Oral Anticoagulants and the Risk of Dementia in Patients With Nonvalvular Atrial Fibrillation: A Population-Based Cohort Study

Non-valvular atrial fibrillation (NVAF) is associated with an increased risk of dementia. Oral anticoagulants (OACs) are essential for stroke prevention in NVAF and studies have shown a possible protective effect on dementia. However, findings have been inconsistent and hampered by methodological limitations. Thus, we assessed whether the use of oral anticoagulants is associated with a decreased incidence of dementia in patients with non-valvular atrial fibrillation. In addition, we explored the impact of the cumulative duration of OAC use on the incidence of dementia.Using the United Kingdom Clinical Practice Research Datalink, we formed a cohort of all patients aged 50 years or more, with an incident diagnosis of NVAF between 1988 and 2017 and no prior OAC use, with follow-up until 2019. Patients were considered unexposed until six months after their first OAC prescription for latency considerations and exposed thereafter until the end of follow-up. We used time-dependent Cox regression models to estimate hazard ratios (HRs), adjusted for 54 covariates, with 95% confidence intervals (CIs) for dementia associated with OAC use, compared with non-use. We also assessed whether the risk varied with cumulative duration of OAC use, compared with non-use, by comparing pre-specified exposure categories defined in a time-varying manner and by modelling the HR using a restricted cubic spline.The cohort included 142,227 patients with NVAF, with 8,023 cases of dementia over 662,667 person-years of follow up (incidence rate 12.1, 95% CI 11.9-12.4 per 1,000 person-years). OAC use was associated with a decreased risk of dementia (HR 0.88, 95% CI 0.84-0.92) compared with non-use. A restricted cubic spline also indicated a decreased risk of dementia, reaching a low at approximately 1.5 years of cumulative OAC use and stabilizing thereafter. Moreover, OAC use decreased the risk in patients aged 75 years and above (HR 0.84, 95% CI: 0.80-0.89), but not in those younger (HR 0.99, 95% CI: 0.90-1.10).In patients with incident NVAF, OACs were associated with a decreased risk of dementia, particularly in the elderly. This warrants consideration when weighing the risks and benefits of anticoagulation in this population.This study provides Class II evidence that in patients with NVAF, OAC use (vs. non use) is associated with a decreased risk of dementia.