Predictive Factors of Discontinuation and Switch of Cholinesterase Inhibitors in Community-Dwelling Patients with Alzheimer's Disease A 2-Year Prospective, Multicentre, Cohort Study

Background: The efficacy of cholinesterase inhibitors (ChEIs), especially over the long term, is still under discussion. There is a lack of data concerning the optimal drug treatment duration and the reasons for discontinuation, particularly outside the clinical trial setting. Objective: To identify predictive factors of discontinuation and switch of ChEIs in a real-world setting. Methods: A multicentre cohort study of 686 patients with mild-to-moderate ambulatory Alzheimer's disease who were diagnosed in 16 Alzheimer's disease expert centres in 2000-2 and who were assessed twice yearly for 2 years. The main outcome measure was ChEI discontinuation and switch (analysed using Cox survival analyses). Results: After 2 years, of the 611 subjects treated with a ChEI at baseline, 100 subjects had switched or discontinued ChEI therapy (incidence rate 12.7 [95% CI 10.2, 15.2] per 100 person-years). The incidences of switching and discontinuation were 9.2 (95% CI 7.0, 11.3) and 3.6 (95% CI 2.3, 4.8) per 100 person-years, respectively. In the multivariate analysis, predictive factors for switching were an ineffective ChEI dose (adjusted hazard ratio [HRa] = 6.91, 95% CI 3.08, 15.49), rapid cognitive decline (HRa = 4.10, 95% CI 1.85, 9.05), hospitalization unrelated to Alzheimer's disease (HRa = 2.33, 95% CI 1.07, 5.09) and anxiety (HRa 2.08, 95% CI 1.16, 3.73). Predictive factors of discontinuation were: hospitalization related (HRa = 9.14, 95% CI 2.69, 31.07) or unrelated (HRa = 4.23, 95% CI 1.54, 11.59) to Alzheimer's disease, use of an anticholinergic drug (HRa = 4.26, 95% CI 1.46, 12.45) and weight loss (HRa = 3.77, 95% CI 1.15, 12.33). Conclusions: This study highlights four types of predictors of switch or discontinuation, reflecting disease progression, reconsideration of ChEI benefits, adverse drug reactions to ChEIs and inappropriate concurrent use of anticholinergic drugs. Attention should be paid to anticholinergic agents and prescribers should be given better information about these drugs.