Relationships of Overt and Silent Brain Lesions With Cognitive Function in Patients With Atrial Fibrillation

David Conen; Nicolas Rodondi; Andreas Müller; Juerg H Beer; Peter Ammann; Giorgio Moschovitis; Angelo Auricchio; Daniel Hayoz; Richard Kobza; Dipen Shah; Jan Novak; Jürg Schläpfer; Marcello Di Valentino; Stefanie Aeschbacher; Steffen Blum; Pascal Meyre; Christian Sticherling; Leo H Bonati; Georg Ehret; Elisavet Moutzouri; Urs Fischer; Andreas U Monsch; Christoph Stippich; Jens Wuerfel; Tim Sinnecker; Michael Coslovsky; Matthias Schwenkglenks; Michael Kühne; Stefan Osswald; Swiss-AF Study Investigators

doi:10.1016/j.jacc.2018.12.039

Relationships of Overt and Silent Brain Lesions With Cognitive Function in Patients With Atrial Fibrillation

J Am Coll Cardiol. 2019 Mar 12;73(9):989-999. doi: 10.1016/j.jacc.2018.12.039.

Authors

David Conen¹, Nicolas Rodondi², Andreas Müller³, Juerg H Beer⁴, Peter Ammann⁵, Giorgio Moschovitis⁶, Angelo Auricchio⁷, Daniel Hayoz⁸, Richard Kobza⁹, Dipen Shah¹⁰, Jan Novak¹¹, Jürg Schläpfer¹², Marcello Di Valentino¹³, Stefanie Aeschbacher¹⁴, Steffen Blum¹⁴, Pascal Meyre¹⁴, Christian Sticherling¹⁴, Leo H Bonati¹⁵, Georg Ehret¹⁰, Elisavet Moutzouri², Urs Fischer¹⁶, Andreas U Monsch¹⁷, Christoph Stippich¹⁸, Jens Wuerfel¹⁹, Tim Sinnecker²⁰, Michael Coslovsky²¹, Matthias Schwenkglenks²², Michael Kühne¹⁴, Stefan Osswald¹⁴; Swiss-AF Study Investigators

Collaborators

Swiss-AF Study Investigators:
Sebastian Berger, Raffaele Bernasconi, Lorin Fröhlich, Tobias Göldi, Rebecca Gugganig, Thomas Kofler, Philipp Krisai, Michel Mongiat, Christiane Pudenz, Javier Ruperti Repilado, Aleksandra Schweizer, Anne Springer, Samuel Stempfel, Thomas Szucs, Jan van der Stouwe, Gian Voellmin, Leon Zwimpfer, Drahomir Aujesky, Juerg Fuhrer, Laurent Roten, Simon Jung, Heinrich Mattle, Luise Adam, Carole Elodie Aubert, Martin Feller, Claudio Schneider, Axel Loewe, Tanja Flückiger, Cindy Groen, Nathalie Schwab, Christopher Beynon, Roger Dillier, Franz Eberli, Simone Fontana, Christine Franzini, Isabel Juchli, Claudia Liedtke, Jacqueline Nadler, Thayze Obst, Xiaoye Schneider, Katrin Studerus, Dominik Weishaupt, Silke Kuest, Karin Scheuch, Denise Hischier, Nicole Bonetti, Corina Bello, Henriette Isberg, Alexandra Grau, Jonas Villinger, Mary-Monica Papaux, Philipp Baumgartner, Mark Filipovic, Marcel Frick, Adriana Anesini, Cristina Camporini, Giulio Conte, Maria Luce Caputo, Francois Regoli, Tiziano Moccetti, Roman Brenner, David Altmann, Manuela Forrer, Michaela Gemperle, Mathieu Firmann, Sandrine Foucras, Benjamin Berte, Andrea Kaeppeli, Brigitta Mehmann, Markus Pfeiffer, Ian Russi, Kai Schmidt, Vanessa Weberndoerfer, Mabelle Young, Melanie Zbinden, Luisa Vicari, Jane Frangi, Tatiana Terrot, Hervé Gallet, Elise Guillermet, Francois Lazeyras, Karl-Olof Lovblad, Patrick Perret, Cheryl Teres, Nathalie Lauriers, Marie Méan, Sandrine Salzmann, Nisha Arenja, Andrea Grêt, Sandra Vitelli, Jane Frangi, Augusto Gallino, Renate Schoenenberger-Berzins, Fabienne Witassek, Ernst-Wilhelm Radue, Pascal Benkert, Thomas Fabbro, Patrick Simon, Ramun Schmid

Affiliations

¹ Cardiology Division, Department of Medicine, University Hospital Basel, Basel, Switzerland; Cardiovascular Research Institute Basel, Basel, Switzerland; Population Health Research Institute, McMaster University, Hamilton, Canada. Electronic address: [email protected].
² Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland; Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
³ Department of Cardiology, Triemli Hospital Zurich, Zurich, Switzerland.
⁴ Departement of Medicine, Cantonal Hospital of Baden and Molecular Cardiology, University Hospital of Zurich, Zurich, Switzerland.
⁵ Department of Cardiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
⁶ Department of Cardiology, Ospedale Regionale di Lugano, Lugano, Switzerland.
⁷ Division of Cardiology, Fondazione Cardiocentro Ticino, Lugano, Switzerland.
⁸ Department of Internal Medicine, HFR-Hôpital Cantonal Fribourg, Fribourg, Switzerland.
⁹ Department of Cardiology, Luzerner Kantonsspital, Lucerne, Switzerland.
¹⁰ Division of Cardiology, Department of Medical Specialties, University Hospital Geneva, Geneva, Switzerland.
¹¹ Department of Cardiology, Bürgerspital Solothurn, Solothurn, Switzerland.
¹² Department of Cardiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
¹³ Department of Cardiology, Ospedale San Giovanni, Bellinzona, Switzerland.
¹⁴ Cardiology Division, Department of Medicine, University Hospital Basel, Basel, Switzerland; Cardiovascular Research Institute Basel, Basel, Switzerland.
¹⁵ Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Basel, Switzerland.
¹⁶ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹⁷ Memory Clinic, Universitäre Altersmedizin, Felix Platter Spital Basel, University of Basel, Basel, Switzerland.
¹⁸ Department of Neuroradiology, University Hospital Zurich, Zurich, Switzerland.
¹⁹ Medical Image Analysis Center (MIAC AG) and Department of Biomedical Engineering, University of Basel, Basel, Switzerland.
²⁰ Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Basel, Switzerland; Medical Image Analysis Center (MIAC AG) and Department of Biomedical Engineering, University of Basel, Basel, Switzerland.
²¹ Cardiovascular Research Institute Basel, Basel, Switzerland.
²² Epidemiology, Biostatistics, and Prevention Institute, University of Zurich, Zurich, Switzerland.

PMID: 30846109
DOI: 10.1016/j.jacc.2018.12.039

Abstract

Background: Patients with atrial fibrillation (AF) have an increased risk of cognitive decline, potentially resulting from clinically unrecognized vascular brain lesions.

Objectives: This study sought to assess the relationships between cognitive function and vascular brain lesions in patients with AF.

Methods: Patients with known AF were enrolled in a multicenter study in Switzerland. Brain magnetic resonance imaging (MRI) and cognitive testing using the Montreal Cognitive Assessment (MoCA) were performed in all participants. Large noncortical or cortical infarcts (LNCCIs), small noncortical infarcts (SNCIs), microbleeds, and white matter lesions were quantified by a central core laboratory. Clinically silent infarcts were defined as infarcts on brain MRI in patients without a clinical history of stroke or transient ischemic attack.

Results: The study included 1,737 patients with a mean age of 73 ± 8 years (28% women, 90% taking oral anticoagulant agents). On MRI, LNCCIs were found in 387 patients (22%), SNCIs in 368 (21%), microbleeds in 372 (22%), and white matter lesions in 1715 (99%). Clinically silent infarcts among the 1,390 patients without a history of stroke or transient ischemic attack were found in 201 patients with LNCCIs (15%) and 245 patients with SNCIs (18%). The MoCA score was 24.7 ± 3.3 in patients with and 25.8 ± 2.9 in those without LNCCIs on brain MRI (p < 0.001). The difference in MoCA score remained similar when only clinically silent LNCCIs were considered (24.9 ± 3.1 vs. 25.8 ± 2.9; p < 0.001). In a multivariable regression model including all vascular brain lesion parameters, LNCCI volume was the strongest predictor of a reduced MoCA (β = -0.26; 95% confidence interval: -0.40 to -0.13; p < 0.001).

Conclusions: Patients with AF have a high burden of LNCCIs and other brain lesions on systematic brain MRI screening, and most of these lesions are clinically silent. LNCCIs were associated with worse cognitive function, even among patients with clinically silent infarcts. Our findings raise the question of MRI screening in patients with AF.

Keywords: atrial fibrillation; cognitive dysfunction; microbleeds; silent cerebral infarcts; white matter lesions.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Atrial Fibrillation / complications*
Brain / pathology*
Cerebral Infarction / complications
Cerebral Infarction / diagnosis*
Cognition / physiology*
Cognitive Dysfunction / diagnosis*
Cognitive Dysfunction / etiology
Cognitive Dysfunction / physiopathology
Female
Follow-Up Studies
Humans
Magnetic Resonance Imaging / methods*
Male
Neuropsychological Tests
Prospective Studies
Risk Factors