Yikang Xu

Donepezil preserves cognition and global function in patients with severe Alzheimer disease

Objective: To evaluate the efficacy and safety of donepezil for severe Alzheimer disease (AD). Methods: Patients with severe AD (Mini-Mental State Examination [MMSE] scores 1 to 12 and Functional Assessment Staging [FAST] scores ≥6) were enrolled in this multinational, double-blind, placebo-controlled trial at 98 sites. Patients were randomized to donepezil 10 mg daily or placebo for 24 weeks. Primary endpoints were the Severe Impairment Battery (SIB) and Clinicians Interview-Based Impression of Change-Plus caregiver input (CIBIC-Plus). Secondary endpoints included the MMSE, the Alzheimer Disease Cooperative Study-Activities of Daily Living-severe version (ADCS-ADL-sev), the Neuropsychiatric Inventory (NPI), the Caregiver Burden Questionnaire (CBQ), and the Resource Utilization for Severe Alzheimer Disease Patients (RUSP). Efficacy analyses were performed in the intent-to-treat (ITT) population using last post-baseline observation carried forward (LOCF). Safety assessments were performed for patients receiving ≥1 dose of donepezil or placebo. Results: Patients were randomized to donepezil (n = 176) or placebo (n = 167). Donepezil was superior to placebo on SIB score change from baseline to endpoint (least squares mean difference 5.32; p = 0.0001). CIBIC-Plus and MMSE scores favored donepezil at endpoint (p = 0.0473 and p = 0.0267). Donepezil was not significantly different from placebo on the ADCS-ADL-sev, NPI, CBQ, or RUSP. Adverse events reported were consistent with the known cholinergic effects of donepezil and with the safety profile in patients with mild to moderate AD. Conclusion: Patients with severe AD demonstrated greater efficacy compared to placebo on measures of cognition and global function.

Donepezil treatment of patients with MCI: A 48-week randomized, placebo-controlled trial

Background: Treatment of mild cognitive impairment (MCI) with cholinesterase inhibitors may improve symptoms. Methods: In this multicenter, randomized, placebo-controlled trial, subjects with MCI entered a 3-week placebo run-in period followed by 48 weeks of double-blind donepezil (5 mg/day for 6 weeks, then 10 mg/day for 42 weeks) or placebo treatment. Primary efficacy variables included change from baseline in the modified Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-Cog) and Clinical Dementia Rating Scale–sum of boxes (CDR-SB) after 48 weeks of treatment (modified intention-to-treat analysis). Secondary efficacy measures evaluated cognition, behavior, and function. Results: The dual primary efficacy endpoint was not reached. We noted a small, but significant, decrease in modified ADAS-Cog scores in favor of donepezil at study endpoint. Little change from baseline in CDR-SB and secondary variables was observed for either group. Patient Global Assessment scores favored donepezil at all time points except week 12 (p ≤ 0.05). Perceived Deficits Questionnaire scores favored donepezil at week 24 (p = 0.05). Clinical Global Impression of Change–MCI scores favored donepezil only at week 6 (p = 0.04). Adverse events were generally mild or moderate. More donepezil-treated subjects (18.4%) discontinued treatment due to adverse events than placebo-treated subjects (8.3%). Conclusions: Donepezil demonstrated small but significant improvement on the primary measure of cognition but there was no change on the primary measure of global function. Most other measures of global impairment, cognition, and function were not improved, possibly because these measures are insensitive to change in MCI. Responses on subjective measures suggest subjects perceived benefits with donepezil treatment.

Economic evaluation of donepezil in moderate to severe Alzheimer disease

Objective: To investigate the costs to society of Alzheimer disease (AD) care in a multinational, randomized, placebo-controlled trial of donepezil in patients with moderate to severe AD. Methods: A total of 290 patients with AD (screening standardized Mini-Mental State Examination score 5 to17) were randomized to receive either donepezil (n = 144; 5 mg/day for 28 days, followed by 10 mg/day as per clinician’s judgment) or placebo (n = 146) for 24 weeks. The authors collected data on patient and caregiver health resource utilization prospectively using the Canadian Utilization of Services Tracking questionnaire. Costs were calculated for patients and caregivers in each group based on resource utilization multiplied by the unit prices for each resource. A cost (the average Ontario minimum wage for 1998 [Can

Donepezil treatment in severe Alzheimer's disease: a pooled analysis of three clinical trials

6.85 per hour]) was assigned to unpaid time that caregivers spent assisting the patient with activities of daily living (ADL). Results: Patient and caregiver demographics at baseline were similar across the two groups. After adjusting for baseline total cost per patient, the mean total societal cost per patient for the 24-week period was donepezil, Can

Effectiveness of Donepezil in Reducing Clinical Worsening in Patients with Mild-to-Moderate Alzheimer’s Disease

9,904 (US

Assessing Therapeutic Efficacy in a Progressive Disease A Study of Donepezil in Alzheimer's Disease

6,686) and placebo, Can

Effect of donepezil on emergence of apathy in mild to moderate Alzheimer's disease

10,236 (US

An MRI substudy of a donepezil clinical trial in mild cognitive impairment

6,910). This net cost saving of Can

Effect of donepezil on cognition in severe Alzheimer's disease: a pooled data analysis.

332 (US

A brief instrument to assess treatment response in the patient with advanced Alzheimer disease.

224) included the average 24-week cost of donepezil treatment. Most of the cost-saving with donepezil treatment was due to less use of residential care by patients, and caregivers spending less time assisting patients with ADL. Conclusion: This cost-consequence analysis reveals economic benefits of treatment of moderate to severe AD with donepezil.