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Pharmacological Therapy

Cholinesterase Inhibitors (ChEI’s)

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  • several medications are available for patients with AD that ease symptoms by slowing down the decline of memory, language and thinking abilities [11]

  • the Canadian Consensus Conference on Dementia recommends that cholinesterase inhibitors (ChEIs) be used for standard symptomatic treatment of mild to moderate AD [11]

  • ChEIs focus on correcting the cholinergic deficiency in the central nervous system [1]

  • currently three ChEIs are marketed for treatment of AD; these are donepezil, rivastigmine, galantamine for treatment of cognitive symptoms of mild to moderate AD [1]

  • usually improved cognitive abilities are seen in the fist 2-3 months, followed by a slowing down of the progression of the symptoms [11]

  • a recent meta-analysis of 16 randomized, double blind, placebo-controlled trials examined the effect on ChEIs on cognitive status confirmed that AD patients treated with ChEIs have a modest but significant therapeutic effect [1]

  • a more recent review of 19 randomized controlled trials concluded that the methodological quality of the trials being reviewed was poor with missing data on patient dropout from the treatment arm and affecting intention to treat analysis, thereby  the beneficial effects of previously described may not be as strong [2]

  • future studies are clearly needed that look at long term effects of these drugs in both sexes as well as clinical outcomes such as function and behaviour and delaying institutionalization and the reduction of caregiver burden

Side effects of ChEIs

A recent meta-analysis of 16 randomized, double blind, placebo-controlled trials examined the side effects and adverse events caused by the use of ChEIs[1] found that:

 

  • AD patients treated with ChEIs have a significantly higher rate of adverse events [1] (examples of adverse events include nausea, vomiting, diarrhea, abdominal pain, fatigue and weight loss etc.)

  • the tolerability of ChEIs was an issue and the proportion of patients in whom adverse events emerged during treatment was 8% higher than those receiving placebo [1]

  • there is weak evidence that women experience more adverse effects than men, possibly due to a lower body weight [10]

  • ChEIs can also have a vagotonic effect on the SA and AV nodes, leading to bradycardia and heart block especially in those patients with coexisting cerebrovascular disease [1]

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1. Lanctot KL, Herrmann N, Yau KK, Khan LR, Liu BA, Loulou MM et al. Efficacy and safety of cholinesterase inhibitors in Alzheimer's Disease: a meta analysis. Canadian Medical Association Journal 2003; 169(6):557-64.

2. Kaduszkiewicz H, Zimmermann T, Beck-Bornholdt HP. Cholinesterase inhibitors for patients with Alzheimer's Disese: systematic review of randomised clinical trials. BMJ 2005; 331(7512):321-7.

10. Haywood WM, Mukaetova-Ladinska EB. Sex influences on cholinestrase inhibitor treatment in elderly individuals with Alzheimer's disease. The American Journal of Geriatric Pharmacology September 2006;273-286.

11. Patterson CJS, Gauthier S, Bergman H, Cohen CA, Feightner JW, Feldman H, Hogan DB. The recognition, assessment and management of dementing disorders: conclusions from the Canadian Consensus Conference on Dementia. Canadian Medical Association Journal 1999; 160 Suppl 12:S1-15.

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