"When we started this study, we hypothesized that the hazard of atrial fibrillation would be higher with longer exposure, but to find such a strong exposure-time association in younger participants was striking," said Dr. Frank J. Wolters from Erasmus Medical Center in Rotterdam, the Netherlands.
"It emphasizes that prevention of dementia doesn't start when people report to their physician with mild memory complaints, but years, if not decades before, by identifying those at risk and optimizing preventive strategies," he said by email.
An earlier report from the Rotterdam Study showed that AF is more prevalent in people with dementia, but the cross-sectional design did not allow conclusions regarding a causal relationship.
Dr. Wolters's team investigated the association between AF and dementia during a follow up of 20 years of nearly 6,200 participants in the Rotterdam Study.
About 5% of the participants had AF at baseline, and 15.3% of these individuals developed dementia during more than 81,000 person-years of follow-up.
Another 11.7% developed AF later, and 15.0% developed dementia during more than 79,000 person-years, the researchers report in JAMA Neurology, online September 21.
People who had AF at the start of the study had a 34% increased risk of dementia (compared with those who did not have prevalent AF), and people who developed AF during follow-up had a 23% increased risk of dementia (compared with those who did not have incident AF).
The association between AF and dementia was strongest in persons younger than the median age (67 years), and in these younger participants, the risk of dementia was higher with increasing duration of AF.
"As we found atrial fibrillation to increase the risk of dementia independent of clinical stroke, either chronic hypoperfusion or more acutely silent infarcts or perhaps cortical microinfarcts could account for the increased risk of dementia," Dr. Wolters said.
"A few observational studies have suggested beneficialeffect of treatment of atrial fibrillation on the risk of dementia, but more evidence on treatment efficacy is sorely needed. This includes insight into whether optimal treatment consists of anticoagulation, heart rhythm, or rate control," he noted.
"With regard to treatment of atrial fibrillation, until further evidence on efficacy becomes available, it is worth realizing that optimal adherence to current guidelines may contribute to prevention of cognitive decline in addition to prevention of stroke," Dr. Wolters added. "Although we found the strongest associations between atrial fibrillation and dementia for younger people, the need to determine treatment efficacy is just as profound in the elderly."
Dr. Sanjay Dixit, director of cardiac electrophysiology at Philadelphia VA Medical Center in Pennsylvania, said by email, "Although the association between AF and dementia has been shown, it's difficult to establish cause and effect. As I point out in my previous review, obstructive sleep apnea (OSA) is considered to be a major contributor to the development of neurocognitive decline and dementia. OSA is very common in the AF population and many consider this to be (a) risk factor in the development of AF. So the question remains whether AF is the cause of dementia or other co-morbidities such as OSA that frequently co-exist in the AF population."
"Look for AF in patients with dementia and also caution patients with AF of the possibility of developing this condition in the future," Dr. Dixit advised. "Since catheter ablation therapy has been shown to have better outcomes for long-term control of AF than drugs, physicians should discuss this with patients and consider referring them to cardiac electrophysiologists early in the course of the disease."
Dr. T. Jared Bunch, director of heart rhythm services for Intermountain Healthcare, Murray, Utah, said by email, "It is great to see another confirmatory study that found essentially the same thing we did 5 years ago. These data in aggregate make the likelihood of the association much more compelling."
"What is interesting in our subsequent work is the patients more sensitive to poor warfarin management (low times in therapeutic range) were at the highest relative risk of dementia compared to older patients," Dr. Bunch explained. "Now we all need to start to unravel the mechanisms behind it and find avenues of preventative treatment. The choice and manner of anticoagulant treatment is one and allowing faster heart rates is another."
Dr. Shih-An Chen and Dr. Tzu-Fan Chao from Taipei Veterans General Hospital, Taipei, Taiwan, who recently reported on the independent association between AF and dementia, struck a more cautious note.
"Only when a lower risk of dementia can be achieved by AF ablation in the prospective and randomized trial can we conclude that AF is the direct cause of dementia," they said in a joint email. "It should also be noted that the development of dementia is multifactorial, and AF only represents one of them."