Donepezil was most likely to effectively improve cognition in patients with Alzheimer’s dementia, according to a new study ranking the safety and effectiveness of four drugs taken to enhance concentration, memory, alertness and mood.

Conversely, those patients who took donepezil were more likely to experience side effects including nausea, vomiting and diarrhea than those who received a placebo, the study found.

“Alzheimer’s dementia is the most common form of dementia in North America, and most people who have moderate to severe Alzheimer’s will be on these medications. This analysis will give both patients and clinicians a full picture of how each of these drugs will likely affect their cognition, as well as their overall health,"

said lead author Dr. Andrea Tricco, a scientist in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital.

Cognitive Enhancers

Although there have been previous reviews of the safety and effectiveness of cognitive enhancers in treating Alzheimer’s dementia, the authors said this was the first to rank their comparative safety and effectiveness.

The study used network meta-analysis, an advanced statistical analysis technique, to systematically review existing evidence from 142 clinical trials of four common cognitive enhancers administered alone or in combination published between 1996 and 2015.

The number of patients in each study ranged from 13 to 2,045, and the review evaluated a total of 33,889 patients.

The researchers compared the safety and effectiveness of any combination of donepezil, rivastigmine, galantamine or memantine in treating moderate to severe Alzheimer’s dementia based on the results of the clinical trials that examined a number of patient outcomes, including cognition, function behaviour, global status, mortality, serious adverse events, falls, bradycardia, headache, diarrhea, vomiting and nausea.

Donepezil was likely the most effective medication for Alzheimer’s dementia across all effectiveness outcomes, including cognition, behaviour and overall health, according to the study.


Donepezil was also the only cognitive enhancer that reached the minimal clinically important threshold — meaning effects on outcomes were observed clinically, as well as statistically — on the Alzheimer’s Disease Assessment cognition scale, making it the likely first choice for those patients and clinicians considering these medications, the authors said.

Although no significant risk of serious harm, falls or reduced heart rate was associated with any of the medications in the study, the data was limited on these specific outcomes.

Previous research by the authors found that cognitive enhancers do not improve cognition or function in people with mild cognitive impairment, and these patients experience significantly more nausea, diarrhea, vomiting and headaches.

The findings of the current study will help guide patients and clinicians who are making decisions about the best course of treatment for Alzheimer’s dementia, said Dr. Tricco.

Tricco, A. C., Ashoor, H. M., Soobiah, C., Rios, P., Veroniki, A. A., Hamid, J. S., Ivory, J. D., Khan, P. A., Yazdi, F., Ghassemi, M., Blondal, E., Ho, J. M., Ng, C. H., Hemmelgarn, B., Majumdar, S. R., Perrier, L. and Straus, S. E. Comparative Effectiveness and Safety of Cognitive Enhancers for Treating Alzheimer’s Disease: Systematic Review and Network Metaanalysis J Am Geriatr Soc. doi:10.1111/jgs.15069

Image: Matthew Herring, Wellcome Images

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