Is Ongoing Anticholinergic Burden Associated With Greater Cognitive Decline and Dementia Severity in Mild to Moderate Alzheimer’s Disease?

BACKGROUND: Use of anticholinergic medication is associated with an increased risk of cognitive impairment and/or dementia. Despite this, the impact of continuing medication with anticholinergic properties in those diagnosed with Alzheimer's Disease (AD) is not clear. METHODS: Analysis of data from NILVAD, an 18-month randomized controlled trial of Nilvadipine in AD. Effects of ongoing Anticholinergic Cognitive Burden (ACB) on cognition (ADAS-Cog: Alzheimer's Disease Cog Subsection) and dementia severity (CDR-sb: Clinical Dementia Rating - Sum of Boxes/DAD: Disability Assessment for Dementia) over 18 months was evaluated adjusting for important clinical covariates. RESULTS: Just over one-quarter (27.90%, n = 142/510) of patients with mild to moderate AD were prescribed a potential/definite anticholinergic. While ACB score was not associated with greater progression on the ADAS-Cog/CDR-sb over time, a higher total ACB predicted greater dementia severity on the DAD, which persisted after robust covariate adjustment (β Coef: -1.53, 95% CI: -2.83 to -0.23, p = .021). There was a significant interaction between APOE ε4 status and ACB score, with carriers experiencing greater progression on both the CDR-Sb (β Coef: 0.36, 95% CI: 0.05-0.67, p = .021) and DAD (β Coef: -3.84, 95% CI: -7.65 to 0.03, p = .049). CONCLUSIONS: Ongoing use of anticholinergic medication was associated with greater dementia progression on the DAD, but not the CDR-sb. APOE ε 4 carriers may be particularly vulnerable to the effect of ongoing anticholinergic medication on dementia severity, with significant APOE ε 4 x ACB score interactions demonstrated on both the DAD and CDR-sb.