Effect of anticholinergic burden on treatment modification, delirium and mortality in newly diagnosed dementia patients starting a cholinesterase inhibitor: A population-based study

Basic Clin Pharmacol Toxicol. 2019 Jun;124(6):741-748. doi: 10.1111/bcpt.13184. Epub 2019 Jan 10.

Abstract

Few studies have evaluated the association between anticholinergic burden and treatment modification after starting a cholinesterase inhibitor in clinical practice. We aimed to evaluate the effect of anticholinergic burden on anti-dementia treatment modification, delirium and mortality. We retrospectively analysed older adults (n = 25 825) who started a cholinesterase inhibitor during 2003-2011 from Korean National Health Insurance Service Senior Cohort Database. High anticholinergic burden was defined as an average daily Anticholinergic Cognitive Burden (ACB) score of >3 during the first 3 months. We investigated the impact of high anticholinergic burden on the rate of treatment modification, delirium and mortality in comparison with minimal ACB (ACB score ≤1) in propensity-matched cohorts (N = 7438). Approximately 6.0% of patients with dementia were exposed to a high anticholinergic burden within the first three months of treatment. In high anticholinergic burden cohorts, significantly more patients experienced treatment modification (34.9% vs. 32.1%) or delirium (5.6% vs. 3.6%) and the mortality rate was also higher (16.8% vs. 14.1%) than controls. A multivariate Cox proportional hazard regression analysis showed that an average ACB score >3 within the first three months significantly increased the risk of treatment modification (hazard ratio (HR): 1.12, 95% confidence interval (CI): 1.02-1.24), delirium (HR: 1.52, CI: 1.17-1.96) and mortality (HR: 1.23, CI: 1.06-1.41). This study showed that high anticholinergic burden negatively affected the treatment response to cholinesterase inhibitors and that an average ACB score >3 was an independent prognostic factor for delirium or mortality in dementia patients.

Keywords: Alzheimer’s disease; anticholinergics; cholinesterase inhibitors; delirium; mortality.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cholinergic Antagonists / adverse effects*
  • Cholinesterase Inhibitors / therapeutic use*
  • Cognitive Dysfunction / chemically induced
  • Cohort Studies
  • Delirium / chemically induced*
  • Delirium / epidemiology
  • Dementia / drug therapy*
  • Dementia / epidemiology
  • Female
  • Hospitalization
  • Humans
  • Male
  • Mortality*
  • Republic of Korea / epidemiology
  • Retrospective Studies

Substances

  • Cholinergic Antagonists
  • Cholinesterase Inhibitors