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Best of 4 Alzheimer’s Drugs

See safety and effectiveness rankings for four Alzheimer's drugs. Ranked on concentration, memory, alertness and mood, learn what the researchers found.

An important study, ranking the safety and effectiveness of four drugs taken to enhance concentration, memory, alertness and moods, found that donepezil was most likely to effectively improve cognition in patients with Alzheimer’s dementia.

However, patients who took donepezil were more likely to experience side effects including nausea, vomiting and diarrhea than those who received a placebo, according to the study, published online in the Journal of the American Geriatrics Society.

Improving Cognition in Alzheimer’s

Drugs for Early to Midstage
Brand Name Generic Name
Aricept® donepezil
Exelon® rivastigmine
Remynil or Razadyne® galantamine
Drugs for Moderate to Severe Stage
Namenda® or Ebixa® memantine

In 2015, 46 million people worldwide had Alzheimer’s disease, according to the study. In 2013, 146,593 people aged 65 and older in Ontario alone used cognitive enhancers, according to a 2016 Ontario Drug Policy Research report.

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

Safety & Effectiveness

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, behavior and overall health, according to the study.

Best Course of Alzheimer’s Treatment

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.

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

“The more information we are able to gather about how each of these medications can affect a patient’s cognition and health, the more likely we are to be able to improve their health outcomes,” she said.



  • St. Michael’s Hospital:

    St. Michael’s Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in more than 29 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, care of the homeless and global health are among the Hospital’s recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Centre, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael’s Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto.
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October 15, 2017 5:14 pm

My mom was prescribed Aricept early on in her affliction, but she did not have Alzheimers rather, vascular dementia which in many ways have symptoms resembling dementia. Does research determine that the drug Aricept is as effective for vascular dementia as it is for Alzheimers?
By the way, I did not see any improvement in cognition.
Thank you

October 15, 2017 7:30 pm

None of these drugs are worth the adverse effects. Evidently this "new" research changed this(see below)conclusion. Who paid for it?
"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."

October 15, 2017 7:41 pm

Joanne, if your mom had "pure" vascular dementia, then no, Aricept would not be beneficial. However, many patients have "mixed dementia", which is vascular dementia and Alzheimer's, and those may benefit from any of the cholinesterase inhibitors and/or memantine. (Studies that included patients with mixed dementia were excluded from the study in this report.)

I would take the results of this study with a huge grain of salt. Their inclusion criteria were very broad and quite questionable. For example, they used studies that reported cognitive function in terms of the MMSE only, and it simply cannot be used that way. They used studies that lasted only two weeks. That's ridiculous. They used studies with as few participants as 13. Studies that small are bound to be poorly designed and unreliable. They included quasi-randomized and nonrandomized studies. They used studies in which the average age of patients was 61. That's way too low unless the studies were on some type of early-onset Alzheimer's, and early-onset familial AD should not be lumped in with sporadic AD. They used studies published as early as 1996, and back then, diagnosis was not nearly as reliable as it is now, and the cohorts probably included a range of other neurodegenerative disorders. They used studies with unacceptably high dropout rates. They lumped together studies using patients with any level of disease severity, and even used studies (20% of those included) that did not determine how severe the dementia was.

One reason I really doubt their findings is that large, well-designed, randomized, double-blind trials have compared Aricept and Exelon head to head in late-stage patients and found Exelon to be significantly superior — as one would expect from the two drugs' different biological activities.

March 26, 2019 11:38 pm

My husband was diagnosed ten yaars ago and prescribed Aricept and then Namenda. He has taken with no adverse side effects, other than vivid dreams. However, He is definitely not early stage any longer, and I'm wondering about the benefits of (especially) Aricept/Donepezil.

B. Berger

B. Berger

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