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

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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.

Key Words

atrial fibrillation
cognitive dysfunction
microbleeds
silent cerebral infarcts
white matter lesions

Abbreviations and Acronyms

AF
atrial fibrillation
FLAIR
fluid-attenuated inversion recovery
LNCCI
large noncortical or cortical infarct
MoCA
Montreal Cognitive Assessment
MRI
magnetic resonance imaging
SNCI
small noncortical infarct
TIA
transient ischemic attack

Cited by (0)

The Swiss-AF cohort study is supported by grants of the Swiss National Science Foundation (grants 33CS30_1148474 and 33CS30_177520), the Foundation for Cardiovascular Research Basel, and the University of Basel. The Department of Radiology, University Hospital Basel, Basel holds a general research agreement with Siemens and receives support from Guerbet, Bracco, and Bayer all unrelated to this work. Dr. Conen has a McMaster University Department of Medicine Mid-Career Research Award; his work is supported by the Hamilton Health Sciences RFA Strategic Initiative Program; and has received consulting fees from Servier, Canada. Dr. Rodondi has received a grant from the Swiss Heart Foundation. Dr. Müller has received consulting fees from Biosense Webster, Switzerland. Dr. Beer has received grants from the Swiss National Science Foundation, the Swiss Heart Foundation, and Bayer; and has received consultancy honoraria from Bayer and Daiichi-Sankyo. Dr. Auricchio has received speaker fees from Boston Scientific and Microport; and is a consultant to Boston Scientific, Microport, Daiichi-Sankyo, and Biosense Webster. Dr. Kobza has received grants from Biotronik, Biosense Webster, Boston Scientific, Medtronic, and Abbott. Dr. Shah has received speaker fees from Biosense Webster, Daiichi-Sankyo, Boehringer Ingelheim, Bristol-Myers Squibb, and Bayer; and has received consultancy honoraria from Biosense Webster. Dr. Sticherling has received speaker honoraria from Biosense Webster and Medtronic; and has received research grants from Biosense Webster, Daiichi-Sankyo, and Medtronic. Dr. Bonati has received grants from the Swiss National Science Foundation, the University of Basel, the Swiss Heart Foundation, The Stroke Association, and AstraZeneca; and has received consulting and advisory board fees from Amgen, Bayer, Bristol-Myers Squibb, and Claret Medical. Dr. Monsch has received honoraria or grant support from AC Immune, AbbVie, Roche, Takeda, and Vifor Pharma. Dr. Stippich has received grants from the Swiss National Science Foundation, Siemens, Bracco, Guerbert, Schering, Bayer, Amgen, Merck Sharp and Dohme, Novartis, Pfizer, and The Medicines Company. Dr. Wuerfel is CEO of the Medical Image Analysis Center, Basel; has served on advisory boards for Actelion, Biogen, Genzyme-Sanofi, Novartis, Roche, and the Guthy Jackson Charitable Foundation; has received research grants from Novartis; has received speaker honoraria from Bayer, Biogen, Genzyme, Novartis, and Teva; and has received support by the European Union (Horizon2020), the German Research Association, the German Ministry of Education and Research (BMBF/KKNMS), and the German Ministry of Economy (BMWi). Dr. Schwenkglenks has received grants unrelated to the submitted work from Amgen, Merck Sharp and Dohme, Novartis, Pfizer, and The Medicines Company; has received fees unrelated to the submitted work from Amgen; and has received a grant from the Swiss National Science Foundation. Dr. Kühne has received consultant fees from Bayer, Boehringer Ingelheim, Pfizer-BMS, Daiichi-Sankyo, Medtronic, Biotronik, Boston Scientific, Biosense Webster, AstraZeneca, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.

Drs. Kühne and Osswald are joint senior authors and contributed equally to this work.

A list of all Swiss-AF investigators is provided in the Online Appendix.