Effect of donepezil on emergence of apathy in mild to moderate Alzheimer's disease
Version of Record online: 2 JUL 2010
Copyright © 2010 John Wiley & Sons, Ltd.
International Journal of Geriatric Psychiatry
Volume 26, Issue 2, pages 150–157, February 2011
How to Cite
Waldemar, G., Gauthier, S., Jones, R., Wilkinson, D., Cummings, J., Lopez, O., Zhang, R., Xu, Y., Sun, Y., Knox, S., Richardson, S. and Mackell, J. (2011), Effect of donepezil on emergence of apathy in mild to moderate Alzheimer's disease. Int. J. Geriat. Psychiatry, 26: 150–157. doi: 10.1002/gps.2507
- Issue online: 12 JAN 2011
- Version of Record online: 2 JUL 2010
- Manuscript Accepted: 8 FEB 2010
- Manuscript Received: 6 NOV 2009
- Neuropsychiatric Inventory;
- Alzheimer's disease
To determine whether donepezil treatment (10 mg/day over 24 weeks) is associated with delayed emergence of apathy in patients with mild to moderate Alzheimer's disease (AD) and to explore relationships between donepezil's effects on apathy and other Neuropsychiatric Inventory (NPI)–measured behavioural symptoms.
Two randomised, double-blind, parallel-group, placebo-controlled studies that met prespecified criteria and were sufficiently similar to allow data pooling were derived from all donepezil AD clinical trials. Patients scoring from 10 to 26 on baseline Mini-Mental Status Examination were included. A clinical milestone for apathy and other NPI items was defined as the first emergence of a composite score (frequency × severity) ≥3. Differences in time to event (i.e. milestone) between donepezil- and placebo-treated groups were assessed using the Kaplan-Meier method and log-rank test. Shift tables were constructed to evaluate clinical milestone status for apathy and other NPI items at baseline and endpoint, and were analysed using the Cochran-Mantel-Haenszel (CMH) test, stratified by baseline status.
Of all NPI items, apathy had the highest proportion of subjects scoring ≥3 at baseline. Donepezil was superior to placebo on both apathy milestone analyses (time-to-event log-rank test and shift table CMH test, p = 0.01). Aberrant motor behaviour demonstrated similar benefit.
Donepezil treatment appears to have resulted in a significant reduction over 6 months of the emergence of apathy in patients with AD. These data suggest that a prospective clinical trial in patients with early AD that includes apathy as a primary outcome measure may be warranted. Copyright © 2010 John Wiley & Sons, Ltd.