Anticholinergic burden and cognitive decline: findings from the ELSA‐Brasil cohort study

Abstract Background Using multiple drugs with anticholinergic properties is common and might lead to cumulative anticholinergic toxicity and increased risk of cognitive decline. The cumulative adverse effects of anticholinergic medications that a person takes are called the “anticholinergic burden”. We hypothesized that a high anticholinergic burden may be a risk factor for cognitive decline. We aimed to investigate the longitudinal association between Anticholinergic Cognitive Burden (ACB) and cognitive decline in the ELSA‐Brasil study during eight years of follow‐up. Method Participants were evaluated in three study waves (2008‐2010, 2012‐2014, and 2017‐2019). The ACB was calculated based on the medications in use. Cognitive performance was evaluated using a standardized battery of tests (immediate recall, late recall, recognition, semantic and phonemic verbal fluency, and the trail‐making tests). A global composite z‐score was derived from these tests. The association of ACB with cognitive performance over time was evaluated using linear mixed‐effects models, adjusted for sociodemographic and clinical variables. Result A total of 15,105 participants were recruited and 2,040 were excluded, leaving 13,065 participants whose data were analyzed. Participants had a mean age of 51.7±9.0 years old, 55% were women, and 53% were white. During the follow‐up time, the ACB burden was associated with a decline in global cognition (β = ‐0.001, 95% CI = ‐0.013, ‐0.002, p = 0.004), memory performance (β = ‐0.002, 95% CI = ‐0.002, 0.000, p = 0.044) and executive function (β = ‐0.002, 95% CI = ‐0.004, 0.000, p = 0.014). Conclusion During eight years of follow‐up, the ACB burden was associated with cognitive decline, particularly in the memory and executive function domains.