ARTICLE IN BRIEF
Atrial fibrillation was significantly associated with a faster average annual decline in cognitive assessment scores and an increased risk of (all-cause) dementia, vascular and mixed dementia.
Atrial fibrillation (AF) was associated with an increased risk of dementia and a faster decline in global cognitive function in older people, but it was not associated with increased risk of Alzheimer's disease (AD). The risk of dementia decreased significantly when AF was treated with oral anticoagulant drugs, according to a new paper published online in the October 10 edition of Neurology.
Although ischemic stroke is a well-known consequence of atrial fibrillation, AF is less recognized as a risk factor for cognitive decline and dementia, lead investigator Chengxuan Qiu, PhD, associate professor at the Aging Research Center department of neurobiology of the Karolinska Institute and Stockholm University in Sweden, told Neurology Today in an email.
“Current evidence has been inconsistent regarding the association of AF with cognitive decline and dementia, especially among older adults. Our longitudinal and population-based study helps further our understanding of the association of AF with dementia and its subtypes in old age, and, importantly, sheds light on the potential cognitive benefits of anticoagulant therapy in older adults with AF,” said Dr. Qiu.
“Our findings emphasize the need to improve the clinical management of patients with AF, which is of particular clinical importance given that a large proportion of older people with AF are under-treated with anticoagulant drugs,” Dr. Qiu said. “While there is currently no cure for dementia, our study suggests that optimal anticoagulation of patients with AF may prevent or delay its onset.”
Because the only oral anticoagulant agent available during the study period was warfarin, which has a risk of bleeding, drug-drug interactions, and requires routine monitoring, Dr. Qiu suggested that future studies compare novel oral anticoagulant drugs to warfarin and their associated cognitive benefits in people with AF.
STUDY DESIGN, FINDINGS
Dr. Qiu and his colleagues in Sweden and Italy conducted a prospective cohort study with 2,685 participants selected from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K). The SNAC-K study was funded by the Swedish Ministry of Health and Social Affairs, Participating County Councils and Municipalities, and the Swedish Research Council.
At baseline (2001-2004), all participants were dementia-free, 60 years or older, and living at home or in institutions in Kungsholmen, a district in central Stockholm. The researchers identified 243 participants (9.1 percent) with prevalent AF at baseline who were older, less educated, and more likely to be men and physically inactive than participants without prevalent AF. They also had more frequent morbidities such as hypertension, diabetes, heart failure, ischemic stroke/transient ischemic attack, and coronary heart disease compared to those without prevalent AF.
Researchers collected data from face-to-face interviews, clinical examination, laboratory testing, and the national Swedish patient registry during the study period between 2001 and 2013, and analyzed the data using multiple models. Participants were regularly assessed for AF, dementia, vascular dementia, and AD.
To analyze the association between AF and cognitive decline, the researchers excluded 53 people with a score less than 24 on the Mini-Mental State Examination (MMSE) or who lacked a MMSE score at baseline, and 369 people who died before the first follow-up assessment, leaving a total of 2,263 participants.
After adjusting for demographic factors, lifestyle factors, and chronic diseases, AF was significantly associated with a faster average annual decline in MMSE scores (95% confidence interval [CI]: -0.31, -0.16), with an increased risk of (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), but not AD (HR=1.33, 95% CI: 0.92-1.94). The significant association of AF with all-cause dementia was statistically evident only among women (HR=1.46, 95% CI: 1.10-2.94) and apolipoprotein E4 (APOE4) carriers (HR=1.74, 95% CI: 1.17-2.59).
Among people with either prevalent or incident AF, use of anticoagulant drugs, but not antiplatelet treatment, was associated with a 60 percent decreased risk of dementia (HR=0.40, 95% CI: 0.18-0.92).
The study is unique in that it focuses on the association between AF and cognitive decline and dementia in an older group of patients, several independent experts told Neurology Today. “The researchers focused on a burning question in antithrombotic therapy, which is whether we should be using oral anticoagulants or antiplatelets such as aspirin or clopidogrel to prevent cognitive decline or dementia in patients with AF,” said Philip B. Gorelick, MD, MPH, FAAN, adjunct professor in the Davee department of neurology at Northwestern's Feinberg School of Medicine, and chief medical officer at Thorek Memorial Hospital in Chicago.
The study also showed some interesting results for subgroups that may benefit from further study, Dr. Gorelick said, noting that, only women and APOE4 carriers with AF had a statistically significant increased risk of dementia. “One possible explanation for this higher risk is that women with stroke lesions who harbor APOE4 are more likely to have Alzheimer brain changes and thus, mixed dementia,” he said.
A major limitation was that this was an observational epidemiological study, which didn't allow the researchers to control the antithrombotic interventions. “We don't know whether the study subjects were compliant with the oral anticoagulant or antiplatelet drugs. The next step should be a clinical trial with a controlled intervention,” said Dr. Gorelick.
Indeed, randomized controlled trials are being organized and implemented to answer key questions and determine whether newer oral anticoagulants will also reduce cognitive decline and dementia in older adults. “Data from the Swedish national study is important because it provides further scientific validation to move forward with these other trials,” said Dr. Gorelick.
A major strength of the study was its large population size, said Steven T. DeKosky, MD, FAAN, Aerts-Cosper professor of Alzheimer's research at the University of Florida College of Medicine in Gainesville. “This allowed researchers to have enough statistical power and a reasonable cross-section of people with AF to make some definitive statements about cognitive decline in this older population.”
“The fact that anticoagulants were beneficial in such a large population provides clear evidence to clinicians that this is the right clinical course of action, assuming patients can tolerate the medication,” Dr. DeKosky said. However, for patients who can't tolerate the risks of bleeding with warfarin or comply with regular monitoring, clinicians are increasingly prescribing antiplatelet drugs, he noted.
The researchers plan to conduct an MRI study next to investigate to what extent cerebral small vessel disease, such as silent cerebral infarcts, white matter hyperintensities, and brain atrophy, mediate the observed association of AF with cognitive decline and dementia.
“MRI scans will be able to answer that question and investigate the role of larger infarctions or larger emboli, whether more subcortical white matter alterations suggest white matter ischemia or frank infarction, or whether none or a mix of these factors are involved,” Dr. DeKosky said. “When someone with AF and cognitive decline has a negative workup for Alzheimer's disease and no clinical history of stroke or infarction visible on an MRI, it is likely that micro emboli are causing the decline.”