Background
Atrial fibrillation (AF) is associated with a risk for stroke, transient ischemic attack, and more recently with other forms of brain injury such as cognitive impairment and dementia. In observational studies, the relative risk of cognitive impairment and dementia among patients with AF and a prior stroke is estimated between 2.43-2.70.1, 2
The Swiss Atrial Fibrillation (Swiss-AF) cohort evaluated for the presence of stroke (clinical and subclinical) in a baseline cohort of enrollees with AF that underwent MRI imaging (n=1,737 patients). Large cortical and noncortical infarcts were found in 22% of patients, small noncortical infarcts were found in 21%, microbleeds in 22%, and white matter lesions in 99%.3 These infarcts, whether labelled as clinical or subclinical were associated with cognitive dysfunction. A more recent analysis from the Swiss-AF cohort reported the outcomes of 1,227 patients that had a baseline brain MRI and another 2 years later. In this analysis, 2.3% patients had a new clinical stroke or TIA. However, at least one infarct was detected in 5.5% patients on the follow-up MRI.4 The presence of a new stroke/cerebral infarct correlated with cognitive dysfunction, whether the event was deemed clinical or subclinical by symptomatic diagnosis. These studies derived from contemporarily managed populations with AF continue to highlight the critical pathway of cerebral ischemic events as a contributing mechanism for cognitive decline and dementia in patients with AF.
Although there are randomized control data that show direct oral anticoagulants (DOAC) lower risk of stroke and intracranial bleeding compared to warfarin therapy5-7, there remains a lack of data to determine if DOAC therapy may lower risk of cognitive decline and dementia in comparison to warfarin therapy. There are mixed data in observational studies that have assessed if DOACs, that are more predictable and effective in prevention of stroke and intracranial bleeds, may further lower risk compared to warfarin.8, 9
Dabigatran etexilate, an oral direct thrombin inhibitor, was studied versus warfarin in patients with non-valvular AF.6Over a median follow-up of 2 years, dabigatran at 150 mg BID compared to warfarin lowered the risk of stroke of systemic embolism and reduced risk of hemorrhagic stroke. We also found in a community analysis of DOAC therapies, dabigatran etexilate had the lowest observed dementia rates despite the longest duration of follow-up.9
A recent consensus statement called for more prospective data regarding the use, adherence, and efficacy of anticoagulation in AF to prevent cognitive decline and dementia.10 TheC ognitive Decline and Dementia in A trialF ibrillation Patients (CAF) Trial (ClinicalTrials.gov Identifier: NCT03061006) was proposed to determine if AF patients randomized to dabigatran etexilate will have long-term higher cognition scores and lower rates of dementia compared to dose-adjusted warfarin (INR: 2.0-3.0).