In people with cognitive impairment, cholinesterase inhibitors reduce risk for falls but increase risk for fainting

Ahuja M, Siddhpuria S, Karimi A, et al. Cholinesterase inhibitors and falls, syncope and injuries in patients with cognitive impairment: a systematic review and meta-analysis. Age Ageing. 2023 Nov 2;52(11):afad205

Review question

In people with cognitive impairment,  does treatment with cholinesterase inhibitor drugs affect risks for falls, fainting, or accidental injury?

Background

People with neurocognitive disorders such as Alzheimer’s disease, vascular dementia, Lewy body dementia, Parkinson’s disease dementia, and other types of dementia suffer from cognitive impairment. Cognitive impairment includes problems with thinking, remembering, using language, and making decisions. It may be noticeable but not affect daily living (e.g., mild cognitive impairment), or it may be serious enough to affect daily living (e.g., impairment associated with dementia).

Cholinesterase inhibitor drugs are used to try to prevent or delay worsening of cognitive impairment. However, we don’t know how these drugs affect risk for falls or injury. This review focused on effects of cholinesterase inhibitors on these risks.

How the review was done

Researchers did a systematic review of studies available up to March 2023. They found 53 randomized controlled trials (RCTs) with 25,399 people.

Key features of the studies were:

• people were adults who had cognitive impairment;
• most studies included people with Alzheimer’s disease; other studies included people with vascular dementia, Lewy body dementia, Parkinson’s disease dementia, mild cognitive impairment, traumatic brain injury, or Huntington’s disease;
• cholinesterase inhibitors (donepezil [Aricept®], rivastigmine [Exelon®, Prometax®], or galantamine [Razadyne®, Reminyl®]) were compared with placebo;
• study outcomes included falls, fainting (syncope), fractures, and accidental injury or trauma;
• most studies were done in the community; a few studies were done in long-term care settings; and
• studies lasted for up to 2 years; most lasted for 12 to 24 weeks.

What the researchers found

Compared with placebo, cholinesterase inhibitors:

• reduce risk for falls;
• increase risk for fainting (about 4 more people out of 1000 fainted); and
• do not reduce or increase risks for fractures or accidental injury.

Conclusion

In people with cognitive impairment,  cholinesterase inhibitors reduce falls but increase risk for fainting by a small amount compared with placebo. The drugs do not increase the risk for fractures or accidental injury.

Cholinesterase inhibitors* vs placebo in people with cognitive impairment

*30 trials evaluated donepezil, 14 trials evaluated galantamine, and 9 trials evaluated rivastigmine.

†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.