Anticholinergic burden and risk of cognitive impairment in elderly nursing home residents with depression

Res Social Adm Pharm. 2020 Mar;16(3):329-335. doi: 10.1016/j.sapharm.2019.05.020. Epub 2019 May 28.


Background: Although the adverse cognitive effects of anticholinergic medications in the elderly are well-documented, little is known regarding the cognitive impact of anticholinergics among nursing home residents with depression.

Objective: This study examined the risk of mild-to-moderate cognitive impairment due to anticholinergic burden among elderly nursing home residents with depression.

Methods: A population-based nested case-control study was conducted using Minimum Data Set (MDS)-linked Medicare data where the base cohort included patients ≥ 65 years with depression who had intact cognition (MDS Cognition score of 0 or 1) and no dementia. Cases were identified as those who had mild-to-moderate cognition (MDS Cognition score of 2-4). Each case was matched on age and sex to one control using incidence density sampling. The study evaluated cumulative anticholinergic burden (defined as score of 3 or more) within 30, 60 and 90 days preceding the event date based on the Anticholinergic Drug Scale (ADS). Conditional logistic regression model stratified on matched case-control sets was performed to evalaute cognitive impairment due to cumulative anticholinergic burden after controlling for other risk factors.

Results: The study sample included 3707 cases with mild-to-moderate cognition and 3707 matched controls with intact cognition. Bivariate analysis showed significant association between cumulative anticholinergic exposure and cognitive impairment (Odds Ratio [OR], 1.15; 95% Confidence Interval [CI],1.04-1.30); after controlling for potential risk factors, cumulative anticholinergic exposure 30 days preceding the event was no longer associated with cognitive impairment, (aOR, 1.07; 95% CI, 0.95-1.21). However, the odds of cognitive impairment increased with cumulative anticholinergic exposure 60 days (aOR 1.16; 1.04-1.30) and 90 days (aOR 1.28; 1.14-1.44) before the event date.

Conclusion: Cumulative anticholinergic use for prolonged exposure periods was associated with modestly increased risk of cognitive impairment in elderly residents with depression who had intact cognition. The findings suggest the need to be cautious when prescribing multiple anticholinergic drugs in residents, including those with intact cognition.

Keywords: Anticholinergic; Depression; Elderly; Mild-to-moderate cognitive impairment; Nursing homes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Case-Control Studies
  • Cholinergic Antagonists* / adverse effects
  • Cognitive Dysfunction* / chemically induced
  • Cognitive Dysfunction* / epidemiology
  • Depression / chemically induced
  • Depression / drug therapy
  • Depression / epidemiology
  • Humans
  • Medicare
  • Nursing Homes
  • United States / epidemiology


  • Cholinergic Antagonists