Among 66,885 Albertans aged 40+ diagnosed with incident non-valvular atrial fibrillation between 2012–2024, females faced a 14% higher adjusted risk of cognitive impairment (aHR 1.14, 95% CI 1.07–1.20) yet a 25% lower risk of vascular dementia (aHR 0.75) and 9% lower all-cause mortality compared to males. NOAC therapy outperformed both warfarin and no anticoagulation in reducing cognitive impairment risk for both sexes, but protection against Alzheimer's disease and vascular dementia specifically emerged only in males.
These findings carry meaningful implications for how clinicians counsel AF patients about anticoagulation beyond stroke prevention. The growing body of evidence linking AF to accelerated cognitive decline has increasingly pointed to cerebral microemboli and silent ischemia as key drivers — pathways NOACs may interrupt more reliably than warfarin due to more consistent anticoagulation. The sex-specific divergence in dementia subtype risk is provocative: females' higher frailty burden and older age at diagnosis (74 vs. 68 years) likely confound pure biological sex effects, even after adjustment. Why NOAC-associated dementia protection appears male-specific remains unexplained and warrants mechanistic investigation.
Critically, this is a preprint posted to medRxiv and has not yet undergone peer review — conclusions could shift upon scrutiny of confounding variables, OAC adherence data, and coding accuracy in administrative databases. As an observational study, causality cannot be established. Still, the scale and population-level design make this incrementally important evidence supporting NOACs as the preferred anticoagulant class for cognitive preservation in AF.