Anticoagulation therapy and dementia in atrial fibrillation: An umbrella review of systematic reviews

Atrial fibrillation (AF) increases the risk of stroke and cognitive decline. While anticoagulation with vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) prevents stroke, their role in reducing dementia risk in patients with AF remains unclear. To evaluate the effect of anticoagulation therapy on dementia incidence in patients with AF, comparing DOACs versus VKAs. We systematically reviewed PubMed, Scopus, Web of Science, Embase, and Cochrane. Systematic reviews and meta-analyses evaluating the effects of anticoagulation therapies on dementia were included. A total of 11 systematic reviews and meta-analyses were included in this umbrella review. Findings from 6 systematic reviews showed that OAC use was associated with a reduced risk of incident dementia in patients with AF, with effect estimates (RR/HR) ranging from 0.46 [0.28-0.78] to 0.79 [0.67-0.93]. For DOACs versus VKAs, most studies found a lower risk of dementia with DOACs, with effect sizes ranging from HR: 0.51 [0.37-0.71] to RR: 0.88 [0.82-0.94]. However, two studies found no significant difference between DOACs and warfarin in dementia risk (OR: 0.65 [0.34-1.25] and RR: 0.91 [0.75-1.12], respectively). Anticoagulation therapy, particularly with DOACs, may help reduce the risk of dementia in AF patients. The evidence remains of moderate to low certainty, and further high-quality, long-term randomized controlled trials are needed to confirm these findings and explore the neuroprotective mechanisms of OACs.