A Population-based Study of Sex Differences in Cognitive Impairment and Dementia Among Incident Atrial Fibrillation Patients and the Influence of Thromboprophylaxis

Background: It is unclear if sex differences exist in cognitive impairment and dementia associated with atrial fibrillation (AF) and whether this relationship is influenced by oral anticoagulation (OAC) therapy. Methods: We identified patients [&ge;]40 years with incident non-valvular AF (NVAF) and without previous history of cognitive impairment or dementia, stroke/transient ischemic attack or contraindication to OAC between April 1st, 2012 and March 31st, 2024, using linked administrative databases in Alberta, Canada. Outcomes included cognitive impairment, Alzheimer's disease, vascular dementia, and all-cause mortality. Survival models were used to estimate association between sex and outcomes, and between OAC therapy and outcome stratified by sex. Results: Of 66,885 patients, 43% were female. Compared to males, females were older (74 vs 68 years), frailer (14.7% vs 10.1%), and more likely to have CHA2DS -VA score [&ge;]2 (73% vs 65%). OAC was initiated in 60% of both sexes within 120 days of diagnosis. Females had a higher risk for cognitive impairment (aHR 1.14 [95% CI 1.07-1.20], p<0.0001), but a lower risk of vascular dementia (aHR 0.75 [95% CI 0.63-0.90], p=0.0016) and all-cause mortality (aHR 0.91 [95% CI 0.88-0.94], p<0.001), with no difference in risk of Alzheimer's disease (aHR 1.01 [95% CI 0.88-1.17], p=0.8496) between the sexes. Non-vitamin-K OAC (NOAC) use was associated with a lower risk of cognitive impairment compared to either warfarin or no OAC in both sexes, but a lower risk of Alzheimer's and vascular dementia in males only. Conclusion: In this large population-based study, we found females have a higher risk of cognitive impairment, but a lower risk of vascular dementia and all-cause mortality compared to males. For both sexes, NOAC use was associated with a lower risk of cognitive impairment compared to no OAC and a lower risk of Alzheimer's and vascular dementia in males only.