Richardson, K., Wharton, S.B. orcid.org/0000-0003-2785-333X, Grossi, C.M. et al. (12 more authors) (2020) Neuropathological correlates of cumulative benzodiazepine and anticholinergic drug use. Journal of Alzheimer's Disease, 74 (3). pp. 999-1009. ISSN 1387-2877
Abstract
Background: Benzodiazepines and anticholinergic drugs have been implicated in causing cognitive decline and potentially increasing dementia risk. However, evidence for an association with neuropathology is limited.
Objective: To estimate the correlation between neuropathology at death and prior use of benzodiazepines and anticholinergic drugs.
Methods: We categorized 298 brain donors from the population-based Medical Research Council Cognitive Function and Ageing Study, according to their history of benzodiazepine (including Z-drugs) or anticholinergic medication (drugs scoring 3 on the Anticholinergic Cognitive Burden scale) use. We used logistic regression to compare dichotomized neuropathological features for those with and without history of benzodiazepine and anticholinergic drug use before dementia, adjusted for confounders.
Results: Forty-nine (16%) and 51 (17%) participants reported benzodiazepine and anticholinergic drug use. Alzheimer’s disease neuropathologic change was similar whether or not exposed to either drug, for example 46% and 57% had intermediate/high levels among those with and without anticholinergic drug use. Although not significant after multiple testing adjustments, we estimated an odds ratio (OR) of 0.40 (95% confidence interval [95% CI] 0.18–0.87) for anticholinergic use and cortical atrophy. For benzodiazepine use, we estimated ORs of 4.63 (1.11–19.24) and 3.30 (1.02–10.68) for neuronal loss in the nucleus basalis and substantial nigra. There was evidence of neuronal loss in the nucleus basalis with anticholinergic drug use, but the association reduced when adjusted for confounders.
Conclusions: We found no evidence that benzodiazepine or anticholinergic drug use is associated with typical pathological features of Alzheimer’s disease; however, we cannot rule out effects owing to small numbers.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 IOS Press and the authors. This is an author-produced version of a paper subsequently published in Journal of Alzheimer's Disease. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Alzheimer’s disease; basal nucleus of Meynert; benzodiazepines; cholinergic antagonists; neurofibrillary tangles; neuritic plaques; neuropathology |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number MEDICAL RESEARCH COUNCIL G0900582/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 09 Mar 2020 12:00 |
Last Modified: | 06 Dec 2021 15:01 |
Status: | Published |
Publisher: | IOS Press |
Refereed: | Yes |
Identification Number: | 10.3233/jad-191199 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:158202 |