Authors:
Alexandros Polymeris (Basel | CH)
Tim Sinnecker (Basel | CH)
Pascal Benkert (Basel | CH)
Nicolas Rodondi (Bern | CH)
Andreas Müller (Zurich | CH)
Jürg Beer (Baden | CH)
Giorgio Moschovitis (Lugano | CH)
Daniel Hayoz (Fribourg | CH)
Jan Novak (Solothurn | CH)
Jürg Schläpfer (Lausanne | CH)
Marcello di Valentino (Bellinzona | CH)
Urs Fischer (Bern | CH)
Andreas Monsch (Basel | CH)
Jens Wuerfel (Basel | CH)
Matthias Schwenkglenks (Zurich | CH)
Michael Kühne (Basel | CH)
Stefan Osswald (Basel | CH)
David Conen (Basel | CH)
Jens Kuhle (Basel | CH)
Leo Bonati (Basel | CH)
Background and Aims
There is emerging evidence that atrial fibrillation (AF) is associated with cognitive dysfunction, increased risk for dementia and reduced brain volume independent of stroke, but the underlying mechanisms of these associations remain unclear. Here, we investigated the association of serum neurofilament light chain (sNfL), a neuroaxonal injury biomarker, with brain atrophy in AF patients.
Methods
Explorative analysis from the prospective observational Swiss-AF cohort study (NCT02105844), which recruited AF patients aged ≥ 65 years without recent stroke. We measured sNfL concentrations in duplicate at baseline using a single molecule array (SIMOA) assay. Brain MRI was obtained at baseline and after two years using a standardized protocol. This included a 3D T1-weighted MPRAGE sequence, on which we applied Structural Image Evaluation using Normalization of Atrophy (SIENA) with optimized parameters for brain extraction to calculate the two-year percentage whole brain volume change (PBVC). We further assessed the normalized brain volume using SIENAX, presence and volume of ischemic infarcts and white matter hyperintensities and count of microbleeds on appropriate sequences on the baseline MRI. We excluded patients with acute infarcts.
Results
We included 232 consecutive Swiss-AF patients (median age 73, 75% male) for whom pilot data were available. In a simple linear regression model, baseline sNfL was significantly associated with two-year PBVC, with a 0.13% whole brain volume decrease per 10 pg/ml higher sNfL levels (95% CI [0.07, 0.19], p < .001). This association remained significant after adjustment for clinical parameters (age, sex, AF type, history of stroke and other vascular risk factors) and baseline MRI variables (aforementioned vascular brain lesions and normalized brain volume).
Conclusion
In AF patients, baseline sNfL was predictive of brain atrophy at two years independent of stroke history, cerebral infarcts and MRI markers of small vessel disease. This association might reflect a chronic neurodegenerative process in AF.