Effect of anticholinergic burden on treatment modification, delirium and mortality in newly diagnosed dementia patients starting a cholinesterase inhibitor: A population‐based study

Abstract

Few studies have evaluated the association between anticholinergic burden and treatment modification after starting a cholinesterase inhibitor in clinical practice.We aimed to evaluate the effect of anticholinergic burden on anti-dementia treatment modification, delirium and mortality. We retrospectively analysed older adults (n = 25 825) who started a cholinesterase inhibitor during 2003-2011 from Korean National Health Insurance Service Senior Cohort Database. High anticholinergic burden was defined as an average daily Anticholinergic Cognitive Burden (ACB) score of >3 during the first 3 months. We investigated the impact of high anticholinergic burden on the rate of treatment modification, delirium and mortality in comparison with minimal ACB (ACB score ≤1) in propensitymatched cohorts (N = 7438). Approximately 6.0% of patients with dementia were exposed to a high anticholinergic burden within the first three months of treatment. In high anticholinergic burden cohorts, significantly more patients experienced treatment modification (34.9% vs. 32.1%) or delirium (5.6% vs. 3.6%) and the mortality rate was also higher (16.8% vs. 14.1%) than controls. A multivariate Cox proportional hazard regression analysis showed that an average ACB score >3 within the first three months significantly increased the risk of treatment modification (hazard ratio (HR): 1.12, 95% confidence interval (CI): 1.02-1.24), delirium (HR: 1.52, CI: 1.17-1.96) and mortality (HR: 1.23, CI: 1.06-1.41). This study showed that high anticholinergic burden negatively affected the treatment response to cholinesterase inhibitors and that an average ACB score >3 was an independent prognostic factor for delirium or mortality in dementia patients.

Anticholinergics and Benzodiazepines on Cognitive Impairment among Elderly with Alzheimer’s Disease: a One year Follow-Up Study

“…Despite the fact that robust evidence exists regarding how ACs can affect both cognition and AChEIs per se due to pharmacodynamics interactions, based on their opposing mechanisms of action [17], most were from cross-sectional and short term follow-up study. A recent 36-month follow-up research showed that high anticholinergic burden negatively affected the treatment response to cholinesterase inhibitors and that an average ACB score >3 was an independent prognostic factor for delirium or mortality among dementia patients [18]. However, no clear relationships between ACs and the change of cognition were noted in this study.…”

Anticholinergic drug use and risk of mortality for people with dementia in Northern Ireland

“…Further observational (cohort and case control) studies have described an associated with anticholinergic medication and increased mortality in people without dementia (Cross et al, 2017;Gray et al, 2015) and people with dementia (Gray et al, 2015;Gray & Hanlon, 2016). For instance in a study of 25,825 people with dementia, researchers found that higher anticholinergic burden significantly increased mortality rates (Ah, Suh, Jun, Hwang, & Lee, 2019). Furthermore, anticholinergic burden has been shown to negatively affect the treatment response to cholinesterase inhibitors (Ah et al, 2019;Carnahan, Lund, Perry, & Chrischilles, 2004;Palmer et al, 2015).…”

Are antidementia drugs associated with reduced mortality after a hospital emergency admission in the population with dementia aged 65 years and older?

“…Increased anticholinergic burden has been associated with increased risk of mortality in older patients [42] . Associations have been identified between anticholinergic medications and increased dementia risk [43] and between anticholinergic burden and mortality in people with dementia [44] . Our results did not identify an association between anticholinergic burden and mortality risk in patients with dementia.…”