Drugs with anticholinergic effects and cognitive impairment, falls and all-cause mortality in older adults: A systematic review and meta-analysis

Br J Clin Pharmacol. 2015 Aug;80(2):209-20. doi: 10.1111/bcp.12617. Epub 2015 May 20.


Aim: The aim was to investigate associations between drugs with anticholinergic effects (DACEs) and cognitive impairment, falls and all-cause mortality in older adults.

Methods: A literature search using CINAHL, Cochrane Library, Embase and PubMed databases was conducted for randomized controlled trials, prospective and retrospective cohort and case-control studies examining the use of DACEs in subjects ≥65 years with outcomes on falls, cognitive impairment and all-cause mortality. Retrieved articles were published on or before June 2013. Anticholinergic exposure was investigated using drug class, DACE scoring systems (anticholinergic cognitive burden scale, ACB; anticholinergic drug scale, ADS; anticholinergic risk scale, ARS; anticholinergic component of the drug burden index, DBIAC ) or assessment of individual DACEs. Meta-analyses were performed to pool the results from individual studies.

Results: Eighteen studies fulfilled the inclusion criteria (total 124 286 participants). Exposure to DACEs as a class was associated with increased odds of cognitive impairment (OR 1.45, 95% CI 1.16, 1.73). Olanzapine and trazodone were associated with increased odds and risk of falls (OR 2.16, 95% CI 1.05, 4.44; RR 1.79, 95% CI 1.60, 1.97, respectively), but amitriptyline, paroxetine and risperidone were not (RR 1.73, 95% CI 0.81, 2.65; RR 1.80, 95% CI 0.81, 2.79; RR 1.39, 95% CI 0.59, 3.26, respectively). A unit increase in the ACB scale was associated with a doubling in odds of all-cause mortality (OR 2.06, 95% CI 1.82, 2.33) but there were no associations with the DBIAC (OR 0.88, 95% CI 0.55, 1.42) or the ARS (OR 3.56, 95% CI 0.29, 43.27).

Conclusions: Certain individual DACEs or increased overall DACE exposure may increase the risks of cognitive impairment, falls and all-cause mortality in older adults.

Keywords: all-cause mortality; cognitive impairment; drugs with anticholinergic effects; falls; older adults; risk scoring systems.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Accidental Falls* / mortality
  • Aged
  • Aged, 80 and over
  • Bias
  • Cholinergic Antagonists / administration & dosage
  • Cholinergic Antagonists / adverse effects*
  • Cognition Disorders / chemically induced*
  • Cognition Disorders / mortality
  • Female
  • Humans
  • Male


  • Cholinergic Antagonists