Serum neurofilament light in atrial fibrillation: clinical, neuroimaging and cognitive correlates

Polymeris, Alexandros A. and Coslovksy, Michael and Aeschbacher, Stefanie and Sinnecker, Tim and Benkert, Pascal and Kobza, Richard and Beer, Jürg and Rodondi, Nicolas and Fischer, Urs and Moschovitis, Giorgio and Monsch, Andreas U. and Springer, Anne and Schwenkglenks, Matthias and Wuerfel, Jens and De Marchis, Gian Marco and Lyrer, Philippe A. and Kühne, Michael and Osswald, Stefan and Conen, David and Kuhle, Jens and Bonati, Leo H. and for the Swiss-AF Investigators, . (2020) Serum neurofilament light in atrial fibrillation: clinical, neuroimaging and cognitive correlates. Brain communications, 2 (2). fcaa166.

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Emerging evidence suggests that atrial fibrillation is associated with cognitive dysfunction independently of stroke, but the underlying mechanisms remain unclear. In this cross-sectional analysis from the Swiss-atrial fibrillation Study (NCT02105844), we investigated the association of serum neurofilament light protein, a neuronal injury biomarker, with (i) the CHA; 2; DS; 2; -VASc score (congestive heart failure, hypertension, age 65-74 or >75 years, diabetes mellitus, stroke or transient ischaemic attack, vascular disease, sex), clinical and neuroimaging parameters and (ii) cognitive measures in atrial fibrillation patients. We measured neurofilament light in serum using an ultrasensitive single-molecule array assay in a sample of 1379 atrial fibrillation patients (mean age, 72 years; female, 27%). Ischaemic infarcts, small vessel disease markers and normalized brain volume were assessed on brain MRI. Cognitive testing included the Montreal cognitive assessment, trail-making test, semantic verbal fluency and digit symbol substitution test, which were summarized using principal component analysis. Results were analysed using univariable and multivariable linear regression. Neurofilament light was associated with the CHA; 2; DS; 2; -VASc score, with an average 19.2% [95% confidence interval (17.2%, 21.3%)] higher neurofilament per unit CHA; 2; DS; 2; -VASc increase. This association persisted after adjustment for age and MRI characteristics. In multivariable analyses, clinical parameters associated with neurofilament light were higher age [32.5% (27.2%, 38%) neurofilament increase per 10 years], diabetes mellitus, heart failure and peripheral artery disease [26.8% (16.8%, 37.6%), 15.7% (8.1%, 23.9%) and 19.5% (6.8%, 33.7%) higher neurofilament, respectively]. Mean arterial pressure showed a curvilinear association with neurofilament, with evidence for both an inverse linear and a U-shaped association. MRI characteristics associated with neurofilament were white matter lesion volume and volume of large non-cortical or cortical infarcts [4.3% (1.8%, 6.8%) and 5.5% (2.5%, 8.7%) neurofilament increase per unit increase in log-volume of the respective lesion], as well as normalized brain volume [4.9% (1.7%, 8.1%) higher neurofilament per 100 cm; 3; smaller brain volume]. Neurofilament light was inversely associated with all cognitive measures in univariable analyses. The effect sizes diminished after adjusting for clinical and MRI variables, but the association with the first principal component was still evident. Our results suggest that in atrial fibrillation patients, neuronal loss measured by serum neurofilament light is associated with age, diabetes mellitus, heart failure, blood pressure and vascular brain lesions, and inversely correlates with normalized brain volume and cognitive function.
Faculties and Departments:03 Faculty of Medicine
UniBasel Contributors:Polymeris, Alexandros and Schwenkglenks, Matthias
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:02 Feb 2021 04:12
Deposited On:26 Jan 2021 16:19

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