ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
Associations of anticholinergic burden of medication with cognitive decline and longitudinal brain atrophy in the Alzheimer's disease spectrum
Stefan Teipel 1,2
Alice Grazia 2,3
Oliver Peters 4,5
Josef Priller 4,5
Anja Schneider 6
Jens Wiltfang 7,8
Claudia Bartels 8
Björn H Schott 7,8
Frank Jessen 9,10
Emrah Duzel 11,12
Renat Yakupov 11,12
Katharina Buerger 13,14
Robert Perneczky 14,15
Christoph Laske 16,17
Annika Spottke 6
Michael Wagner 6
Jonas Peltner 6,18
Ingo Kilimann 1,2
Britta Haenisch 6,18,19
1. German Center of Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Rostock, Germany
2. Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany
3. German Center of Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Rostock, Germany
4. Charite - Universitatsmedizin Berlin Klinik fur Psychiatrie und Psychotherapie Campus Charite Mitte, Berlin, Germany
5. Department of Psychiatry and Psychotherapy, Charité, Berlin, Germany
6. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
7. German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany
8. Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Goettingen, Germany
9. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
10. Department of Psychiatry, University of Cologne, Medical Faculty, Cologne, Germany
11. German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
12. Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany
13. Department of Radiology, Ludwig Maximilian University Hospital, Munich, Germany
14. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
15. Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
16. German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany
17. Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
18. Research Division, Federal Institute for Drugs and Medical Devices, Bonn, Germany
19. Center for Translational Medicine, Medical Faculty, University of Bonn, Bonn, Germany
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Abstract
Abstract Background: Anticholinergic side effects of pharmacological treatment are a risk factor for cognitive decline in older people. Here, we aimed to assess the effect of anticholinergic burden of treatment on longitudinal rates of cognitive change and atrophy in functionally related brain regions in people from the Alzheimer's disease (AD) spectrum. Methods: We determined associations of anticholinergic burden of pharmacological treatment with rates of global cognition, episodic memory and executive function decline as well as basal forebrain and hippocampus atrophy in participants of the memory clinic based DELCODE cohort, spanning the range from cognitively normal through subjective cognitive decline, mild cognitive impairment and AD dementia. We had 794 cases with neuropsychological outcomes, and a subset of 703 cases with MRI outcomes. Effects were assessed using mixed effect models in a Bayesian framework using prior-insensitive cross-validated Bayes factors (CV-BF) and parameter estimates. Results: We found moderate evidence for an association of anticholinergic burden with baseline levels of cognitive impairment for the PACC5 as a global cognitive function score (CV-BF = 9.0) with more impairments with higher burden, but not with basal forebrain and hippocampus volumes, and weak evidence for an association of anticholinergic burden with longitudinal rates of change in the trailmaking test B as an executive function score (CV-BF = 2.5), but not for other cognitive scores and not for brain volumes. Conclusion: In the presence of prodromal or manifest AD, in a memory clinic-based cohort anticholinergic burden had only a modest effect on cognitive decline and no effect on atrophy in brain regions that are related to the cholinergic system.
Summary
Keywords
Alzheimer's disease, Cholinergic basal forebrain, Hippocampus, MRI, Treatement
Received
21 November 2025
Accepted
10 February 2026
Copyright
© 2026 Teipel, Grazia, Peters, Priller, Schneider, Wiltfang, Bartels, Schott, Jessen, Duzel, Yakupov, Buerger, Perneczky, Laske, Spottke, Wagner, Peltner, Kilimann and Haenisch. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Stefan Teipel; Alice Grazia
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.