To treat or not to treat? A meta-analysis of the use of cholinesterase inhibitors in mild cognitive impairment for delaying progression to Alzheimer's disease.
BACKGROUND
Individual randomized clinical trials (RCTs) with cholinesterase inhibitors (ChEIs) aiming to delay the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD) have not found significant benefit of their use for this purpose. The objective of this study is to meta-analyze the RCTs conducted with ChEIs in order to assess whether pooled analysis could show the benefit of these drugs in delaying the progression from MCI to AD.


METHODS
We searched for references of published and unpublished studies on electronic databases (Medline, Embase, Web of Science, and Clinical Trial Database Registry, particularly the Clinicaltrials.gov--http://www.clinicaltrials.gov ). We retrieved 173 references, which yielded three references for data extraction. A total of 3.574 subjects from four RCTs were included in the meta-analysis. Among 1,784 subjects allocated in the ChEI-treatment group, 275 (15.4%) progressed to AD/dementia, as opposed to 366 (20.4%) out of 1,790 subjects in the placebo group. The relative risk (RR) for progression to AD/dementia in the ChEI-treated group was 0.75 [CI(95%) 0.66-0.87], z = -3.89, P < 0.001. The patients on the ChEI group had a significantly higher all-cause dropout risk than the patients on the placebo group (RR = 1.36 CI(95%) [1.24-1.49]; z = 6.59, P < 0.001). The RR for serious adverse events (SAE) in the ChEI-treated group showed no significantly statistical difference from the placebo group (RR = 0.95 [CI(95%) 0.83-1.09], z = -0.72, P = 0.47). The subjects in the ChEI-treated group had a marginally, non-significant, higher risk of death due to any cause than those in the placebo-treated group (RR = 1.04, CI(95%) 0.63-1.70, z = 0.16, P = 0.86).


CONCLUSIONS
The long-term use of ChEIs in subjects with MCI may attenuate the risk of progression to AD/dementia. This finding may have a significant impact on public health and pharmaco-economic policies.
Diniz
Breno Satler
BS
Laboratory of Neuroscience (LIM 27), Institute and Department of Psychiatry, Faculty of Medicine, University of Sao Paulo, Rua Ovidio Pires de Campos, 785, 3th floor, Sao Paulo, SP, CEP: 05403-010, Brazil. brenosatler@usp.br
Pinto
Jony Arrais
JA
Gonzaga
Maria Luiza Cavichioli
ML
Guimarães
Fabiana Meira
FM
Gattaz
Wagner Farid
WF
Forlenza
Orestes Vicente
OV
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000517:prevention & control* / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000523:psychology; D018450:Disease Progression; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors