A Cohort Study of Anticholinergic Medication Burden and Incident Dementia and Stroke in Older Adults

J Gen Intern Med. 2021 Jun;36(6):1629-1637. doi: 10.1007/s11606-020-06550-2. Epub 2021 Mar 22.


Background: Anticholinergic medications may increase risk of dementia and stroke, but prospective studies in healthy older people are lacking.

Objective: Compare risk of incident dementia and stroke by anticholinergic burden among initially healthy older people.

Design: Prospective cohort study.

Setting: Primary care (Australia and USA).

Participants: 19,114 community-dwelling participants recruited for the ASPREE trial, aged 70+ years (65+ if US minorities) without major cardiovascular disease, dementia diagnosis, or Modified Mini-Mental State Examination score below 78/100.

Measurements: Baseline anticholinergic exposure was calculated using the Anticholinergic Cognitive Burden (ACB) score. Dementia was adjudicated using Diagnostic and Statistical Manual of Mental Disorders volume IV criteria, and stroke using the World Health Organization definition.

Results: At baseline, 15,000 participants (79%) had an ACB score of zero, 2930 (15%) a score of 1-2, and 1184 (6%) a score of ≥ 3 (indicating higher burden). After a median follow-up of 4.7 years and adjusting for baseline covariates, a baseline ACB score of ≥ 3 was associated with increased risk of ischemic stroke (adjusted HR 1.58, 95% CI 1.06, 2.35), or dementia (adjusted HR 1.36, 95% CI 1.01, 1.82), especially of mixed etiology (adjusted HR 1.53, 95% CI 1.06, 2.21). Results were similar for those exposed to moderate/highly anticholinergic medications.

Limitations: Residual confounding and reverse causality are possible. Assessment of dose or duration was not possible.

Conclusions: High anticholinergic burden in initially healthy older people was associated with increased risk of incident dementia and ischemic stroke. A vascular effect may underlie this association. These findings highlight the importance of minimizing anticholinergic exposure in healthy older people.

Trial registration: ClinicalTrials.gov NCT01038583.

Keywords: anticholinergic burden; dementia; potentially inappropriate medication; stroke.

Publication types

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

MeSH terms

  • Aged
  • Australia
  • Cholinergic Antagonists / adverse effects
  • Cohort Studies
  • Dementia* / chemically induced
  • Dementia* / epidemiology
  • Humans
  • Prospective Studies
  • Stroke* / chemically induced
  • Stroke* / diagnosis
  • Stroke* / epidemiology


  • Cholinergic Antagonists

Associated data

  • ISRCTN/ISRCTN83772183
  • ClinicalTrials.gov/NCT01038583