The use of direct oral anticoagulants (DOACs) was associated with a reduction in dementia risk compared to traditional blood thinners – like warfarin – in patients with atrial fibrillation (AFib), particularly in Asians, according to a study published Sept. 5 in JACC: Asia. This benefit may reverse with increased age and necessitates further follow-up study.

Khi Yung Fong, et al., conducted a literature review of studies comparing the incidence of dementia between AFib patients treated with warfarin compared to DOACs. Overall, 10 studies including more than 342,000 patients were analyzed.

Results showed that DOAC use was associated with a significantly lower risk of dementia in nine studies when compared to warfarin use. After stratifying by region, a benefit for DOACs was seen in Asian patients but not European patients. Only one study included the American region. A similar benefit for DOACs was seen in patients 65-75 years old, though it was not statistically significant for patients over 75 years old.

In addition to stroke increasing risk of dementia and cognitive decline, there is evidence of stroke-independent risk of dementia in AFib patients. Other proposed factors include dietary intake, because patients taking warfarin must limit consumption of vitamin K. Low vitamin K levels are associated with both cognitive decline and Alzheimer's disease. Additionally, the green leafy vegetables with high amounts of vitamin K are often high in B12 and folate, which are associated with lower rates of cognitive decline and dementia. According to the researchers, the benefits of DOACs over warfarin may not be solely related to the impact of DOACs alone.

“Asian patients are more likely to be sensitive to vitamin K antagonism, which puts them at high risk for bleeding events, contributing to dementia development or a reduction in warfarin dose to subtherapeutic levels,” said Vern Hsen Tan, MBBS, the study’s senior author. “Asians are also often at a lower body weight compared to non-Asians, perhaps allowing the DOACs to exert supratherapeutic effects at a standard dose.”

The authors conclude that overall, the use of DOACs in AFib significantly reduces dementia risk compared to warfarin. Tan adds that moving forward, “We would highly recommend DOACs for Asian patients, in particular, as they saw the most benefit of dementia reduction. Nevertheless, the data suggestion of a reversal of this benefit with increasing age warrants further study.”