More Evidence Links Atrial Fibrillation and Dementia Risk

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Medscape Today

Atrial fibrillation (AF) is significantly associated with cognitive impairment and dementia, independent of history of clinical stroke, a new meta-analysis has found.
Previous research had highlighted the association between AF and cognitive decline, but it was assumed that this association was mediated through clinical stroke because patients with AF are 4 to 5 times more likely to develop clinical stroke, said lead author Shadi Kalantarian, MD, MPH, research fellow, Massachusetts General Hospital Cardiac Arrhythmia Service, Boston.
"We wanted to know if this association was independent of that stroke history, and we observed that it was," he told Medscape Medical News.
The study, the first to collect and present separate data for dementia and cognitive impairment, provides the most comprehensive evidence to date of the potential effects that AF has on cognition, but also highlights "critical gaps" in understanding the mechanism underlying the association, said Dr. Kalantarian.
The study is published in the March 5 issue of the Annals of Internal Medicine.
21 Studies
Researchers searched 5 large databases — MEDLINE, PsycINFO, Cochrane Library, CINAHL, and EMBASE — as well as reference lists, with no language restrictions, for studies that reported the association between AF and cognitive impairment or total dementia.

Dr. Shadi Kalantarian

The analysis included 21 studies representing geographically diverse regions, such as Asia, North and South America, Europe, and Australia. Fourteen studies reported the association between AF and cognitive impairment or dementia in patients with or without a history of stroke, and 7 studies examined the association of AF with cognitive impairment or dementia after stroke.
In a combined analysis of the 14 studies that investigated the association between AF and dementia or cognitive impairment, 9 of which were prospective, AF was significantly associated with the risk for cognitive impairment (relative risk [RR], 1.40; 95% confidence interval [CI], 1.19 - 1.64).
There was significant heterogeneity, however, possibly due to variance in participant characteristics. With use of a random-effects model, pooled estimates were almost the same for prospective and cross-sectional studies.
Heterogeneity was still seen in prospective studies, possibly because of different outcome measures. When the analysis was restricted to dementia outcomes, which are more accurately diagnosed than cognitive impairment, the heterogeneity was eliminated but the association didn't change substantially (RR, 1.38; 95% CI, 1.22 - 1.56).
Limiting the analysis to studies using the Mini-Mental State Examination, the most widely used screening tool for cognitive decline, also did not appreciably change the results.
In the 7 studies reporting cognitive impairment or dementia after a stroke, AF was associated with a more than 2-fold increased risk (RR, 2.70; 95% CI, 1.82 - 4.00).
To evaluate the association independent of stroke history, the investigators did a meta-analysis of studies that either excluded patients with a history of stroke or adjusted for stroke in the multivariate adjusted model. For this analysis, the RR was 1.34 (95% CI, 1.13 - 1.58).
Dr. Kalantarian emphasized that the association was independent of "clinically overt stroke," that is, strokes with which patients had been diagnosed, and that they had reported.
Possible Mechanisms
Shared risk factors, such as hypertension, congestive heart failure, and diabetes, which tend to accumulate as the population ages, might explain the association between AF and cognitive decline. Another explanation could be the hypercoagulable state in patients with AF or stasis of blood in the left atrium that may lead to formation of thrombi in the left atrial appendage and then to stroke.
Other unproven mechanisms, said Dr. Kalantarian, could involve cerebral hypoperfusion — that is, less blood going to the brain might affect cognition — or the proinflammatory state in both AF and dementia.
Perhaps the most plausible explanation is that AF increases the risk for silent infarcts, which would mediate the association between AF and cognitive impairment, said Dr. Kalantarian. However, 1 study in the analysis that excluded patents with a history of stroke with detailed imaging also showed an association between AF and cognitive impairment.
"That's only 1 study in the literature, and it says that there's a gap in our knowledge," said Dr. Kalantarian. "We think that silent infarct is a major contributor, but we can't say that it's 100% the underlying mechanism and that other things are not contributing. It's probably multifactorial; that other factors are contributing as well."
Priority should be given to studies that will elucidate the underlying mechanism, she added.
The authors used several objective criteria to assess the quality of individual studies. Of the 9 prospective studies in the broader population, 6 had "reasonably good quality" in that they matched 5 or 6 of the 7 quality criteria, said Dr. Kalantarian.
However, 6 of the 21 studies met 3 or fewer quality criteria, mainly because of a higher potential for misclassification of AF or outcome, inadequate adjustments for potential confounders, and the presence of attrition bias. Sensitivity analyses that excluded these studies did report similar results, though.
Another possible limitation was that stroke was mostly self-reported or derived from medical records and rarely confirmed by imaging.
The study results warrant further well-designed longitudinal studies with better adjustment for potential confounders and with detailed information on subtype of dementia, according to the authors. As well, clinical trials to evaluate interventions that may lower the risk for cognitive impairment in patients with AF are also needed, they said.
In future trials, "investigators should consider cognitive function as a new outcome to be assessed in interventional studies for the treatment of AF," the authors write.
Critical Question
Asked to comment on these findings for Medscape Medical News, Stefan Knecht, MD, professor, neurology, St. Mauritius Therapieklinik, Meerbusch, Germany, said he's not convinced that the meta-analysis adequately answers the critical question of whether cognitive impairment is linked to something other than stroke in patients with AF.
For one thing, he said, asking patients for their history of stroke is a weak tool because if they have had "silent" strokes, they wouldn't be aware of it, and so would not report it.
. Given the propensity of AF to cause strokes, it's not clear by what means other than some sort of stroke AF would affect brain function, he pointed out.
"There are actually several questions still to be answered," he said. "What kinds of strokes occur in AF to cause cognitive impairment? How much of a problem is this? How much of this is related to the type of treatment patients receive? And what can we do about it?"
The paper simply confirms that a relationship does exist between AF and cognitive impairment, but the authors do little to disentangle possible mechanisms, added Dr. Knecht.
"Could they have done so? I think so. For example, they could have tried to sort out differences in cognitive impairments in patient with versus patients without a history of stroke."
Dr. Kalantarian noted that she and her colleagues didn't have enough data to separate out different domains of cognition.
"The methodology of cognitive assessment is so variable and not many studies look at specific domains of cognitive function," she said. "That's why we were not able to say, for example, that patients with AF are more prone to have executive dysfunction."
Dr. Kalantarian and Dr. Knecht have disclosed no relevant financial relationships.
Ann Intern Med. 2013;158:338-346. Abstract

 

Afib increases risk of dementia (part 2)

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Group Health

Dr. Dublin's study, which ran from 1994 to 2008, followed 3,045 people. The researchers relied on Group Health's advanced electronic data systems to determine whether participants had atrial fibrillation. The cognitive function of all study participants was evaluated every two years with tests and interviews as part of ACT. Patients whose ACT tests indicated possible dementia had additional tests including physical, neurological, and psychological exams, and many also had brain scans. A panel of experts determined the correct diagnosis for patients with cognitive problems.

Atrial fibrillation affects 3 million Americans. Dr. Dublin says that some ways it might increase dementia risk are:


•weakening the heart's pumping ability, leading to less oxygen going to the brain;


•increasing the chance of tiny blood clots going to the brain, causing small, clinically undetected strokes;


•a combination of these plus other factors that contribute to dementia such as inflammation.

Dr. Dublin said an important next step is studying whether any treatments for atrial fibrillation reduce the risk of developing dementia. The researchers also hope their results reach primary care providers, who are often the main doctors caring for people with atrial fibrillation, dementia, or both.

"Right now, we think we are protecting our patients' brains as long as they don't have a stroke, but tiny insults over time can add up," said Dr. Dublin, who is a primary care physician at Group Health. "This paper is a wakeup call, telling us that we need to learn more about how to protect brain function, while continuing to give patients with atrial fibrillation the best possible care."


Source: Group Health Research Institute

Afib increases risk of dementia

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Group Health

The most common kind of chronically irregular heartbeat, known as atrial fibrillation, is associated with a greater risk of dementia, including Alzheimer's disease. This discovery by scientists at Group Health Research Institute and their collaborators was published online in advance of print on August 1 in the Journal of the American Geriatrics Society.

"Both atrial fibrillation and dementia increase with age," said Sascha Dublin, MD, PhD, a Group Health Research Institute assistant investigator who led the research. "Before our prospective cohort study, we knew that atrial fibrillation can cause stroke, which can lead to dementia. Now we've learned that atrial fibrillation may increase dementia risk in other, more subtle ways as well."

The results of Dr. Dublin's study suggest a relationship between atrial fibrillation and dementia beyond the connection through stroke. The people in the study had a mean age of 74 years when the study began. None had dementia or a history of stroke. At the beginning of the study, 4.3 percent had atrial fibrillation, and an additional 12.2 percent developed it during the study. In the course of the study, 18.8 percent developed some type of dementia. People with atrial fibrillation were more likely to have other cardiovascular risk factors and disease than were those without the condition. So the researchers looked to see if atrial fibrillation increased dementia risk more than just through its association with other kinds of heart disease.

Participants were followed for an average of seven years. Over this time, those with atrial fibrillation had a 40 percent to 50 percent higher risk of developing dementia of any type, including probable Alzheimer's disease, compared to those without atrial fibrillation. This was true even for people who did not also have a stroke during the follow-up period.

The research was part of Adult Changes in Thought (ACT), an ongoing joint project of the Group Health and University of Washington studying risk factors for dementia in older adults. Started in 1994 ACT is led by Dr. Dublin's co-author Group Health Vice President for Research and Group Health Research Institute Executive Director Eric B. Larson, MD, MPH. ACT focuses on finding ways to delay or prevent dementia, including Alzheimer's disease, and declines in memory and thinking. It aims to deepen understanding of how the body-especially the brain-ages. ACT participants are members of Group Health Cooperative, a nonprofit health care system in the U.S. Pacific Northwest.

Common heart problem raises Alzheimer's risk

By Julie Steenhuysen, Reuters

CHICAGO - Atrial fibrillation, a common heart rhythm problem, raises the risk of developing Alzheimer's disease, especially in people under age 70, U.S. researchers said on Friday.


They said the heart condition boosts the risk of all forms of dementia by 44 per cent. And in people under age 70, it doubles the risk of Alzheimer's disease, the most common form of dementia.


"In patients under age 70, if they had atrial fibrillation, they were 130 per cent more likely to develop Alzheimer's disease," Dr. John Day of Intermountain Medical Center in Utah, who worked on the study, said in a telephone interview.


"It appears to be a much more aggressive form of Alzheimer's disease," Day said.


Atrial fibrillation is the most common heart rhythm problem, affecting about 2.2 million Americans. It occurs when the heart beats chaotically, leaving blood to pool and possibly clot. If the clot leaves the heart, it can cause a stroke.


"Previous studies have shown that patients with atrial fibrillation are at higher risk for some types of dementia, including vascular dementia," said Dr. Jared Bunch of Intermountain, who presented the results at the Heart Rhythm Society meeting in Boston.


"To our knowledge, this is the first......read the whole story

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Study makes first connection between heart disorder and Alzheimer's disease

EurekAlert
Contact: Jess Gomez
jess.gomez@imail.org
801-507-7455
Intermountain Medical Center

Study of more than 37,000 patients shows relationship between atrial fibrillation and development of Alzheimer's disease
Researchers at Intermountain Medical Center in Salt Lake City believe that they have made a breakthrough connection between atrial fibrillation, a fairly common heart rhythm disorder, and Alzheimer's disease, the leading form of dementia among Americans.

In a study presented Friday, May 15, at "Heart Rhythm 2009," the annual scientific sessions of the Heart Rhythm Society in Boston, researchers unveiled findings from the study of more than 37,000 patients that showed a strong relationship between atrial fibrillation and the development of Alzheimer's disease.

The study, which drew upon information from the Intermountain Heart Collaborative Study, a vast database from hundreds of thousands of patients treated at Intermountain Healthcare hospitals, found:

• Patients with atrial fibrillation were 44 percent more likely to develop dementia than patients without the heart disorder.

• Younger patients with atrial fibrillation were at higher risk of developing all types of dementia, particularly Alzheimer's. Atrial fibrillation patients under age 70 were 130 percent more likely to develop Alzheimer's.

• Patients who have both atrial fibrillation and dementia were 61 percent more likely to die during the study period than dementia patients without the rhythm problem.

• Younger atrial fibrillation patients with dementia may be at higher risk of death than older AF patients with dementia.

Intermountain Medical Center cardiologist T. Jared Bunch, M.D., the study's lead researcher, presented the findings at the scientific session.

"Previous studies have shown that patients with atrial fibrillation are at higher risk for some types of dementia, including vascular dementia. But to our knowledge, this is the first large-population study to clearly show that.......read the whole story

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