MedicalResearch: What are the main findings of the study?
Dr. Bunch: The main findings of the study are:
1) Atrial fibrillation patients treated with warfarin anticoagulation that have lower percentages of time in therapeutic range have significantly higher risks of all forms of dementia.
2) The dementia relative risk related to lower percentages of time in therapeutic range was higher than all other variables associated with stroke or risk of bleeding.
3) The risk of dementia related to lower percentages of time in therapeutic range was highest in younger patients in the study (<80 years).
MedicalResearch: Were any of the findings unexpected?
Dr. Bunch: We previously found an association of all forms of dementia in patients with atrial fibrillation compared to those without including Alzheimers disease. At that time we did not know the mechanisms behind the association. One possibility that we considered was that atrial fibrillation patients over time would have small strokes undetectable by conventional imaging. These strokes over time may ultimately result in enough injury to cause dementia. In this regard, patients with frequent low levels of anticoagulation would be at higher risk for dementia. The results of this study did confirm that suspicion.
However, we also found that patients that tended to have frequent levels of anticoagulation with warfarin that were too high also had a significant risk of dementia. This likely suggests that small bleeds (micro bleeds) may also be part of the dementia process. In patients on warfarin with low percentages of time in therapeutic range are likely at higher risk of dementia due to the accumulative effects of micro clots and/or micro bleeds.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. Bunch: There is good news, those patients that were in a therapeutic range with their warfarin therapy over 75% of the time have very low long-term dementia rates. As a physician this highlights the important of education of the patient regarding warfarin and the need for frequent assessment of the INR. These findings also suggest that similar studies need to be performed in patients on the novel anticoagulants that typically have a more predictable metabolism and anticoagulant effect. I am hopeful that a more stable blood effect will lower risk of dementia in atrial fibrillation patients.
MedicalResearch: What recommendations do you have for future research as a result of this study?
Dr. Bunch: I am hopeful that these findings will prompt all future prospective studies of anticoagulants in patients with atrial fibrillation to include an analysis for cognition. In addition, I am hopeful left atrial appendage closure device trials will also study the effect of the device on cognition. With these devices there is clearly a lowering of risk of cranial bleed and a similar reduction for large strokes compared to warfarin. However, much less is known about micro embolic events that may persist despite device closure. We also need to study in warfarin patients if education and clinical decision choices can increase time in therapeutic range and if these processes will lower dementia risk.