Dementia Medications and Risk of Falls, Syncope, and Related Adverse Events: Meta-Analysis of Randomized Controlled Trials

Authors

  • Dae Hyun Kim MD, MPH,

    1. From the Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
    2. Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School, Boston, Massachusetts; and Departments of
    3. Epidemiology
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  • Rebecca T. Brown MD,

    1. From the Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
    2. Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School, Boston, Massachusetts; and Departments of
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  • Eric L. Ding ScD,

    1. Nutrition, Harvard School of Public Health, Boston, Massachusetts.
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  • Douglas P. Kiel MD, MPH,

    1. From the Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
    2. Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School, Boston, Massachusetts; and Departments of
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  • Sarah D. Berry MD, MPH

    1. From the Division of Gerontology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
    2. Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School, Boston, Massachusetts; and Departments of
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  • The abstract was presented at the Presidential Poster Session of the 2010 American Geriatrics Society Annual Scientific Meeting, Orlando, Florida, May 13, 2010.

Address correspondence to Dae Hyun Kim, 110 Francis Street, LMOB Suite 1A, Boston, MA 02215. E-mail: dkim2@bidmc.harvard.edu

Abstract

OBJECTIVES: 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.

DESIGN: 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.

SETTING: Community and nursing homes.

PARTICIPANTS: 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.

MEASUREMENTS: Falls, syncope, fracture, and accidental injury.

RESULTS: 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.

CONCLUSION: 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.

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