Neuropathological Correlates of Cumulative Benzodiazepine and Anticholinergic Drug Use


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.

Publication DOI:
Divisions: College of Health & Life Sciences > Aston Pharmacy School
Additional Information: Copyright ©2020 IOS Press
Uncontrolled Keywords: Alzheimer's disease,basal nucleus of Meynert,benzodiazepines,cholinergic antagonists,neuritic plaques,neurofibrillary tangles,neuropathology,Neuroscience(all),Clinical Psychology,Geriatrics and Gerontology,Psychiatry and Mental health
Publication ISSN: 1875-8908
Last Modified: 24 May 2024 07:15
Date Deposited: 11 Mar 2020 16:30
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Related URLs: https://content ... sease/jad191199 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2020
Published Online Date: 2020-02-27
Accepted Date: 2020-01-30
Authors: Richardson, Kathryn
Wharton, Stephen B
Grossi, Carlota M
Matthews, Fiona E
Fox, Chris
Maidment, Ian (ORCID Profile 0000-0003-4152-9704)
Loke, Yoon K
Steel, Nicholas
Arthur, Antony
Myint, Phyo Kyaw
Boustani, Malaz
Campbell, Noll
Robinson, Louise
Brayne, Carol
Savva, George M



Version: Accepted Version

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