Recent evidence suggests an increased risk of cognitive impairment and dementia in patients with atrial fibrillation (AF). Findings from the ongoing Swiss-AF cohort study in 2’415 patients showed that patients with AF have a high burden of cerebral infarcts and other vascular brain lesions on systematic brain magnetic resonance imaging (MRI) scanning. These lesions are associated with a significant loss in neurocognitive function, in their range comparable to one decade of age. Moreover, the vast majority (80%) of the detected brain lesions including infarcts were clinically silent, and they had a similar impact on cognitive performance as clinically overt stroke. However, cardiovascular comorbidities promoting the development of AF are very common in this well characterized AF population. Hence, the possibly causal role of AF cannot be evaluated since control patients in sinus rhythm with comparable comorbidities are lacking.Aim: The aim of the present study is to explore the causal role of AF in the development of brain lesions and cognitive deficits, independent of confounding cardiovascular risk factors and comorbidities. To this end, we plan to initiate a control group of patients in sinus rhythm (Swiss-AF Control study), who can be followed and compared to AF patients included in the Swiss-AF Cohort using the existing Swiss-AF network and infrastructure. Methodology: We will include patients aged =65 years in documented sinus rhythm and without a history of AF. The yearly study visits will take place at one of the 14 study centres already running the Swiss-AF Cohort Study. Detailed clinical history, resting electrocardiogram, vital parameters, extensive cognitive assessment, brain MRI screening and blood sampling will be performed at baseline and after 2 years comparable to the protocol of the Swiss-AF Cohort study. Potential Significance: Given the rising prevalence AF and vascular dementia studies assessing the potential relationship between those two growing epidemics are urgently needed. The comparison of control patients in sinus rhythm to the Swiss-AF cohort patients will enable us to explore potential causal interrelationships of AF with structural brain lesions and cognitive dysfunction. In addition, identifying mechanisms and new predictors of cognitive decline induced by AF will help to develop new prevention and treatment strategies. Thus, the proposed study has the potential to deliver important aspects for the planning of targeted interventional studies. Helping to better understanding the relationships between AF and dementia will have a high impact at the patient level and will also contribute to improve current issues of socioeconomics and public health.