Alzheimer Disease Linked to High Cumulative Doses of Zolpidem in Elderly

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blue sleeping pills next to a clock
Zolpidem has been associated with memory loss and decline in cognitive function.

High cumulative doses of zolpidem are associated with a greater risk for developing Alzheimer disease (AD) in elderly patients, according to a retrospective study published in the Journal of the American Geriatric Society.

In this retrospective cohort study, investigators evaluated patients 65 and older (n=6922) who had never received an AD diagnosis. Following propensity score matching, researchers identified subjects who were taking zolpidem (n=3461) vs subjects who were not taking the medication (n=3461).

Approximately 71% of patients taking zolpidem did so under 90 cumulative defined daily dose (cDDD) throughout the first year after the index date (35.2%, <28 cDDD and 35.8%, 28-90 cDDD). 

A smaller percentage (16%) of zolpidem-taking patients were in the high-cumulative dose range of >180 cDDD.  In patients in the high cumulative dose group in the first year of therapy, there was a higher risk for AD compared with subjects who were not taking zolpidem (HR 2.97; 95% CI, 1.61–5.49) or patients who were in the low cumulative dose group (<28 cDDD; HR 4.18; 95% CI, 1.77-9.86).

At 6-year follow-up, a total of 75 patients received an AD diagnosis. Of these, 1.2% (n=43) were zolpidem users and 0.9% (n=32) were not. The incidence of AD was 0.7% in the <28 cDDD group, 1.2% in the group receiving 28-90 cDDD, 1.1% in the 91-180 cDDD group, and 2.7% in the group receiving >180 cDDD of zolpidem.

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The researchers noted that patients’ medical histories, neurological data, and biomarker data were unavailable at baseline, which presents a potential limitation to the study’s findings. In addition, the database used for this retrospective study did not provide data on the subjects’ lifestyle, socioeconomic status, or physical activity level, all of which are potentially associated with AD progression.

In addition to warranting caution against prescribing zolpidem in elderly patients, the investigators suggest that healthcare providers should also reduce current dependence on the medication via “non-pharmacologic intervention, such as cognitive behavior therapy, [which] can be considered for older patients who use zolpidem.”


Cheng HT, Lin FJ, Erickson SR, Hong JL, Wu CH. The association between the use of zolpidem and the risk of Alzheimer’s disease among older people [published online September 7, 2017]. J Am Geriatr Soc. doi:10.1111/jgs.15018