Abstract
Background
The interrelationships between atrial fibrillation (AF), brain lesions and cognitive function are poorly understood. We aimed to investigate the relationship of AF with brain lesions and cognition.
Methods
We enrolled 1,480 patients with and 959 without AF in a multicenter prospective study (Swiss-AF; NCT02105844). We assessed brain structure, and cognition using the Montreal Cognitive Assessment (MoCA). Brain magnetic resonance imaging (MRI) was performed to assess large non-cortical and cortical infarcts (LNCCI), small non-cortical infarcts (SNCI), white matter hyperintensities (WMH), and microbleeds. Using causal mediation analyses, we investigated the direct (lesion-independent) and indirect (lesion-mediated) effects of AF on cognition.
Results
Mean age in AF patients is 75.0 vs. 74.2 years in no-AF patients, 28.6% vs. 36.9% are female, and comorbidities are comparable. The prevalence of MRI-detected brain infarcts (LNCCI and/or SNCI) is 40.1% in AF patients vs. 24.0% in no-AF patients, adjusted OR (95% CI): 1.78 (1.30; 2.44), p = 0.0003. WMH (Fazekas ≥2) are more prevalent in AF patients (59.2% vs 44.4%), adjusted OR (95% CI): 2.03 (1.50; 2.77), p = 4.6e-06. The mean MoCA score is 25.3 in AF patients and 26.4 in no-AF patients. In mediation analysis, the total effect of AF on cognition is −1.05 MoCA points, decomposed into a direct effect of −0.99 and an indirect, lesion-mediated, effect of −0.06 points.
Conclusions
The prevalence of ischemic brain infarcts and WMH is higher in patients with AF than without AF despite comparable comorbidities. AF is associated with lower cognitive function, primarily through a direct effect rather than mediated by brain lesions.
Plain Language Summary
Atrial fibrillation is a common heart rhythm disorder in which there is an irregular heartbeat. It has been associated with damage to the brain and reduced cognitive function, which is the mental processes involved in thinking, learning, and processing information. However, the relationship is poorly understood. We assessed brain structure and cognitive function in people with similar characteristics that either had or did not have atrial fibrillation. We found that people with atrial fibrillation had more brain damage visible by brain imaging and lower cognitive function, compared to people without atrial fibrillation. The brain damage seen did not seem to be the main cause of the lower cognitive function. The main driver of lower cognitive function was most probably the arrhythmia itself.
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Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request. To protect participant privacy, this information is not publicly available. Supplementary Data 1 contains the source data for Fig. 3.
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Acknowledgements
The Swiss-AF study is supported by grants of the Swiss National Science Foundation (grant numbers 33CS30_148474, 33CS30_177520, 32473B_176178, 32003B_197524, and 324730_192394), the Swiss Heart Foundation (FF22036), the Foundation for Cardiovascular Research Basel (FCVR), and the University of Basel.
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PK Conceptualization, Methodology, Formal analysis, Data curation, Writing – original draft. SA Methodology, Formal analysis, Writing – original draft. MC Conceptualization, Methodology, Formal analysis, Data curation, Writing – original draft. NR Methodology, Formal analysis, Data acquisition, Writing – original draft. TR Investigation, Data acquisition, Writing – review & editing. ASM Investigation, Data acquisition, Writing – review & editing. JHB Investigation, Data acquisition, Writing – review & editing. PA Investigation, Data acquisition, Writing – review & editing. AA Investigation, Data acquisition, Writing – review & editing. GM Investigation, Data acquisition, Writing – review & editing. RK Investigation, Data acquisition, Writing – review & editing. DS Investigation, Data acquisition, Writing – review & editing. MDV Investigation, Data acquisition, Writing – review & editing. GC Investigation, Data acquisition, Writing – review & editing. G.E. Investigation, Data acquisition, Writing – review & editing. E.H. Investigation, Data acquisition, Writing – review & editing. A.M. Investigation, Data acquisition, Writing – review & editing. R.E.P. Methodology, Data curation, Formal analysis, Writing – original draft. N.R. Investigation, Data acquisition, Writing – review & editing. L.R. Investigation, Data acquisition, Writing – review & editing. M.S. Methodology, Data curation, Formal analysis, Writing – review & editing. C.S. Investigation, Writing – review & editing. P.B. Investigation, Writing – review & editing. C.S.Z. Investigation, Data curation, Writing – review & editing. T.S. Investigation, Data curation, Writing – review & editing. M.D. Investigation, Writing – review & editing. F.M. Investigation, Writing – review & editing. L.H.B. Investigation, Data curation, Writing – review & editing. D.C. Investigation, Funding acquisition, Formal analysis, Writing – review & editing. S.O. Conceptualization, Methodology, Supervision, Project administration, Funding acquisition, Writing – original draft. M.K. Conceptualization, Methodology, Supervision, Project administration, Funding acquisition, Writing – original draft.
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Philipp Krisai (PK) reports speaker fees from BMS/Pfizer and Biosense Webster, and research grants from the Swiss National Science Foundation, Swiss Heart Foundation, Foundation for Cardiovascular Research Basel, Machaon Foundation. Michael Kühne (MK) reports grants from Bayer, grants from BMS, grants from Boston Scientific, grants from Daiichi Sankyo, grants from Pfizer, personal fees from Abbott, personal fees from Boston Scientific, personal fees from Daiichi Sankyo, and royalties from Springer (ECG book). Stefan Osswald (SO) reports grants from Swiss National Science Foundation, Swiss Heart Foundation, Foundation for Cardiovascular Research Basel. Felix Mahfoud (FM) has been supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219, Project-ID 322900939), and Deutsche Herzstiftung. In the past 24 months, Saarland University has received scientific support from Ablative Solutions, Medtronic and ReCor Medical. Until May 2024, FM has received speaker honoraria/consulting fees from Ablative Solutions, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. Matthias Schwenkglenks (MS) reports grants from Swiss National Science Foundation, for the conduct of the study; grants from Amgen, grants from MSD, grants from Novartis, grants from Pfizer, grants from Roche, grants and personal fees from BMS and personal fees from Sandoz, all outside the submitted work. David Conen (DC) reports speaker fees from Servier, consulting fees from Trimedics. Giorgio Moschovitis (GM) has received advisory board or speaker’s fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Gebro Pharma, Novartis and Vifor, all outside of the submitted work. All other authors declare no competing interest.
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Krisai, P., Aeschbacher, S., Coslovsky, M. et al. Ischemic brain infarcts, white matter hyperintensities, and cognitive impairment are increased in patients with Atrial Fibrillation. Commun Med (2026). https://doi.org/10.1038/s43856-026-01389-w
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DOI: https://doi.org/10.1038/s43856-026-01389-w
