Persistence with Cholinesterase Inhibitor Treatment in Alzheimer's Disease

Three cholinesterase inhibitors (ChEI) are approved in Canada for the symptomatic treatment of Alzheimer's disease (AD): donepezil, rivastigmine, and galantamine.This class of drugs provides modest improvement of some symptoms of the disease but it does not alter its course 1 .The fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD) concluded that the three ChEI demonstrated comparable efficacy for mild to severe AD, and that a trial of one of these medications should be proposed for most patients with AD 2 .As ChEI are relatively costly and their clinical benefits are mild, persistence with treatment has been an issue since their arrival on the Canadian market.In most provinces, these medications are reimbursed according to very specific criteria.For example, in Quebec, reimbursement of these medications is conditional on a clear diagnosis, a general rating of disease severity in five clinical domains, and specific cut-offs on the Mini-Mental Status Examination (MMSE).Upon renewing ChEI prescription, reimbursement is granted if the patient improves, stabilises, or does not deteriorate significantly in several clinical domains and on the MMSE.These criteria, which are based on the results of clinical trials with ChEI, are far from perfect, but they do serve as a general guide to their use in clinical practice.In clinical trials, patients are followed very closely and their symptoms are monitored on a regular basis.This will tend to reinforce persistence to treatment, but may be difficult to reproduce in real-life clinical practice.In that respect, the setting of clinical trials is "artificial".Nevertheless, the rate of withdrawal from ChEI after six months of treatment has varied between 20% and 30% in clinical trials, depending on the molecule used and the method of administration (immediate release vs extended release, oral vs transdermal, etc.) [3][4][5] .There are few clinical trials beyond six month duration, and they have usually demonstrated similar withdrawal rates.In this issue of the Canadian Journal of Neurological Sciences, Saleh et al investigated persistence to ChEI in a small group of patients in a memory clinic in rural Saskatchewan 6 .Several factors were examined including socio-demographic, cognitive, functional and behavioural measures.The level of education was the only factor associated with discontinuation of ChEI.Out of the 63 patients initially started on ChEI, 19 discontinued treatment, and those with fewer years of formal education had higher rates of drug discontinuation at six months.Authors explain this finding by speculating that patients with more years of formal education were better able to understand the importance of treatment persistence and dealing with its side effects.The main limitation of this study is its modest sample size, meaning that type II error cannot be excluded.Also, it is unclear why such a small proportion of all patients evaluated (318) was included in the study.We assume that some individuals referred to this clinic were already on ChEI, and they were excluded, but this cannot be the case for most patients.Nevertheless, this study population represents a "real life"

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