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

“There are many studies showing an increased rate of all types of dementia in patients with [AF],” said Hugh Calkins, MD, FHRS, FACC, FAHA, FESC, the Catherine Ellen Poindexter Professor of Cardiology and director of the electrophysiology laboratory and arrhythmia service at Johns Hopkins University. “New data [have] also shown that treatment of AF lowers the risk of cognitive dysfunction,” he told Neurology Advisor.

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

To address this gap, these researchers conducted a longitudinal, community-based study in South Korea to examine associations between incident AF and the risk for dementia, as well as the influence of stroke and the administration of oral anticoagulants on these associations. The sample consisted of 262,611 participants aged ≥60 years who did not have AF, dementia, valvular heart disease, or stroke at the time of enrollment.


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The following results were observed:

  • During a follow-up period of 1,629,903 person-years (0.64%/year), there were 10,435 cases of incident AF.   
  • The incidence of dementia was 4.1 per 100 person-years in the AF group, compared with 2.7 per 100 person-years in a propensity score-matched AF-free group.
  • After adjustment for covariates including age, sex, and clinical variables such as hypertension, cardiovascular events, and alcohol and smoking habits, AF was found to increase the risk for dementia (hazard ratio [HR], 1.52; 95% CI, 1.43-1.63), even in the absence of stroke (HR, 1.27, 95% CI 1.18-1.37).
  • AF was specifically shown to increase the risk for Alzheimer disease (HR 1.31, 95% CI, 1.20-1.43) and vascular dementia (HR, 2.11; 95% CI, 1.85-2.41).
  • Oral anticoagulant use was found to have a preventive effect on dementia risk among those with AF (HR, 0.61; 95% CI, 0.54-0.68), and higher scores on the CHA2DS2-VASc were associated with a greater risk for dementia.

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 align with those of a 2018 population-based cohort study (n=2685) which found an association between AF and rapid decline on the Mini-Mental State Examination (β, −0.24; 95% CI, −0.31 to −0.16) and an increased risk 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).4 Findings 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, results of an epidemiologic review published in 2018 reinforced these findings, with investigators reporting that the available evidence largely “suggests that AF contributes to cognitive decline and dementia, independent of a history of stroke.”3

According to Paul J Wang, MD, professor of medicine in the division of cardiology at Stanford University Medical Center and director of the Stanford Cardiac Arrythmia Service, the proposed “mechanisms underlying the AF-dementia link include ischemic stroke, chronic inflammation, and hypoperfusion of the brain.”

Despite these findings, however, there is currently “not enough evidence to treat AF purely with a goal of reducing or preventing dementia,” Dr Calkin noted. “It is important to follow anticoagulation guidelines in all [people with] AF, and if a patient with AF has symptoms, then a rhythm control strategy with medications or catheter ablation is warranted.”

“This is an important topic, but needs to be further elucidated. Prospective trials are needed and underway,” Dr Wang told Neurology Advisor.

Dr Calkins echoed this notion and added that “additional large-scale randomized trials are needed to confirm that treatment of AF prevents or slows the development of dementia.”

To gain further insight into this topic and its related clinical implications, Neurology Advisor interviewed Rebecca Gottesman, MD, PhD, professor of neurology and epidemiology in the division of cerebrovascular neurology at Johns Hopkins University and director of research at Johns Hopkins Bayview Neurology.

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

Dr Gottesman: A number of studies have shown that AF is an independent risk factor for cognitive decline and perhaps even dementia. The association appears to extend beyond just having shared risk factors for both AF and cognitive decline.

The most well-documented mechanism is through strokes, which can lead to cognitive problems and even dementia. It is also probable that many patients with AF have silent infarcts, which similarly adversely affect cognition. But there may be other mechanisms that don’t involve these structural changes, perhaps related to hypoperfusion in patients with AF.

Neurology Advisor: What are the relevant screening and treatment recommendations that clinicians should follow?

Dr Gottesman: The steps that clinicians take to reduce stroke risk are likely the most important things that can be done to reduce dementia risk. Anticoagulation to reduce stroke risk will probably also reduce silent infarction risk, so it is likely to help preserve cognitive function in patients with AF. There is no evidence that rate control makes a difference in either stroke risk or dementia risk, however.

The American Heart Association’s recommendation for screening in primary stroke prevention consists of pulse palpation in older adults, with an electrocardiogram in the event of an irregular pulse, but with no other recommendations for active AF screening needed.5 For dementia and cognitive impairment, it’s likely that a similar screening approach is best.

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Neurology Advisor: What are remaining research needs pertaining to the link between AF and cognitive decline and dementia?

Dr Gottesman: We still very much need to understand the underlying mechanisms. Furthermore, I mentioned that there’s 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 with anticoagulation will also reduce cognitive impairment and dementia, there isn’t evidence specifically proving this. It is also important to study whether different criteria differentially identify the level of risk for cognitive decline and dementia. For example, a CHA2DS2-VASc score is defined based on stroke risk and informs the clinician about risk for stroke, thus informing decisions about anticoagulation, but a lower threshold might need to be considered for risk for dementia, which might warrant initiation of anticoagulation at a different risk level, at least theoretically.

In addition, there is increasing interest in atrial structural changes that can have an impact on stroke risk. As more research is 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 cognitive decline 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.