Atrial fibrillation is the most common heart rhythm disorder. Individuals with atrial fibrillation have an increased risk of stroke and are treated with medications called oral anticoagulants to reduce this risk. Recent studies have also shown that people with atrial fibrillation have a higher risk of dementia. There are many types of dementia and the presence of atrial fibrillation increases the risk of various types of dementia, including Alzheimer's disease. This increased risk could be related, among other things, to small recurrent strokes that, even if they go unnoticed, gradually deteriorate the brain. Oral anticoagulants could therefore effectively prevent the occurrence of these small brain attacks and thus reduce the risk of dementia. The main objective of this study will be to estimate the potential benefit of oral anticoagulant therapy (reduced risk of dementia) in individuals with atrial fibrillation. We will determine all patients with a first diagnosis of atrial fibrillation and compare the number of patients with dementia in those treated with oral anticoagulants to untreated patients during follow-up. We will then study the benefit according to the duration of the oral anticoagulant treatment, and according to the timing of initiation of the treatment.
Oral anticoagulation is essential in the management of atrial fibrillation (AF) to prevent the physical disability and mortality associated with stroke occurrence but may also play a role in maintaining cognitive functions. Indeed, patients with AF have an increased risk of dementia compared to the general population. This association has been shown not only with vascular dementia but also with other types of dementia including Alzheimer's disease. In addition to the easily explainable link between AF and vascular dementia in relation to the occurrence of strokes, the association with other types of dementia may be related to repeated microembolisms, but other mechanisms may also be involved. However, few studies have assessed the potential preventive role of oral anticoagulants on the risk of dementia in patients with AF. Thus, we will conduct a population-based cohort study to assess whether the use of oral anticoagulants is associated with the incidence of dementia among patients with non-valvular atrial fibrillation. We will form a cohort of all patients aged 50 years or older newly diagnosed with non-valvular AF between 1988 and 2017. Exposure to oral anticoagulants will be modelled as a time-dependent variable. We will use Cox proportional hazards models to estimate hazard ratios with 95% confidence intervals of dementia associated with use of oral anticoagulants compared with no use. In secondary analyses, we will assess whether this risk varies with cumulative duration of use and with time between AF and oral anticoagulant initiation. Several sensitivity analyses will be performed to assess the robustness of our results.
We will identify all patients within our cohort with a first-time read code for dementia recorded any time after cohort entry. The diagnostic codes for dementia have been previously validated in the CPRD.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Christel Renoux - Corresponding Applicant - McGill University
Alvi Rahman - Collaborator - McGill University
Erica Moodie - Collaborator - McGill University
James Brophy - Collaborator - McGill University
Jason Guertin - Collaborator - Université Laval
Jean-François Boivin - Collaborator - McGill University
Madeleine Durand - Collaborator - Centre Hospitalier de l'Universite de Montreal
Sophie Dell'Aniello - Collaborator - McGill University
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