Jane Hecker

Efficacy and Tolerability of Donepezil in Vascular Dementia Positive Results of a 24-Week, Multicenter, International, Randomized, Placebo-Controlled Clinical Trial

Background and Purpose— Clinical observations suggest that patients with vascular dementia (VaD) may benefit from treatment with cholinesterase inhibitors. This study evaluated the efficacy and safety of donepezil for relieving symptoms of dementia in VaD. Methods— Patients (n=603; mean age, 73.9 years; 55.2% men) with probable (70.5%) or possible (29.5%) VaD, according to criteria of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l’Enseignement en Neurosciences (AIREN), were randomized to 24 weeks of treatment with donepezil 5 mg/d (n=198), donepezil 10 mg/d (5 mg/d for first 28 days; n=206), or placebo (n=199). Analyses were based on the intent-to-treat population. Results— At week 24, both donepezil groups showed significant improvement in cognition versus placebo on the Alzheimer’s Disease Assessment Scale–cognitive subscale (mean change from baseline score effect size: donepezil 5 mg/d, −1.90; P =0.001; donepezil 10 mg/d, −2.33; P <0.001). Significant improvements in patients’ global function were seen versus placebo at week 24 (observed cases), on the Clinician’s Interview-Based Impression of Change–Plus version only for patients on donepezil 5 mg/d (P =0.014), and on the Sum of the Boxes of the Clinical Dementia Rating only for patients on 10 mg/d (P =0.007). Donepezil-treated patients showed significant benefits in activities of daily living over placebo on the Alzheimer’s Disease Functional Assessment and Change Scale (mean change from baseline score effect size at week 24: donepezil 5 mg/d, −1.31, P =0.02; donepezil 10 mg/d, −1.31, P =0.02). Donepezil was well tolerated. Withdrawal rates due to adverse events were relatively low (placebo, 11.1%; donepezil 5 mg/d, 11.1%; donepezil 10 mg/d, 21.8%; P =0.005 versus placebo). Conclusions— These data demonstrate that donepezil is an effective and well-tolerated treatment for VaD and show it may have an important place in the management of this condition.

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 Alzheimers 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 clinicians 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.

efficacy of Donepezil on maintenance of activities of daily living in patients with moderate to severe Alzheimer's disease and the effect on Caregiver burden

OBJECTIVES: This study investigated the efficacy of donepezil treatment on activities of daily living (ADLs) and social functioning in patients with moderate to severe Alzheimers disease (AD) and the possible benefits of this treatment on caregiving time and stress levels.

Environmental stress, psychological stress and allostatic load

Abstract The mechanism by which chronic caregiving stress results in poor health is not well understood. The objective was to determine whether such a mechanism may be allostatic load, a novel concept specifying physiological systems that may suffer cumulative wear and tear following chronic stress, leading collectively to poor health. The study examines the association of allostatic load with environmental and psychological stress in the contexts of dementia caregiving and relinquishment of care, and is a 2-year longitudinal comparison of three groups: 80 new dementia spouse caregivers, 120 veteran caregivers, and 60 non-caregivers. Data comprised allostatic load markers and environmental and psychological stress measures. Cross-lagged analyses produced a statistically significant association between psychological stress and one allostatic load component (primary mediators). Psychological stress was a better predictor of primary mediators than environmental stress. Primary mediators rose with time for caregivers, but not for non-caregivers. A greater rise was evident for caregivers who had relinquished their role by the second year, although the level of psychological stress actually declined. Primary mediators are a key component of the relationship between allostatic load and prior stress. When allostatic load is treated as an outcome of stress, it is important to distinguish environmental and psychological stress.

Functional, Cognitive and Behavioral Effects of Donepezil in Patients with Moderate Alzheimer's Disease

Summary Objective: To investigate the efficacy and safety of donepezil in a subgroup of patients with Alzheimers disease (AD) of moderate severity from a previous trial. Methods: Two hundred and seven patients with moderate AD (standardized Mini-Mental State Examination [sMMSE] score 10-17) were randomized to treatment in this 24-week, double-blind, placebo-controlled trial. Patients received either donepezil, 5mg/day for the first 28 days and 10mg/day thereafter according to the clinicians judgement (n = 102), or placebo (n = 105). The primary outcome measure was the Clinicians Interview-Based Impression of Change with caregiver input (CIBIC-plus) at week 24 using a last observation carried forward (LOCF) analysis. Results: Baseline patient demographics were similar between treatment groups. Mean age was 74.3 years (range 48–92). Least-squares (LS) mean sMMSE scores at baseline were 13.6 ± 0.3 for the donepezil group and 13.9 ± 0.3 for the placebo group. LS mean CIBIC-plus scores for donepezil-treated patients were improved from, or close to, baseline severity at all visits, and were significantly different from placebo at weeks 8,12,18, and 24 (week 24 LOCF mean difference = 0.53, p = 0.0003). LS mean change from baseline scores on the sMMSE and Severe Impairment Battery (SIB) for the donepezil group improved throughout the study, and were significantly different from placebo at each visit for the sMMSE (week 24 LOCF mean difference = 2.06, p = 0.0002) and from week 8 for the SIB (week 24 LOCF mean difference = −4.44, p = 0.0026). LS mean change scores on the Disability Assessment for Dementia remained at or above baseline levels throughout the study for the donepezil group, while the placebo group showed a steady decline; treatment differences were significant at each visit (week 24 LOCF mean difference = −9.25, p < 0.0001). LS mean change scores on the Neuropsychiatric Inventory 12-item total improved throughout the study for the donepezil group and were significantly different from placebo at weeks 4 and 24 (week 24 LOCF mean difference = 5.92, p = 0.0022). Eighty-one per cent of donepezil-treated and 89% of placebo-treated patients completed the trial, with 9% and 5%, respectively, discontinuing due to adverse events (AEs). Eighty-two per cent of donepezil-treated and 80% of placebo-treated patients experienced AEs, the majority of which were rated mild in severity and, in general, were similar between treatment groups. Conclusion:The significant treatment responses observed with donepezil in these patients reinforce the findings from earlier studies that show donepezil to have important benefits, compared with placebo, across functional, cognitive, and behavioral symptoms, with good tolerability, in patients with AD of moderate severity.

The long-term efficacy and tolerability of donepezil in patients with vascular dementia

To determine the long‐term tolerability and efficacy of donepezil in patients with vascular dementia (VaD).

Driving into Danger? Compulsory Driving Licence Cancellation in Alzheimer's Disease

The American Academy of Neurology has recently recommended that patients with a diagnosis of Alzheimer’s disease and a Clinical Dementia Rating (CDR) score =1 (mild dementia) should be prohibited from driving [ 11. Recommendations also include driving performance evaluation and close supervision for patients with very mild or questionable dementia (CDR = 0.5), as the Academy believes these patients pose a significant driving hazard. Justification for these guidelines was based on an evidence-based review of driving safety in dementia, study of road crash statistics, evaluation of driving performance and analysis of driving task components in patients with dementia.

Brief checklist for non-cognitive symptoms of dementia

Objective:  To describe the development and psychometric utility of the behavioural and psychological symptoms of dementia (BPSD) checklist, a brief caregiver‐rated measure of the frequency of non‐cognitive symptoms of dementia of any type.

Evaluation of donepezil in Alzheimer's disease -Experience from an Australian memory clinic

Objectives: To describe our experience using cholinesterase inhibitors for mild‐moderate Alzheimers disease in a memory clinic. In particular we reviewed response in cognition, activities of daily living and quality of life for patients.