Cholinesterase inhibitors in mild cognitive impairment: a meta-analysis of randomized controlled trials.
OBJECTIVE
Despite being commonly regarded as an initial stage of dementia (particularly of Alzheimer's type, AD), mild cognitive impairment (MCI) is usually not treated and no recommendations for management have been established. Cholinesterase inhibitors have been proposed to halt the progression of MCI to AD and several randomized controlled studies (RCT) have been undertaken to prove this hypothesis. Here we have analyzed the results of RCT of ChEI in MCI.


METHODS
Four long-term RCT of ChEI in MCI were identified. A meta-analysis was conducted with the Mantel-Haenszel method using a fixed model. We compared a major parameter of efficacy (the proportion of those who progressed to dementia within two years) and two parameters of safety, i.e. the total number of adverse events and the number of adverse events leading to drug discontinuation.


RESULTS
The use of ChEI resulted in approximately 24% reduction of risk of conversion from MCI to dementia at the cost of more than 50% increase of adverse events and more than 130% increase of adverse events leading to drug discontinuation, as compared to placebo. Moreover, in the case of galantamine a considerable increase in deaths was observed in the active treatment group; whether this outcome is a class effect of all ChEI or is limited to galantamine cannot be established due to the lack of data from donepezil and rivastigmine trials.


CONCLUSIONS
Because of the questionable efficacy : risk ratio, we believe that it is too early to recommend ChEI in MCI. The sine qua non condition is to establish the factors that predict the risk of conversion from MCI to AD.
Sobów
Tomasz
T
Klinika Psychiatrii Wieku Podeszłego i Zaburzeń Psychotycznych, Uniwersytet Medyczny, Czechosłowacka 8/10, 92-216 Łódź. tmsobow@csk.umed.lodz.pl
Kłoszewska
Iwona
I
D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors