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Cholinesterase inhibitors slow cognitive decline and do not affect falls in people with Parkinson’s disease

Pagano G, Rengo G, Pasqualetti G, et al. Cholinesterase inhibitors for Parkinson`s disease: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2014 Sep 15. Epub ahead of print.

Review question

In people with Parkinson’s disease who do not have dementia, what is the effect of cholinesterase inhibitors on cognitive function compared with placebo?


Parkinson's disease is a disorder of the nervous system that affects movement. Physical signs of the disease may include tremor (shaking), slowed movement, rigid muscles, impaired posture and balance, and speech and writing changes. Non-physical signs may include impaired cognitive function. Donepezil (Aricept®), rivastigmine (Exelon®) and galantamine (Razadyne®) are cholinesterase inhibitors, a class of drugs that has been used to treat Alzheimer’s disease.

How the review was done

The researchers did a systematic review, searching for published studies up to May 2014. They found 4 randomized controlled trials, with 941 people (average age 68 to 74 years, 39% to 86% men).

People in the studies had Parkinson’s disease. Studies of people with dementia with Lewy bodies were not included.

Any dosage of rivastigmine, donepezil, or galantamine for at least 4 weeks was compared with placebo.

What the researchers found

1 trial was of high quality. The other 3 had unclear quality.

1 trial assessed rivastigmine, and 3 assessed donepezil. No trials assessed galantamine.

Compared with placebo, cholinesterase inhibitors

  • slowed cognitive decline;
  • did not affect falls; and
  • increased rates of tremor and adverse drug reactions.


Cholinesterase inhibitors slow cognitive decline and do not affect rate of falls. They increase tremor and adverse drug reactions.

Cholinesterase inhibitors vs placebo in people with Parkinson’s disease


Number of trials (number of people)

Rate of events with cholinesterase inhibitors

Rate of events with placebo

Effect of cholinesterase inhibitors at 10 to 24 weeks

Mini-Mental State Examination

4 trials (982 people)



Slower decline in cognition


3 trials (920 people)



About 24 fewer people out of 1000 died*


3 trials (873 people)



No difference in rate of falls†


2 trials (834 people)



About 65 more people out of 1000 had tremors

Adverse drug reactions

3 trials (936 people)



About 19 more people out of 100 had adverse drug reactions

*Based on a small number of deaths, and therefore the result may not be reliable.

†Although the rates for the 2 groups look a little different, the differences were not statistically significant. This means that the differences could simply be due to chance rather than due to the different treatments.

Related Topics


Cognitive function
Mental processes, including thinking, learning and remembering.
A harmless, inactive, and simulated treatment.
Randomized controlled trials
Studies where people are assigned to one of the treatments purely by chance.
Systematic review
A comprehensive evaluation of the available research evidence on a particular topic.

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