Review
Mechanisms and Clinical Manifestations of Cognitive Decline in Atrial Fibrillation Patients: Potential Implications for Preventing Dementia

https://doi.org/10.1016/j.cjca.2022.10.013Get rights and content

Abstract

Atrial fibrillation (AF) patients face an approximate 1.5-fold increased risk of cognitive decline compared with the general population. Among poststroke AF patients, the risk of cognitive decline is even higher with an estimated threefold increase. This article provides a narrative review on the current evidence and highlights gaps in knowledge and areas for future research. Although earlier studies hypothesized that the association between AF and cognitive decline is mainly a consequence of previous ischemic strokes, more recent evidence also suggests such an association in AF patients without a history of clinical stroke. Because AF and cognitive decline mainly occur among elderly individuals, it is not surprising that both entities share multiple risk factors. In addition to clinically overt ischemic strokes, silent brain infarcts and other brain injury are likely mechanisms for the increased risk of cognitive decline among AF patients. Oral anticoagulation for stroke prevention in AF patients with additional stroke risk factors is one of the only proven therapies to prevent brain injury. Whether a broader use of oral anticoagulation, or more intense anticoagulation in some patients are beneficial in this context needs to be addressed in future studies. Although direct studies are lacking, it is reasonable to recommend optimal treatment of comorbidities and risk factors for the prevention of cognitive decline and dementia.

Résumé

Chez les patients atteints de fibrillation auriculaire (FA), le risque de déclin cognitif est environ 1,5 fois plus élevé qu’au sein de la population générale. Après un accident vasculaire cérébral (AVC), ce risque est encore plus élevé chez ces patients; selon les estimations, il serait alors plus que triplé. Dans le présent article, nous procédons à une revue narrative des données probantes actuelles, cernons les lacunes dans les connaissances et mettons en lumière certaines avenues de recherche. Bien que les auteurs de précédentes études aient formulé l’hypothèse selon laquelle l’association entre la FA et le déclin cognitif serait principalement une conséquence d’AVC ischémiques antérieurs, des données probantes plus récentes pointent également vers une telle association chez les patients atteints de FA sans antécédents cliniques d’AVC. Étant donné que la FA et le déclin cognitif surviennent principalement chez les personnes âgées, il n’est pas étonnant que les deux entités partagent de multiples facteurs de risque. En plus des AVC ischémiques manifestes sur le plan clinique, les infarctus cérébraux silencieux et d’autres lésions cérébrales représentent des mécanismes probables d’accroissement du risque de déclin cognitif chez les patients atteints de FA. La prise d’anticoagulants oraux en prévention des AVC chez les patients atteints de FA qui présentent d’autres facteurs de risque d’AVC constitue l’un des seuls traitements éprouvés pour empêcher la survenue de lésions cérébrales. L’opportunité d’un recours plus large aux anticoagulants oraux ou d’un traitement anticoagulant plus intensif chez certains patients dans ce contexte devra être l’objet d’études ultérieures. Malgré le manque d’études directes, on peut raisonnablement recommander la prise en charge optimale des maladies concomitantes et des facteurs de risque aux fins de prévention du déclin cognitif et de la démence.

Section snippets

Epidemiology of Cognitive Decline and Atrial Fibrillation

Although there seems to be a decrease in the age-adjusted incidence in North America1 and Europe2 the worldwide absolute estimated number of people with dementia is expected to increase from 57.4 (95% uncertainty interval, 50.4-65.1) million cases in 2019 to 152.8 (95% uncertainty interval, 130.8-175.9) million cases in 2050, because of the increasing age of societies around the world.3 Dementia is a leading cause for dependence and disability, and significantly increases the risk for adverse

Association of AF and Cognitive Decline/Dementia

There are many observational studies in the literature on the association of AF and cognitive decline or dementia, and some of the most relevant publications are summarized in Table 1. An increasing number of expert and consensus statements underscore the growing interest in this topic.20, 21, 22

The Rotterdam Study was among the first studies to describe this relationship in 1997. They reported a significant association of AF with cognitive dysfunction (odds ratio [OR], 1.7; 95% confidence

AF burden

In clinical practice, AF is usually classified into paroxysmal AF (self-terminating, in most cases within 48 hours, might continue up to 7 days), persistent AF (episodes are sustained > 7 days, including episodes that are terminated), and permanent AF (agreement between the physician and the patient to accept the arrhythmia and not perform any antiarrhythmic treatment/procedure).28 If the presence of AF per se is the main reason for thrombus formation, more AF episodes (ie, a greater AF burden)

Oral anticoagulation

There is unequivocal evidence that oral anticoagulation prevents clinical strokes among AF patients with additional stroke risk factors. Dose-adjusted warfarin reduces the risk of ischemic strokes by 64%91 and non-vitamin K oral anticoagulants are at least as effective and safer than vitamin k antagonists.92 Because of the association of overt strokes with cognitive decline as discussed previously, oral anticoagulation very likely reduces cognitive dysfunction although direct evidence is

Treatment of Risk Factors and Lifestyle

Nearly all patients with AF do have additional cardiovascular risk factors and comorbidities. In Swiss-AF 69%, 27%, 22%, and 15% of the participants had a history of hypertension, coronary artery disease, congestive heart failure, and diabetes at study enrollment, respectively.71 Despite a lack of clinical trials specifically addressing this topic in AF patients, optimal treatment of comorbidities and risk factors probably has a beneficial effect on cognitive function. A systematic review and

Conclusion

AF and cognitive dysfunction are major public health issues and key contributors to health care costs. The crucial contribution of overt ischemic strokes has already been recognized, but AF patients have a greater risk of cognitive decline and dementia even in the absence of overt strokes, highlighting the potential importance of covert brain injuries, which are highly prevalent in this population. Specific trials are needed to test interventions for the prevention of brain injury and cognitive

Funding Sources

None.

Disclosures

David Conen: advisory board fees, Roche Diagnostics and Trimedics; speaker fees, Servier and BMS/Pfizer. Steffen Blum: research grants from the Swiss National Science Foundation, the Mach-Gaensslen Foundation, and the Gottfried and Julia Bangerter-Rhyner Foundation outside the submitted work.

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