Factors associated with response to acetylcholinesterase inhibition in dementia: a cohort study from a secondary mental health care case register in london

PLoS One. 2014 Nov 20;9(11):e109484. doi: 10.1371/journal.pone.0109484. eCollection 2014.


Background: Acetylcholinesterase inhibitors (AChEIs) are widely used to delay cognitive decline in Alzheimer's disease. Observational studies in routine clinical practice have shown cognitive improvement in some groups of patients receiving these agents but longitudinal trajectories before and after AChEI initiation have not previously been considered.

Objectives: To compare trajectories of cognitive function before and after AChEI initiation and investigate predictors of these differences.

Method: A retrospective longitudinal study was constructed using data from 2460 patients who received AChEIs and who had routine data on cognitive function (Mini-Mental State Examination; MMSE) before and after AChEI initiation. Longitudinal MMSE change was modelled using three-piece linear mixed models with the following segments: 0-12 months prior to AChEI initiation, 0-6 months and 6-36 months after initiation.

Results: MMSE decline was reversed (in that the slope was improved by an average 4.2 units per year, 95% CI 3.5-4.8) during the 6-month period following AChEI initiation compared with the slope in the one year period before AChEI initiation. The slope in the period from 6-36 months following AChEI initiation returned to the pre-initiation downward trajectory. The differences in slopes in the 1 year period prior to AChEI initiation and in the 6 months after initiation were smaller among those with higher MMSE scores at the time of AChEI initiation, among those who received a vascular dementia diagnosis at any point, and among those receiving antipsychotic agents.

Conclusion: In this naturalistic observational study, changes in cognitive trajectories around AChEI initiation were similar to those reported in randomised controlled trials. The magnitude of the difference in slopes between the 1 year period prior to AChEI initiation and the 6 month period after AChEI initiation was related to level of cognitive function at treatment initiation, vascular comorbidity and antipsychotic use.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cholinesterase Inhibitors / therapeutic use*
  • Cognition / drug effects*
  • Dementia / drug therapy*
  • Dementia / psychology*
  • Female
  • Humans
  • London
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Registries
  • Retrospective Studies


  • Cholinesterase Inhibitors

Grant support

The data resource and all authors are funded by the National Institute for Health Research (NIHR) Biomedical Research Centre and Dementia Biomedical Research Unit at South London and Maudsley NHS Foundation Trust and King's College London. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.