A RiskBenefit Assessment of Dementia Medications

Authors: Jacob S Buckley Shelley R Salpeter

Publish Date: 2015/05/05

Volume: 32, Issue: 6, Pages: 453-467

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Abstract

We performed a systematic literature search of MEDLINE through November 2014 for Englishlanguage trials and observational studies on treatment of dementia and mild cognitive impairment Additional references were identified by searching bibliographies of relevant publications Whenever possible pooled data from metaanalyses or systematic reviews were obtained Studies were included for review if they were randomized trials or observational studies on dementia or mild cognitive impairment that evaluated efficacy outcomes or adverse outcomes associated with treatment Studies were excluded if they evaluated nonFDA approved treatments or if they evaluated treatment in disorders other than dementia and mild cognitive impairmentThe literature search found 540 potentially relevant studies of which 257 were included in the systematic review In pooled trial data cholinesterase inhibitors ChEIs produce small improvements in cognitive functional and global benefits in patients with mild to moderate Alzheimer’s and Lewy body dementia but the clinical significance of these effects are unclear There is no significant benefit seen for vascular dementia The efficacy of ChEI treatment appears to wane over time with minimal benefit seen after 1 year There is no evidence for benefit for those with advanced disease or those aged over 85 years Adverse effects are significantly increased with ChEIs in a dosedependent manner A two to fivefold increased risk for gastrointestinal neurological and cardiovascular side effects is related to cholinergic stimulation the most serious being weight loss debility and syncope Those aged over 85 years have double the risk of adverse events compared with younger patients Memantine monotherapy may provide some cognitive benefit for patients with moderate to severe Alzheimer’s and vascular dementia but the benefit is small and may wane over the course of several months Memantine exhibits no significant benefit in mild dementia or Lewy body dementia or as an addon treatment with ChEIs Memantine has a relatively favorable sideeffect profile at least under controlled trial conditionsChEIs produce small shortlived improvements in cognitive function in mild to moderate dementia which may not translate into clinically meaningful effects Marginal benefits are seen with severe disease longterm treatment and advanced age Cholinergic side effects including weight loss debility and syncope are clinically significant and could be especially detrimental in the frail elderly population in which the risks of treatment outweigh the benefits Memantine monotherapy may have minimal benefits in moderate to severe dementia balanced by minimal adverse effects

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