Adam H Dyer1,2, Claire Murphy1, Ricardo Segurado3, Brian Lawlor2,4, Sean P Kennelly1,2. 1. Department of Age-Related Healthcare, Tallaght University Hospital, Dublin. 2. Department of Medical Gerontology, School of Medicine, Trinity College Dublin, Dublin, Ireland. 3. Centre for Support and Training in Analysis and Research (CSTAR), University College Dublin, Dublin, Ireland. 4. Mercer's Institute for Research on Ageing, St James's Hospital, Dublin, Ireland.
Abstract
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.
RCT Entities:
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.
Authors: Martin Taylor-Rowan; Olga Kraia; Christina Kolliopoulou; Anna H Noel-Storr; Ahmed A Alharthi; Amanda J Cross; Carrie Stewart; Phyo K Myint; Jenny McCleery; Terry J Quinn Journal: Cochrane Database Syst Rev Date: 2022-08-22