Literature Review
LONDON—Atrial fibrillation in the elderly general population was independently associated with accelerated loss of brain volume and cognitive function in a major longitudinal study, according to data presented at the 2015 European Society of Cardiology Congress. These findings from the population-based Age, Gene/Environment Susceptibility–Reykjavik Study (AGES-Reykjavik) have the potential to change the management of atrial fibrillation, said David O. Arnar, MD, PhD, a cardiologist at Landspítali–The National University Hospital of Iceland in Reykjavik.
David O. Arnar, MD, PhD
“These data potentially suggest it’s better for the brain to remain in sinus rhythm than to pursue rate control in atrial fibrillation,” Dr. Arnar said. “We also have … postablation studies that show [that] doing an ablation procedure to restore sinus rhythm delays the onset of cognitive dysfunction. So, I think we have more and more data that are suggesting [that] atrial fibrillation may be bad for the brain in more ways than just causing cerebral infarcts. That possibility needs to be considered as an end point in future studies of treatment strategies.”
Five Years of Follow-Up Data
The AGES-Reykjavik Study is an ongoing project designed to investigate the genetic and environmental factors that contribute to clinical and subclinical diseases in older individuals. The new data Dr. Arnar presented are an outgrowth of an earlier report from AGES-Reykjavik, which concluded that atrial fibrillation was associated with smaller brain volume and diminished cognitive performance, independent of cerebral infarcts. The observed deficits were smallest in subjects with no history of atrial fibrillation, larger in those with paroxysmal atrial fibrillation, and largest in participants with persistent or permanent atrial fibrillation. However, this was a cross-sectional analysis, which by definition doesn’t permit drawing conclusions regarding cause and effect.
That earlier report was the impetus for the new study featuring a mean of 5.2 years of longitudinal follow-up. The study included 2,472 elderly, nondemented subjects with a mean baseline age of 76 who underwent brain MRI and structured cognitive function testing, with repeated assessments roughly a half-decade later.
A total of 121 subjects had ECG-confirmed atrial fibrillation or a history of atrial fibrillation at entry. Another 132 people developed new-onset atrial fibrillation during follow-up. Since the participants with prevalent or incident atrial fibrillation had significantly higher levels of cardiovascular risk factors, alcohol consumption, history of cerebral infarcts, and other potential confounders, extensive multivariate statistical adjustments were required in analyzing the data, Dr. Arnar said.
During the follow-up period, the atrial fibrillation-free subjects experienced a mean 1.8% reduction in gray matter volume, compared with a 2.7% decrease in individuals with prevalent atrial fibrillation and a 3.88% reduction in those with incident atrial fibrillation. All differences were statistically significant.
Loss of white matter volume over time followed a similar pattern: a mean loss of 5.35% in the no-atrial-fibrillation group, compared with a 5.5% drop in those with prevalent atrial fibrillation and a 6.56% decrease in individuals with incident atrial fibrillation.
The volume of white matter lesions rose by 31.6% in the elderly no-atrial-fibrillation group, 26.9% in those with prevalent atrial fibrillation, and 43.5% in subjects with new-onset atrial fibrillation during follow-up.
“It surprised us that the changes were most pronounced in those with incident atrial fibrillation rather than prevalent atrial fibrillation,” Dr. Arnar said. “How do we explain that? Well, I don’t know, but you wonder if the effect of atrial fibrillation on the brain could be most pronounced initially, and then as atrial fibrillation goes on, an adaptation process occurs so that the rate of change in the brain becomes less pronounced as the atrial fibrillation becomes more chronic.”
Cognitive Measures
Turning to the results of cognitive function testing, a composite measure of processing speed declined over time by 10% in the no-atrial-fibrillation group, 12.7% in participants with prevalent atrial fibrillation, and 13.9% in participants with incident atrial fibrillation. All differences were statistically significant.
The rate of decline in executive function was 8% in the no-atrial-fibrillation subjects, 10.2% in subjects with prevalent atrial fibrillation, and 11.8% in subjects with incident atrial fibrillation. Similarly, scores on memory testing dropped by 9.3% in the no-atrial-fibrillation group, 9.9% in people with prevalent atrial fibrillation, and 11.9% in people with incident atrial fibrillation.
The mechanism by which atrial fibrillation accelerates brain aging is unknown. It may be multifactorial, and candidate processes include altered autonomic regulation of blood flow, microemboli causing brain atrophy, and atrial fibrillation-induced diminution of cerebral blood flow, Dr. Arnar said.
In addition, the investigators obtained cerebral blood flow data via phase contrast MRI for 2,125 study participants. Those with no history of atrial fibrillation averaged a total cerebral blood flow of 540 mL/min. Subjects with a history of atrial fibrillation who were in sinus rhythm at the time of the brain scan averaged 520 mL/min. And subjects in atrial fibrillation when they were scanned averaged less than 480 mL/min.