Anticholinergic burden in middle and older age is associated with lower cognitive function, but not with brain atrophy

Jure Mur; Riccardo E Marioni; Tom C Russ; Graciela Muniz-Terrera; Simon R Cox

doi:10.1111/bcp.15698

Anticholinergic burden in middle and older age is associated with lower cognitive function, but not with brain atrophy

Br J Clin Pharmacol. 2023 Jul;89(7):2224-2235. doi: 10.1111/bcp.15698. Epub 2023 Mar 9.

Authors

Jure Mur^{1

2

3}, Riccardo E Marioni², Tom C Russ^{3

4

5}, Graciela Muniz-Terrera^{4

6}, Simon R Cox¹

Affiliations

¹ Lothian Birth Cohorts Group, Department of Psychology, University of Edinburgh, Edinburgh, UK.
² Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
³ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
⁴ Edinburgh Dementia Prevention, University of Edinburgh, Edinburgh, UK.
⁵ Division of Psychiatry, Centre for Clinical Brain Science, University of Edinburgh, Edinburgh, UK.
⁶ Department of Social Medicine, Ohio University, Athens, Ohio, USA.

Abstract

Aims: The aim of this study is to estimate the association between anticholinergic burden, general cognitive ability and various measures of brain structural MRI in relatively healthy middle-aged and older individuals.

Methods: In the UK Biobank participants with linked health-care records (n = 163,043, aged 40-71 at baseline), of whom about 17 000 had MRI data available, we calculated the total anticholinergic drug burden according to 15 different anticholinergic scales and due to different classes of drugs. We then used linear regression to explore the associations between anticholinergic burden and various measures of cognition and structural MRI, including general cognitive ability, 9 separate cognitive domains, brain atrophy, volumes of 68 cortical and 14 subcortical areas and fractional anisotropy and median diffusivity of 25 white-matter tracts.

Results: Anticholinergic burden was modestly associated with poorer cognition across most anticholinergic scales and cognitive tests (7/9 FDR-adjusted significant associations, standardised betas (β) range: -0.039, -0.003). When using the anticholinergic scale exhibiting the strongest association with cognitive functions, anticholinergic burden due to only some classes of drugs exhibited negative associations with cognitive function, with β-lactam antibiotics (β = -0.035, P_FDR < 0.001) and opioids (β = -0.026, P_FDR < 0.001) exhibiting the strongest effects. Anticholinergic burden was not associated with any measure of brain macrostructure or microstructure (P_FDR > 0.08).

Conclusions: Anticholinergic burden is weakly associated with poorer cognition, but there is little evidence for associations with brain structure. Future studies might focus more broadly on polypharmacy or more narrowly on distinct drug classes, instead of using purported anticholinergic action to study the effects of drugs on cognitive ability.

Keywords: anticholinergic drugs; brain structural magnetic resonance imaging; cognitive ability; primary care.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Atrophy / chemically induced
Atrophy / pathology
Brain / diagnostic imaging
Central Nervous System Diseases*
Cholinergic Antagonists / adverse effects
Cognition
Cognitive Dysfunction* / chemically induced
Cognitive Dysfunction* / epidemiology
Humans
Middle Aged
Neurodegenerative Diseases*

Substances

Cholinergic Antagonists

Abstract

Publication types

MeSH terms

Substances

Grants and funding