Are patients with atrial fibrillation at increased risk of developing dementia?

Pasquale Santangeli
Pasquale Santangeli

A recent study, published in Heart Rhythm, found that atrial fibrillation was independently associated with dementia. The lead author of the study, Pasquale Santangeli (Texas Cardiac Arrhythmia Institute, St David’s Medical Centre, Austin, USA), spoke to Cardiac Rhythm News about the link between atrial fibrillation and dementia.

Prior to your study, atrial fibrillation was associated with an increased risk of developing or worsening dementia in patients who have suffered an acute stroke or who already have cognitive impairment. What evidence supports this association?

The association between atrial fibrillation and an increased risk of developing dementia after an acute stroke has been consistently reported in previous studies.

In our systematic review, we reported a total of seven prospective studies that were specifically designed to evaluate the risk of dementia after an acute stroke. Remarkably, atrial fibrillation was consistently shown to be associated with an increased risk of post-stroke dementia in all these studies. With regard to patients who already have evidence of cognitive decline, atrial fibrillation has been also shown to be associated with worsening cognitive function; although, in this setting, it is more difficult to isolate the effect of atrial fibrillation. Indeed, in these patients cognitive function might worsen independently of the presence of atrial fibrillation.

Previously, was the view that atrial fibrillation increased the risk of dementia in patients without these potential confounders “controversial”?

If we look at all the available studies evaluating the risk of new-onset dementia in patients with atrial fibrillation not suffering an acute stroke and with normal baseline cognitive function, only about 50% of the studies reported a significant longitudinal association between these two conditions. Prior to our analysis, the reasons for such heterogeneity of results were unclear. We showed that the major determinant of a positive association between atrial fibrillation and the risk of developing dementia was the length of the study follow-up. In brief, relatively long follow-up periods appear necessary to disclose a relationship between presence of atrial fibrillation and risk of developing dementia.

Briefly, what did your study find about the association between atrial fibrillation and incident dementia?

Our study systematically reviewed data from nine large observational studies enrolling more than 77,000 patients with normal baseline cognitive function and not suffering an acute stroke. In brief, the results of our analysis show that atrial fibrillation significantly increases the risk of developing dementia over follow-up, independently from other baseline confounders. Based on our findings, patients with atrial fibrillation constitute a subset at increased risk of developing dementia, and periodical screening for dementia over long-term periods is warranted in order to reach an early diagnosis and treatment of the condition.

If there is a link between atrial fibrillation and dementia, what is the potential pathophysiology behind this association?

From a pathophysiological perspective, the inherent risk of cerebrovascular thromboembolism, including silent embolic events, together with global brain hypoperfusion due to impaired cardiac haemodynamics, may all account for the increased risk of developing dementia in patients with atrial fibrillation. On the other hand, properly designed studies are necessary to evaluate what is the underlying pathophysiology linking atrial fibrillation with increased risk of dementia.

In your study, you conclude that patients with atrial fibrillation should be periodically screened for dementia. What should this screening process involve?

The studies included in our pooled analysis adopted established tools of screening for cognitive impairment, which included the Mini-Mental State Exam (MMSE), neuropsychological tests, and established criteria from the Diagnostic Statistical Manual of Mental Disorders (DSM). Other tools, such as the Montreal Cognitive Assessment (MoCA), have been proven to have fairly adequate sensitivity and specificity for cognitive impairment screening. Further studies are warranted to evaluate which one is the best tool to screen patients with atrial fibrillation for dementia.

Should patients be made aware of the potential association between atrial fibrillation and dementia at diagnosis (ie, so that they can be aware of the signs and symptoms)?

Patients with atrial fibrillation should understand that dementia is a condition potentially associated with their arrhythmia, especially at long-term follow-up. Patient awareness is a critical part of dementia prevention. Patients and families should have basic skills and knowledge to recognise the signs and symptoms of dementia, and feel confident in recording and appropriately reporting these to doctors.

In your study, you also suggest that studies should investigate whether established therapies for atrial fibrillation could reduce the risk of developing dementia. How should these studies be designed?

The most reliable way to evaluate whether maintaining stable sinus rhythm in patients with atrial fibrillation by means of rhythm-control therapies (eg, catheter ablation and/or antiarrhythmic drugs) is associated with a reduction of the risk of developing dementia is to design a large randomised trial with a long follow-up period.

Some large trials and registries that are ongoing might provide valuable information in this sense. The CABANA (Catheter ablation versus antiarrhythmic drug therapy for atrial fibrillation trial) study is currently randomising patients with atrial fibrillation to either catheter ablation or pharmacologic therapy with rate or rhythm control drugs. With an estimated more than 3,000 patients enrolled, CABANA is the first ablation trial with an adequate power to detect differences in mortality, which constitutes the primary endpoint of the trial. The ongoing SAFARI (Safety of Atrial Fibrillation Ablation Registry Initiative) registry is a collaborative US nationwide registry for collecting data related to atrial fibrillation ablation. SAFARI will include more than 5,000 patients undergoing catheter ablation of atrial fibrillation and will assess the safety and effectiveness of atrial fibrillation ablation in a wide variety of clinical settings.

Neither the CABANA nor the SAFARI have included dementia among the assessed outcomes, despite they are potentially powered enough to evaluate this endpoint. Based on our findings, the inclusion of dementia among the endpoints assessed in these large ongoing studies might provide important information.