Both atrial fibrillation (AF) and dementia are highly prevalent pathologies, with reported rates of approximately 33.5 million and 40 million worldwide.1,2 Experts anticipate that the prevalence of both conditions will continue to increase along with the growing elderly population, and accumulating research suggests that AF may increase the risk for cognitive decline and dementia.2,3

Thereare many studies showing an increased rate of all types of dementia in patientswith [AF], said Hugh Calkins, MD, FHRS, FACC, FAHA, FESC, the Catherine Ellen Poindexter Professor of Cardiology and director ofthe electrophysiology laboratory and arrhythmia service at Johns Hopkins University.New data [have] also shown thattreatment of AF lowers the risk of cognitive dysfunction, he told NeurologyAdvisor.

However,findings on the topic have been mixed overall, which may be the result of methodologicdifferences such as variation in age ranges and methods used to assess AF and dementia.2In addition, most of these studies focused on prevalent AF rather than incidentAF, as noted by the authors of a study published in the July 2019 issue of the EuropeanHeart Journal.2

To addressthis gap, these researchers conducted a longitudinal, community-based study in SouthKorea to examine associations between incident AF and the risk for dementia, aswell as the influence of stroke and the administration of oral anticoagulants on theseassociations. The sample consistedof 262,611 participants aged 60years who did not have AF, dementia, valvular heartdisease, or stroke at the time of enrollment.

The following results were observed:

Based on these findings, clinicians should be vigilant for clinical manifestations implying any cognitive decline and functional impairment in [patients with AF], especially those with a high CHA2DS2-VASc score,the authors wrote.2

These results alignwith those of a 2018 population-based cohort study (n=2685) which found an associationbetween AF and rapid decline on the Mini-Mental State Examination (, 0.24; 95% CI, 0.31 to 0.16) and an increasedrisk for all-cause dementia (HR,1.40; 95% CI, 1.11-1.77) and vascular and mixed dementia (HR, 1.88; 95% CI, 1.09-3.23).4Findings further revealed that the use of anticoagulants was associated with a 60%reduction in dementia risk among patients with both prevalent and incident AF (HR,0.40; 95% CI, 0.18-0.92).

Similarly, resultsof an epidemiologic review published in 2018 reinforced these findings, with investigatorsreporting that the available evidence largely suggests that AF contributes to cognitivedecline and dementia, independent of a history of stroke.3

According to Paul JWang, MD, professor of medicine in the division of cardiology at Stanford UniversityMedical Center and director of the Stanford Cardiac Arrythmia Service, theproposed mechanisms underlying the AF-dementia link include ischemic stroke, chronic inflammation, andhypoperfusion of the brain.

Despite these findings, however, there is currently not enoughevidence to treat AF purely with a goal of reducing or preventing dementia, DrCalkin noted. It is important to follow anticoagulation guidelines in all [peoplewith] AF, and if a patient with AF has symptoms, then a rhythm control strategywith medications or catheter ablation is warranted.

Thisis an important topic, but needs to be further elucidated. Prospective trials areneeded and underway, Dr Wang told Neurology Advisor.

Dr Calkinsechoed this notion and added that additional large-scale randomized trials areneeded to confirm that treatment of AF prevents or slows the development of dementia.

To gain furtherinsight into this topic and its related clinical implications, Neurology Advisorinterviewed Rebecca Gottesman, MD, PhD, professor of neurology and epidemiologyin the division of cerebrovascular neurology at Johns Hopkins University and director of research at Johns Hopkins Bayview Neurology.

Neurology Advisor: What isknown thus far about associations between AF and dementia, including proposed mechanismsby which AF might influence the development of cognitive dysfunction and dementia?

Dr Gottesman: A number of studieshave shown that AF is an independent risk factor for cognitive decline and perhapseven dementia. The association appears to extend beyond just having shared riskfactors for both AF and cognitive decline.

The most well-documented mechanism is through strokes, which canlead to cognitive problems and even dementia. It is also probable that many patientswith AF have silent infarcts, which similarly adversely affect cognition. But theremay be other mechanisms that dont involve these structural changes, perhaps relatedto hypoperfusion in patients with AF.

Neurology Advisor: What arethe relevant screening and treatment recommendations that clinicians shouldfollow?

Dr Gottesman: The steps thatclinicians take to reduce stroke risk are likely the most important things thatcan be done to reduce dementia risk. Anticoagulation to reduce stroke risk willprobably also reduce silent infarction risk, so it is likely to help preserve cognitivefunction in patients with AF. There is no evidence that rate control makes a differencein either stroke risk or dementia risk, however.

The American Heart Associations recommendation for screeningin primary stroke prevention consists of pulsepalpation in older adults, with an electrocardiogram in the event of an irregularpulse, but with no other recommendations for active AF screening needed.5For dementia and cognitive impairment, its likely that a similar screening approachis best.

Neurology Advisor: What areremaining research needs pertaining to the link between AF and cognitive declineand dementia?

Dr Gottesman: We still verymuch need to understand the underlying mechanisms. Furthermore, I mentioned thattheres no evidence that rate control reduces cognitive impairment or dementia frequency,yet if episodes of rapid ventricular response contribute to hypoperfusion, for example,perhaps there are meaningful sequelae of alterations in rate.

Finally, although it is likely that reducing stroke risk withanticoagulation will also reduce cognitive impairment and dementia, there isntevidence specifically proving this. It is also important to study whether differentcriteria differentially identify the level of risk for cognitive decline and dementia.For example, a CHA2DS2-VASc score is definedbased on stroke risk and informs the clinician about risk for stroke, thus informingdecisions about anticoagulation, but a lower threshold might need to be consideredfor risk for dementia, which might warrant initiation of anticoagulation at a differentrisk level, at least theoretically.

In addition, there is increasing interest inatrial structural changes that can have an impact on stroke risk. As more researchis done about these changes as a cause of embolic stroke of undetermined source,it will be important to consider whether there is also an increased risk for cognitivedecline and dementia with these cardiac non-AF structural changes.

References

1. Patel NJ, Atti V, Mitrani RD, Viles-Gonzalez JF, Goldberger AJ. Global rising trends of atrial fibrillation: a major public health concern. Heart. 2018;104(24):1989-1990.

2. Kim D, Yang PS, Yu HT, et al. Risk of dementia in stroke-free patients diagnosed with atrial fibrillation: data from a population-based cohort. Eur Heart J. 2019;40(28):2313-2323.

3. Ding M, Qiu C. Atrial fibrillation, cognitive decline, and dementia: an epidemiologic review. Curr Epidemiol Rep. 2018;5(3):252-261.

4. Ding M, Fratiglioni L, Johnell K, et al. Atrial fibrillation, antithrombotic treatment, and cognitive aging: a population-based study. Neurology. 2018;91(19):e1732-e1740.

5. Meschia JF, Bushnell C, Boden-Albala B, et al. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(12):3754-3832.

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Exploring the Link Between Atrial Fibrillation and Dementia - Neurology Advisor