI subscale score (delusion; EO-AD: 13.0%, LO-AD: 50.6%, p < 0.001). There were no differences in cognitive functions or dementia severity between two groups. CONCLUSION: In EO-AD, behavioral and psychological symptoms are relatively fewer than LO-AD at the first medical assessment. Copyright (c) 2007 John Wiley & Sons, Ltd.     

重复经颅磁刺激对阿尔茨海默病患者精神行为症状的疗效分析

目的 探讨重复经颅磁刺激（rTMS）对轻、中度阿尔茨海默病（AD）患者精神行为症状（BPSD）的疗效.方法 将38例有BPSD的AD患者随机分为rTMS治疗组（20例）和对照组（18例）,分别接受20次5 Hz rTMS真刺激和伪刺激治疗,治疗期间维持原有的胆碱酯酶抑制剂治疗.治疗前及治疗后2周、6周采用神经精神科问卷（NPI）观察疗效,采用治疗不良反应量表（TESS）观察不良反应.结果 38例患者均完成治疗,治疗6周时治疗组NPI评分（16.69±6.62）分较治疗前（27.65±4.38）分明显降低,差异有统计学意义（t=6.16,P＜0.05）;且显著低于对照组（23.44±5.49）分,差异有统计学意义（t=3.33,P＜0.05）.两组TESS总评分比较差异无统计学意义（x^2=2.06,P＞0.05）.结论 rTMS可能是控制轻、中度AD患者BPSD的一种有效而安全的治疗方法.     

Kampo therapy as an alternative to pharmacotherapy using antipsychotic medicines for behavioral and psychological symptoms of dementia (BPSD)

The behavioral and psychological symptoms of dementia (BPSD), including aggression, agitation, screaming, wandering, hallucinations, and delusions, occur in 50–90% of patients with dementia, and have a negative impact on the activity of daily living (ADL) of patients, as well as caregivers. Patients with severe BPSD often require management with antipsychotic medicines. However, an increased mortality rate has been reported in patients with dementia taking antipsychotic medicine and, thus, there is an urgent need to develop safer treatments for BPSD. Kampo medicines are an alternative to antipsychotic medicines and several Kampo medicines have been reported to be effective in the treatment of BPSD. Oren‐gedoku‐to has been reported to be effective for the treatment of irritability and sullenness in patients with vascular dementia, as well as improving excitement, depression, anxiety, and restlessness of patients with cerebrovascular lesions. Choto‐san has been reported to be effective in the treatment of delirium, insomnia, and hallucinations/delusions in patients with vascular dementia. Toki‐syakuyaku‐san has been reported to improve emotional lability, restlessness, and sleep disturbances in patients with dementia. Yokukan‐san has been reported to be effective for hallucinations, agitation/aggression, irritability/lability, and aberrant motor activity, as well as being effective in the treatment of visual hallucinations in patients with dementia with Lewy bodies (DLB). A multicenter randomized crossover study confirmed that Yokukan‐san is effective in the treatment of BPSD and is well‐tolerated. Kampo medicines do not induce extrapyramidal or anticholinergic symptoms and have no adverse effects on ADL or cognitive function. Thus, Kampo therapy is recommended for patients who cannot tolerate treatment with neuroleptics, patients who have extrapyramidal symptoms and gait disturbance, and patients with DLB. In future, to confirm the effectiveness of Kampo medicines in the treatment of BPSD, further studies, such as randomized control trials, are needed. In addition, basic studies are required to elucidate the processes by which Kampo medicines are metabolized, as well as any interactions between Western and Kampo medicines.     

Management of behavioral and psychological symptoms of dementia in long‐term care facilities in Japan

Background: An increasing number of old people, and their medical requirements, cannot be managed by their families in their homes, which has been the traditional and prevalent practice in Japan. The number of people with dementia is increasing and behavioral and psychological symptoms of dementia (BPSD) make care difficult. In the present study, we investigated management techniques for BPSD in long‐term care facilities in Japan by using the data mining method, which looks at the reported behaviors of care providers. Methods: First, interviews were conducted with 15 care providers to develop items for a questionnaire. These data were analyzed qualitatively and synthesized with criteria from the professional literature. The resulting self‐report questionnaire on techniques used to manage different symptoms of dementia was completed by 275 care providers. We applied the association rule as a data mining method examining 15 management techniques related to 13 BPSD. Results: Analysis identified four types of management techniques: (i) emotional and behavior‐concordance techniques; (ii) acceptance and supportive techniques; (iii) restraining techniques; and (iv) avoidance techniques. Different management techniques, and combinations of techniques, were found to vary in use and effectiveness with different BPSD. Conclusions: Good management techniques for many BPSD have been developed and are being implemented by care providers. The present study has the potential to inform researchers and care providers in Japan about the types of management techniques in current use, as well as areas of potential need for staff training.     

Effect of yokukansan on the behavioral and psychological symptoms of dementia in elderly patients with Alzheimer's disease

Objective

The aim of this study was to investigate the effects of yokukansan (YKS) on the behavioral and psychological symptoms of dementia (BPSD) in elderly patients with Alzheimer's disease (AD).

Methods

Fifteen patients with AD (mean age: 80.2 ± 4.0 years) participated in the study. The Mini-Mental State Examination (MMSE) was used for the assessment of cognitive function. BPSD were evaluated using the Neuropsychiatric Inventory (NPI). The Barthel Index was used for the assessment for the activities of daily living (ADL). The treatment with YKS along with sulpiride, a dopamine D₂ selective antipsychotic, was performed for 12 weeks.

Results

Fourteen patients completed the trial. After the 12 weeks of treatment with YKS, significant improvement of the mean NPI score was observed while no significant improvement was observed in the control group. The average dose of sulpiride at the end of the present study was less in the YKS group than in the control group. The MMSE results did not change either in the YKS group or in the control group. The Barthel Index did not significantly change either in the YKS group or in the control group. No serious adverse effects were noted.

Conclusions

Twelve weeks of the YKS treatment significantly improved BPSD with less antipsychotics in elderly patients with AD. The YKS treatment did not cause any cognitive decline or ADL decline and no serious adverse effects were noted. The present study suggests that YKS is beneficial for the treatment of BPSD and that it can possibly reduce the doses of antipsychotics required for the treatment of BPSD. Further studies with larger patient populations using a double-blind placebo-controlled design should be performed.     

阿立哌唑与利培酮口服液治疗门诊老年期痴呆精神行为症状的对照研究

目的 探讨阿立哌唑和利培酮口服液治疗门诊老年期痴呆精神行为症状(BPSD)的疗效和安全性.方法 将68例老年期痴呆伴BPSD患者随机分成阿立哌唑组35例,利培酮口服液组33例,疗程8周,采用痴呆病理行为评定量表(BEHAVE-AD)及激越性问卷(CMAI)评定疗效,采用治疗中需处理的不良反应症状量表(TESS)评定副反应.结果 两组治疗后第6、8周末BEHAVE-AD和CMAI评分与治疗前比较均显著下降(P＜0.01),两组之间比较治疗前及治疗后各时间点比较BEHAVE-AD评分差异无统计学意义(P＞0.05).两组不良反应比较,阿立哌唑组不良发生率明显低于利培酮口服液组,差异有统计学意义(P＜0.01).结论 阿立哌唑和利培酮口服液治疗老年期痴呆伴发BPSD均有较好疗效,两者总体疗效、起效时间相当,而阿立哌唑的安全性优于利培酮口服液.     

The use of psychotropic drugs for behavioral and psychological symptoms of dementia among residents in long-term care facilities in Japan

Objective: To examine whether the use of psychotropic drugs (PDs) was related to behavioral and psychological symptoms of dementia (BPSD) focusing on the prevalence, numbers of symptoms, severity, and care burden among the elderly with BPSD living in long-term care facilities in Japan.

Method: We conducted a cross-sectional survey among older people with dementia or similar symptoms (n = 312) using a questionnaire for care staff in 10 selected long-term care facilities. A brief questionnaire form of the Neuropsychiatric Inventory was used to assess BPSD.

Results: PDs were used in 45% among all participants and 47.5% among those exhibiting at least one BPSD. We found that use of PDs was associated with greater numbers, severity, and care burden of BPSD. Also, there was significantly more use of PDs among people who had specific BPSD symptoms, such as delusions, anxiety, and disinhibition, compared with those who did not.

Conclusion: The use of PDs among residents in long-term care facilities with dementia or similar symptoms was relatively low compared with previous reports from other countries. Nonetheless, the greater numbers, severity, and care burden of BPSD were associated with the use of PDs.     

伴行为和精神症状痴呆患者的脑葡萄糖代谢研究

目的:研究有、无痴呆的行为和精神症状(BPSD)的阿尔茨海默病(AD)患者脑葡萄糖代谢的不同特点,以探讨AD患者BPSD的病理生理及其与大脑神经病理之间的关系。方法:对13例符合美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)诊断标准的AD患者,其中6例有BPSD(BPSD组),7例无BPSD(NBPSD组),并进行PET检查,对各脑区局部脑葡萄糖代谢率(rCMRglc)及多个核团进行测定,并用统计参数图(SPM)对两组脑PET图像进行像素间比较。结果:①BPSD组的AD患者额叶放射性减低者多于NBPSD组(4/6∶2/7);②应用感兴趣区(ROI)方法进行比较,BPSD组和NBPSD组在所选脑区中的rCMRglc差异无显著性(P>0.05);③应用SPM方法进行比较发现,BPSD组和NBPSD组rCMRglc显著减低的脑区主要分布在前额叶、顶枕交界处和颞下回。BPSD组比NBPSD组rCMRglc减低面积大,左侧额叶上回、右侧颞叶前内部、右侧岛叶前下部葡萄糖代谢减低。结论:AD患者,不管有无BPSD,rCMRglc减低区主要位于前额叶、顶枕叶交界处和颞叶下回;有BPSD的AD患者比无BPSD的患者rCMRglc的减低区面积大,分布广,程度重,提示BPSD可能是AD病程中的一个症状,而并非是另一种AD类型;额叶rCMRglc减低可能与BPSD的发生有关。     

痴呆的行为和精神症状的药物治疗调查

目的：了解抗精神病药治疗痴呆的行为和精神症状（BPSD）的情况。方法：调查443例伴有明显的行为和精神症状、用抗精神病药治疗其行为和精神症状有效的阿尔茨海默病和血管性痴呆患者。结果：常用于治疗BPSD的抗精神病药有奋乃静、利培酮、氟哌啶醇、氯丙嗪、氯氮平、硫利达嗪、舒必利等,其起始剂量与有效剂量均较小,大多单一用药。用药剂量与年龄呈负相关。主要不良反应是锥体外系反应、便秘或排尿困难、嗜睡或步态不稳、吞咽困难等。抗精神病药不良反应发生率为16．0％,典型抗精神病药发生率（18．4％）显著高于非典型抗精神病药（9．6％）。结论：多种抗精神病药治疗BPSD均有效,治疗剂量低。非典型抗精神病药的安全性优于典型抗精神病药。     

The effects of behavioral and psychological symptoms on caregiver burden in frontotemporal dementia,Lewy body dementia,and Alzheimer's disease: clinical experience in China

Background and aims: Caregivers of individuals with neurodegenerative diseases, including frontotemporal dementia (FTD), Lewy body dementia (DLB), and Alzheimer's disease (AD), experience high levels of psychological and physical stress, likely due to behavioral and psychological symptoms of dementia (BPSD). This study is the first to simultaneously evaluate the effects of BPSD on caregiver burden in these three types of dementia.

Method: A total of 214 dementia patients, including probable FTD (n = 82), DLB (n = 22), and AD (n = 110), as well as their primary caregivers, were assessed using psychological inventories and cognitive evaluation. The FTD group was further divided into the three established clinical variants: behavioral variant frontotemporal dementia (bvFTD, n = 51), non-fluent variant primary progressive aphasia (nfvPPA, n = 15), and semantic variant primary progressive aphasia (svPPA, n = 16). Cognitive impairment and neuropsychiatric symptoms were assessed using the Mini Mental State Examination, Montreal Cognitive Assessment, Clock Drawing Test, and Neuropsychiatric Inventory (NPI), respectively. Caregiver burden was assessed using the Zarit Burden Inventory (ZBI).

Results: FTD patients had higher NPI and ZBI scores than DLB and AD patients, whose scores were similar. Logistic regression analysis revealed that the factors influencing caregiver burden for each group were: FTD: total NPI scores, agitation, and aberrant motor behavior; bvFTD: total NPI scores; DLB: total NPI scores; and AD: total NPI scores, onset age, apathy, and ADL. Caregivers of bvFTD patients had the highest levels of burden, which were significantly greater than for caregivers of nfvPPA, svPPA, DLB, and AD patients.

Conclusion: BPSD was highly correlated with emotional burden in caregivers of FTD, DLB, and AD patients. The highest burden was observed in bvFTD caregivers.     

Effects of aging on behavioral symptoms in Alzheimer's disease

Aim:  The aim of the present study was to evaluate the relationship between aging and the behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease (AD).
Methods:  Eligible subjects were consecutively referred AD patients with BPSD. According to patient age at the time of the test, the AD patient group ( n  = 79, whole AD group (WADG)) was divided into two groups: a relative older group (OG) in the whole AD group (WAD) (age at the time of test was 81 years or more, n  = 40) and a relative younger group (YG) in the WAD (age at the time of test was below 81 years, n  = 39). A comparison was made of the demographic data (sex difference, educational level and severity of dementia), cognitive functions and BPSD between the groups. BPSD was evaluated using the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). The factor analysis of BPSD was conducted in the WADG as well as in the OG and YG.
Results:  Sex difference, educational level, severity of dementia and cognitive functions were not different; however, the total score of the BEHAVE-AD symptom domain in diurnal rhythm was significantly higher in the OG than in the YG (Student's t -test: P  < 0.05). Factor analysis showed that psychosis was the first factor in the OG, but was the third factor in the YG and that the psychotic symptoms were caused by anxieties and phobias in the OG.
Conclusion:  From these results, we found that the effects of aging on the BPSD in AD were characterized by diurnal rhythm disturbance and psychosis.