IntroductionNon-valvular atrial fibrillation (NVAF) is known as a robust risk factor for stroke. Recent reports have suggested a risk of dementia with NVAF, but much remains unknown regarding the relationship between this mechanism and the potential protective effects of novel anticoagulants (direct oral anticoagulants (DOACs), or non-vitamin K oral anticoagulants).Methods and analysisThis study, the strategy to obtain warfarin or DOAC’s benefit by evaluating registry, is an investigator-initiated, multicentre, prospective, observational, longitudinal cohort study comparing the effects of warfarin therapy and DOACs on cerebrovascular diseases and cognitive impairment over an estimated duration of 36 months. Once a year for 3 years, the activities of daily living and cognitive functioning of non-demented patients with NVAF will be assessed. Demographics, risk factors, laboratory investigations, lifestyle, social background and brain MRI will be assessed.Ethics and disseminationThis protocol has been approved by the ethics committee of the National Center for Geriatrics and Gerontology (No. 1017) and complies with the Declaration of Helsinki. Informed consent will be obtained before study enrolment and only coded data will be stored in a secured database. The results will be published in peer-reviewed journals and presented at scientific meetings to ensure the applicability of the findings in clinical practice.Trial registration numberUMIN000025721.