Sedative Load in Community-Dwelling Older Adults with Mild-Moderate Alzheimer's Disease: Longitudinal Relationships with Adverse Events, Delirium and Falls

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.