TY - JOUR
T1 - Sedative Load in Community-Dwelling Older Adults with Mild–Moderate Alzheimer’s Disease
T2 - Longitudinal Relationships with Adverse Events, Delirium and Falls
AU - NILVAD Study Group
AU - Dyer, Adam H.
AU - Murphy, Claire
AU - Lawlor, Brian
AU - Kennelly, Sean P.
AU - Segurado, Ricardo
AU - Olde Rikkert, Marcel G.M.
AU - Howard, Robert
AU - Pasquier, Florence
AU - Börjesson-Hanson, Anne
AU - Tsolaki, Magda
AU - Lucca, Ugo
AU - Molloy, D. William
AU - Coen, Robert
AU - Riepe, Matthias W.
AU - Kálmán, János
AU - Kenny, Rose Anne
AU - Cregg, Fiona
AU - O'Dwyer, Sarah
AU - Walsh, Cathal
AU - Adams, Jessica
AU - Banzi, Rita
AU - Breuilh, Laetitia
AU - Daly, Leslie
AU - Hendrix, Suzanne
AU - Aisen, Paul
AU - Gaynor, Siobhan
AU - Sheikhi, Ali
AU - Taekema, Diana G.
AU - Verhey, Frans R.
AU - Nemni, Raffaello
AU - Nobili, Flavio
AU - Franceschi, Massimo
AU - Frisoni, Giovanni
AU - Zanetti, Orazio
AU - Konsta, Anastasia
AU - Anastasios, Orologas
AU - Nenopoulou, Styliani
AU - Tsolaki-Tagaraki, Fani
AU - Pakaski, Magdolna
AU - Dereeper, Olivier
AU - Sayette, Vincent de la
AU - Sénéchal, Olivier
AU - Lavenu, Isabelle
AU - Devendeville, Agnès
AU - Calais, Gauthier
AU - Crawford, Fiona
AU - Mullan, Michael
AU - Aalten, Pauline
AU - Berglund, Maria A.
AU - Claassen, Jurgen A.
N1 - Publisher Copyright:
© 2020, Springer Nature Switzerland AG.
PY - 2020/11/1
Y1 - 2020/11/1
N2 - Background: Older adults are frequently prescribed medications with sedative effects, which are associated with numerous adverse consequences. However, the prevalence and longitudinal associations of sedative medication use in community-dwelling older adults with mild–moderate Alzheimer’s disease (AD) has not been explored to date. Objectives: Our objective was to assess the prevalence of sedative medication use in community-dwelling older adults with mild–moderate AD and examine the longitudinal association between sedative medication use and adverse events (AEs). Methods: The association between baseline sedative load (SL) and AEs, unscheduled healthcare utilisation, delirium and falls was assessed in older adults with mild–moderate AD over 18 months using secondary analysis of NILVAD trial data (collected from 2014 to 2016). Baseline medication use was assessed, and the SL model was applied to each participant’s medication individually. The SL model classifies medications into one of four categories: (1) primary sedatives, (2) medications with a sedating component or prominent side effect, (3) medications with sedation as a potential adverse reaction and (4) all other medications with no known sedative side effects. Medications in group 1 were assigned an SL score of 2, those in group 2 were assigned an SL score of 1, and those in categories 3 and 4 an SL score of 0. SL scores for each medication participants were taking were summed and the total SL calculated as an arithmetic sum of individual medications score. A total SL score ≥ 3 was classed as high. Statistical analysis was conducted using Poisson regression and mixed-effects linear regression, with adjustment for important clinical covariates. We also assessed the impact of SL on dementia progression and cognitive decline. Results: Over half (55.7% [284/510]) of those with mild–moderate AD (age 72.8 ± 8.3 years, 61.9% female) were prescribed a regular medication with sedation as a primary effect or prominent side effect, with 22.2% (113/510) having a high SL (≥ 3). The most common medications contributing to SL were antidepressants, antipsychotics, anxiolytics and hypnotics. Over 18 months, increasing baseline SL was associated with incident AEs (incidence rate ratio [IRR] 1.15; 95% confidence interval [CI] 1.11–1.19; p < 0.001), serious AEs (IRR 1.23; 95% CI 1.11–1.36; p < 0.001) and unscheduled general practitioner visits (IRR 1.23; 95% CI 1.13–1.34; p < 0.001). Further, increasing SL was associated with a greater likelihood of incident delirium (IRR 1.30; 95% CI 1.11–1.53; p < 0.001) and falls (IRR 1.20; 95% CI 1.03–1.42; p = 0.02). Associations persisted after robust covariate adjustment. SL was not associated with accelerated cognitive decline or AD progression. Conclusions: In the current study, over half of older adults with mild–moderate AD were prescribed at least one drug with a sedative effect, and a significant minority had a high SL. Increasing baseline SL was associated with a greater likelihood of incident AEs, delirium and falls, highlighting the need for optimal prescribing in this potentially vulnerable cohort.
AB - Background: Older adults are frequently prescribed medications with sedative effects, which are associated with numerous adverse consequences. However, the prevalence and longitudinal associations of sedative medication use in community-dwelling older adults with mild–moderate Alzheimer’s disease (AD) has not been explored to date. Objectives: Our objective was to assess the prevalence of sedative medication use in community-dwelling older adults with mild–moderate AD and examine the longitudinal association between sedative medication use and adverse events (AEs). Methods: The association between baseline sedative load (SL) and AEs, unscheduled healthcare utilisation, delirium and falls was assessed in older adults with mild–moderate AD over 18 months using secondary analysis of NILVAD trial data (collected from 2014 to 2016). Baseline medication use was assessed, and the SL model was applied to each participant’s medication individually. The SL model classifies medications into one of four categories: (1) primary sedatives, (2) medications with a sedating component or prominent side effect, (3) medications with sedation as a potential adverse reaction and (4) all other medications with no known sedative side effects. Medications in group 1 were assigned an SL score of 2, those in group 2 were assigned an SL score of 1, and those in categories 3 and 4 an SL score of 0. SL scores for each medication participants were taking were summed and the total SL calculated as an arithmetic sum of individual medications score. A total SL score ≥ 3 was classed as high. Statistical analysis was conducted using Poisson regression and mixed-effects linear regression, with adjustment for important clinical covariates. We also assessed the impact of SL on dementia progression and cognitive decline. Results: Over half (55.7% [284/510]) of those with mild–moderate AD (age 72.8 ± 8.3 years, 61.9% female) were prescribed a regular medication with sedation as a primary effect or prominent side effect, with 22.2% (113/510) having a high SL (≥ 3). The most common medications contributing to SL were antidepressants, antipsychotics, anxiolytics and hypnotics. Over 18 months, increasing baseline SL was associated with incident AEs (incidence rate ratio [IRR] 1.15; 95% confidence interval [CI] 1.11–1.19; p < 0.001), serious AEs (IRR 1.23; 95% CI 1.11–1.36; p < 0.001) and unscheduled general practitioner visits (IRR 1.23; 95% CI 1.13–1.34; p < 0.001). Further, increasing SL was associated with a greater likelihood of incident delirium (IRR 1.30; 95% CI 1.11–1.53; p < 0.001) and falls (IRR 1.20; 95% CI 1.03–1.42; p = 0.02). Associations persisted after robust covariate adjustment. SL was not associated with accelerated cognitive decline or AD progression. Conclusions: In the current study, over half of older adults with mild–moderate AD were prescribed at least one drug with a sedative effect, and a significant minority had a high SL. Increasing baseline SL was associated with a greater likelihood of incident AEs, delirium and falls, highlighting the need for optimal prescribing in this potentially vulnerable cohort.
UR - http://www.scopus.com/inward/record.url?scp=85092553918&partnerID=8YFLogxK
U2 - 10.1007/s40266-020-00800-y
DO - 10.1007/s40266-020-00800-y
M3 - Article
C2 - 32924095
AN - SCOPUS:85092553918
SN - 1170-229X
VL - 37
SP - 829
EP - 837
JO - Drugs and Aging
JF - Drugs and Aging
IS - 11
ER -