The Efficacy and Safety of Yokukansankachimpihange for Treating Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease: An Open-Label Pilot Study

Previous clinical trials have demonstrated the efficacy of yokukansan, a traditional Japanese medicine, for the treatment of behavioral and psychological symptoms of dementia (BPSD). However, less evidence is available for the treatment of BPSD with yokukansankachimpihange (YKSCH), which consists of yokukansan and two additional herbal ingredients. The present study was conducted to investigate the efficacy and safety of YKSCH for treating BPSD in patients with Alzheimer’s disease (AD). We enrolled outpatients with mild-to-moderate AD who exhibited BPSD and obtained a Neuropsychiatric Inventory (NPI) score of >3 including subscale scores for “agitation”, “anxiety”, “irritability”, and “sleep and night-time behavior change”. A daily YKSCH dose of 7.5 g was administered for 12 weeks with concomitant administration of anti-dementia medication. BPSD was evaluated using the NPI at baseline and every 4 weeks during the intervention. We also examined apathy using the Japanese translation of the Apathy Scale, the short version of the Japanese version of the Zarit Caregiver Burden Interview, and the Modified Crichton Rating Scale for Predicting Activities of Daily Living. Cognitive dysfunction was evaluated using the Mini Mental State Examination and the AD Assessment Scale-Cognitive (Japanese version). Five participants were enrolled. The NPI total score tended to decrease between the baseline and 8-week evaluations during the YKSCH intervention (Wilcoxon signed rank test, P = 0.063). In terms of the NPI subscale scores, “apathy”, “agitation”, “delusions”, and “sleep and night-time behavior change” decreased after the intervention in those who exhibited each symptom at baseline. There were no significant differences in the other scores examined. No serious adverse events were observed. YKSCH could ameliorate BPSD in patients with mild-to-moderate AD with agitation, anxiety, irritability, and sleep and night-time behavior change, and it was well-tolerated.

Role of antipsychotics for treating behavioral and psychological symptoms of dementia

Over the past three decades, concerns about the high prevalence of antipsychotic use in the nursing homes(NHs) for the management of behavioral and psychological symptoms of dementia continue to be emphasized and intervened by many. However, despite the numerous side effects and the recent blackbox warning by the United States Food and Drug Administration about the increased risks for stroke and sudden death associated with the use of antipsychotics in dementia, the prevalence of antipsychotic use in NHs remains high. While the use of antipsychotics appeared to have modest efficacy in reducing symptoms of aggression and psychosis in dementia, there is insufficient evidence to routinely recommend the use of alternative psychopharmacological treatments for these symptoms. Hence, clinicians have to balance the safety warnings against the need to treat these symptoms in order to prevent harm to the resident that may result from his/her dangerous behaviors. Although the use of antipsychotics may be warranted in some cases, organizational, resource and training support should be provided to encourage and equip NH staff to participate in interventions so as to minimize inappropriate use of these medicines in NHs. This review will discuss the place in therapy, the trend and appropriateness of antipsychotic use in NHs, as well as the effectiveness of current and future strategies for reducing antipsychotic use in the NHs.

Gabapentin for the treatment of behavioral and psychological symptoms of dementia

Objective: To examine the efficacy of gabapentin for the treatment of behavioral and psychological symptoms of dementia (BPSD). Design: A retrospective chart review. Settings: Tertiary care geriatric psychiatry inpatient unit. Participants: 230 patients with BPSD. Measurements: The socio-demographic information, type of behaviors, co-morbid psychiatric and medical diagnoses, daily doses of medications and side-effects were recorded. Results: Of the 230 patients, 22 were treated with gabapentin. Twenty of these patients were on a combination of gabapentin and an antipsychotic medication while two patients were treated with gabapentin monotherapy. Eighteen of the 20 patients in the combination group tolerated the treatments with little or no side effects as did the two patients in the monotherapy group. Conclusions: Gabapentin may be a safe option for the treatment of BPSD in combination with antipsychotic medications. Gabapentin may also be effective as monotherapy in certain patients with BPSD.

Improving the Appropriateness of Antipsychotic Prescribing for Behavioral and Psychological Symptoms of Dementia (BPSD): A Pilot Study of the Psychotropic Use Monitoring (PUM) Program

In nursing homes, antipsychotic prescribing decisions (APDs) for managing behavioral and psychological symptoms of dementia (BPSD) depend on the nursing staff’s feedback. Inappropriate APDs can result in the lack of timeliness, objectivity and important clinical information when nursing staff’s feedback on residents’ behavior and pharmacotherapy outcomes. Currently, there are no reported interventions for improving psychiatrists’ APDs through nursing staff’s monitoring and feedback processes. This one-group pre-and-post pilot study aimed to evaluate the feasibility and impact of implementing a newly-developed Psychotropic Use Monitoring (PUM) program for improving the appropriateness of APDs in a 50-bed dementia ward of a nursing home. The PUM intervention involved 16 pharmacist-trained nursing staff, who monitored and reported residents’ BPSD changes and psychotropic side effects for 24 weeks, while carrying out their routine care duties. A face-to-face interview was then administered to determine the nursing staff’s perceptions of PUM. Data of 51 residents were collected from hardcopy individual patient records to evaluate the changes in APDs and the number of resident falls before and after implementing PUM. The nursing staff reported increases in their knowledge, awareness, confidence, and actual frequency of monitoring for side effects, as well as their ability in differentiating and managing BPSD (p < 0.05). After PUM, there was a significant increase in the number of APDs due to side effect-related reasons (4 versus 16) (p < 0.031). Although not significant, the number of APDs with no documented reasons (5 versus 9) and the number of resident falls (7 versus 15) appeared to be lesser after PUM. This study demonstrated the nursing staff’s positive participation in PUM intervention, specifically in monitoring and feedback of side effects. Furthermore, a potential exists for PUM to encourage more judicious APDs, which may be useful in settings with heavy patient load, limited human resources and dependence on foreign nursing staff from differing cultural backgrounds.

Quantitative evaluation of severity of behavioral and psychological symptoms of dementia in patients with vascular dementia

To quantitatively evaluate severity of behavioral and psychological symptoms of dementia(BPSD)for vascular dementia(VD).Changes of 51 patients with VD in BPSD between the first and 24th week were assessed using the Neuropsychiatric Inventory(NPI)and the behavioral pathology in Alzheimer’s disease(BEHAVE-AD)rating scale,in detrended fluctuation analysis(DFA)represented by diurnal activity(DA),evening activity(EA),and nocturnal activity(NA),and the relationships were analyzed.The subscores of activity disturbances,diurnal rhythm disturbances,and anxieties and phobias in the BEHAVE-AD score,and that of agitation,irritability,and sleep disorder in the NPI score were significantly increased compared with the first week,as was for the changes for EA in the DFA value.A linear correlation was observed between the changes of activity disturbances plus anxieties and phobias,and those of DA,and between the development of diurnal rhythm and those of EA,the vehement and autism scores and those of DA,and the difference in sleep disorder scores and those of EA,respectively.Analysis of DA,NA,and EA may reflect the fluctuational degrees of VD-BPSD,can provide a useful assessment of VD-BPSD accompanied by clinical scores for VD.

An association between the location of white matter changes and the behavioral and psychological symptoms of dementia in Alzheimer's disease patients

Objective:The frontal lobe may be involved in circuits associated with depression,apathy,aggression,and other psychiatric symptoms.Although white matter changes(WMC)are related to the severity of behavioral and psychological symptoms of dementia(BPSD)in patients with Alzheimer’s disease(AD),it is unclear which part of the WMC may play the most important role in BPSD.This study was designed to investigate the relationship between the location of WMC and the severity of BPSD in AD patients.Methods:Among patients diagnosed with Alzheimer’s disease between 2009 and2014,387 patients were retrospectively reviewed after those with pre‐existing organic brain syndrome,psychiatric diseases,or toxic‐metabolic encephalopathy were excluded.Patients’demographic and laboratory data,WMC measured with brain computed tomography and scored using the age‐related white matter changes(ARWMC)scale,and neuropsychological tests,including the cognitive abilities screening instrument(CASI),the Mini‐Mental State Examination(MMSE),the clinical dementia rating scale with sum‐box(CDR‐SB),and the neuropsychiatric inventory(NPI)were analyzed.Results:There was no significant difference in the NPI between patients with and without a history of stroke,hypertension,and diabetes.No significant difference in the NPI was identified between different sexes or different Apolipoprotein E(APOE)alleles.The NPI score was significantly correlated with the duration of education(r=–0.4515,P=0.0172),CASI(r=–0.2915,P<0.0001),MMSE(r=–0.8476,P<0.0001),and CDR‐SB(r=2.2839,P<0.0001).WMC in the right frontal lobe showed a significant difference in NPI in comparison to those without WMC(P=0.0255).After adjusting for age,duration of education,and CASI,WMC in the right frontal lobe remained significantly associated with the NPI score(β=3.8934,P=0.042).Conclusions:WMC involving the right frontal lobe may play an important role in the BPSD in AD patients during their dementia diagnosis.Further studies are necessary to confirm whether controlling the risk factors of WMC can slow the progression of BPSD.

Rehabilitative Outcomes after Hip Fracture in a Special Care Unit for Persons with Dementia and Behavioral and Psychotic Symptoms

Aim: Hip fracture implies severe problems to older people;special concerns regard persons with dementia, due either to cognitive impairment, or to behavioral and psychic symptoms. This study illustrates rehabilitative outcomes of these patients discharged by a special care unit ruled by “GentleCare” principles. Method: 54 patients [89% females, aged 82.3 years (range 66 - 94)] followed a post-surgery rehabilitative program carried out by a physiotherapist and an occupational therapist, supported by a psychologist. The multidimensional assessment consisted of cognition evaluation (Mini Mental State Examination, Clinical Dementia Rating, Global Deterioration Scale), functional evaluation (Barthel Index, Tinetti Gait and Balance, Bedford Alzheimer Nursing Severity scale), behavioral evaluation (UCLA Neuropsychiatric Inventory) and comorbidity evaluation (Cumulative Illness Rating Scale). Results: All parameters improved, including the 5 most frequent behavioral and psychic symptoms that usually preclude admission in ordinary rehabilitation units. 24% of improvement in Barthel Index total score was explained by agitation and apathy at discharge, in a multiple linear regression model: better functional levels corresponded to smoother behavioral problems. Most patients improved;70.5% of them were discharged to home. Conclusion: A prosthetic approach enables valuable results in the rehabilitation of severely demented patients with hip fracture also in presence of behavioral symptoms.

Predictors of Comorbid Psychological Symptoms among Patients with Social Anxiety Disorder after Cognitive-Behavioral Therapy

Aim: The present study aimed to examine the predictors of comorbid psychological symptoms in social anxiety disorder (SAD) after cognitive-behavioral therapy (CBT). Methods: One hundred fourteen SAD patients completed manualized group CBT. We examined associations between the personality dimensions of NEO Five Factor Index (NEO-FFI) and the subscales of Symptom Checklist-90 Revised (SCL-90-R) in SAD patients after CBT using multiple regression analysis. Results: High levels of conscientiousness at baseline predicted symptom reduction on 4 SCL-90-R scales, including somatization, obsessive-compulsive, anxiety and global severity index in patients with SAD after CBT. And high levels of agreeableness predicted symptom reduction on 2 SCL-90-R scales, including Hostility and Paranoid Ideation. High levels of openness predicted psychoticism. Conclusion: The present study suggested that high levels of three NEO-FFI dimensions (openness, agreeableness, conscientiousness) might predict comorbid psychological symptoms reduction in SAD patients after CBT. For the purpose of improving comorbid psychological symptoms with SAD patients, it might be useful to pay more attention to these dimensions of NEO-FFI at baseline.

Characteristics of Patients with Decreased Cognitive Function Undergoing Treatment for Acute Exacerbation of Chronic Heart Failure—Basic Survey for Standardization of Nursing to Prevent Discontinuation of Treatment

The purpose of this study is to clarify the characteristics of patients with decreased cognitive function undergoing treatment for acute exacerbation phase of chronic heart failure as a basic survey with a view to the standardization of nursing to prevent discontinuation of treatment of patients with declining cognitive function in the acute exacerbation phase of chronic heart failure. As the first stage of the research, using the interview guide created based on the background of discontinuation of treatment and symptomatic monitoring from 33 target literature sources, seven certified chronic heart failure nurses and 15 certified dementia nurses were given semi-structured interviews. Data obtained from the interviews was analyzed by qualitative induction. As a result, we obtained opinions/views on 8 situations namely, “cognitive function at hospitalization”, “characteristics at hospitalization, “characteristics when receiving examinations, procedures or treatment”, “characteristics of course of treatment”, “characteristics related to difficulties in grasping the symptoms of chronic heart failure and indices of deterioration”, “characteristics when using diuretics”, “characteristics concerning compliance with dietary restrictions” and “support required for discharge from hospital” concerning patients with declining cognitive function. In the future, it is necessary to prepare nursing protocols incorporating these contents for standardization of nursing.

Evidence for using dextromethorphan-quinidine for the treatment of agitation in dementia

Behavioral and psychological symptoms including agitation are common in dementia,and are associated with decreased quality of life,increased risk of institutionalization,and greater patient and caregiver distress.Pharmacological agents used for management of behavioral and psychological symptoms of dementia are limited by their tolerability,prompting a need for identifying efficacious and safe pharmacological treatments for managing agitation in dementia.The combination of dextromethorphan and quinidine sulfate is approved for pseudobulbar affect,and may be effective in managing agitation in dementia.A review of literature found only one randomized controlled trial that evaluated the use of dextromethorphan-quinidine for the management of agitation in dementia when compared to placebo.Data from this trial demonstrated that dextromethorphan-quinidine decreased agitation in dementia,and was well tolerated.Although promising,further research is needed before dextromethorphan-quinidine combination can be accepted as a standard treatment for agitation in dementia.

多感官刺激联合多领域认知训练对阿尔茨海默病患者精神行为症状的影响

目的探讨多感官刺激联合多领域认知训练对阿尔茨海默病患者(Alzheimer’s disease,AD)精神行为症状的影响。方法便利抽样选取2023年2-4月某医院神经内科病房收治的AD患者共94例,对照组予常规护理,试验组在此基础上实施多感官刺激联合多领域认知训练。干预前后采用神经精神量表(neu-ropsychiatric inventory,NPI)、科恩-曼斯菲尔德激越行为量表(Cohen-Mansfield agitation inventory,CMAI)、汉密尔顿焦虑量表(Hamilton anxiety scale,HAMA)和汉密尔顿抑郁量表(Hamilton depression scale,HAMD)评价两组患者的精神行为、情绪变化。结果试验组患者在接受干预后的NPI、CMAI、HAMA和HAMD评分明显低于对照组(均P<0.05)。结论对AD患者实施多感官刺激联合多领域认知训练,可有效降低其激越行为的发生率,改善焦虑和抑郁等负面情绪。

老年期痴呆的BPSD非药物治疗及其与ApoE基因多态性相关性的临床研究

目的分析老年期痴呆的行为精神症状(behavioral and psychological symptom of dementia,BPSD)的非药物治疗效果及其与载脂蛋白E(apolipoprotein E,ApoE)基因多态性的关系。方法选取2016年1月至2022年12月江西省人民医院收治的90例老年期痴呆患者为研究对象,根据随机数字表法将其分为常规组、对照组和观察组,每组各30例。常规组患者给予盐酸美金刚片治疗,对照组患者在常规组基础上加以音乐疗法,观察组患者在常规组基础上加以重复经颅磁刺激治疗,三组均连续治疗12周。比较三组患者的BPSD严重程度、痴呆严重程度、认知功能、日常生活能力、ApoE基因多态性。结果治疗前,三组患者的神经精神问卷(neuropsychiatric inventory,NPI)、临床痴呆评定量表(clinical dementia rating,CDR)、简明精神状态检查量表(mini-mental state examination,MMSE)、日常生活能力评定量表(activity of daily living scale,ADL)评分比较差异均无统计学意义(P>0.05);治疗后,三组患者的NPI、CDR评分均显著低于本组治疗前,MMSE、ADL评分均显著高于本组治疗前(P<0.05);观察组和对照组患者的NPI、CDR评分均显著低于常规组,MMSE、ADL评分均显著高于常规组(P<0.05)。ApoE共有ε2、ε3、ε4三种等位基因,其中ε3表达频率最高,共55例,其次为ε4和ε2;三组患者的ApoE不同基因检出率比较差异无统计学意义(P>0.05)。ApoEε4型患者的NPI评分显著高于ApoEε3型与ApoEε2型(P<0.05)。结论非药物治疗老年期痴呆患者效果显著,可减轻BPSD和痴呆表现,提高患者的认知功能和日常生活能力,ApoEε4型基因与老年期痴呆患者的BPSD存在紧密联系。

Comprehensive Management of Daily Living Activities,behavioral and Psychological Symptoms,and Cognitive Function in Patients with Alzheimer's Disease:A Chinese Consensus on Alzheimer's Disease

Alzheimer's disease(AD)is the most common cognitive disorder in the elderly.Its main clinical manifestations are cognitive decline(C),behavioral and psychological symptoms(B),and a decline in the activities of daily living(A),also known as ABC symptoms.Early identification and evaluation of ABC symptoms are helpful for establishing the accurate diagnosis,comprehensive treatment,and prognosis of AD.To guide Chinese clinical practice for optimization of the comprehensive management of AD,in 2018,The Academy of Cognitive Disorder of China gathered 22 neurologists and gerontologists in China to build a consensus on the comprehensive management of AD.Based on a review of the evidence,the consensus summarizes the pathogenesis,pathological changes,clinical manifestations,evaluation,diagnosis,drug and non-drug treatment,and patient care for AD.Focus group discussion was used to establish a flowchart of comprehensive ABC management for AD patients.The new consensus provides a feasible AD management process for clinicians.

生慧益智汤联合盐酸多奈哌齐对轻中度阿尔茨海默病患者精神行为症状的影响

目的基于“神志病”视角,探究生慧益智汤联合盐酸多奈哌齐对轻中度阿尔茨海默病(Alzheimer,s disease,AD)患者精神行为症状(behavioral and psychological symptoms of dementia,BPSD)的临床疗效。方法选取符合纳入标准的AD患者70例,随机分为治疗组和对照组,每组35例。对照组患者给予盐酸多奈哌齐,治疗组患者给予生慧益智汤联合盐酸多奈哌齐治疗,疗程6个月。治疗前后采用AD认知评定量表(Alzheimer's disease assessment scale-cognitive subscale,ADAS-cog)和神经精神症状问卷(neuropsychiatric inventory,NPI)评分,评估患者认知功能及精神行为异常表现,并观察治疗期间药物不良反应。结果治疗后2组患者ADAS-cog、NPI评分较治疗前均显著降低(P<0.05),治疗组明显低于对照组(P<0.05)。NPI在抑郁、焦虑、情感淡漠领域,2组患者治疗后评分均低于治疗前(P<0.05),且治疗组明显低于对照组(P<0.05);此外治疗组患者治疗后妄想、易激惹、睡眠/夜间行为异常评分低于治疗前(P<0.05),且评分低于对照组(P<0.05)。2组患者不良反应发生率比较差异无统计学意义(P>0.05)。结论轻中度AD患者BPSD以抑郁、淡漠、易激惹、焦虑、睡眠/夜间行为异常、妄想为主,生慧益智汤联合多奈哌齐能整体改善认知功能、减轻上述BPSD症状。中西医结合疗效优于单用多奈哌齐,值得临床推广应用。

痴呆特别照料单元的现状和展望

在痴呆负担日益沉重的背景下,痴呆特别照料单元(Dementia Special Care Units,DSCU)作为旨在为阿尔茨海默病等痴呆症患者提供专病照料的有效手段逐渐受到重视。经过长期发展,DSCU在物理空间、人力资源建设、效果评价等方面已经形成成熟的建设策略,实践证明规范的DSCU可以帮助控制痴呆相关精神行为异常(Behavioral and psychological symptoms of dementia,BPSD),使痴呆患者获益。本文就DSCU的发展、建设、展望作一综述。

基于Kales概念模型的护理干预对痴呆患者激越行为的影响

目的 探讨基于Kales概念模型的护理干预对痴呆患者激越行为的影响。方法 选取2021年12月至2022年12月在北京市某三级甲等综合医院老年科住院的80例痴呆患者作为研究对象。采用随机数字表法将患者分为对照组和观察组。对照组(n=40)接受常规护理,观察组(n=40)在常规护理的基础上实施基于Kales概念模型的护理干预,分别比较干预前、干预2w后、干预4w后两组患者激越行为及生活质量。结果 重复测量方差分析显示,两组患者干预3个时间点激越行为得分和生活质量得分的时间效应、组间效应和交互效应比较,差异具有统计学意义(均P<0.05)。干预后观察组患者激越行为得分均低于对照组,两组比较,差异具有统计学意义(P<0.001)。干预后观察组患者生活质量得分均高于对照组,两组比较,差异有统计学意义(P<0.01)。结论 基于Kales概念模型的护理干预有助于改善痴呆患者激越行为,提高痴呆患者生活质量。

聚焦心理护理对维持性血液透析患者的焦虑症状、压力知觉和行为陷阱的影响

目的:探讨聚焦心理护理在维持性血液透析患者中的应用效果。方法:选取2019年12月—2022年1月抚州市第一人民医院收治的维持性血液透析患者160例,按随机数字表法分为两组,各80例。对照组采用常规护理,观察组实施聚焦心理护理,两组持续护理4周。比较两组焦虑症状、主观幸福感、压力知觉、行为陷阱、生活质量和护理满意度。结果:护理后,观察组焦虑自评量表(SAS)、压力知觉量表(PSS)评分均低于对照组,总体幸福感评估量表(GWB)评分高于对照组(P<0.05)。护理后,观察组行为陷阱评分低于对照组,健康调查简表(SF-36)评分均高于对照组(P<0.05)。观察组护理总满意度(97.50%)高于对照组(88.75%)(P<0.05)。结论:聚焦心理护理能够减轻维持性血液透析患者焦虑症状,有效提升患者主观幸福感,减轻压力知觉和行为陷阱,促进生活质量改善,从而获得更高的患者满意度。

A Meta-analysis of Mood Stabilizers for Alzheimer's Disease

The objective of this study was to assess the clinical evidence for or against mood stabilizers as a treatment for Alzheimer’s disease (AD).We searched 5 databases from their inception to January 2010.Five randomized clinical trials of mood stabilizers to treat human patients suffering from AD were included.These trials assessed the effectiveness of mood stabilizers as an adjunct treatment to conventional anti-dementia drugs on behavioral and psychological symptoms, especially on agitation.Methodological quality was assessed using the Jadad score.The results suggested a significant effect in favor of placebo on the Mini-Mental Status Examination [n=270, weight mean difference (WMD), -0.89; 95% confidence intervals (CIs) -1.69 to -0.09, P=0.03] and on the Neuropsychiatric Inventory total (NPI total) (n=51, WMD, 3.71; 95% CIs 0.15 to 7.26, P=0.04).There were no significant differences in change scores on total Brief Psychiatric Rating Scale (BPRS total), NPI/BPRS agitation, Cohen-Mansfield Agitation Inventory total and Physical Self Maintenance Scale between mood stabilizers and placebo.Only one of these studies was free of methodological limittions (Jadad score=5).In conclusion, based on the existing evidence, mood stabilizers are ineffective or even harmful as a treatment for AD.

Risperidone Versus Yokukansan in the Treatment of Severe Alzheimer’s Disease

PURPOSE: Patients with AD commonly exhibit behavioral and psychological symptoms of dementia (BPSD). This study is aimed to compare the efficacy of yokukansan (YKS) and risperidone (RIS) on BPSD in patients with severe Alzheimer’s disease (AD). METHODS: Thirty eight inpatients with AD were investigated. Patients were randomly as-signed to the YKS group (N = 18) or the RIS group (N = 20) and treated for 4 weeks. The primary outcomes were changes in the scores on the Neuropsychiatric Inventory (NPI), the Mini-Mental State Examination (MMSE), the Bar-thel Index, and the Cohen-Mansfield Agitation Inventory (CMAI). The frequency of extrapyramidal symptoms (EPS) and other adverse events were recorded at every visit. RESULTS: All participants in both groups completed the trial. The Barthel Index did not significantly change either in the RIS group or the YKS group. The MMSE scores did not change either in the RIS group or the YKS group. Significant improvements in mean total NPI and CMAI scores showed in both groups. Between the YKS and the RIS groups, there were no significant differences in the NPI or the CMAI scores. EPS and other serious adverse effects were not observed in either group. CONCLUSIONS: In this 4-week trial, YKS treatment significantly improved BPSD in the patients with severe AD. The present study suggests that YKS is as effective as RIS on BPSD with severe AD.