CONCOMITANT USE OF ANTICHOLINERGIC MEDICATION ATTENUATES BENEFITS OF CHOLINESTERASE INHIBITORS IN ALZHEIMER’S DISEASE: A LARGE COHORT STUDY OF SURVIVAL AND COGNITIVE FUNCTION

Abstract

Acetylcholinesterase inhibitors (AChEIs) are the only licensed treatments in the early stages of Alzheimer's disease (AD). Despite directly opposing AChEIs’ pharmacological actions, anticholinergic drugs (ACDs) are frequently prescribed in people with dementia. Our aim was to investigate predictors of concomitant use of ACHEIs and ACDs, as well as effects on mortality and cognitive decline. A large mental health care database in South London was used to assemble a cohort of patients diagnosed with Alzheimer's disease (AD) prescribed AChEIs. Using logistic regression, we identified predictors of ACD prescription and conducted a survival analysis adjusting for a wide range of potential confounders. Effects of ACD prescription on cognitive decline were studied using Generalized Additive Models for Location, Scale and Shape and Linear Mixed Estimation Models. Of 1990 patients with AD prescribed AChEIs (mean age 81 years, 66% female) almost one third were co-prescribed ACDs. Predictors of ACD prescription were higher levels of social deprivation and difficulties with mental health, physical health, or functioning. The use of ACDs was associated with a 20% increased risk of death in a cox regression model accounting for demographics, deprivation and cognitive scores. This association was no longer significant after adjusting for co-morbidities or functional decline. Among ACD receivers the Mini Mental State Examination (MMSE) score improvement in the 6 months’ post diagnosis was significantly attenuated (slope difference 2.30 MMSE points), but no effect was found on long-term cognitive decline. Comparison of longitudinal change in MMSE