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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

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Abstract

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We searched for references of published and unpublished studies on electronic databases (Medline, Embase, Web of Science, and Clinical Trial Database Registry, particularly the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 [CI95% 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 CI95% [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 [CI95% 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, CI95% 0.63–1.70, z = 0.16, P = 0.86).

Conclusion

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.

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Conflict of interest

Dr. Gattaz has received research support and speakership honoraria from AstraZeneca, Bristol Myers-Squibb, Eli Lilly, and Janssen-Cilag.

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Authors and Affiliations

  1. 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

    Breno Satler Diniz, Jony Arrais Pinto Jr, Maria Luiza Cavichioli Gonzaga, Fabiana Meira Guimarães, Wagner Farid Gattaz & Orestes Vicente Forlenza

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  1. Breno Satler Diniz
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Correspondence to Breno Satler Diniz or Orestes Vicente Forlenza.

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Diniz, B.S., Pinto, J.A., Gonzaga, M.L.C. et al. 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. Eur Arch Psychiatry Clin Neurosci 259, 248–256 (2009). https://doi.org/10.1007/s00406-008-0864-1

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