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Mechanisms of cognitive decline in patients with atrial fibrillation: the Swiss AF-Brain Study

Research Project
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01.01.2021
 - 31.12.2024

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia, and a major cause of heart failure and stroke. Evidence has emerged that the risk of cognitive impairment and dementia is increased in patients with AF, even in the absence of stroke. Our current understanding of the mechanisms underlying cognitive decline in AF is limited. AIMS AND METHODS: The main research aims of this proposal are first, to discover mechanisms for cognitive decline in patients with AF. Second, we aim to develop risk models helping to identify those patients at greatest risk for cognitive decline. The present proposal is a Large Nested Study embedded in the Swiss Atrial Fibrillation Cohort (Swiss-AF, 33CS30_177520), which provides an ideal and unique framework to achieve our research aims. In Swiss-AF, we have recruited 2415 patients with AF and without dementia at baseline at 14 study sites in Switzerland and investigated them with brain magnetic resonance imaging (MRI) and blood sampling at baseline, as well as annual neurocognitive testing for a median follow-up duration of 3 years. In the present project, we aim to perform neurocognitive testing to assess cognitive decline in 900 patients 7 years after inclusion in the Swiss-AF Cohort. 500 of these patients will additionally undergo follow-up brain MRI and blood sampling at 7 years. MRI includes assessment of vascular brain lesions, global and regional brain volume loss between baseline and 7 years, as well as advanced quantitative imaging: arterial spin labelling (ASL) to detect alterations of regional and global brain perfusion; resting-state functional MRI to reveal the impact of brain network function; magnetization prepared 2 rapid acquisition gradient echoes mapping (MP2RAGE) to quantify T1 relaxation times as a marker for micro-structural brain tissue integrity; and quantitative susceptibility mapping (QSM) to sensitively detect haemorrhages as well as quantify regional and global occult iron deposition as a marker of neurodegeneration. We will measure neurofilament light-chain (NfL) as a neuronal injury marker, as well as other brain pathology markers including glial fibrillary acidic protein (GFAP), and S100 protein (S100b) in the baseline and 7-year blood samples. In addition we will perform Mendelian randomisation studies using available genotyped data to identify risk factors causally related to cognitive decline. The risk model for cognitive decline will be constructed with the clinical, neuroimaging, and biomarker data at baseline of all 900 patients with AF followed-up at 7 years. SIGNIFICANCE: Mechanistic insights into cognitive decline in AF may help identify patients at risk and lead to the discovery of potential targets for prevention.

Funding

Mechanisms of cognitive decline in patients with atrial fibrillation: the Swiss AF-Brain Study

SNF Schweizerischer Nationalfonds, 04.2021-03.2025 (48)
PI : Bonati, Leo.
CI : Kühne, Michael,Wuerfel, Jens.

Members (3)

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Leo Bonati

Principal Investigator
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Michael Kühne

Co-Investigator
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Jens Wuerfel

Co-Investigator