Journal Article

DZNE-2026-00287

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Associations of anticholinergic burden of medication with cognitive decline and longitudinal brain atrophy in the Alzheimer's disease spectrum.

Teipel, S. (First author)DZNE* ; Grazia, A.Extern* ; Peters, O.Extern* ; Priller, J.Extern* ; Schneider, A.DZNE* ; Wiltfang, J.DZNE* ; Bartels, C. ; Schott, B. H.DZNE* ; Jessen, F.DZNE* ; Duezel, E.DZNE* ; Yakupov, R.DZNE* ; Buerger, K.DZNE* ; Perneczky, R.DZNE* ; Laske, C.DZNE* ; Spottke, A.DZNE* ; Wagner, M.DZNE* ; Peltner, J.DZNE* ; Kilimann, I.DZNE* ; Haenisch, B. (Last author)DZNE*

2026
Frontiers Research Foundation Lausanne

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Please use a persistent id in citations: doi:10.3389/fnagi.2026.1751326

Abstract: 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.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.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 trail-making test B as an executive function score (CV-BF = 2.5), but not for other cognitive scores and not for brain volumes.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.

Keyword(s): Alzheimer’s disease ; MRI ; cholinergic basal forebrain ; hippocampus ; treatement

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Contributing Institute(s):

1. Pharmacoepidemiology (AG Hänisch)
2. Clinical Dementia Research (Rostock /Greifswald) (AG Teipel)
3. Translational Dementia Research (Bonn) (AG Schneider)
4. Molecular biomarkers for predictive diagnostics of neurodegenerative diseases (AG Wiltfang)
5. Epigenetics and Systems Medicine in Neurodegenerative Diseases (AG Fischer)
6. Clinical Alzheimer’s Disease Research (AG Jessen)
7. Clinical Neurophysiology and Memory (AG Düzel)
8. Clinical Research (Munich) (Clinical Research (Munich))
9. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)
10. Parkinson Genetics (AG Gasser)
11. Clinical Research Platform (CRP) (AG Spottke)
12. Neuropsychology (AG Wagner)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)
2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
3. 352 - Disease Mechanisms (POF4-352) (POF4-352)

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