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

https://doi.org/10.1016/j.jamda.2019.08.006Get rights and content

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 (β = 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.

Section snippets

Methods

This is a longitudinal analysis of data from NILVAD, a Europe-wide, multicenter randomized clinical trial of the antihypertensive nilvadipine in mild to moderate AD. We examined the relationship between ongoing BDZR use and cognitive function at 18-month follow-up in addition to the effect of BDZR use on adverse events, delirium, and falls at 18 months.

Study Participants

Of 448 participants, just under two-thirds (62.28%) were female and mean age was 72.46 years [standard deviation (SD) 8.2]. Median number of years since AD diagnosis was 1.09 years [interquartile range (IQR) 0.47-2.26] and the median years since AD symptom onset was 3.7 years (IQR 2.45-5.42). In terms of cognitive profile, the median MMSE score of included patients at initial assessment was 21 (IQR 18-24) and the mean baseline ADAS-Cog score was 34.08 (SD 10.53). Based on initial MMSE

Discussion

This is the first study to our knowledge to assess the cognitive consequences of ongoing BDZR use in patients with mild to moderate AD. We found no association between ongoing BDZR use and cognitive scores (ADAS-Cog) at 18 months. However, ongoing use of BDZR medication was associated with adverse events, incident delirium, and falls. Thus, consistent with previous literature, these results support avoidance of BDZR drugs (where possible) in older adults with AD.

The prevalence of ongoing BDZR

Conclusion and Implications

The current study found that ongoing BDZR use in those with mild to moderate AD was not associated with accelerated cognitive decline. However, use was significantly associated with adverse events, incident delirium, and falls. Our results add to the mounting evidence of the adverse consequences of ongoing BDZR use in this population and support previous guidelines aimed at discontinuation in older adults, particularly in those with AD.

Acknowledgments

NILVAD Study Group

Brian Lawlor, Mercer's Institute for Research on Ageing, St. James's Hospital and Department of Medical Gerontology, Trinity College, Dublin, Ireland; Ricardo Segurado, CSTAR and School of Public Health, Physiotherapy and Sport Science, University College Dublin (UCD), Dublin, Ireland; Sean Kennelly, Department of Age Related Healthcare, Tallaght Hospital, Dublin 24, and Department of Medical Gerontology, Trinity College Dublin; Marcel G. M. Olde Rikkert, Department of

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    Funding from the NILVAD study was from the European Commission Framework 7 Programme Health Theme Collaborative Project (grant 279093; PI: Brian Lawlor).

    The authors declare no conflicts of interest.

    The full author list of the NILVAD Study Group is listed at the end of the article.

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