Cholinesterase inhibitors for mild cognitive impairment
- PMID: 22972133
- PMCID: PMC6464825
- DOI: 10.1002/14651858.CD009132.pub2
Cholinesterase inhibitors for mild cognitive impairment
Abstract
Background: Mild cognitive impairment is hypothesised to represent a pre-clinical stage of dementia but forms a heterogeneous group with variable prognosis.
Objectives: To assess the safety and efficacy of cholinesterase inhibitors in people with mild cognitive impairment.
Search methods: Trials were identified from the Cochrane Dementia and Cognitive Improvement Group's Specialised Register, which is frequently updated from the major healthcare databases (MEDLINE, EMBASE, CINAHL, PsycINFO and Lilacs) as well as trial registers and grey literature.
Selection criteria: Double-blind, placebo-controlled randomised trials of any cholinesterase inhibitor in people with mild cognitive impairment.
Data collection and analysis: Data were extracted from the published reports of the included studies, combined by meta-analysis where appropriate, and treatment efficacy and risk of adverse events were estimated.
Main results: Nine studies (from eight published reports) of 5149 individuals with mild cognitive impairment (however defined) were included in the review. Limited pooling of results was possible owing to different lengths of trials. Meta-analysis of the three studies reporting conversion to dementia gives no strong evidence of a beneficial effect of cholinesterase inhibitors on the progression to dementia at one, two or three years. The risk ratio (RR) for conversion at two years was significantly different from unity (0.67; 95% confidence interval (CI) 0.55 to 0.83), but this is based on only two studies reported in the same article. There was essentially no effect of cholinesterase inhibitors on cognitive test scores.Based on the results from 4207 individuals, there were significantly more adverse events in the cholinesterase inhibitor groups (RR 1.09; 95% CI 1.02 to 1.16), but no more serious adverse events or deaths. Gastrointestinal side effects were much more common (diarrhoea: RR 2.10; 95% CI 1.30 to 3.39; nausea: RR 2.97; 95% CI 2.57 to 3.42; vomiting: RR 4.42; 95% CI 3.23 to 6.05). Cardiac problems were no more likely in either group (RR 0.71; 95% CI 0.25 to 2.02). Other side effects reported significantly more often in the cholinesterase inhibitor group were muscle spasms/leg cramps (RR 7.52; 95% CI 4.34 to 13.02), headache (RR 1.34; 95% CI 1.05 to 1.71), syncope or dizziness (RR 1.62; 95% CI 1.36 to 1.93), insomnia (RR 1.66; 95% CI 1.36 to 2.02) and abnormal dreams (RR 4.25; 95% CI 2.57 to 7.04).
Authors' conclusions: There is very little evidence that cholinesterase inhibitors affect progression to dementia or cognitive test scores in mild cognitive impairment. This weak evidence is overwhelmed by the increased risk of adverse events, particularly gastrointestinal. Cholinesterase inhibitors should not be recommended for mild cognitive impairment.
Conflict of interest statement
None.
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Comment in
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Little evidence that cholinesterase inhibitors prevent progression of mild cognitive impairment to dementia, but they are associated with adverse effects.Evid Based Ment Health. 2013 May;16(2):39. doi: 10.1136/eb-2012-101087. Epub 2013 Jan 7. Evid Based Ment Health. 2013. PMID: 23299054 No abstract available.
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ACP Journal Club. Review: cholinesterase inhibitors do not reduce progression to dementia from mild cognitive impairment.Ann Intern Med. 2013 Feb 19;158(4):JC3. doi: 10.7326/0003-4819-158-4-201302190-02003. Ann Intern Med. 2013. PMID: 23420252 No abstract available.
References
References to studies included in this review
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- Doody RS, Ferris SH, Salloway S, Sun Y, Goldman R, Watkins WE, et al. Donepezil treatment of patients with MCI: a 48‐week randomized, placebo‐controlled trial. Neurology 2009;72:1555‐61. - PubMed
-
- Feldman HH, Ferris S, Winblad B, Sfikas N, Mancione L, He Y, et al. Effect of rivastigmine on delay to diagnosis of Alzheimer's disease from mild cognitive impairment: the InDDEx study. Lancet Neurology 2007;6:501‐12. - PubMed
-
- Narasimhalu K, Effendy S, Sim CH, Lee JM, Chen I, Hia SB, et al. A randomized controlled trial of rivastigmine in patients with cognitive impairment no dementia because of cerebrovascular disease. Acta Neurologica Scandinavica 2010;121:217‐24. - PubMed
-
- Peters O, Lorenz D, Fesche A, Schmidtke K, Hüll M, Perneczky R, et al. A combination of galantamine and memantine modifies cognitive function in subjects with amnestic MCI. Journal of Nutrition, Health & Aging 2012;16:544‐8. - PubMed
References to studies excluded from this review
-
- Anon. Study of donepezil for MCI shows only minor improvement in patients with mild cognitive impairment. Geriatric Psychopharmacology Update 2009;13(8):1.
-
- Barnes DE, Yaffe K, Petersen RC, Thomas RG, Thal LJ. Vitamin E and donepezil for the treatment of mild cognitive impairment. New England Journal of Medicine 2005;352:2379‐88. - PubMed
-
- Bokde A, Lopz‐Bayo P, Meindl T, Teipel SJ, Reiser M, Moller HJ, et al. Effect of rivastigmine in a double‐blind study in MCI subjects: a functional magnetic resonance imaging study. International Journal of Neuropsychopharmacology 2008;11:29‐30.
-
- Chen X, Magnott VA, Duff K, Boles Ponto LL, Schultz SK. Donepezil effects on cerebral blood flow in older adults with mild cognitive deficits. Journal of Neuropsychiatry & Clinical Neurosciences 2006;18(2):175‐85. - PubMed
-
- Crane PK, Doody RS. Donepezil treatment of patients with MCI: a 48‐week randomized, placebo‐controlled trial. Neurology 2009;73(18):1514‐5. - PubMed
References to ongoing studies
-
- 24‐week, randomized, double‐blind, placebo‐controlled, parallel group study of the Exelon® [rivastigmine] transdermal patch in 120 APOE e4 positive amnestic MCI patients, 2011. http://clinicaltrials.gov/ct2/show/NCT01602198 (accessed 3 August 2012).
Additional references
-
- Agrell B, Dehlin O. The clock‐drawing test. Age and Ageing 1998;27:399‐403. - PubMed
-
- Albert MS, DeKosky ST, Dickson D, Dubois, B, Feldman, HH, Fox, NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging‐Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia 2011;7:270‐9. - PMC - PubMed
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