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J Am Geriatr Soc. 2011 Jun;59(6):1019-31. doi: 10.1111/j.1532-5415.2011.03450.x. Epub 2011 Jun 7.

Dementia medications and risk of falls, syncope, and related adverse events: meta-analysis of randomized controlled trials.

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  • 1Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.



To evaluate the effect of cholinesterase inhibitors (ChEIs) and memantine on the risk of falls, syncope, and related events, defined as fracture and accidental injury.


Meta-analysis of randomized controlled trials that were identified from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (no language restriction, through July 2009), and manual search.


Community and nursing homes.


Participants in fifty-four placebo-controlled randomized trials and extension studies of ChEIs and memantine that reported falls, syncope, and related events in cognitively impaired older adults.


Falls, syncope, fracture, and accidental injury.


ChEI use was associated with greater risk of syncope (odds ratio (OR)=1.53, 95% confidence interval (CI)=1.02-2.30) than placebo but not with other events (falls: OR=0.88, 95% CI=0.74-1.04; fracture: OR=1.39, 95% CI=0.75-2.56; accidental injury: OR=1.13, 95% CI=0.87-1.45). Memantine use was associated with fewer fractures (OR=0.21, 95% CI=0.05-0.85) but not with other events (falls: OR=0.92, 95% CI=0.72-1.18; syncope: OR=1.04, 95% CI=0.35-3.04; accidental injury: OR=0.80, 95% CI=0.56-1.12). There was no differential effect according to type and severity of cognitive impairment, residential status, or length of follow-up, although because of underreporting and small number of events, a potential benefit or risk cannot be excluded.


ChEIs may increase the risk of syncope, with no effects on falls, fracture, or accidental injury in cognitively impaired older adults. Memantine may have a favorable effect on fracture, with no effects on other events. More research is needed to confirm the reduction in fractures observed for memantine.

© 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

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