Silent Brain Lesions Linked to Cognitive Decline in AF

Batya Swift Yasgur MA, LSW

March 13, 2019

Patients with atrial fibrillation (AF) have a high burden of clinically "silent" large noncortical or cortical infarcts (LNCCIs), which are associated with poor cognitive function, a new Swiss study suggests.

A multicenter group of investigators administered MRI and cognitive testing to over 1700 AF patients with a mean age of 73 and found LNCCIs in almost one quarter of patients. Roughly one fifth of patients had microbleeds and one fifth had small noncortical infarcts. Almost all patients (99%) had white matter lesions.

Of the 1400 patients who did not have a history of stroke or transient ischemic attack (TIA), clinically silent infarcts were found in 15% of those with LNCCIs and 18% of those with small neocortical infarcts (SNCIs).

LNCCIs were found to be the strongest predictor of reduced cognitive performance.

"One of the key findings from this cohort is that these large ischemic infarcts, which are subclinical, still have a significant impact on cognition, similar to clinical stroke," lead author David Conen, MD, MPH, associate professor in the division of cardiology, department of medicine, McMaster University, Hamilton, Ontario, Canada, told | Medscape Cardiology.

The study was published online March 4 in the Journal of the American College of Cardiology.

Study of Silent Infarcts 'Lacking'

"Although the relationship of AF with death, stroke and congestive heart failure (CHF) have been known for years, more recent evidence suggests that patients with AF also face an increased risk of cognitive dysfunction and dementia," the authors write.

The association may be attributable to the higher stroke risk among patients with AF, but the risk for dementia is also increased, even in people without a clinical history of stroke.

Silent infarcts, microbleeds, or other brain lesions may explain this association; but, to date, systematic investigations in patients with AF are lacking.

"Microbleeds are of particular interest because patients with AF usually need lifelong oral anticoagulation for stroke prevention," and use of this therapy in patients with significant microbleed burden is "controversial."

The researchers aimed to assess the relationships of clinically known and unknown vascular brain lesions, as detected by MRI, with cognitive function in patients with AF by focusing on large infarcts and infarcts involving the brain cortex, "which may originate from embolic mechanisms and therefore represent AF-related sequelae."

They also looked at cerebral small-vessel disease, which shares vascular risk factors with AF, including white matter disease, SNCIs, and microbleeds.

"Both cerebral small vessel disease and embolic stroke are key mechanisms underlying the development of dementia," they note.

The researchers drew on patients from the Swiss Atrial Fibrillation (SWISS-AF) study, an ongoing prospective cohort study conducted across 14 centers in Switzerland.

Patients in this study were required to be ≥ 65 years old and have a history of documented AF.

In addition, the researchers aimed to enroll patients between ages 45 and 65 years who were in the active workforce.

The final cohort consisted of 1737 participants (mean age, 73 [±8] years; 28% female), of whom 90% were being treated with anticoagulants at the time of study enrollment and 18% were receiving antiplatelet therapy.

Participants received brain MRI scans as well as cognitive testing, using the Montreal Cognitive Assessment (MoCA) tool.

Broader Risk Control

LNCCI was detected in 22% of participants (median volume of 1623 mm3), and SNCIs (median volume 63 mm3) were observed in 21%.

The authors describe the overlap between LNCCI and SNCI as "small" (68% of patients with SNCIs had no LNCCIs, and 75% of patients with LNCCIs had no SNCIs, meaning that 30% of the study population had either LNCCIs or SNCIs).

Microbleeds (median count 1) and white matter lesions (median volume 3918 mm3) were observed in 22% and 99% of participants, respectively.

The extent of white matter lesions was at least "moderate" in over half (54%) of participants.

When the researchers excluded patients with a history of stroke or TIA, they found that 15% had evidence of a silent LNCCI (median volume 525 mm3) and 18% had evidence of a silent SNCI (median volume 57 mm3).

The least square mean MoCA was 24.9 (95% confidence interval, 24.3 -25.5) vs 25.9 (25.3 - 26.5) among patients with and without an LNCCI, respectively (P < .001).

In patients with an SNCI vs patients without an SNCI, the MoCA was 25.0 (24.4 - 25.6) vs 25.9 (25.3 - 26.4), respectively (P < .001); and in patients with microbleeds vs without microbleeds, it was 25.4 (24.7 - 26.0) vs 25.8 (25.2 - 26.4), respectively (P = .07).

The difference in MoCA score remained similar, even when only clinically silent LNCCIs were considered (24.9 ± 3.1 vs 25.8 ± 2.9; P < .001).

A multivariable regression model that included all vascular brain lesion parameters found LNCCI volume to be the strongest predictor of reduced MoCA score (β = −0.26; [−0.40 to −0.13]; P < .001).

When the researchers excluded patients with a clinical history of stroke or TIA, they found that the difference in the MoCA score remained similar between patients with or without silent LNCCI, with or without silent SNCI, and with or without microbleeds.

"This is a cross-sectional study, so we can't say anything about causality or directionality of effect," Conen remarked.

"It is still interesting that 90% of patients were being treated with oral anticoagulants, as recommended by clinical guidelines, but we still found a really impressive number of subclinical brain lesions, leaving questions as to whether oral anticoagulants for stroke prevention are enough to prevent all brain damage," he said.

"Our study raises but doesn't answer the question of whether one blood thinner is enough to prevent all brain damage in these patients and that other measures — one of them being risk factors control, such as hypertension, which is also associated with brain damage — should be taken care of more carefully," he suggested.

The study also raises the question of whether high-risk patients should perhaps be screened with brain MRIs, although that would be expensive, he added.

'Convincing' Evidence

Commenting on the study for | Medscape Cardiology, Jagat Narula, MD, PhD, professor of medicine and the Philip J. and Harriet L. Goodhart Chair in Cardiology, Icahn School of Medicine at Mount Sinai, New York City, who was not involved with the study, called it "important" and said that, "unlike AF where the origin of the embolic insult is obvious, it is being increasingly recognized that vascular pathology could contribute to cognitive decline or vascular dementia, commonly found in the aging population."

Narula, who is the coauthor of an accompanying editorial and vice president elect of the World Heart Federation, suggested that "appropriate control of vascular risk factors at midlife may reduce the incidence of late-life dementia, and there may be a possibility of modifying the evolution to cognitive decline."

The findings might "invoke the necessity of more extensive imaging workup for the patients with cardiovascular disease, [but] the cost associated with such a presumption would be prohibitive," warned Narula, who is the director of cardiovascular imaging at Mount Sinai Health System.

Nevertheless, "the evidence of the association of cardiovascular risk factors with cognitive dysfunction is convincing and a strategy for prevention, although the clinical trial data that demonstrated the benefit of prevention of cardiovascular risk factors needs confirmation."

Conen agreed, adding that his group is "working hard to identify those at high risk and finding risk predictors that might define a smaller subgroup of patient that might benefit from brain imaging, using clinical factors and biomarkers."

The Swiss-AF cohort study is supported by grants from the Swiss National Science Foundation, the Foundation for Cardiovascular Research Basel, and the University of Basel. Conen has a McMaster University Department of Medicine Mid-Career Research Award, his work is supported by the Hamilton Health Sciences RFA Strategic Initiative Program, and he has received consulting fees from Servier Canada. The other authors' disclosures are listed on the original paper. Narula and coauthors have reported no relevant financial relationships.

JACC. Published online March 4, 2019. Article, Editorial


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