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SLEEP 2026 | Does long-term hypnotic use increase the risk of cognitive impairment?
Bhanu Prakash Kolla, MD, MRCPsych, Mayo Clinic, Rochester, MN, discusses findings from a large retrospective cohort study examining the relationship between hypnotic use and cognitive impairment. He explains how adjusting for insomnia severity, genetic risk factors, and prescribing propensity challenged the long-held assumption that long-term use of certain hypnotics increases the risk of mild cognitive impairment or dementia. This interview took place at the 40th annual meeting of the Associated Professional Sleep Societies (APSS) in Baltimore, MD.
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Transcript
For a very long time, there have been longitudinal studies that have shown that there is an association between hypnotic use, or sleep medications, and cognitive impairment. As this literature built, people started looking at potential confounders, and the big one there, of course, is insomnia. And as we started accounting for insomnia, and especially the severity of insomnia, that association seems to be diluted or, in most cases, completely gone...
For a very long time, there have been longitudinal studies that have shown that there is an association between hypnotic use, or sleep medications, and cognitive impairment. As this literature built, people started looking at potential confounders, and the big one there, of course, is insomnia. And as we started accounting for insomnia, and especially the severity of insomnia, that association seems to be diluted or, in most cases, completely gone. So we still don’t know if the risk is coming from insomnia per se or hypnotics. So what we decided to do in our cohort, and we had a pretty large cohort of patients at the Mayo Clinic Biobank with a lot of clinical data, but also, importantly, genetic data. So we had about 50,000-odd subjects. Once we applied our exclusions, we had about 15,000 without hypnotics, close to 9,000 on hypnotics, and then we divided them into those on the Z-drugs, on trazodone, on benzodiazepines, mixed groups, and then further divided them into those who were on these medications for at least one year, which we call long-term use, or those who got either just one prescription or a short-term prescription. Then we adjusted for all these potential covariates that could influence the risk for dementia, also for the APOE status of the genotype, which can also be a risk factor for Alzheimer’s disease, and finally for a propensity for being on a hypnotic. So we calculated a propensity score to see how likely it is that somebody gets on a hypnotic. And once we applied these adjustments, to our surprise, what we found was that for Z-drugs, trazodone, and mixed groups, there was a lower risk of cognitive impairment if they were on the medication long term as compared to not being on the medication, showing that at least there is no increased risk. Potentially there is a protective effect, but that needs to be further evaluated.
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