Review: in people with dementia, cholinesterase inhibitors may increase syncope and memantine may reduce fractures

Sirpa Hartikainen, J. Simon Bell

Research output: Contribution to journalComment / DebateOtherpeer-review

1 Citation (Scopus)


Question: What is the effect of dementia medications (cholinesterase inhibitors and memantine) on the risk of falls and fall-related adverse events in older adults with mild cognitive impairment or dementia?
Outcomes: Falls; fall-related adverse events (syncope, fracture or accidental injury).

Design: Systematic review with meta-analysis.
Data sources: MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched from inception to July 2009 for randomised controlled trials (RCTs). Unpublished safety data from RCTs were identified by searching pharmaceutical clinical trial registries, medical and safety review documents from the US Food and Drug Administration and hand searching reference lists of review articles.
Study selection and analysis: A minimum of two reviewers appraised the studies and selected placebo-controlled RCTs of memantine or any cholinesterase inhibitor (ChEIs: donepezil, galantamine, rivastigmine or tacrine) in adults with a diagnosis of mild cognitive impairment, Alzheimer’s disease, mixed dementia, vascular dementia, dementia with Lewy bodies, Parkinson’s disease with dementia or frontotemporal dementia. Eligible studies were examined for data on falls, syncope, fracture or accidental injury; trials with no such data on these adverse events were excluded. A minimum of two reviewers rated study quality and quality of adverse event reporting, and extracted data. Mean Mini-Mental State Examination scores were used to define severity of cognitive impairment (severe≤10, moderate to severe 11–15, mild to moderate 16–20 and mild >20). Random effects meta-analyses were conducted using Stata SE version 11 software. If no outcome events occurred in a treatment arm, 0.5 was added to each cell to enable calculation of the OR and 95% CI. Heterogeneity was investigated using the I2 statistic and Cochran Q test. Subgroup meta-analyses were performed to assess if risks of falls or fall-related adverse events differed according to severity or type of dementia.

ChEIs: 40 RCTs met inclusion criteria (falls: n=9882, 589 events;syncope: n=8227, 131 events; fracture: n=3554, 50 events; accidental injury: n=13 001, 828 events). ChEIs increased the risk of syncope compared with placebo (OR 1.53, 95% CI 1.02 to 2.30).There were no significant differences between ChEIs and placebo for falls, fracture or accidental injury (table 1). Memantine: 14 RCTs met inclusion criteria (falls: n=3584, 304 events; syncope:n=1695, 15 events; fracture: n=976, 13 events; accidental injury: n=3285, 163 events). Memantine decreased the risk of fracture compared with placebo (OR 0.21, 95% CI 0.05 to 0.85).There were no significant differences between memantine and placebo for falls, syncope or accidental injury (table 1). For both drugs, risks of falls or fall-related adverse events did not differ significantly according to severity or type of dementia.

CONCLUSIONSMemantine may reduce fracture risk in people with dementia, but this needs to be conformed in further studies. ChEIs have no effect on falls, fracture or accidental injury, but may increase risk of syncope. The small numbers of events and potential under-reporting of adverse events mean that an effect cannot be ruled out for the outcomes where no effect was detected.
Original languageEnglish
Pages (from-to)111-111
Number of pages1
JournalEvidence-Based Mental Health
Issue number4
Publication statusPublished - Nov 2011
Externally publishedYes

Cite this