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)

1 LNFP - Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559
2 Service de Neurologie, CHU Amiens-Picardie
3 GU - University of Gothenburg
4 Department of Psychiatry
5 Institute of Psychiatry
6 CHU Lille
7 LilNCog - Lille Neurosciences & Cognition - U 1172
8 CMRR - Centre Mémoire de Ressources et de Recherche [Lille-Bailleul]
9 Aristotle University of Thessaloniki
10 Istituto di Ricerce Farmacologiche Mario Negri
11 IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri" [Milan, Italy]
12 USD - University of San Diego
13 ICRIN - Irish Clinical Research Infrastructures Network
14 Unità operativa di neurologia riabilitativa, Centro IRCCS Santa Maria Nascente"
15 UniGe - Università degli studi di Genova = University of Genoa
16 Multimedica-Santa Maria, Castellanza
17 UNIGE - Université de Genève = University of Geneva
18 Istituto Centro San Giovanni di Dio Fatebenefratelli
19 IRCCS San Giovanni di Dio Fatebenefratelli
20 LAMIH - Laboratoire d'Automatique, de Mécanique et d'Informatique industrielles et Humaines - UMR 8201
21 Maastricht University [Maastricht]

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.

Domaines: Sciences du Vivant [q-bio]

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, 2020, 21 (2), pp.194-200. ⟨10.1016/j.jamda.2019.08.006⟩. ⟨hal-03606786⟩