What Promotes Dementia in Atrial Fibrillation Patients?

Why are anticoagulated atrial fibrillation patients at higher risk of developing dementia?

One explanation is that anticoagulation excursions cause microbleed and embolic-related strokes, respectively. Anticoagulation has a U-shaped hazard curve: too little causes cerebral infarcts, and too much leads to hemorrhages.

In addition, coronary artery disease (CAD) is comorbid in 20% of atrial fibrillation patients, a population that typically uses antiplatelet therapy and oral anticoagulants together. This regimen increases the risk for bleeding, especially if it is prolonged.

Recently, a team of researchers from the Intermountain Medical Center in Utah investigated the relationship between anticoagulation and dementia in atrial fibrillation patients, with the rationale that the standard of care for CAD is aspirin plus a P2Y₁₂ adenosine diphosphate receptor inhibitor such as clopidogrel, and combination anticoagulation especially increases the risk of brain hemorrhage.

The researchers followed 992 adult atrial fibrillation patients undergoing warfarin anticoagulation for a median of 4 years. They excluded patients with a history of stroke, transient ischemic attack (TIA), or dementia.

Forty patients developed dementia during the study period. The dementia subtype (e.g. Alzheimer’s) and CHADS₂ scores did not differ relative to time outside therapeutic range of anticoagulation.

Patients with supratherapeutic international normalized ratios (INRs) for more than 25% of the study period had a 2.65 times greater risk of developing dementia compared with patients who were supratherapeutic for less than 10% of the time.

Increased age, heart failure, and vascular disease all increased dementia risk, but renal disease did not.

Patients on an antiplatelet agent such as aspirin and/or clopidogrel were at greater risk of dementia directly related to their percentage time spent outside the therapeutic range. The authors asserted that the risk of bleeding in patients undergoing triple therapy is falsely low because clinicians generally do not use triple therapy in patients with higher bleed risk.

Health care professionals should weigh atrial fibrillation patients’ bleeding and thrombosis risk across disease states. It is crucial to balance the risk of anticoagulation therapy-related dementia with inherent stroke risk.

The authors concluded that the risk of repeated microvascular bleeds and clots is as clinically critical as single macrovascular events.

They noted that pre-dementia cognitive impairment confounds their results because of a tendency for poorer medication adherence, and by extension, poorer anticoagulation control.

This article appeared ahead of print in the Journal of Cardiovascular Electrophysiology.