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Cognitive Outcomes of Long-term Benzodiazepine and Related Drug (BDZR) Use in People Living With Mild to Moderate Alzheimer's Disease: Results From NILVAD

Maria A. Berglund Jurgen A. Claassen Rianne A. de Heus Daan L. K. de Jong Olivier Godefroy 1, 2 Siobhan Hutchinson Aikaterini Ioannou Michael Jonsson Annette Kent Jrgen Kern Petros Nemtsas Minoa-Kalliopi Panidou Laila Abdullah Daniel Paris Angelina M. Santoso Gerrita J. Van Spijker Martha Spiliotou Georgia Thomoglou Anders Wallin 3 Adam H. Dyer Claire Murphy Brian Lawlor Sean P. Kennelly Ricardo Segurado 4 Sean Kennelly Marcel G. M. Olde Rikkert Robert Howard 5 Florence Pasquier 6, 7, 8 Anne Brjesson-Hanson Magda Tsolaki 9 Ugo Lucca 10 D. William Molloy Robert Coen Matthias W. Riepe Janos Kalman Rose Anne Kenny Fiona Cregg Sarah O'Dwyer Cathal Walsh Jessica Adams Rita Banzi 11 Laetitia Breuilh Leslie Daly Suzanne Hendrix Paul Aisen 12 Siobhan Gaynor 13 Ali Sheikhi Diana G. Taekema Frans R. Verhey Raffaello Nemni 14 Flavio Nobili 15 Massimo Franceschi 16 Giovanni Frisoni 17, 18 Orazio Zanetti 19 Anastasia Konsta Orologas Anastasios Styliani Nenopoulou Fani Tsolaki-Tagaraki Magdolna Pakaski Olivier Dereeper Vincent de La Sayette Olivier Senechal 20 Isabelle Lavenu Agnes Devendeville Gauthier Calais Fiona Crawford Michael Mullan Pauline Aalten 21 
Abstract : Objective: Benzodiazepines and related drugs (BDZRs) have been associated with an increased risk of Alzheimer's disease (AD) in later life. Despite this, it remains unclear whether ongoing BDZR use may further accelerate cognitive decline in those diagnosed with mild to moderate AD. Design: This study was embedded within NILVAD, a randomized controlled trial of nilvadipine in mild to moderate AD. Cognition was measured at baseline and 18 months using the Alzheimer Disease Assessment Scale, Cognitive Subsection (ADAS-Cog). We assessed predictors of long-term BDZR use and analyzed the effect of ongoing BDZR use on ADAS-Cog scores at 18 months. Additionally, the impact of BDZR use on adverse events, incident delirium, and falls over 18-month follow-up was assessed adjusting for relevant covariates. Setting and Participants: 448 participants with mild to moderate AD recruited from 23 academic centers in 9 European countries. Results: Overall, 14% (62/448) were prescribed an ongoing BDZR for the study duration. Increasing total number of (non-BDZR) medications was associated with a greater likelihood of BDZR prescription (odds ratio 1.16, 95% confidence interval 1.05-1.29). At 18 months, BDZR use was not associated with greater cognitive decline on the ADAS-Cog controlling for baseline ADAS-Cog scores, age, gender, study arm, and other clinical covariates (beta = 1.62, -1.34 to 4.56). However, ongoing BDZR use was associated with a greater likelihood of adverse events [incidence rate ratio (IRR) 1.19, 1.05-1.34], incident delirium (IRR 2.31, 1.45-3.68), and falls (IRR 1.66, 1.02-2.65) over 18 months that persisted after robust adjustment for covariates. Conclusions and Implications: This study found no effect of ongoing BDZR use on ADAS-Cog scores in those with mild to moderate AD over 18 months. However, ongoing use of these medications was associated with an increased risk of adverse events, delirium, and falls. Thus, BDZR use should be avoided where possible and deprescribing interventions should be encouraged in older adults with AD. (C) 2019 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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Soumis le : samedi 12 mars 2022 - 12:10:57
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Maria A. Berglund, Jurgen A. Claassen, Rianne A. de Heus, Daan L. K. de Jong, Olivier Godefroy, et al.. Cognitive Outcomes of Long-term Benzodiazepine and Related Drug (BDZR) Use in People Living With Mild to Moderate Alzheimer's Disease: Results From NILVAD. Journal of the American Medical Directors Association, Elsevier, 2020, 21 (2), pp.194-200. ⟨10.1016/j.jamda.2019.08.006⟩. ⟨hal-03606786⟩



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