A 2-year prospective cohort study of antidementia drug non-persistency in mild-to-moderate Alzheimer's disease in Europe : predictors of discontinuation and switch in the ICTUS study

CNS Drugs. 2014 Feb;28(2):157-70. doi: 10.1007/s40263-013-0133-3.


Background: There is no consensus on when and how to discontinue cholinesterase inhibitors (ChEI). Predictors of non-persistency of antidementia drugs have been poorly investigated, mostly during short-term periods and using administrative data.

Objective: The aim of this study was to investigate the incidence and predictors of ChEI switch and discontinuation among subjects with ascertained Alzheimer's disease (AD).

Methods: A total of 557 community-dwelling, mild-to-moderate AD subjects initiating ChEIs in 29 European clinic centres were assessed twice-yearly for 2 years. Antidementia drug exposure was recorded through a physician-administered structured questionnaire to document any change in drug therapy (start and stop dates, reasons). Discontinuation was defined as >35 days without any antidementia drug. Switch was defined as a change for any antidementia drug strategy within 35 days after ChEI cessation. Two separate time-dependent multivariate Cox survival analyses were conducted to identify predictors of discontinuation and switch.

Results: The incidences of discontinuation and switch were 9.65 and 12.47/100 person-years, respectively. Behavioural disturbances, low body mass index, falls, decline in Mini-Mental State Examination (MMSE) score, and AD-related hospitalization predicted discontinuation. MMSE score, decline in activities of daily living score, aberrant motor behaviour, shorter AD duration and higher nurse resource use predicted a switch. An ineffective ChEI dose and clinic specialty predicted both outcomes. Sensitivity analyses using a 60-day cut-off provided stable results.

Conclusion: Several predictors were identified: adverse drug events and their predisposing factors, perceived loss of efficacy or disease progression on cognitive or functional scales, behavioural disturbances, hospitalization and professional practices. The latter implies a need for harmonization in AD drug prescription practice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / epidemiology
  • Cholinesterase Inhibitors / administration & dosage
  • Cholinesterase Inhibitors / adverse effects
  • Cholinesterase Inhibitors / therapeutic use*
  • Cohort Studies
  • Europe
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Medication Adherence / statistics & numerical data*
  • Neuropsychological Tests
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Severity of Illness Index


  • Cholinesterase Inhibitors