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. 2024 Oct 14;54(13):1-8.
doi: 10.1017/S0033291724002046. Online ahead of print.

Associations of benzodiazepine use with cognitive ability and age-related cognitive decline

Merete Osler  1   2 , Maarten Pieter Rozing  1   3 , Ida Kim Wium-Andersen  1 , Martin Balslev Jørgensen  4   5 , Erik Lykke Mortensen  6 , Gunhild Tidemann Okholm  1   7
Affiliations

Associations of benzodiazepine use with cognitive ability and age-related cognitive decline

Merete Osler et al. Psychol Med. .

Abstract

Background: It remains uncertain whether long-term use of benzodiazepines is associated with age-related cognitive decline, and if cognitive ability in early life is the driver of any association. This study examines the association of cognitive ability in young adulthood with later use of benzodiazepines and explores whether the use of benzodiazepines during adult life is associated with cognitive decline in late midlife.

Methods: The study samples include cognitive tests on the Børge Priens Prøve (BPP) from the conscription board examination (age 19 years) from 335 513 men born 1949-1961 and data from re-examinations of 5183 men 44 years later. Cognitive decline was defined as the difference between scores at the conscription board and the re-examination. Information on purchases of benzodiazepines was obtained from the Danish National Prescription Registry, 1995-2022. Associations were analysed using Cox proportional hazards and linear regression.

Results: In total, 120 911 (36%) men purchased benzodiazepines during a follow-up of 20 years. Lower cognitive scores in young adulthood were associated with a higher risk of initiating benzodiazepines (hazard ratio [95% CI] = 0.71[0.68-0.75]). Men with the highest cumulative use of benzodiazepines had larger cognitive decline (β-coefficient [95% CI] = -1.66 [-2.09 to -1.23] BPP scores) compared with never users. Current benzodiazepine users showed a larger cognitive decline than never users (β-coefficient [95% CI] = -2.42[-3.18 to -1.66] BPP scores) and this partially explained the above association. These estimates for cognitive decline were relatively small and may lack clinical relevance.

Conclusion: Low cognitive ability increases the risk of benzodiazepine use in adulthood and cognitive decline is more pronounced in those with the highest benzodiazepine use compared with never-use, but the difference lacks clinical significance.

Keywords: benzodiazepines; cognitive ability; cognitive decline; cohort study.

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Conflict of interest statement

None

Figures

Figure 1.
Figure 1.
Association (beta-coefficients and 95% confidence intervals) between use of benzodiazepines in cumulative diazepam milligram equivalents (DME) (n = 5183) and cognitive decline measured with changes in Børge Priens Prøve (BPP) scores over 44 years. Legends in black concern the analysis with all users, whereas the gray legends are the analyses with current users excluded. *Adjusted for age at re-examination, re-test interval, BPP at conscription, years of education, alcohol use, smoking, and psychiatric hospital contact.
See this image and copyright information in PMC

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