Projects & Collaborations 2 foundShow per page10 10 20 50 Mechanisms of cognitive decline in patients with atrial fibrillation: the Swiss AF-Brain Study Research Project | 3 Project MembersBACKGROUND: 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. Swiss Atrial Fibrillation Cohort Study Research Project | 7 Project MembersAtrial fibrillation (AF) is the most common cardiac arrhythmia in the general population. Due to the demographic change with increasing life expectancy, the incidence of AF is expected to further increase in the near future. Patients suffering from AF have an increased risk of serious complications, including stroke and heart failure. Recent studies found that patients with AF have an increased risk of cognitive decline and dementia over time. However, the magnitude of the problem, associated risk factors and underlying mechanisms remain unclear. Specific aims:1.To assess cognitive functions in patients with AF in the long-term2.To correlate structural brain damage and their short-term changes with long-term cognitive decline3.To quantify health care cost among patients with AF in SwitzerlandStatus of study: Enrollment of 2415 AF patients was completed in August 2017. Follow-up investigations are ongoing. Procedures: Study questionnaires, clinical examinations, blood samples (incl. genetics) for bio-banking, advanced 12-lead ECG, bMRI, cognitive assessments, disability, quality of life, and financial costs. Follow-up: Yearly clinical follow-up, covariate update, 12-lead ECG, cognitive assessments, and outcome evaluations. bMRI and blood sampling will be repeated after 2 years in all patients.Main clinical outcome measures: Death, stroke, systemic embolism, hospitalization for heart failure, myocardial infarction, any unplanned hospitalization, major bleeding and clinically relevant non-major bleedingPreliminary results: Overall, 2415 patients were enrolled in Swiss-AF. The mean age (± standard deviation) of the population was 73 ± 8.5 years; 27.1% were female. 45% of the patients had paroxysmal AF, whereas 29% and 26% had persistent and permanent AF, respectively. A history of stroke, bleeding, heart failure and hypertension was present in 13%, 26%, 15% and 69%, respectively. Median (interquartile range) CHA2DS2-VASc score was 3 (2-5). Of 2173 patients (90%) with oral anticoagulation, 56.2% were on non-vitamin-K antagonist oral anticoagulants.Impact: By establishing a national, comprehensive and interdisciplinary AF network, this cohort study is highly responsive to the current SNSF call for longitudinal studies and has the unique potential to provide important novel insights on long-term disease progression and clinical outcomes in patients with AF. The main focus on cognitive functioning and neurological complications is of major public health importance. Several major unmet clinical needs that will provide clinicians with better tools to take care of this growing patient population will be addressed. The current project also has a great potential to identify novel treatment targets for several important and currently unresolved public health problems, including AF, cognitive dysfunction or stroke. Detailed cost assessments will help to define more efficient patient care that will lead to less disability and reduced costs for the society as a whole. 1 1
Mechanisms of cognitive decline in patients with atrial fibrillation: the Swiss AF-Brain Study Research Project | 3 Project MembersBACKGROUND: 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.
Swiss Atrial Fibrillation Cohort Study Research Project | 7 Project MembersAtrial fibrillation (AF) is the most common cardiac arrhythmia in the general population. Due to the demographic change with increasing life expectancy, the incidence of AF is expected to further increase in the near future. Patients suffering from AF have an increased risk of serious complications, including stroke and heart failure. Recent studies found that patients with AF have an increased risk of cognitive decline and dementia over time. However, the magnitude of the problem, associated risk factors and underlying mechanisms remain unclear. Specific aims:1.To assess cognitive functions in patients with AF in the long-term2.To correlate structural brain damage and their short-term changes with long-term cognitive decline3.To quantify health care cost among patients with AF in SwitzerlandStatus of study: Enrollment of 2415 AF patients was completed in August 2017. Follow-up investigations are ongoing. Procedures: Study questionnaires, clinical examinations, blood samples (incl. genetics) for bio-banking, advanced 12-lead ECG, bMRI, cognitive assessments, disability, quality of life, and financial costs. Follow-up: Yearly clinical follow-up, covariate update, 12-lead ECG, cognitive assessments, and outcome evaluations. bMRI and blood sampling will be repeated after 2 years in all patients.Main clinical outcome measures: Death, stroke, systemic embolism, hospitalization for heart failure, myocardial infarction, any unplanned hospitalization, major bleeding and clinically relevant non-major bleedingPreliminary results: Overall, 2415 patients were enrolled in Swiss-AF. The mean age (± standard deviation) of the population was 73 ± 8.5 years; 27.1% were female. 45% of the patients had paroxysmal AF, whereas 29% and 26% had persistent and permanent AF, respectively. A history of stroke, bleeding, heart failure and hypertension was present in 13%, 26%, 15% and 69%, respectively. Median (interquartile range) CHA2DS2-VASc score was 3 (2-5). Of 2173 patients (90%) with oral anticoagulation, 56.2% were on non-vitamin-K antagonist oral anticoagulants.Impact: By establishing a national, comprehensive and interdisciplinary AF network, this cohort study is highly responsive to the current SNSF call for longitudinal studies and has the unique potential to provide important novel insights on long-term disease progression and clinical outcomes in patients with AF. The main focus on cognitive functioning and neurological complications is of major public health importance. Several major unmet clinical needs that will provide clinicians with better tools to take care of this growing patient population will be addressed. The current project also has a great potential to identify novel treatment targets for several important and currently unresolved public health problems, including AF, cognitive dysfunction or stroke. Detailed cost assessments will help to define more efficient patient care that will lead to less disability and reduced costs for the society as a whole.
