Syndromes of behavioural and psychological symptoms in mild Alzheimer's disease

OBJECTIVES: Behavioural and psychological symptoms of dementia (BPSD) are common in Alzheimer's disease (AD), and are associated with significant distress for patient and carer. Certain behavioural and psychological symptoms have been associated with each other, leading to the suggestion that differences in symptom patterns among patients with AD may represent different syndromes within AD. The purpose of this study is to see if patients with AD could be meaningfully classified into syndromes, based on the relationships between their BPSD. METHODOLOGY: The sample was recruited through a memory clinic. Two hundred and forty first visit patients with a diagnosis of very mild to mild AD were included. BPSD were assessed using the BEHAVE-AD. Latent class analysis was used to assess for different classes or groups of patients within the sample, based on their behavioural and psychological symptoms. RESULTS: Three classes were identified; Class 1 with a low prevalence of behavioural and psychological symptoms; Class 2 an anxiety/depressive symptom class and Class 3 an aggressive symptom class. CONCLUSIONS: The three classes (or groups) of patients obtained by LCA in this sample may be explained by a 'latent', as yet, unidentified factor. Further research is required to determine if these classes are stable over time, and to identify possible latent variables.     

Incidence and relationship between behavioural and psychological symptoms in Alzheimer's disease

Objectives. To evaluate the frequency and type of psychological and behavioural symptoms in Alzheimer's disease (AD) patients in Poland, in various stages of the disease. Method. One hundred and sixty-nine patients with a diagnosis of probable AD in Global Deterioration (GDS) stages 3, 4, 5, 6 and 7 of dementia were examined in a search for behavioural and psychological symptoms. Results. Behavioural and psychotic symptoms were most often found in GDS stages 5 and 6 of AD, except for depressive disorder, which was observed most frequently in GDS stage 4 and whose frequency decreased towards the terminal stages of dementia. From an analysis of the relationship between behavioural symptoms in the Polish AD patients, the following syndromes may be discriminated: psychotic syndrome (delusions and hallucinations), delusions with aggressive behaviour and hallucinations and anxiety. With more severe dementia, the syndromes, which could be the result of delirium, became more common. Conclusions. Diagnosis of delirium should be considered in moderately severe and severe dementia whenever a sudden change in patients' behaviour occurs. Copyright © 1998 John Wiley & Sons, Ltd.     

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.     

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.     

Instruments to measure behavioural and psychological symptoms of dementia

Reliable and valid measurement of behavioural and psychological symptoms of dementia (BPSD) is important for research and clinical practice. Here we provide an overview of the different instruments and discuss issues involved in the choice of the most appropriate instrument to measure BPSD in research. A list of BPSD instruments was generated. For each instrument Pubmed and SCOPUS were searched for articles that reported on their use or quality. Eighty‐three instruments that are used to measure BPSD were identified. Instruments differ in length and detail, whether the interview is with participants, informants or by observation, the target sample and the time frames for use. Reliability and validity is generally good, but reported in few independent samples. When choosing a BPSD instrument for research the research question should be carefully scrutinised and the symptoms of interest, population, quality, detail, time frame and practical issues should be considered. Copyright © 2014 John Wiley & Sons, Ltd.     

A longitudinal evaluation of behavioural and psychological symptoms of probable Alzheimer's disease

BACKGROUND: Non-cognitive symptoms are a frequent feature of Alzheimer's disease (AD). Much of the literature that has accumulated pertains to cross-sectional prevalence of these symptoms. There has been relatively little attention paid to the longitudinal course of Behavioural and Psychological Symptoms of Dementia (BPSD). AIMS: The purpose of this study is to examine the longitudinal course of BPSD in a group of patients with mild AD. METHODS: A retrospective review of a database was performed to identify patients with NINCDS/ADRDA criteria for probable AD and who had been evaluated three times at yearly interval over a two-year period. Fifty-two subjects were identified with probable AD that had completed follow-up for 24 months. The BEHAVE-AD was used to evaluate BPSD and data was analysed using a Markov analysis. RESULTS: Activity disturbance is a common and relatively persistent symptom in the mild stages of AD. Anxiety, paranoid ideation, and aggression were moderately persistent. Affective symptoms were not persistent with less than half the patients having the symptoms a year later. CONCLUSIONS: Activity disturbance is common and persistent in early AD. Paranoid and delusional ideation shows moderate persistence and depressive symptoms infrequently last longer than a year. These findings may have clinical relevance for the pharmacological and non-pharmacological management of BPSD.     

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.     

Pathological diagnosis of combined Alzheimer's disease and argyrophilic grain dementia in a very elderly man who presented with advanced behavioural and psychological symptoms

This case report describes a Japanese man who presented with slowly progressive memory disturbances that began at the age of 79 years. The man also displayed conspicuous behaviour and psychological symptoms in the early stage of dementia. Computed tomography revealed atrophy of the amygdala and severe hippocampal deterioration, particularly in the anterior portion. Lateral ventricular dilatation, mainly affecting the anterior and inferior horns, was also observed. Interestingly, cerebral neocortical atrophy in the frontal and temporal lobes was considerably mild for the patient's age. Apolipoprotein E gene analysis showed epsilon 3 homozygosity. The patient died at the age of 96 years, and his clinical diagnosis was Alzheimer's disease with severe behavioural and psychological symptoms of dementia. In addition to indicating considerable hippocampal atrophy, an autopsy revealed numerous neurofibrillary tangles and argyrophilic grains in the brain, as well as extensive senile plaques. Cerebral amyloid angiopathy was also recognized. The pathological findings were suggestive of both Alzheimer's disease and argyrophilic grain dementia; other neurodegenerative disorders were not apparent. The clinicopathologic findings of the present case suggest significant consideration should be made when determining the clinical diagnosis and pathogenesis of senile dementia.     

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.     

Light therapy for behavioural and psychological symptoms of dementia

OBJECTIVES: To review literature concerning the efficacy, clinical practicability and safety of light treatment for behavioural and psychological symptoms of dementia (BPSD). METHOD: Data collection included computer literature searches (MEDLINE, PsycINFO and Cochrane) and checks of references, covering the period of January 1980-September 2003. Trials were searched for evidence for treatment efficacy and for their consideration of the treatment's clinical practicability and evidence of adverse effects. RESULTS: Results from randomised controlled trials (RCT) indicated some evidence of improvement in aspects of sleep disturbances and circadian activity rhythmicity. One RCT study indicated better response in patients with vascular dementia compared to Alzheimer's disease. By and large, non-RCT studies reported improvement in BPSD including sleep disturbances, agitation and activity rhythm disturbances. Few studies commented on the treatment's practicability and safety. CONCLUSION: Although there is some evidence for influence of light therapy on sleep and circadian activity rhythmicity, it is not possible to draw any conclusion about efficacy of light therapy for BPSD, or about practicability in clinical settings and safety. There are still too few well designed studies. Suggestions for further research are presented.     

Five Alzheimer's disease cases with refractory behavioural psychological symptoms of dementia treated with blonanserin

The aim of the present study was to determine the efficacy, side‐effects and tolerability of blonanserin for treating refractory behavioural psychological symptoms of dementia (BPSD). The present study was a 12‐week, prospective, structured clinical trial of blonanserin for the treatment of BPSD. The degree of cognitive function, activities of daily living score, and the degree of BPSD were determined using the Mini‐Mental State Examination (MMSE), Disability Assessment for Dementia (DAD), Neuropsychiatric Inventory (NPI) and the Rating Scale for Aggressive Behaviour in the Elderly (RAGE). The severity of extrapyramidal symptoms was assessed using the Drug‐Induced Extrapyramidal Symptoms scale (DIEEPS). Five patients were enrolled. These patients met the NINCDS‐ADRDA criteria. The patients were prescribed more than two kinds of existing antipsychotic drugs and were considered refractory cases; the drugs were discontinued because they were ineffectual and side‐effects appeared. Each drug was prescribed independently for at least 2 weeks. The mean changes (at baseline and at the last week, respectively) in the MMSE (12.25, 9.25), in the DAD (6.5, 6.75), in the RAGE (5.5, 5.3) and in the DIEEPS (0.5, 1.5) were minimal. The mean changes in the NPI were two or fewer points. Some side‐effects (one gait abnormality and one pneumonia) were observed. The results of this preliminary study show that blonanserin does not have adequate efficacy for the treatment of refractory BPSD.     

老年性阿尔茨海默病与血管性痴呆患者的行为和精神症状的比较

目的探讨阿尔茨海默病痴呆患者的行为和精神症状。方法选取本院2011年5月至2015年5月诊治的痴呆性老年患者80例,其中血管性痴呆(VD)患者40例为VD组,阿尔茨海默病(AD)患者40例为AD组,均行AD行为评分表(Behave-AD)评定,比较两组患者的行为和精神症状。结果 AD组患者偏执和妄想发生率、行为紊乱发生率、攻击行为发生率、焦虑和恐惧发生率均明显高于VD组,AD组患者偏执和妄想评分、行为紊乱评分、攻击行为评分、焦虑和恐惧评分、总评分均明显高于VD组,差异有统计学意义(P0.05)。AD组患者幻觉发生率高于VD组,AD组患者日间节律紊乱发生率、情感障碍发生率均低于VD组,AD组患者幻觉评分高于VD组,AD组患者日间节律紊乱评分、情感障碍评分均低于VD组,但差异无统计学意义(P0.05)。结论 AD患者偏执和妄想、行为紊乱、攻击行为、焦虑和恐惧等病症较为严重,其发生机制可能与AD患者存在较明显的额-枕叶萎缩有关。     

A double-blind randomised comparison of risperidone and haloperidol in the treatment of behavioural and psychological symptoms in Chinese dementia patients.

BACKGROUND: Behavioural and psychological symptoms (BPSD) are common during the course of dementia and present severe problems to patients and their caregivers. OBJECTIVES: To assess the therapeutic efficacy and safety of haloperidol and risperidone in treating BPSD in Chinese dementia patients. METHODS: A 12-week double-blind randomised comparison of haloperidol and risperidone treatments was conducted in 58 patients with DSM-IV diagnosis of dementia of Alzheimer's type or vascular dementia. They were randomly assigned to receive flexible doses (0.5 to 2 mg/day) of haloperidol or risperidone. Clinical response was evaluated using the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), Simpson-Angus Scale, Functional Assessment Staging and Cantonese version of the Mini-Mental State Examination. RESULTS: The mean doses at the last week were 0.90 mg/day of haloperidol and 0.85 mg/day of risperidone. Both haloperidol and risperidone significantly reduced the severity of BPSD (scores on CMAI and BEHAVE-AD), with no significant between-group differences. Haloperidol-treated patients showed a worsening on Simpson-Angus scale while there was no significant change in this measure in risperidone-treated patients. CONCLUSIONS: Low-dose haloperidol and risperidone were well tolerated and associated with reductions in the severity and frequency of behavioural symptoms in subjects with dementia. Risperidone may have a more favourable risk-benefit profile in view of its lower propensity to induce extrapyramidal symptoms.