Impact of donepezil hydrochloride on the care burden of family caregivers of patients with Alzheimer's disease

Background: To evaluate the impact of donepezil hydrochloride on the care burden on family members of patients with Alzheimer's disease (AD). At present, donepezil is the only drug approved for the treatment of AD in Japan. Although the care burden on primary caregivers of AD patients comprises both physical and psychological burdens and donepezil is recognized to improve cognitive dysfunction and associated symptoms, there are few data on the effects of the drug on the care burden. Methods: Of the uninstitutionalized AD patients who visited a dementia clinic between June 2008 and May 2009 with their primary family caregivers, 416 subjects who satisfied the enrollment criteria were registered for the study. All participants provided informed consent. Assessment included changes in scores on the Japanese version of the Zarit Caregiver Burden Interview (J‐ZBI) and the Mini‐Mental State Examination (MMSE), as well as the presence of behavioral and psychological symptoms of dementia (BPSD). Caregivers answered the questionnaires at baseline and after 12 weeks treatment with donepezil (starting dose 3 mg, p.o., once daily, followed by 5 mg after 1 or 2 weeks). Results: There were significant changes in mean scores on the J‐ZBI (?1.9 ± 9.5; P < 0.01) and MMSE (+0.9 ± 2.9; P < 0.01) from baseline to Week 12, without significant correlation between these two scores. In patients with BPSD, there was a significant decrease in J‐ZBI scores over the 12 weeks (P = 0.013); in contrast, in patients without BPSD, the decrease in the J‐ZBI score did not reach statistical significance (P = 0.418). Conclusions: The results indicate that donepezil improves cognitive function and some of the BPSD. As a possible consequence of improvements in BPSD, donepezil may also reduce caregivers' burden.     

Behavioral and psychological symptoms of dementia in untreated Alzheimer's disease patients

Background: To ascertain the prevalence of psychotic symptoms and behavioral disturbances of dementia patients is useful for families and health care professionals in order to anticipate the progression of Alzheimer’s disease (AD) and to recognize deterioration. This study aimed to determine whether behavioral and psychological symptoms of dementia (BPSD) are related to severity of untreated AD. Methods: Two hundred and two patients were classified into three groups by Functional Assessment Staging score as follows: mild group (n = 92) was at stages 3 or 4; moderate group (n = 80) was at stage 5; and severe group (n = 30) was at stages 6 or 7. We then compared the prevalence of BPSD among the groups. Psychiatric symptoms of BPSD were defined as including hallucinations, delusions, delusional misidentification syndrome and depressive mood; while behavioral disturbances included physical aggression, wandering, adverse sleep and hyperphagia. Results: In our study, depressive mood, physical aggression and wandering were statistically associated with the severity of AD. Conclusion: These results are meaningful for caregivers in helping them to understand the anticipated progression of AD and to recognize deterioration. In the care of AD patients, it is necessary to be aware of characteristics of each BPSD.     

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.     

Improvement in delusions and hallucinations in patients with dementia with Lewy bodies upon administration of yokukansan,a traditional Japanese medicine

Background: This multicentre open‐label trial examined the efficacy and safety of the traditional Japanese medicine, or Kampo medicine, yokukansan (YKS), for behavioural and psychological symptoms of dementia (BPSD) in patients with dementia with Lewy bodies. Methods: Sixty‐three dementia with Lewy bodies patients with probable BPSD (M : W, 30 : 33; mean age, 78.2 ± 5.8 years) were enrolled and treated with YKS for 4 weeks. Results: Significant improvements in Neuropsychiatric Inventory scores (mean decrease, 12.5 points; P < 0.001) and Zarit Burden Interview‐Japanese edition tests (mean decrease, 3.6 points; P= 0.024) were observed. In patients who consented to an assessment after 2 weeks of treatment, a time‐dependent significant improvement was observed in the Neuropsychiatric Inventory score (n= 23; mean decrease, 14.4; P < 0.001), each subscale, including delusions and hallucinations, the Zarit Burden Interview‐Japanese edition (n= 22; mean decrease, 8.2; P < 0.01) and the behavioural pathology in Alzheimer's disease insomnia subscale. The Mini‐Mental State Examination and the Disability Assessment for Dementia (DAD) showed no significant change. Adverse events were observed in 11 (18%) patients. Three patients (5%) discontinued YKS due to adverse reactions, namely, spasticity and exacerbation of BPSD, edema, and nausea. Hypokalaemia (<3.5 mEq/L) was present in four patients (6%) at the study endpoint. Worsening of extrapyramidal symptoms was not observed. Conclusion: YKS improved BPSD in dementia with Lewy bodies patients and caregiver burden scores without deterioration in cognitive function. YKS is useful for the treatment of delusions and hallucinations in BPSD.     

Improvement in behavioural symptoms in patients with moderate to severe Alzheimer's disease by memantine: a pooled data analysis

INTRODUCTION: Behavioural disturbances are a common and distressing aspect of Alzheimer's disease (AD). This pooled analysis evaluated the specific benefits of memantine on behavioural disturbances in patients with moderate to severe AD. METHODS: Data were pooled from six 24/28-week, randomised, placebo-controlled, double-blind studies. Of the 2,311 patients included in these studies, 1,826 patients with moderate to severe AD (MMSE <20) were included in this analysis, corresponding to the extended indication for memantine in Europe. In this subgroup, 959 patients received memantine 20 mg/day and 867 received placebo. Behavioural symptoms were rated using the Neuropsychiatric Inventory (NPI) total and single-item scores at weeks 12 and 24/28. RESULTS: At weeks 12 and 24/28, ITT analysis demonstrated that memantine treatment produced statistically significant benefits over placebo treatment in NPI total score (p=0.001 and p=0.008), and in NPI single items: delusions (p=0.007 week 12, p=0.001 week 24/28), hallucinations (p=0.037 week 12), agitation/aggression (p=0.001 week 12, p=0.001 week 24/28), and irritability/lability (p=0.005 week 24/28), LOCF population. Analysis of the patients without symptoms at baseline indicated reduced emergence of agitation/aggression (p=0.002), delusions (p=0.047), and disinhibition (p=0.011), at week 12, and of agitation/aggression (p=0.002), irritability/lability (p=0.004), and night-time behaviour (p=0.050) at week 24/28 in those receiving memantine. OC analyses yielded similar results. CONCLUSIONS: The data suggest that memantine is effective in treating and preventing the behavioural symptoms of moderate to severe AD. Specific persistent benefits were observed on the symptoms of delusions and agitation/aggression, which are known to be associated with rapid disease progression, increased caregiver burden, early institutionalisation, and increased costs of care.     

New therapeutic strategies for behavioral and psychological symptoms of dementia]

Interventional studies, with the aim of reducing the burden of care through drug or non-drug therapies of behavioral and psychological symptoms of dementia (BPSD), have been scarce. However, we are now able to do pharmacological management for BPSD with new drugs such as atypical neuroleptics, SSRIs, and cholinesterase inhibitors. Delusions of theft are one of the most frequently observed BPSD in patients with AD. In addition, the delusions and ensuing aggression and anxiety are major factors that increase the burden of caregivers. Delusions of theft in patients with AD were eliminated or reduced with low-dose atypical neuroleptics (risperidone). This significantly reduced the burden of care overall for caregivers. New therapeutic strategies such as cholinesterase inhibitors for visual hallucinations in DLB and SSRIs for overeating and stereotyped behavior in FTLD might also remarkably reduce the burden of care for these patients. For many dementia patients, there are still no drugs that offer a principal cure. It is, therefore, important to evaluate their BPSD correctly at the earliest possible time, so that the burden of caring can be reduced through appropriate drug treatment. This reduction is critical for the continuation of satisfactory at-home care and might contribute to the health economics.     

Behavioral and psychological symptoms in Alzheimer's disease: frequency and relationship with duration and severity of the disease

The occurrence of behavioral and psychological symptoms of dementia (BPSD) is currently recognized as an important aspect of Alzheimer's disease (AD). We evaluated the frequency and severity of BPSD with the Neuropsychiatric Inventory across the various degrees and phases of the disease in 50 consecutive AD outpatients. Apathy, aberrant motor activity, dysphoria and anxiety were the symptoms most frequently reported by the caregivers, ranging in the whole study sample from 46 to 74%. A clear trend towards increasing frequency with the severity of disease was found for delusions, hallucinations and aberrant motor activity. A major effect of the duration of the disease was found in the probability of developing hallucinations and aberrant motor activity. Apart from hallucinations, all BPSD were present starting from a mild degree of dementia. A better understanding of the global spectrum of BPSD in AD is warranted in order to improve the allocation of health resources toward the treatment of dementia.     

Behavioral and psychological symptoms of dementia characteristic of mild Alzheimer patients

In order to clarify the characteristics of Behavioral and Psychological Symptoms of Dementia (BPSD) in patients with mild Alzheimer's disease (AD), BPSD among the severities of Clinical Dementia Rating (CDR) in 74 patients with AD were compared using the Neuropsychiatric inventory (NPI). The result, when compared between mild (CDR = 0.5, 1) and moderate or severe (CDR = 2, 3) AD, was a significant difference in frequency of euphoria, disinhibition and aberrant motor behavior, but no significant difference was found in frequency of delusions, hallucinations, agitation, dysphoria, anxiety, apathy and irritability. In addition, a significant difference was found in the mean scores of the composite score for euphoria, apathy, disinhibition and aberrant motor behavior, but no significant difference was found in the mean scores of the composite score for delusions, hallucinations, agitation, dysphoria, anxiety and irritability. That is, the mild AD groups (CDR 0.5 or 1) had delusions, hallucinations, agitation, dysphoria, anxiety, apathy and irritability as frequently as the moderate or severe AD groups (CDR 2 or 3), and had the equivalent level of composite scores to the moderate or severe AD groups (CDR 2 or 3) in delusion, hallucination, agitation, dysphoria, anxiety and irritability. Therefore, it was supposed that psychotic symptoms (delusion, hallucination) and emotional symptoms (agitation, dysphoria, anxiety, irritability) are important BPSD in patients with mild AD as well as those with moderate or severe AD, and there are needs for health, welfare and medical services for these symptoms.     

Effect of Yi-Gan San on psychiatric symptoms and sleep structure at patients with behavioral and psychological symptoms of dementia

OBJECTIVE: Recently, traditional herbal medicines have been reported to be effective for behavioral and psychological symptoms of dementia (BPSD). This study aims to examine the efficacy of Yi-Gan San (YGS) in the improvement of BPSD and sleep disorders in patients with dementia. METHODS: Five patients (1 male and 4 female) with dementia in accordance with DSM-IV criteria were investigated. Participants were treated with YGS for 4 weeks. The Nursing Home version of Neuropsychiatric Inventory (NPI-NH) for the assessment of BPSD, the Mini-Mental State Examination (MMSE) for cognitive function, polysomnography for evaluation of sleep structure, and the Pittsburgh Sleep Quality Index for subjective sleep quality were carried out at baseline and at the end of treatment. RESULTS: All patients completed the trial. Significant improvements in the total NPI-NH score (34.0+/-6.5 to 12.8+/-6.6) as well as delusions, hallucinations, agitation/aggression, anxiety, and irritability/lability, whereas MMSE scores were unchanged. PSG revealed increases in total sleep time, sleep efficiency, stage 2 sleep, and decreases in the number of arousals and periodic limb movements. Subjective sleep quality was also improved. No adverse effects were observed. CONCLUSION: YGS was effective for BPSD and sleep disturbances, and well tolerated in patients with dementia. Further examinations using a double-blind placebo-controlled design are necessary.     

Investigation of the short- and long-term effects of donepezil on cognitive function in Alzheimer's disease

Background: Donepezil is effective in maintaining cognitive function in patients with mild to moderate Alzheimer's disease (AD). However, not all patients respond to donepezil. In the present study, we examined the short‐ and long‐term effects of donepezil on cognitive function after 2 years treatment. Methods: The present retrospective study was performed on 122 AD outpatients who had been taking donepezil for ≥1 year. All subjects underwent periodic examination of cognitive function (Mini‐Mental State Examination (MMSE), Rorschach Cognitive Index (RCI)) and clinical evaluation on the Clinical Dementia Rating (CDR); first before starting treatment and then at 4‐month intervals after initiation of donepezil. Patients were divided into three groups: (i) MG, the ‘maintained’ group, in which the global CDR score was maintained during treatment; (ii) DeG, the ‘declined’ group, in which the global CDR score increased; and (iii) DrG, the drop out group, who discontinued the treatment. Changes in scores on the MMSE and RCI were compared before treatment and at 4‐month intervals within each group. In addition, over each 4‐month period, MMSE and RCI scores were compared between the three groups. Furthermore, to investigate the condition of effective treatment, the reasons why donepezil treatment was discontinued in the DrG were examined. Results: The most frequent reason for discontinuation was the appearance of behavioral and psychiatric symptoms of dementia (BPSD), which were more frequently observed in the DrG. Although depression and/or disinclination were more frequent in the MG, hyperactivity was more frequent in the DeG and DrG. Before treatment, patients in the DrG exhibited significantly lower scores on the MMSE than did patients in the MG and DeG. Upon examination 4 months after starting treatment, patients in the MG showed cognitive improvement on the MMSE and RCI, whereas those in the DeG showed cognitive deterioration on the MMSE. Conclusion: The results of the present study suggest that when a short‐term beneficial effect of the donepezil on cognitive functions is seen, long‐term effect may also be expected at 2 years. Periodic clinical evaluation and examination of cognitive function is indispensable for effective donepezil treatment.     

Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease

OBJECTIVE: This subanalysis of a large, double-blind, placebo-controlled trial examined the prevalence of behavioral symptoms in moderate to severe Alzheimer's disease (AD), and the effect of treatment with donepezil. METHODS: Two hundred ninety patients with moderate to severe AD (standardized Mini-Mental State Examination scores 5-17) were randomized to receive 24 weeks of once-daily doses of donepezil 5 mg/day for 28 days, and 10 mg/day thereafter per the clinician's judgment (n = 144), or placebo (n = 146). The outcome measure of interest was the 12-item Neuropsychiatric Inventory (NPI). RESULTS: Baseline demographics were similar between the treatment groups. Least squares mean (+/- SE) baseline NPI 12-item total scores were 19.55 +/- 1.48 and 19.30 +/- 1.45, respectively. At baseline, the most common symptoms were apathy/indifference (67%), aberrant motor behavior (53%), depression/dysphoria (52%), anxiety (49%), and agitation/aggression (45%). NPI individual item change from baseline scores at Week 24 using a last observation carried forward (LOCF) analysis showed benefits with donepezil treatment compared with placebo for all items, with significant treatment differences for depression/dysphoria, anxiety, and apathy/indifference (p < .05). Symptoms present at baseline that improved significantly for donepezil- compared with placebo-treated patients at Week 24 LOCF included anxiety, apathy/indifference, and irritability/lability (p < .05). When patients who were not receiving psychoactive medications at baseline were analyzed separately, significant improvements in NPI (continued) 12-item total score were observed with donepezil compared with placebo at most visits and at Week 24 LOCF (p < .05). CONCLUSIONS: Behavioral symptoms of the magnitude observed in this moderate to severe AD population improved with donepezil.     

Role of serotonin transporter polymorphisms in the behavioural and psychological symptoms in probable Alzheimer disease patients

BACKGROUND/AIMS: Alzheimer disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in AD has been demonstrated. This is an investigation of whether the linked polymorphic region and variable number tandem repeat variants of the serotonin transporter (SERT) are associated with BPSD. METHODS: The longitudinal measures of BPSD of our large cohort of 367 AD patients were assessed by the Neuropsychiatric Inventory. Measures with good evidence of serotonergic involvement (delusions, hallucinations, depression, anxiety, agitation/aggression and irritability) were related to genotype and allele frequencies of the linked polymorphic region and variable number tandem repeat variants. RESULTS: Analysis revealed significant relationships between the linked polymorphic region variant long allele with irritability and the variable number tandem repeat 10-repeat allele with psychosis, but no associations were found with depression, anxiety or agitation/aggression. CONCLUSION: Our data and review of previous studies suggest SERT could play a minor role in development of psychosis and aggressive/irritable tendencies; however, further investigations are required in large, well-characterized cohorts.     

Impact of donepezil on caregiving burden for patients with Alzheimer's disease

Comprehensive Alzheimer's disease (AD) treatment should address caregiver well-being. We predicted that caregiver burden would be lower among caregivers of AD patients who received donepezil relative to caregivers of patients not treated with donepezil. A self-administered, nationwide survey of AD caregivers was used to match caregivers of patients treated with donepezil (n = 274) to caregivers of patients not treated with donepezil (n = 274). The Caregiver Burden Scale measured time demands and distress linked to commonly performed caregiving tasks. Respondents were three-quarters female, with an average age of 60 years. Results demonstrated that donepezil caregivers reported significantly lower scores on difficulty of caregiving. This difference remained when statistical controls for multiple patient and caregiver variables were imposed. However, selection factors must be recognized as a possible explanation for differences. The groups reported no difference on the time-demand subscale. In conclusion, better management of AD symptoms through donepezil treatment may reduce the burden of caregiving, providing physicians with a pharmacologic approach to improving quality of life for AD patients and their families.     

Effects of Yokukansan on behavioral and psychological symptoms of dementia in regular treatment for Alzheimer's disease

Yokukansan (YKS) is used frequently against behavioral and psychological symptoms of dementia (BPSD) together with donepezil in patients with Alzheimer's disease (AD). Here, we investigated the efficacy and safety of YKS in patients with AD in a non-blinded, randomized, parallel-group comparison study. Patients who had at least one symptom score of four or more on the Neuropsychiatric Inventory (NPI) subscales were enrolled in the study. The subjects were randomly assigned to the YKS-treated group (YKS/donepezil combination therapy group) and the non-YKS-treated group (donepezil monotherapy group). TSUMURA Yokukansan (TJ-54, 7.5 g, t.i.d.) was administered in a four-week study treatment period. The subjects were evaluated twice at the start (Week 0) and completion (Week 4) of the study treatment in terms of NPI, Mini-Mental Status Examination (MMSE), Disability Assessment for Dementia (DAD), Zarit Burden Interview, and Self-rating Depression Scale (SDS). The efficacy analysis was performed in 29 patients (YKS-treated group) and 32 patients (non-YKS-treated group). The NPI total score improved significantly more in the YKS-treated group than in the non-YKS-treated group. In the NPI subscales of agitation/aggression and irritability/lability, the YKS-treated group showed significantly greater improvement than the non-YKS-treated group, but no statistically significant improvement was seen with YKS in the other subscales. There were no significant differences between the YKS-treated group and the non-YKS-treated group in MMSE, DAD, Zarit Burden Interview and SDS. No adverse reactions were noted in either group. The results of this study showed that YKS is safe and effective in the treatment of BPSD in AD patients.     

Caregiver burden associated with behavioral and psychological symptoms of dementia in elderly people in the local community

BACKGROUND: Despite many studies about the association between caregiver burden and behavioral and psychological symptoms of dementia (BPSD), there have been no population-based studies to evaluate caregiver burden associated with each BPSD. OBJECTIVE: To evaluate caregiver burden associated with the individual BPSD in elderly people living in the community. METHODS: The subjects were 67 participants with dementia living with their caregivers (diagnosed in the third Nakayama study): 51 Alzheimer's disease, 5 vascular dementia and 11 other. The Neuropsychiatric Inventory (NPI) and NPI Caregiver Distress Scale (NPI-D) were used to assess subjects' BPSD and related caregiver distress, respectively. RESULTS: In the subjects exhibiting BPSD, aberrant motor behavior had the highest mean NPI score, and depression/dysphoria had the lowest. Agitation/aggression had the highest mean NPI-D score, and euphoria/elation had the lowest. Delusion, agitation/aggression, apathy/indifference, irritability/lability and aberrant motor behavior showed a correlation between the NPI and NPI-D scores. CONCLUSION: The burden associated with BPSD is different for each symptom and does not always depend on frequency and severity of BPSD. These findings suggest that some symptoms, such as agitation/aggression and irritability/lability, may affect the caregivers significantly, although their frequency and severity are low.     

Reducing the burden of caring for Alzheimer's disease through the amelioration of "delusions of theft" by drug therapy

BACKGROUND: Delusions of theft (delusions involving the theft of possessions) are one of the most frequent neuropsychiatric manifestations of Alzheimer's disease (AD). OBJECTIVE: The current study investigated the presence and extent of such delusions before and after drug treatment in a group of AD patients, and the consequent effects on the burden of care on caregivers. METHOD: The study was an open-label cohort design. The delusions studied consisted only of those involving theft of possessions. Sixteen AD patients served as subjects in order to assess the efficacy of Risperidone administration, in the reduction or elimination of these delusions. The caregiver burden was evaluated using the Zarit Caregiver Burden Interview (ZBI) before the administration of Risperidone and 12 weeks after administration, for cases where delusions of theft were eliminated or reduced. RESULTS: The burden of care on caregivers was significantly reduced (p < 0.001) through the elimination or reduction of delusions of theft. CONCLUSION: Delusions of theft are considered to be a major factor in increasing the burden of care, and the treatment of these, through appropriate drug therapy, is therefore of great importance in the continuation of satisfactory care in the home.     

Treatment of behavioral and psychological symptoms of Alzheimer-type dementia with Yokukansan in clinical practice

The efficacy and safety of the kampo medicine Yokukansan (YKS, TJ-54) in the treatment of behavioral and psychological symptoms of dementia (BPSD) were investigated in patients with Alzheimer's disease (AD) in an open-label study. This study included 26 patients who had been diagnosed as having AD and were not treated with donepezil hydrochloride. These patients were administered YKS (7.5 g/day) for four weeks to investigate the changes in neuropsychological test results and care burden in the period from the start to completion of the study treatment. The Neuropsychiatric Inventory (NPI) was used for evaluation of BPSD, the Mini-Mental State Examination (MMSE) for evaluation of cognitive functions, the Zarit burden interview for evaluation of the caregiver's burden, Disability Assessment of Dementia (DAD) for evaluation of activities of daily living (ADL) and Self-Rating Depression Scale (SDS) for evaluation of the caregiver's depression. No significant change was seen in MMSE and DAD after four weeks of treatment, but the mean NPI total score decreased significantly. Furthermore, among the NPI subscales, a statistically significant decrease in score was not seen, however, a clinically significant decrease was seen in terms of hallucinations, agitation, anxiety, irritability or abnormal behavior. No significant changes were seen in caregiver's burden after four weeks of treatment. No serious adverse reactions to YKS were observed. The results of this study suggested that YKS may be an effective and well-tolerated drug in the treatment of BPSD in AD patients.     

Clinical profiles of late‐onset semantic dementia,compared with early‐onset semantic dementia and late‐onset Alzheimer's disease

Background: Semantic dementia (SD) has been recognized as a representative of dementia with presenile onset; however, recent epidemiological studies have shown that SD also occurs in the elderly. There have been few studies about the differences of clinical profiles between early‐onset SD (EO‐SD) and late‐onset SD (LO‐SD). Age‐associated changes in the brain might cause some additional cognitive and behavioural profiles of LO‐SD in contrast to the typical EO‐SD cases. The aim of the present study was to clarify the characteristics of neuropsychological, and behavioural and psychological symptoms of dementia (BPSD) profiles of LO‐SD patients observed in screening tests in comparison with EO‐SD patients and late‐onset Alzheimer's disease (LO‐AD) patients as controls. Methods: Study participants were LO‐SD (n = 10), EO‐SD (n = 15) and LO‐AD (n = 47). We examined the Mini‐Mental State Examination (MMSE), the Raven's Coloured Progressive Matrices (RCPM), the Short‐Memory Questionnaire (SMQ), the Neuropsychiatric Inventory (NPI) and the Stereotypy Rating Inventory (SRI). Results: Both SD groups scored significantly lower than the LO‐AD patients in ‘naming’ of the MMSE. In the ‘construction’ score of the MMSE and the RCPM score, however, the LO‐SD patients as well as the LO‐AD patients were significantly lower than the EO‐SD patients. In the SMQ score, ‘euphoria’ and ‘disinhibition’ scores of the NPI, the SRI total and subscale scores, both SD groups were significantly higher, whereas in the ‘delusion’ score of the NPI, both SD groups were significantly lower than the LO‐AD patients. Conclusions: Visuospatial and constructive skills of LO‐SD patients might be mildly deteriorated compared with EO‐SD patients, whereas other cognitive and behavioural profiles of LO‐SD are similar to EO‐SD. Age‐associated changes in the brain should be considered when we diagnose SD in elderly patients.     

Risperidone is effective for wandering and disturbed sleep/wake patterns in Alzheimer's disease

Behavioral and psychological symptoms of dementia (BPSD), especially aggressiveness, wandering, and sleep disturbance, are a major burden for caregivers. Daily sleep/wake patterns and wandering of institutionalized patients with Alzheimer's disease (AD) were visually monitored, and 34 patients who manifested wandering were selected and randomly classified into 2 groups: the risperidone group and the nonrisperidone group. After an administration of low-dose risperidone for the risperidone group, the BPSD were reassessed. The binding potentials of dopamine D2 receptor for preadministration and postadministration of risperidone were assessed using positron emission tomography (PET) for 1 case. After the use of risperidone, aggressiveness and wandering were reduced and the nighttime sleeping hours were increased. The PET revealed that the binding potential of dopamine receptor was increased after administration of the drug, associated with improved sleep/wake patterns and behavioral abnormality. Possible serotonergic modulation of dopaminergic function might explain the neurobiological basis of the effect of risperidone.     

The effects of olanzapine in reducing the emergence of psychosis among nursing home patients with Alzheimer's disease

BACKGROUND: Elderly patients with Alzheimer's disease (AD) commonly exhibit psychotic symptoms, prompting clinicians to administer antipsychotics. This article compares the effects of olanzapine and placebo in the emergence of hallucinations or delusions in AD patients with symptoms of agitation/aggression but little or no psychotic symptomatology at baseline. METHOD: A multicenter, double-blind, placebo-controlled study was conducted in nursing home patients with AD according to DSM-IV criteria and symptoms of agitation/aggression and/or psychosis. Patients (N = 206) were randomly assigned to receive either placebo or fixed-dose olanzapine (5, 10, or 15 mg/day) for up to 6 weeks. This article analyzes data from a subgroup of patients (N = 165) with no or minimal delusions and/or hallucinations at baseline as measured by the Neuropsychiatric Inventory-Nursing Home Version (NPI/NH). Three subsets of patients were identified on the basis of their symptoms at baseline: those with no clinically significant hallucinations, those with no clinically significant delusions, and those with no clinically significant delusions or hallucinations. RESULTS: Of the patients without hallucinations or delusions at baseline (N = 75), the placebo-treated patients showed significantly greater development of these symptoms compared with olanzapine-treated patients overall (NPI/NH hallucinations + delusions mean change score, +2.73 vs. +0.27, p = .006). Similarly, of the patients without baseline hallucinations (N = 153), the placebo-treated patients showed greater hallucinations score increases than did olanzapine-treated patients overall (+1.25 vs. +0.33, p = .026), whereas patients without baseline delusions (N = 87) showed no significant treatment effects. Olanzapine had a favorable safety profile in each patient subset. CONCLUSION: These results suggest that, overall, olanzapine effectively attenuated emergence of psychosis in a short-term trial of patients with Alzheimer's disease.