This site uses cookies to measure how you use the website so it can be updated and improved based on your needs and also uses cookies to help remember the notifications you’ve seen, like this one, so that we don’t show them to you again. If you could also tell us a little bit about yourself, this information will help us understand how we can support you better and make this site even easier for you to use and navigate.

Effectiveness of donepezil in reducing clinical worsening in patients with mild-to-moderate alzheimer’s disease


Wilkinson, David, Schindler, Rachel, Schwam, Elias, Waldemar, Gunhild, Jones, Roy W., Gauthier, Serge, Lopez, Oscar L., Cummings, Jeffrey, Xu, Yikang, Feldman, Howard H.


Dementia And Geriatric Cognitive Disorders, Volume: 28, No.: 3, Pages.: 244-251

Year of Publication



Background: Therapeutic endpoints based on reduced clinical worsening represent clinically relevant and realistic goals for patients suffering from progressive neurodegenerative disorders such as Alzheimer’s disease (AD).; Methods: Data from 906 patients (388 receiving placebo; 518 receiving donepezil) with mild-to-moderate AD [Mini-Mental State Examination (MMSE) score 10-27] were pooled from 3 randomized, double-blind placebo-controlled studies. Clinical worsening was defined as decline in (1) cognition (MMSE), (2) cognition and global ratings (Clinician’s Interview-Based Impression of Change plus Caregiver Input/Gottfries-Bråne-Steen scale) or (3) cognition, global ratings and function (various functional measures).; Results: At week 24, lower percentages of donepezil-treated patients than placebo patients met the criteria for clinical worsening, regardless of the definition. The odds of declining were significantly reduced for donepezil-treated versus placebo patients (p < 0.0001; all definitions). Among patients meeting criteria for clinical worsening, mean declines in MMSE scores were greater for placebo than donepezil-treated patients.; Conclusion: In this population, donepezil treatment was associated with reduced odds of clinical worsening of AD symptoms. Moreover, patients worsening on donepezil were likely to experience less cognitive decline than expected if left untreated. This suggests that AD patients showing clinical worsening on donepezil may still derive benefits compared with placebo/untreated patients.; Copyright 2009 S. Karger AG, Basel.

Bibtex Citation

@article{Wilkinson_2009, doi = {10.1159/000241877}, url = {}, year = 2009, publisher = {S. Karger {AG}}, volume = {28}, number = {3}, pages = {244--251}, author = {David Wilkinson and Rachel Schindler and Elias Schwam and Gunhild Waldemar and Roy W. Jones and Serge Gauthier and Oscar L. Lopez and Jeffrey Cummings and Yikang Xu and Howard H. Feldman}, title = {Effectiveness of Donepezil in Reducing Clinical Worsening in Patients with Mild-to-Moderate Alzheimer{&}rsquo$mathsemicolon$s Disease}, journal = {Dementia and Geriatric Cognitive Disorders} }


aged, aged, 80 and over, alzheimer disease, disease progression, donezepil, double-blind method, drug therapy, female, humans, indans, male, middle aged, neuropsychological tests, nootropic agents, odds ratio, piperidines, psychology, therapeutic use, treatment outcome

Countries of Study


Types of Dementia

Alzheimer’s Disease

Types of Study

Randomised Controlled Trial

Type of Outcomes


Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions

Anti-Alzheimer medications, e.g.: donezepil, galantamine, rivastigmine, memantime