. 2026 Jan 27.

doi: 10.1038/s43856-026-01389-w. Online ahead of print.

Ischemic brain infarcts, white matter hyperintensities, and cognitive impairment are increased in patients with Atrial Fibrillation

Philipp Krisai^{1

2}, Stefanie Aeschbacher^{3

4}, Michael Coslovsky^{4

5}, Nikki Rommers⁵, Tobias Reichlin⁶, Andreas S Müller⁷, Jürg H Beer⁸, Peter Ammann⁹, Angelo Auricchio¹⁰, Giorgio Moschovitis¹⁰, Richard Kobza¹¹, Dipen Shah¹², Marcello Di Valentino¹³, Giulio Conte¹⁰, Georg Ehret¹², Elisa Hennings^{3

4}, Andreas Monsch¹⁴, Rebecca E Paladini^{3

4}, Nicolas Rodondi^{15

16}, Laurent Roten⁶, Matthias Schwenkglenks^{17

18}, Christian Sticherling^{3

4}, Patrick Badertscher^{3

4}, Christine S Zuern^{3

4}, Tim Sinnecker^{19

20}, Marco Duering²⁰, Felix Mahfoud^{3

4}, Leo H Bonati^{19

21}, David Conen²², Stefan Osswald^#^{3

4}, Michael Kühne^#^{3

4}; eMBA, for the Swiss-AF Investigators

Collaborators, Affiliations

Collaborators

eMBA, for the Swiss-AF Investigators:
Steffen Blum, Désirée Carmine, Ludvig Dahlheim, Corinne Girroy, Andreas Gasser, Ruben Kerler, Vincent Meier, Christine Meyer-Zürn, Pascal B Meyre, Andreas U Monsch, Christian Müller, Raffaele Peter, Adrian Schweigler, Gian Völlmin, Priska Zuber, Drahomir Aujesky, Urs Fischer, Juerg Fuhrer, Simon Jung, Heinrich Mattle, Seraina Netzer, Luise Adam, Carole Elodie Aubert, Martin Feller, Axel Loewe, Elisavet Moutzouri, Claudio Schneider, Tanja Flückiger, Cindy Groen, Lukas Ehrsam, Sven Hellrigl, Alexandra Nuoffer, Damiana Rakovic, Nathalie Schwab, Rylana Wenger, Tu Hanh Zarrabi Saffari, Nicolas Rodondi, Alain Bernheim, Roger Dillier, Michèle Deubelbeiss, Franz Eberli, Christine Franzini, Daniel Hofer, Raban Jeger, Isabel Juchli, Claudia Liedtke, Samira Murugiah, Jacqueline Nadler, Thayze Obst, Jasmin Roth, Fiona Schlomowitsch, Xiaoye Schneider, Peter Sporns, Katrin Studerus, Noreen Tynan, Dominik Weishaupt, Caroline Wiederkehr, Andreas Müller, Corinne Friedli, Silke Kuest, Karin Scheuch, Denise Hischier, Nicole Bonetti, Alexandra Grau, Jonas Villinger, Eva Laube, Marcel Frick, Stefanie Leuenberger, Franziska Rutz, Jürg-Hans Beer, Adriana Anesini, Cristina Camporini, Maria Luce Caputo, Rebecca Peronaci, Francois Regoli, Martina Ronchi, Roman Brenner, David Altmann, Karin Fink, Michaela Gemperle, Jessica Meier, Mathieu Firmann, Sandrine Foucras, Daniel Hayoz, Martine Rime, Benjamin Berte, Kathrin Bühler, Amir Jadidi, Virgina Justi, Frauke Kellner-Weldon, Melanie Koch, Brigitta Mehmann, Sonja Meier, Myriam Roth, Andrea Ruckli-Kaeppeli, Ian Russi, Kai Schmidt, Mabelle Young, Elia Rigamonti, Carlo Cereda, Alessandro Cianfoni, Maria Luisa De Perna, Jane Frangi-Kultalahti, Patrizia Assunta Mayer Melchiorre, Anica Pin, Serena Staglianò, Tatiana Terrot, Luisa Vicari, Hervé Gallet, Elise Guillermet, Francois Lazeyras, Karl-Olof Lovblad, Patrick Perret, Philippe Tavel, Nathalie Lauriers, Marie Méan, Alessandra Pia Porretta, Sandrine Salzmann, Jürg Schläpfer, Andrea Grêt, Jan Novak, Sandra Vitelli, Frank-Peter Stephan, Augusto Gallino, Marcello Di Valentino, Helena Aebersold, Fabienne Foster, Marco Düring, Tim Sinnecker, Anna Altermatt, Michael Amann, Petra Huber, Manuel Hürbin, Esther Ruberte, Alain Thöni, Jens Würfel, Vanessa Zuber, Michael Coslovsky, Pia Neuschwander, Patrick Simon, Ramun Schmid, Christian Baumann, Nico Ruckstuhl

Affiliations

¹ Cardiology Division, Department of Medicine, University Hospital Basel, University Basel, Basel, Switzerland. philipp.krisai@usb.ch.
² Cardiovascular Research Institute Basel, University Hospital Basel, University Basel, Basel, Switzerland. philipp.krisai@usb.ch.
³ Cardiology Division, Department of Medicine, University Hospital Basel, University Basel, Basel, Switzerland.
⁴ Cardiovascular Research Institute Basel, University Hospital Basel, University Basel, Basel, Switzerland.
⁵ Department of Clinical Research, University Basel, University Hospital Basel, Basel, Switzerland.
⁶ Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁷ Department of Cardiology, Triemli Hospital Zürich, Zürich, Switzerland.
⁸ Department of Medicine, Cantonal Hospital of Baden and Molecular Cardiology, University Hospital of Zürich, Zürich, Switzerland.
⁹ Department of Cardiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
¹⁰ Division of Cardiology, Ente Ospedaliero Cantonale (EOC), Cardiocentro Ticino Institute, Regional Hospital of Lugano, Lugano, Switzerland.
¹¹ Department of Cardiology, Luzerner Kantonsspital, Lucerne, Switzerland.
¹² Division of Cardiology, Department of Medical Specialities, University Hospital Geneva, Geneva, Switzerland.
¹³ Division of Cardiology, Ospedale San Giovanni, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
¹⁴ Memory Clinic, Universitäre Altersmedizin, Felix Platter Spital Basel, University of Basel, Basel, Switzerland.
¹⁵ Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
¹⁶ Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹⁷ Epidemiology, Biostatistics, and Prevention Institute, University of Zürich, Zürich, Switzerland.
¹⁸ Health Economics Facility, Department of Public Health, University of Basel, Basel, Switzerland.
¹⁹ Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Basel, Switzerland.
²⁰ Medical Image Analysis Center (MIAC) and Department of Biomedical Engineering, University of Basel, Basel, Switzerland.
²¹ Rheinfelden Rehabilitation Clinic, Rheinfelden, Switzerland.
²² Population Health Research Institute, McMaster University, Hamilton, Canada.

^# Contributed equally.

PMID: 41593217
DOI: 10.1038/s43856-026-01389-w

Free article

Ischemic brain infarcts, white matter hyperintensities, and cognitive impairment are increased in patients with Atrial Fibrillation

Philipp Krisai et al. Commun Med (Lond). 2026.

Free article

. 2026 Jan 27.

doi: 10.1038/s43856-026-01389-w. Online ahead of print.

Authors

Collaborators

eMBA, for the Swiss-AF Investigators:
Steffen Blum, Désirée Carmine, Ludvig Dahlheim, Corinne Girroy, Andreas Gasser, Ruben Kerler, Vincent Meier, Christine Meyer-Zürn, Pascal B Meyre, Andreas U Monsch, Christian Müller, Raffaele Peter, Adrian Schweigler, Gian Völlmin, Priska Zuber, Drahomir Aujesky, Urs Fischer, Juerg Fuhrer, Simon Jung, Heinrich Mattle, Seraina Netzer, Luise Adam, Carole Elodie Aubert, Martin Feller, Axel Loewe, Elisavet Moutzouri, Claudio Schneider, Tanja Flückiger, Cindy Groen, Lukas Ehrsam, Sven Hellrigl, Alexandra Nuoffer, Damiana Rakovic, Nathalie Schwab, Rylana Wenger, Tu Hanh Zarrabi Saffari, Nicolas Rodondi, Alain Bernheim, Roger Dillier, Michèle Deubelbeiss, Franz Eberli, Christine Franzini, Daniel Hofer, Raban Jeger, Isabel Juchli, Claudia Liedtke, Samira Murugiah, Jacqueline Nadler, Thayze Obst, Jasmin Roth, Fiona Schlomowitsch, Xiaoye Schneider, Peter Sporns, Katrin Studerus, Noreen Tynan, Dominik Weishaupt, Caroline Wiederkehr, Andreas Müller, Corinne Friedli, Silke Kuest, Karin Scheuch, Denise Hischier, Nicole Bonetti, Alexandra Grau, Jonas Villinger, Eva Laube, Marcel Frick, Stefanie Leuenberger, Franziska Rutz, Jürg-Hans Beer, Adriana Anesini, Cristina Camporini, Maria Luce Caputo, Rebecca Peronaci, Francois Regoli, Martina Ronchi, Roman Brenner, David Altmann, Karin Fink, Michaela Gemperle, Jessica Meier, Mathieu Firmann, Sandrine Foucras, Daniel Hayoz, Martine Rime, Benjamin Berte, Kathrin Bühler, Amir Jadidi, Virgina Justi, Frauke Kellner-Weldon, Melanie Koch, Brigitta Mehmann, Sonja Meier, Myriam Roth, Andrea Ruckli-Kaeppeli, Ian Russi, Kai Schmidt, Mabelle Young, Elia Rigamonti, Carlo Cereda, Alessandro Cianfoni, Maria Luisa De Perna, Jane Frangi-Kultalahti, Patrizia Assunta Mayer Melchiorre, Anica Pin, Serena Staglianò, Tatiana Terrot, Luisa Vicari, Hervé Gallet, Elise Guillermet, Francois Lazeyras, Karl-Olof Lovblad, Patrick Perret, Philippe Tavel, Nathalie Lauriers, Marie Méan, Alessandra Pia Porretta, Sandrine Salzmann, Jürg Schläpfer, Andrea Grêt, Jan Novak, Sandra Vitelli, Frank-Peter Stephan, Augusto Gallino, Marcello Di Valentino, Helena Aebersold, Fabienne Foster, Marco Düring, Tim Sinnecker, Anna Altermatt, Michael Amann, Petra Huber, Manuel Hürbin, Esther Ruberte, Alain Thöni, Jens Würfel, Vanessa Zuber, Michael Coslovsky, Pia Neuschwander, Patrick Simon, Ramun Schmid, Christian Baumann, Nico Ruckstuhl

Affiliations

¹ Cardiology Division, Department of Medicine, University Hospital Basel, University Basel, Basel, Switzerland. philipp.krisai@usb.ch.
² Cardiovascular Research Institute Basel, University Hospital Basel, University Basel, Basel, Switzerland. philipp.krisai@usb.ch.
³ Cardiology Division, Department of Medicine, University Hospital Basel, University Basel, Basel, Switzerland.
⁴ Cardiovascular Research Institute Basel, University Hospital Basel, University Basel, Basel, Switzerland.
⁵ Department of Clinical Research, University Basel, University Hospital Basel, Basel, Switzerland.
⁶ Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁷ Department of Cardiology, Triemli Hospital Zürich, Zürich, Switzerland.
⁸ Department of Medicine, Cantonal Hospital of Baden and Molecular Cardiology, University Hospital of Zürich, Zürich, Switzerland.
⁹ Department of Cardiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
¹⁰ Division of Cardiology, Ente Ospedaliero Cantonale (EOC), Cardiocentro Ticino Institute, Regional Hospital of Lugano, Lugano, Switzerland.
¹¹ Department of Cardiology, Luzerner Kantonsspital, Lucerne, Switzerland.
¹² Division of Cardiology, Department of Medical Specialities, University Hospital Geneva, Geneva, Switzerland.
¹³ Division of Cardiology, Ospedale San Giovanni, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.
¹⁴ Memory Clinic, Universitäre Altersmedizin, Felix Platter Spital Basel, University of Basel, Basel, Switzerland.
¹⁵ Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland.
¹⁶ Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹⁷ Epidemiology, Biostatistics, and Prevention Institute, University of Zürich, Zürich, Switzerland.
¹⁸ Health Economics Facility, Department of Public Health, University of Basel, Basel, Switzerland.
¹⁹ Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Basel, Switzerland.
²⁰ Medical Image Analysis Center (MIAC) and Department of Biomedical Engineering, University of Basel, Basel, Switzerland.
²¹ Rheinfelden Rehabilitation Clinic, Rheinfelden, Switzerland.
²² Population Health Research Institute, McMaster University, Hamilton, Canada.

^# Contributed equally.

PMID: 41593217
DOI: 10.1038/s43856-026-01389-w

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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Conflict of interest statement

Competing interests: 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.

References

1. Lloyd-Jones, D. M. et al. Lifetime risk for development of atrial fibrillation: the Framingham Heart Study. Circulation 110, 1042–1046 (2004).
1. Krijthe, B. P. et al. Projections on the number of individuals with atrial fibrillation in the European Union, from 2000 to 2060. Eur. Heart J. 34, 2746–2751 (2013).
1. Prince, M. et al. The global prevalence of dementia: A systematic review and metaanalysis. Alzheimers Dement 9, 63–75 (2013).
1. Kalantarian, S., Stern, T. A., Mansour, M. & Ruskin, J. N. Cognitive impairment associated with atrial fibrillation: a meta-analysis. Ann. Intern. Med. 158, 338–346 (2013).
1. Conen, D. et al. Relationships of Overt and Silent Brain Lesions With Cognitive Function in Patients With Atrial Fibrillation. J. Am. Coll. Cardiol. 73, 989–999 (2019).

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Ischemic brain infarcts, white matter hyperintensities, and cognitive impairment are increased in patients with Atrial Fibrillation

Collaborators

Affiliations

Ischemic brain infarcts, white matter hyperintensities, and cognitive impairment are increased in patients with Atrial Fibrillation

Authors

Collaborators

Affiliations

Abstract

Plain language summary

Conflict of interest statement

References

LinkOut - more resources

Full Text Sources