Rivard L, Khairy P, Talajic M, et al. - Given the growing evidence of an association between atrial fibrillation (AF) and cognitive decline and dementia, researchers report the protocol for a prospective, multicentric, double-blind, randomized-controlled trial, the Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation (BRAIN-AF), which will be performed to find out if a reduced risk of stroke, transient ischemic attack, or cognitive decline can be achieved with oral anticoagulation therapy vs standard of care in patients with nonvalvular AF and a low risk of stroke. In a randomized manner, they will assign participants to receive either rivaroxaban (15 mg daily) or standard of care (placebo in patients without vascular disease or acetylsalicylic acid 100 mg daily in patients with vascular disease). They will assess the composite of stroke, transient ischemic attack, and cognitive decline (defined by a reduction in the Montreal Cognitive Assessment score ≥ 3 at any follow-up visit following baseline) as the primary outcome. Until the occurrence of 609 adjudicated primary outcome events, the enrollment of nearly 3,250 patients in approximately 130 clinical sites will be done.