Anticholinergic medication burden and cognitive function in participants of the ASPREE study

Jonathan C. Broder, Joanne Ryan, Raj C. Shah, Jessica E. Lockery, Suzanne G. Orchard, Julia F.M. Gilmartin-Thomas, Michelle A. Fravel, Alice J. Owen, Robyn L. Woods, Rory Wolfe, Elsdon Storey, Anne M. Murray, Michael E. Ernst

Research output: Contribution to journalArticleResearchpeer-review


Study Objective: What is the association between anticholinergic burden and specific domains of cognitive function in older adults who are initially without major cognitive impairment?. Design: Post-hoc analysis of longitudinal observational data from the ASPirin in Reducing Events in the Elderly (ASPREE) study. Patients: 19,114 participants from Australia and the United States aged 70 years and older (65 years and older for US minorities) were recruited and followed for a median of 4.7 years. At enrollment, participants were free of known cardiovascular disease, major physical disability, or dementia. Measurements: Cognitive assessments administered at baseline and biennially at follow-up visits included the Modified Mini-Mental State examination (3MS), Hopkins Verbal Learning Test–Revised (HVLT-R) delayed recall, Controlled Oral Word Association Test (COWAT), and Symbol Digit Modalities Test (SDMT). Anticholinergic burden was calculated at baseline using the Anticholinergic Cognitive Burden (ACB) scale and grouped as scores of 0 (no burden), 1-2 (low to moderate), or 3+ (high). Main Results: Linear mixed effects models were used to assess the relationship between ACB score and cognition over time. After adjusting for sex, age, education, minority status, smoking status, hypertension, diabetes, depression, chronic kidney disease, country, and frailty, participants with a high ACB score had worse performance over time for 3MS (Adjusted [Adj] B=-0.092, P=0.034), HVLT-R delayed recall (Adj B=-0.104, P<0.001), COWAT (Adj B=-0.151, P<0.001), and SDMT (Adj B=-0.129, P=0.026), than participants with an ACB score of 0. A low to moderate ACB score was also associated with worse performance over time for HVLT-R delayed recall (Adj B=-0.037, P=0.007) and COWAT (Adj B=-0.065, P=0.003), compared to those with no ACB. Conclusions: Anticholinergic burden predicts worse cognitive function over time in initially dementia-free older adults, particularly for executive function (COWAT) and episodic memory (HVLT-R).

Original languageEnglish
Pages (from-to)134-144
Number of pages11
Issue number2
Publication statusPublished - Feb 2022


  • Anticholinergic Cognitive Burden
  • anticholinergic medications
  • dementia
  • episodic memory
  • executive function
  • global cognition
  • processing speed

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