Question  Are cholinesterase inhibitors or memantine associated with cognitive outcomes in clinical trials for Alzheimer disease?

Findings  In this meta-analysis, participants receiving cholinesterase inhibitors or memantine had 1.4 points per year difference on the Alzheimer Disease Assessment Scale–cognitive subscale compared with those receiving neither medication, a significant difference that is roughly the same size as the expected effect of new therapeutic drugs being investigated in the clinical trials.

Meaning  Differences in the use of cholinesterase inhibitors and memantine between treatment and placebo groups of clinical trials may lead to the conclusion that a treatment is effective when it is not, or vice versa.


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Kennedy RE, Cutter GR, Fowler ME, Schneider LS. Association of Concomitant Use of Cholinesterase Inhibitors or Memantine With Cognitive Decline in Alzheimer Clinical TrialsA Meta-analysisJAMA Netw Open. 2018;1(7):e184080. doi:10.1001/jamanetworkopen.2018.4080