Dario Mirski

Effects of rivastigmine treatment on the neuropsychiatric and behavioral disturbances of nursing home residents with moderate to severe probable Alzheimer's disease: A 26-week, multicenter, open-label study

BACKGROUND Alzheimers disease (AD) is the most common form of dementia and is characterized clinically by a gradual decline in cognitive performance, an increasingly impaired ability to perform activities of daily living, and neuropsychiatric and behavioral disturbances. OBJECTIVE The goal of this study was to assess the effect of rivastigmine on the neuropsychiatric and behavioral disturbances of nursing home residents with moderate to severe probable AD and to evaluate the safety and tolerability of rivastigmine in this population. METHODS This prospective, 26-week, open-label study was conducted in 13 centers in the United States and involved a total of 29 nursing homes. The effects of rivastigmine 3 to 12 mg/d for 26 weeks were assessed in nursing home residents with moderate to severe probable AD. Efficacy was evaluated using the Neuropsychiatric Inventory-Nursing Home (NPI-NH) scale for neuropsychiatric and behavioral disturbances; the Mini-Mental State Examination and the naming subset of the Alzheimers Disease Assessment Scale-Cognitive subscale for cognitive performance; and the simplified Clinicians Interview-Based Impression of Change Plus Caregiver Input for global functioning. RESULTS A total of 173 patients (141 women, 32 men; mean [SD]age, 82.6 [5.9] years) were enrolled. After 26 weeks of rivastigmine treatment, the mean (SD) change from baseline for all treated patients in the observed cases population was -2.5 (16.4) (n = 100; P = 0.138); it was -0.8 (16.5) (n = 149; P = 0.576) for the last-observation-carried-forward population. Patients with at least 1 neuropsychiatric symptom present at baseline showed a 3.2-point mean improvement in NPI-NH total score (n = 92; P = 0.062), with 49% of these patients demonstrating a clinically meaningful (ie, > or = 30%) reduction from baseline. At 26 weeks, scores for 8 of the 12 neuropsychiatric and behavioral disturbances in patients with the specific symptom present at baseline showed statistically significant improvements from baseline (delusions [n = 32; P = 0.007], hallucinations [n = 15; P < 0.001], agitation [n = 58; P = 0.044], apathy/indifference [n = 37; P < 0.001], irritability/lability [n = 50; P < 0.001], aberrant motor behavior [n = 32; P < 0.001], nighttime disturbances [n = 22; P < 0.001], and appetite/eating changes [n = 28; P = 0.002]) in the observed cases population. Limitations of this study include that it was open label and not restricted to patients with behavioral disturbances at baseline. CONCLUSION In the current study, rivastigmine treatment for 26 weeks in nursing home residents with moderate to severe probable AD was associated with decreased NPI-NH item scores for a wide range of behavioral disturbances in the subgroup of patients with behavioral symptoms at baseline.

Effects of rivastigmine on cognitive function in patients with traumatic brain injury

Objective: To compare the efficacy and safety of rivastigmine (3 to 6 mg/day) vs placebo over 12 weeks in patients with traumatic brain injury and persistent cognitive impairment. Methods: This prospective, randomized, double-blind, placebo-controlled study was conducted in 157 patients at least 12 months after injury. The primary efficacy measures were the Cambridge Neuropsychological Test Automated Battery (CANTAB) Rapid Visual Information Processing (RVIP) A′ subtest and the Hopkins Verbal Learning Test (HVLT). The primary efficacy outcome was the proportion of patients who demonstrated 1.0 SD or greater improvement from baseline at week 12 on CANTAB RVIP A′ or HVLT. Results: The percentage of responders at week 12 on either the CANTAB RVIP A′ or HVLT was 48.7% for rivastigmine and 49.3% for placebo (p = 0.940). Furthermore, for the overall study population, there were no significant differences for any of the secondary efficacy variables. In a subgroup of patients with moderate to severe memory impairment (n = 81), defined as 25% impairment or greater on HVLT at baseline, rivastigmine was significantly better than placebo for a number of measures, including the proportion of HVLT responders and CANTAB RVIP mean latency. Conclusions: Rivastigmine was safe and well tolerated in patients with traumatic brain injury with cognitive deficits. Rivastigmine shows promising results in the subgroup of patients with traumatic brain injury with moderate to severe memory deficits.

Long-term effects of rivastigmine treatment on neuropsychiatric and behavioral disturbances in nursing home residents with moderate to severe Alzheimer's disease: results of a 52-week open-label study.

SUMMARY Objectives: To evaluate the safety and efficacy of long-term treatment with rivastigmine (3–12 mg/day) and its effects on neuropsychiatric and behavioral disturbances in nursing home patients with moderate to severe probable Alzheimers disease (AD). Methods: A prospective, multicenter 26-week open-label extension to a 26-week open-label study (52 week results) of rivastigmine treatment in patients with Mini-Mental State Examination (MMSE) scores of 6–15 inclusive, residing in nursing homes at 13 centers in the US. Effects of treatment with rivastigmine for up to 52 weeks on neuropsychiatric and behavioral symptoms were examined using the Neuropsychiatric Inventory-Nursing Home (NPI-NH) scale. Cognitive function was assessed by the MMSE, and the Naming Objects and Fingers Test (NOFT) subset of the Alzheimers Disease Assessment Scale – Cognitive subscale (ADAS-Cog). Global functioning was assessed using the simplified Clinicians Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus). Results: Rivastigmine (3–12 mg/day) significantly improved neuropsychiatric and behavioral symptoms compared to baseline (in patients with specific behavioral disturbances at baseline) in observed cases (OC) and last observation carried forward (LOCF) analyses. Over 52 weeks, treatment with rivastigmine significantly improved 10 of 12 individual NPI-NH domains from baseline in LOCF patients with symptoms present at baseline. Cognitive function was stable, indicated by the lack of decline in MMSE and the NOFT. Global function was stabilized or improved in greater than half of the patients as indicated by the simplified CIBIC-Plus scores. Conclusion: Rivastigmine showed potential benefit in the long-term treatment of behavioral symptoms as well as cognitive and global functioning in nursing home residents with moderate to severe AD with concurrent behavioral symptoms present at baseline. Although these results suggest that treatment with rivastigmine may have beneficial behavioral effects and cognitive benefits on patients with moderate to severe AD, they are subject to the limitations of an open-label study.

Impact of Rivastigmine Use on the Risk of Nursing Home Placement in a US Sample

AbstractIntroduction: Although numerous studies have evaluated predictors of nursing home placement (NHP), few have focused on the effects of cholinesterase inhibitor (ChEI) use on NHP. The objective of this study was to compare the risk of NHP between rivastigmine patients versus no-ChEI patients (control group), and secondly, between rivastigmine versus donepezil patients. Methods: A retrospective analysis of a large US medical claims database was performed. Eligible subjects were identified from those who had continuous medical coverage from 1 April 2000 to 30 June 2002. Rivastigmine and donepezil subjects were new users, defined as having received no ChEI treatment during the initial 6 months of the study. Control subjects were diagnosed with Alzheimer’s disease (AD) at some point after the initial 6-month period. All subjects were followed from baseline (initiation of ChEI therapy or initial AD diagnosis) to the date of NHP or 30 June 2002, whichever occurred first. Results: In the rivastigmine (n = 1181), donepezil (n = 3864), and control (n = 517) groups, 3.7%, 4.4% and 11.0% of subjects, respectively, had an NHP (p < 0.001 for rivastigmine versus control). A Cox proportional hazard model, controlling for age, gender, comorbidities and behavioural disorders, showed that the control subjects were almost 3-fold more likely to have NHP than rivastigmine subjects (hazard ratio [HR] = 2.71; 95% CI 1.82, 4.03). The difference in the risk of NHP was not significant between the rivastigmine and donepezil groups (HR = 1.23; 95% CI 0.89, 1.71). Discussion: This study demonstrated that rivastigmine decreased the risk of NHP in a large insured population.

Risk of Antipsychotic Drug Use in Patients with Alzheimer’s Disease Treated with Rivastigmine

AbstractBackground and Objective: Cholinesterase inhibitors may offer some improvement in the behavioural symptoms of Alzheimer’s disease. The dual inhibitory mechanism of action of rivastigmine (inhibition of acetylcholinesterase and butyrylcholinesterase) may improve behavioural symptoms and may delay the need for antipsychotics. This study was conducted to investigate the effect of rivastigmine on the time to first antipsychotic drug use among patients with Alzheimer’s disease, compared with patients with Alzheimer’s disease not treated with a cholinesterase inhibitor. Design and Methods: This study used MarketScan® research databases from 1 January 1999 to 31 March 2002. Patients were included if they: (a) were diagnosed with Alzheimer’s disease on two occasions or filled a prescription for rivastigmine for the first time during the index period from 1 July 2000 to 31 December 2001; (b) were 65 years of age and older; (c) had continuous health and prescription insurance coverage during the entire study period; and (d) had not used an antipsychotic medication within 18 months prior to their index Alzheimer’s disease prescription or diagnosis. The ‘no cholinesterase inhibitor’ group included patients who were newly diagnosed with Alzheimer’s disease, but did not use any cholinesterase inhibitors. Chi-square, Student’s t-, and log-rank tests were used to test differences in study variables between groups. Cox proportional hazards models were used to estimate predicted risk of first antipsychotic drug use. Results: The study included 497 patients in the rivastigmine group and 749 patients in the ‘no cholinesterase inhibitor’ group. The rivastigmine group patients were younger compared with the ‘no cholinesterase inhibitor’ group patients (p < 0.01). The overall usage of antipsychotics was considerably lower for patients taking rivastigmine (9.8%) compared with those not taking cholinesterase inhibitors (25.6%). Patients taking rivastigmine were 64% less likely (relative risk = 0.36; p < 0.0001) to take antipsychotics compared with patients not taking cholinesterase inhibitors, after adjusting for demographic covariates, comorbid conditions, and use of other CNS drugs and anticonvulsants. Age was the only other factor that influenced antipsychotic use; older patients were significantly more likely to start antipsychotics than younger patients. Conclusion: This study provides initial evidence that patients with Alzheimer’s disease treated with rivastigmine have a reduced risk of initiating therapy with an antipsychotic drug compared with patients who receive no cholinesterase inhibitor treatment. These findings may imply that rivastigmine use could delay the onset of behavioural symptoms that require treatment with antipsychotic medications.

A Pilot Study Evaluating the Efficacy and Safety of Rivastigmine in Patients with Mixed Dementia

Background and objectiveThe two most common causes of dementia in the elderly are Alzheimer’s disease (AD) and vascular dementia (VaD), which can coexist as mixed dementia. The object of this study was to assess the efficacy and safety of rivastigmine in patients with mixed dementia (AD with VaD).Study designThis 26-week open-label pilot study was conducted at 19 centres in the US. To reduce bias, the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) raters were blinded to all efficacy measures and to patient dosage information. Patients were treated with rivastigmine and titrated to their highest tolerated dose, up to 12 mg/day (6mg twice daily). The primary efficacy measure was cognitive function assessed by the ADAS-Cog subscale (without the concentration/distractibility item, to be consistent with cognitive outcome measures used in previous rivastigmine trials).ResultsForty-seven percent of patients treated with rivastigmine 6–12 mg/day demonstrated improvement on the ADAS-Cog at 26 weeks, with >25% of patients having a clinically significant improvement of ≥4 points. Treatment with rivastigmine (6–12 mg/day) was well tolerated by the majority of patients. The most common adverse effects occurring in >10% of patients were nausea, vomiting, dizziness and diarrhoea.ConclusionThis pilot study suggests that rivastigmine treatment may have beneficial effects in the treatment of patients with mixed dementia.

Long-Term Effects of Rivastigmine Treatment on the Need for Psychotropic Medications in Nursing Home Patients with Alzheimer’s Disease

AbstractBackground and objective: Neuropsychiatric symptoms and behavioural disturbances occur in most patients with Alzheimer’s disease (AD), are a source of stress for caregivers, and are the primary cause of patient institutionalisation. These symptoms often are treated with psychotropic medications. However, adverse drug interactions, adverse effects and nursing home regulations make reducing the use of psychotropic medications in elderly AD patients an important goal of therapy. Fifty-two-week data including data from a 26-week prospective open-label, multicentre study and its 26-week open-label extension were analysed. Patients and methods: 173 patients with moderate to severe AD residing in nursing homes were treated with rivastigmine 1.5–6mg twice daily. In the study, psychotropic drug use and behavioural symptoms were measured at baseline and at 52 weeks. Results: Results showed that 40% of patients who were receiving psychotropic medications at baseline had discontinued use or reduced their dose of psychotropic medications at week 52. Furthermore, significant improvements were observed from baseline in 10 of the 12 behavioural domains of the Nursing Home version of the Neuropsychiatric Inventory, including delusions (mean change from baseline −2.0; p = 0.002), hallucinations (mean change −3.1; p < 0.001), anxiety (mean change −1.1; p = 0.014), and euphoria (mean change −3.2; p = 0.006). Conclusion: These data suggest favourable tolerability, behavioural and pharmacoeconomic outcomes in nursing home residents with AD who are treated with rivastigmine.

The validation of a caregiver assessment of dementia : The dementia severity scale

Objective:The objective of this study was to refine and validate the Dementia Severity Scale (DSS), a newly developed assessment of dementia severity from a caregivers perspective. The Dementia Severity Scale is designed to measure deficits in activities of daily living (ADL), behavioral disturbances, and the caregivers perception of the patients current cognitive abilities. Methods:Community dwelling caregiver/patient dyads were recruited from 12 clinical sites. Patients had a primary dementia diagnosis for at least one year. In this cross-sectional study, caregivers were administered the Dementia Severity Scale, the Quality of Life-Alzheimers Disease (QOL-AD), the Progressive Deterioration Scale (PDS), and the Neuropsychiatric Inventory (NPI). Patients were administered the Mini-Mental State Examination (MMSE) and the QOL-AD. To evaluate test-retest reliability, 25% of caregivers were randomized to a second visit. Results:One hundred eighty-three caregiver/patient dyads were recruited. Mean caregiver age was 67.5; mean patient age was 78.8; 93% of patients had probable Alzheimer disease. Eighty-eight (48.1%) patients were male. Exploratory factor analysis established 6 subscales (Activities of Daily Living [ADL], Instrumental ADL [IADL], Communication, Agitation, Memory, and Disorganized Thinking). Cronbachs alphas ranged from 0.82 to 0.90 for the 6 subscales. Test-retest reliability was good with intraclass correlation coefficients ranging from 0.79 to 0.89. DSS subscales were moderately-to-highly correlated with the QOL-AD, NPI, MMSE, and PDS. Subscales significantly discriminated among severity levels of dementia, identified by both physician ratings and MMSE scores. Conclusion:The Dementia Severity Scale demonstrated excellent psychometric properties and appears to be useful both in clinical practice and research endeavors. Further research is needed to establish the longitudinal sensitivity of the Dementia Severity Scale to the progression of dementia.

P2-328 Impact of rivastigmine use on the risk of nursing home placement in a us sample

INTRODUCTION Although numerous studies have evaluated predictors of nursing home placement (NHP), few have focused on the effects of cholinesterase inhibitor (ChEI) use on NHP. The objective of this study was to compare the risk of NHP between rivastigmine patients versus no-ChEI patients (control group), and secondly, between rivastigmine versus donepezil patients. METHODS A retrospective analysis of a large US medical claims database was performed. Eligible subjects were identified from those who had continuous medical coverage from 1 April 2000 to 30 June 2002. Rivastigmine and donepezil subjects were new users, defined as having received no ChEI treatment during the initial 6 months of the study. Control subjects were diagnosed with Alzheimers disease (AD) at some point after the initial 6-month period. All subjects were followed from baseline (initiation of ChEI therapy or initial AD diagnosis) to the date of NHP or 30 June 2002, whichever occurred first. RESULTS In the rivastigmine (n=1181), donepezil (n=3864), and control (n=517) groups, 3.7%, 4.4% and 11.0% of subjects, respectively, had an NHP (p <0.001 for rivastigmine versus control). A Cox proportional hazard model, controlling for age, gender, comorbidities and behavioural disorders, showed that the control subjects were almost 3-fold more likely to have NHP than rivastigmine subjects (hazard ratio [HR]=2.71; 95% CI 1.82, 4.03). The difference in the risk of NHP was not significant between the rivastigmine and donepezil groups (HR=1.23; 95% CI 0.89, 1.71). DISCUSSION This study demonstrated that rivastigmine decreased the risk of NHP in a large insured population.