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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
Dyer AH, Murphy C, Lawlor B, Kennelly SP, NILVAD Study Group.. Journal of the American Medical Directors Association, 2019-10-08
Topic: Amyloid, tau and blood-test diagnosis
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.
Key findings
- Objective Benzodiazepines and related drugs (BDZRs) have been associated with an increased risk of Alzheimer's disease (AD) in later life.
- 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.
Why it matters
In this study, ongoing use of benzodiazepines and related drugs was not associated with greater cognitive decline over 18 months in people with mild to moderate Alzheimer disease. It addresses whether these medications worsen decline, not whether they treat, cure or prevent the disease.
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Study details
- Study designrandomized controlled trial
- Participants448
- Effect sizeRR 2.31; RR 1.66
- Evidence strengthHigh
How this study scored 64/100
Published in a peer-reviewed journal, and it is a randomised controlled trial.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of the American Medical Directors Association) |
| Journal's citation record | 2 / 4 | Journal of the American Medical Directors Association: journal h-index 172 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 448 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 3 / 7 | Cited 38 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.8 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 2 / 6 | Cited 2.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 17 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Anders Wallin: h-index 72 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Geneva: institution h-index 1,049 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 18 institution(s) in 8 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31604674) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 64 / 100 | — |
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APA 7th
Dyer, A. H., Murphy, C., Lawlor, B., Kennelly, S. P., & NILVAD Study Group. (2020). 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. https://doi.org/10.1016/j.jamda.2019.08.006
Vancouver
Dyer AH, Murphy C, Lawlor B, Kennelly SP, NILVAD Study Group. 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. doi:10.1016/j.jamda.2019.08.006. PMID: 31604674.
BibTeX
@article{dyer2020-31604674,
author = {Dyer, A. H. and Murphy, C. and Lawlor, B. and Kennelly, S. P. and {NILVAD Study Group}},
title = {{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 = {Journal of the American Medical Directors Association},
year = {2020},
doi = {10.1016/j.jamda.2019.08.006},
pmid = {31604674},
url = {https://doi.org/10.1016/j.jamda.2019.08.006}
}
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