Behavioral and psychological symptoms in patients with dementia as a target for pharmacotherapy with risperidone

OBJECTIVE: To examine the effect of risperidone on specific behavioral and psychological symptoms of dementia (BPSD). METHOD: We conducted a post hoc exploratory analysis of an integrated database from 3 randomized, controlled trials of risperidone versus placebo in treating 1150 nursing home residents with BPSD. Changes in scores were measured for items on the Cohen-Mansfield Agitation Inventory (CMAI) and Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). RESULTS: On the CMAI, risperidone was significantly more effective in treating hitting (p = .000), hurt self or other (p = .005), cursing or verbal aggression (p = .000), repetitive sentences or questions (p = .001), scratching (p = .041), general restlessness (p = .001), grabbing onto people (p = .028), constant request for attention (p = .041), pacing and aimless wandering (p = .013), and performing repetitious mannerisms (p = .045). On the BEHAVE-AD, risperidone was significantly more effective in treating physical threats and/or violence (p = .000), verbal outbursts (p = .000), other anxieties (p = .01), agitation (p = .000), tearfulness (p = .03), and nonparanoid delusions (p = .02). CONCLUSIONS: The items from the BEHAVE-AD and CMAI that were improved with risperidone included psychotic, agitated, and aggressive symptoms. These data suggest that risperidone is more effective than placebo in treating a variety of symptoms associated with dementia.     

Reliability and validity of the Cohen–Mansfield agitation inventory in institutionalized elderly

The reliability and validity of the Cohen–Mansfield Agitation Inventory (CMAI) were studied in residents of a long-term care facility. The CMAI demonstrated high internal consistency, but only marginally adequate interrater reliability. Correlations with the Behavioral Syndromes Scale for Dementia (BSSD) and the Behavioral Pathology in Alzheimer's Disease (Behave—AD) provide support for the contention that the CMAI is valid measure of agitation with nursing home residents.     

Prevalence of neuropsychiatric symptoms in a large sample of Dutch nursing home patients with dementia

OBJECTIVE: To estimate the prevalence of neuropsychiatric symptoms of dementia patients in Dutch nursing homes. METHODS: Cross-sectional study in a large sample of 1322 demented patients living in 59 dementia special care units (SCUs) in The Netherlands. Symptoms were observed by licensed vocational nurses during regular care-giving in a 2-week observational period prior to assessment. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory- Nursing home version (NPI-NH; frequency X severity score >/= 4) and the Cohen-Mansfield Agitation Inventory (CMAI; symptoms occurring at least once a week). RESULTS: More than 80% of these patients suffered from at least one clinically significant symptom, as defined with the NPI-NH frequency X severity score >/= 4. Measured with the NPH-NH agitation/aggression, apathy and irritability were the most frequently observed behaviors, with prevalences of 30-35%. Using the CMAI, 85% of the patients showed at least one symptom of agitation, of which general restlessness was observed most frequently (44%). Other frequently observed symptoms with prevalence rates of 30% were cursing or verbal aggression, constant request for attention, negativism, repetitious sentences, mannerisms, pacing, and complaining. Physically aggressive symptoms such as hitting, kicking, biting occurred less often (less than 13%). CONCLUSIONS: Prevalence rates of neuropsychiatric symptoms in Dutch nursing home patients with dementia residing in SCUs are high, especially agitation and apathy. Insight into the prevalence rates of individual symptoms in patients with dementia has important practical consequences for the accurate planning of staff allotment and stresses the need for patient oriented care.     

Aggressive behaviors among demented nursing home residents in Japan

This study investigates the frequency of aggressive behaviors in a sample of elderly nursing home residents with dementia in Japan. Behavioral data were collected on 391 residents using the Cohen-Mansfield Agitation Inventory (CMAI). Data were also gathered on residents' age, sex, and ability to perform self-care. Another scale was used to code the degree of resistance that each resident manifested during bathing, toileting, dressing and eating. In addition, qualitative data were collected from caregivers regarding their main caregiving problems with dementia residents. Findings show that 45.4% of the sample manifested aggressive behavior during the 2-week study period. Men were significantly more likely to manifest physically aggressive behavior, but there was no gender difference for verbal aggression. Age had no relationship to aggressive behavior. Residents who were most dependent in self-care had significantly higher frequencies of aggressive behaviors. Caregivers reported that most aggressive behavior took place during personal care. The majority of caregivers identified verbal agitation rather than physical aggression as their main caregiving problem. This study represents the first time that the CMAI has been translated and used in Japan and the first time empirical data has been collected on the behavior of dementia patients in Japanese nursing homes.     

Psychosis, depression and behavioural disturbances in Sydney nursing home residents: prevalence and predictors

BACKGROUND: There is wide variation in the rates of behavioural and psychological symptoms of dementia (BPSD) reported in nursing homes. AIMS: This study aimed to investigate: (1) the prevalence of BPSD in nursing home residents using the BEHAVE-AD; (2) the relationships of BPSD with (a) demographic, (b) dementia, (c) diurnal and (d) nursing home variables; and (3) the inter-relationships between different types of BPSD, as measured by subscales of the BEHAVE-AD. RESULTS: Over 90% of residents exhibited at least one behavioural disturbance. Specifically, there was evidence of psychosis in 60%, depressed mood in 42% and activity disturbances or aggression in 82% of residents. Younger, more functionally impaired residents with a chart diagnosis of psychosis had higher BPSD rates, as did those residing in larger nursing homes. Individual BPSD were significantly intercorrelated. CONCLUSIONS: BPSD are ubiquitous in nursing home residents. Behavioural disturbances are frequently associated with psychosis and/or depression. The findings suggest the need for psychogeriatric services to nursing homes and smaller facilities.     

Quetiapine treatment for behavioral and psychological symptoms in patients with senile dementia of Alzheimer type

The purpose of this study was to assess the effect of quetiapine in the treatment of behavioral and psychological symptoms of dementia (BPSD) in patients with senile dementia of Alzheimer type (SDAT). Sixteen SDAT patients with BPSD were recruited and quetiapine (25- 200 mg/day) was prescribed for 8 weeks. BPSD were evaluated with the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and Cohen-Mansfield Agitation Inventory (CMAI) at week 0 (baseline) and week 8 (endpoint). The severity of the extrapyramidal symptoms was also assessed by the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) at baseline and endpoint. Significant improvements were seen in the CMAI total score and in the BEHAVE-AD subscales of delusions, activity disturbances, aggressiveness, diurnal rhythm disturbances and in the BEHAVE-AD overall severity. There was no significant difference between the baseline and endpoint in the DIEPSS score. These data indicate that quetiapine is effective in controlling BPSD with favorable adverse-event profiles.     

A 1-year follow-up study of behavioral and psychological symptoms in dementia among people in care environments

BACKGROUND: Behavioral and psychological symptoms in dementia (BPSD) are common and distressing for patients and caregivers, but little is known about the natural history of these symptoms, particularly among patients in care facilities. This information is essential for informed clinical management. We report a 1-year follow-up study of the prevalence, incidence, and outcome of the 3 main BPSD (agitation, depression, and psychosis) in care facilities. METHOD: 136 elderly residents with dementia (29% living in social care facilities and 71% in nursing home care) were assessed longitudinally on 2 occasions a year apart using a range of standardized psychiatric schedules, including the Neuropsychiatric Inventory. RESULTS: The overall prevalence of BPSD was stable over the year (76% at baseline and 82% at follow-up). Subjects with subclinical symptoms at baseline were more likely to develop clinically significant BPSD during follow-up than those who were symptom free (83% vs. 52%; Mann-Whitney U test, z = 2.36, p = .01). Agitation was the most common individual syndrome (55%). Although overall BPSD were persistent, > or = 45% of dementia patients with any of the major syndromes experienced resolution, indicating the development of different BPSD in many residents. There was no evidence that residents taking neuroleptics were more likely to experience resolution of BPSD than neuroleptic-free residents. CONCLUSION: BPSD are highly frequent and persistent among residents of care facilities with dementia. This emphasizes the need for ongoing treatment trials. The pattern of resolution with the development of new symptoms indicates that short focused periods of treatment may be a more effective management approach. In addition, the potential value in treating patients with subclinical BPSD to prevent the development of full-blown syndromes needs to be investigated.     

Treatment of verbal agitation with a selective serotonin reuptake inhibitor

The objective of this study was to examine the safety and efficacy of paroxetine as an alternative to neuroleptic medications for the treatment of verbal agitation in demented patients. An open case series design was used, and the setting included two nursing homes and an outpatient geriatric clinic. Participants were eight consecutive nursing home residents and seven community-dwelling older adults diagnosed with dementia who exhibited verbal agitation in the form of repetitive questions or unwarranted request for attention. Patients received paroxetine orally in doses of 10 mg to 40 mg per day. The Cohen-Mansfield Agitation Inventory (CMAI) was used to rate the frequency of verbal agitation. A baseline score was obtained before starting paroxetine. Six scores were then obtained at 2-week intervals over a period of 3 months. All patients had reduction (2-4 points per item) in the CMAI scores at the end of the first month of treatment with paroxetine. Scores were further reduced (up to 5 points per item, 67%-71% reduction from baseline) in five patients at the end of the third month of treatment. Most patients tolerated paroxetine well. In this report, the use of paroxetine was associated with reduction in verbal agitation. This finding supports the possibility that verbal agitation in demented patients could be a manifestation of underlying depression.     

Psychosis associated behavioral and psychological signs and symptoms in mild cognitive impairment and Alzheimer's dementia

Objectives: The aim of this study is to determine the prevalence of psychosis in mild cognitive impairment (MCI, Petersen's criteria) and patients with Alzheimer's dementia, and to characterize the associated behavioral and psychological signs and symptoms of dementia (BPSD).

Method: A cross-sectional analysis of baseline data from an ongoing, prospective, longitudinal study on BPSD was performed, including 270 MCI and 402 AD patients. BPSD assessment was performed through Middelheim Frontality Score (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory (CMAI) and Cornell Scale for Depression in Dementia (CSDD). Psychosis was considered to be clinically relevant when delusions and/or hallucinations occurred at least once in the last two weeks prior to the BPSD assessment.

Results: The prevalence of psychosis in AD (40%) was higher than in MCI (14%; p < 0.001). AD patients with psychosis showed more severe frontal lobe, BPSD, agitation and depressive symptoms (MFS, Behave-AD, CMAI and CSDD total scores), whereas MCI patients with psychosis only showed more severe frontal lobe and physically non-aggressive agitated behavior. In addition, only in psychotic AD patients, all BPSD and types of agitation were more severe compared to non-psychotic AD patients. Comparing MCI and AD patients, MCI patients with psychosis did not show more severe frontal lobe, behavioral and psychological (Behave-AD), depressive symptoms or agitation than AD patients without psychosis.

Conclusion: AD patients clearly display psychosis associated BPSD, whereas MCI patients only display more severe frontal lobe symptoms and physically non-aggressive agitated behavior, but also less pronounced than in AD.     

Assessment of agitation in elderly patients with dementia: correlations between informant rating and direct observation

BACKGROUND: Assessment of behavior problems in elderly persons with dementia is important for understanding and managing those behaviors. The most common method for assessing agitation is the use of informant ratings; however, these ratings may be affected by staff bias, inaccurate or insufficient memory, or stress. An alternative method is direct observation, which is more objective, but very costly and necessitates time sampling, thereby limiting the period covered by the assessment. To date, little research attention has been given to the degree to which these two methods converge. METHODS: In the present study, 175 elderly persons with dementia who manifested problem behaviors were recruited from 11 nursing home facilities in Maryland. The average age for the participants was 87 years; 78% were female. Two methods were employed for assessing agitation: the Agitated Behaviors Mapping Instrument (ABMI), which is based upon direct observations, and the Cohen-Mansfield Agitation Inventory (CMAI), which is a frequency rating scale completed by a formal caregiver. The ABMI and CMAI contain some identical items for tapping behavior problems. RESULTS: Data analysis revealed significant Pearson correlations between identical items on the two assessment instruments, as well as significant correlations of summary measures based on these different instruments, demonstrating a strong convergence between informant ratings and direct observations. CONCLUSIONS: Informant ratings can achieve moderate agreement with direct observation when valid instruments and informants are used.     

A comparison of the Cohen-Mansfield agitation inventory with the cerad behavioral rating scale for dementia in community-dwelling persons with Alzheimers disease

In a group of 242 community-dwelling patients with Alzheimers disease (AD), a longitudinal comparison was made of two caregiver-administered instruments for assessment of behavioral disturbance; the Cohen-Mansfield Agitation Inventory (CMAI) and the CERAD Behavioral Rating Scale for Dementia (BRSD). We examined records of the 206 patients with baseline and 12-month follow-up data for the CMAI and the BRSD who also had tests of cognitive (Mini-mental State; MMSE) and global function (Clinical Dementia Rating; CDR and Functional Assessment Staging; FAST). Among 114 AD subjects, the correlation between total CMAI at baseline and 1 month readministration was 0.83 (p<0.0001). In the same subjects, stratified into 5 groups by MMSE scores, the correlations between BRSD baseline and 1-month scores ranged from 0.70–0.89 (p<0.0001). There was high correlation between total scores of both instruments at baseline and 12 months. In addition, all CMAI subscales except Verbally Aggressive correlated significantly with total BRSD score at both time points. At baseline, BRSD subscales for irritability\aggression, behavioral dysregulation and psychotic symptoms and at 12 months, irritability\aggression and behavioral dysregulation correlated with total CMAI scores. Neither scale changed significantly over 1 year, but there was wide individual variation. CMAI and BRSD scores correlated with 1-year change in the FAST, but not with MMSE or CDR (which weighs cognition heavily), suggesting that behavioral disturbance may be more strongly related to ability to manage activities of daily living (executive function) than to other aspects of cognition. The CMAI and BRSD appear to be interchangeable as measures of agitation, with the CMAI possibly more useful for patients who lack language and the BRSD more sensitive to apathy and depression.     

Reliability and validity of the Norwegian version of the Brief Agitation Rating Scale (BARS) in dementia

Objective: To examine the test–retest reliability and validity of the Norwegian Brief Agitation Rating Scale (BARS), a short form of the Cohen-Mansfield Agitation Inventory (CMAI) assessing the frequency of agitation in dementia.

Methods: We investigated the internal consistency, test–retest reliability and the validity of BARS. In the validity study, we compared the BARS scores with the Neuropsychiatric Inventory – Nursing Home Version subscale Agitation/Aggression (NPI-NH/AA) and the Cornell Scale for Depression in Dementia subscale Agitation (CSDD/A).

Results: In the reliability study, Cronbach's alpha was 0.76; the test–retest reliability of the BARS showed a Spearman's rho of 0.64, but this increased to 0.86 when we deleted the item ‘complaining’. In the validation study, the BARS score correlated with the NPI-NH/AA and the CSDD/A scores, Spearman's rho 0.55 and 0.52, respectively. These correlations changed when controlling for the Clinical Dementia Rating (CDR) Scale stages. The highest correlations between the BARS and the NPI-NH/AA and the BARS and the CSDD/A were found among patients with CDR score 2.

Conclusions: The study indicates that the Norwegian version of BARS is a reliable and valid instrument to test agitation in dementia, but a version without the item ‘complaining’ would be better.     

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.     

Behavioural problems in Sydney nursing homes

The prevalence of significant behavioural disturbance in 46 Sydney nursing homes was examined. All 2445 residents were rated on a brief screening questionnaire by senior nurses, who decided that 704 (29%) displayed at least one problem behaviour for much of the time. Primary care nurses (PCNs) then rated these ‘screen-positive’ residents using the Cohen-Mansfield Agitation Inventory (CMAI). In one nursing home the PCNs rated all 100 residents on the CMAI and found that 24 of 58 ‘screen-negative’ residents displayed CMAI behaviours once daily or more. Of CMAI behaviours rated as occurring daily or more often, 30% were manifested by ‘screen-negative’ residents. Prevalence figures based on ‘screen-positive’ residents are underestimates. Interrater reliability between PCNs was good. We report that at least 3.3% of residnets paced and 0.45% screamed several times an hour. Each of the following behaviours was manifested daily or more often by 10– 15% of the residents: restlessness, pacing, repetitive sentences, constant calls for help, cursing/verbal aggression and complaining. Aggressive behaviours (eg hitting, kicking, biting) were less common, and a relationship to cognitive impairment was demonstrated. Increased research on assessment and management of these behaviours is needed.     

Aromatherapy as a safe and effective treatment for the management of agitation in severe dementia: the results of a double-blind,placebo-controlled trial with Melissa

BACKGROUND: Behavioral and psychological symptoms in dementia are frequent and are a major management problem, especially for patients with severe cognitive impairment. Preliminary reports have indicated positive effects of aromatherapy using select essential oils, but there are no adequately powered placebo-controlled trials. We conducted a placebo-controlled trial to determine the value of aromatherapy with essential oil of Melissa officinalis (lemon balm) for agitation in people with severe dementia. METHOD: Seventy-two people residing in National Health Service (U.K.) care facilities who had clinically significant agitation in the context of severe dementia were randomly assigned to aromatherapy with Melissa essential oil (N = 36) or placebo (sunflower oil) (N = 36). The active treatment or placebo oil was combined with a base lotion and applied to patients' faces and arms twice a day by caregiving staff. Changes in clinically significant agitation (Cohen-Mansfield Agitation Inventory [CMAI]) and quality of life indices (percentage of time spent socially withdrawn and percentage of time engaged in constructive activities, measured with Dementia Care Mapping) were compared between the 2 groups over a 4-week period of treatment. RESULTS: Seventy-one patients completed the trial. No significant side effects were observed. Sixty percent (21/35) of the active treatment group and 14% (5/36) of the placebo-treated group experienced a 30% reduction of CMAI score, with an overall improvement in agitation (mean reduction in CMAI score) of 35% in patients receiving Melissa balm essential oil and 11% in those treated with placebo (Mann-Whitney U test; Z = 4.1, p < .0001). Quality of life indices also improved significantly more in people receiving essential balm oil (Mann-Whitney U test; percentage of time spent socially withdrawn: Z = 2.6, p = .005; percentage of time engaged in constructive activities: Z = 3.5, p = .001). CONCLUSION: The finding that aromatherapy with essential balm oil is a safe and effective treatment for clinically significant agitation in people with severe dementia, with additional benefits for key quality of life parameters, indicates the need for further controlled trials.     

Temporal patterns of agitation in dementia.

OBJECTIVE: This study investigated the temporal pattern of agitated behaviors in nursing home residents with dementia and compared it with temporal patterns of pleasure, interest in the environment, and sleep. METHODS: Trained research assistants recorded direct observations of agitation and affect by the Agitation Behavior Mapping Instrument and the Lawton's Modified Behavior Stream for 174 participants from 12 nursing homes. RESULTS: The temporal pattern found for total agitation showed a gradual increase from the morning until approximately 4 pm with a decrease thereafter. Only 26% of the sample showed a clear increase of their agitation in the later hours in comparison to the morning hours based on our criterion. Pleasure did not show a consistent pattern, whereas levels of interest peaked during lunch and dinner times. CONCLUSIONS: The results fit with a hypothesis of fatigue of daytime nursing staff members and disruption during shift change and may also be partially accounted for by resident fatigue. Although the literature supports the notion that there is a peak in overall agitation around 4 pm, the term "sundowning" is not supported and should be replaced. The phenomenon of increased levels of agitation during later hours characterizes only a minority of agitated nursing home residents, albeit the most highly agitated.     

A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia.

OBJECTIVE: To compare citalopram and risperidone for the treatment of psychotic symptoms and agitation associated with dementia, with a priori hypotheses that risperidone would be more efficacious for psychosis and citalopram for agitation. METHODS: A 12-week randomized, controlled trial in nondepressed patients with dementia hospitalized because of behavioral symptoms (N = 103) was conducted at the University of Pittsburgh Medical Center. Participants were consecutively recruited on an inpatient unit if they had at least one moderate to severe target symptom (aggression, agitation, hostility, suspiciousness, hallucinations, or delusions). Once they improved sufficiently, they were discharged to nursing homes, personal care homes, or residential homes for continued treatment. Planned pre-post and mixed model analyses of the main outcome measures of Neurobehavioral Rating Scale and Side Effect Rating Scale at baseline and at weekly/biweekly intervals were conducted. RESULTS: Completion rates did not differ for citalopram and risperidone (overall completion rate: 44%). Agitation symptoms (aggression, agitation, or hostility) and psychotic symptoms (suspiciousness, hallucinations, or delusions) decreased in both treatment groups but the improvement did not differ significantly between the two groups. There was a significant increase in side effect burden with risperidone but not with citalopram such that the two groups differed significantly. CONCLUSION: No statistical difference was found in the efficacy of citalopram and risperidone for the treatment of either agitation or psychotic symptoms in patients with dementia. These findings need to be replicated before citalopram or other serotonergic antidepressants can be recommended as alternatives to antipsychotics for the treatment of agitation or psychotic symptoms associated with dementia.