Author + information
- Lin Y. Chen, MD, MS∗ (, )
- Sunil K. Agarwal, MD, PhD,
- Faye L. Norby, MS, MPH,
- Rebecca F. Gottesman, MD, PhD,
- Laura R. Loehr, MD, PhD,
- Elsayed Z. Soliman, MD, MSc, MS,
- Thomas H. Mosley, PhD,
- Aaron R. Folsom, MD, MPH,
- Josef Coresh, MD, PhD and
- Alvaro Alonso, MD, PhD
- ↵∗Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, 420 Delaware Street SE, MMC 508, Minneapolis, Minnesota 55455
The association of atrial fibrillation (AF) with an increased risk of cognitive impairment or dementia is independent of clinical stroke (1) and may be mediated by subclinical cerebral infarcts (SCIs) (2). However, little is known about whether AF burden (i.e., the percentage of time a person is in AF) is related to cognitive function. Moreover, if such a relationship exists, whether it is mediated by clinical stroke or SCIs is unknown. We hypothesized that a higher AF burden would be independently associated with lower cognitive function after adjustment for clinical stroke but that this association would be attenuated after adjustment for SCIs. We tested our hypothesis in a sample of participants from the U.S. community-based ARIC (Atherosclerosis Risk in Communities) study.
After the baseline examination (1987 to 1989), ARIC participants underwent 4 additional examinations. The last examination (visit 5) in 2011 to 2013 was attended by 6,538 participants, with cognitive tests conducted as part of the ARIC-NCS (ARIC Neurocognitive Study), an ancillary study to the main ARIC study (3). In addition, a subset of ARIC visit 5 examination participants (n = 1,906) were selected to undergo brain magnetic resonance imaging (MRI) scans. From July 2013 to March 2014, a total of 325 participants at 2 field centers who presented for their brain MRI scans at visit 5/NCS examinations wore the Zio Patch (iRhythm Technologies, Inc., San Francisco, California), a leadless electrocardiogram monitor (4).
AF was defined as an irregularly irregular rhythm with absent P waves lasting ≥30 s. AF burden was defined as the percentage of analyzable recording time that a participant was in AF. Participants were administered a battery of neuropsychological tests covering various cognitive domains (Table 1). SCIs on brain MRI scans were defined as focal, nonmass lesions ≥3 mm that were bright on T2-weighted images and proton density and dark on T1-weighted images.
The mean age of participants in the study was 76.9 ± 5.2 years, and 172 (52.9%) participants were women. All participants except 6 were white. Twenty-six (8%) participants were found to have AF according to results of heart rhythm monitoring, and 15 (4.6%) had had a prior ischemic stroke. The Zio Patch performed well in this study: the median (interquartile range) wear time and analyzable time were 13.9 (13.3 to 14.0) days and 13.6 (12.8 to 13.8) days, respectively (of a possible maximum of 14 days). The distribution of AF burden was bimodal: 14 participants with AF had an AF burden ranging from 1% to 6% and 12 had an AF burden at 100%.
Presence of AF per se was not significantly associated with lower cognitive scores after adjustment for clinical stroke. By contrast, an AF burden of 100% was significantly associated with lower cognitive scores. After adjustment for risk factors in model 2, participants with an AF burden of 100% (compared with participants without AF) had lower z scores on the Digit Span Backward (DSB) test, the Trail Making Test, part B (TMT-B), and Animal Naming (Table 1). Furthermore, the associations of 100% AF burden with lower DSB, TMT-B, and Animal Naming z scores remained significant even after adjustment for prevalent ischemic stroke and SCIs. By contrast, participants with an AF burden of 1% to 6% did not have lower cognitive test scores than those without AF (p values for difference based on AF burden for DSB, TMT-B, and Animal Naming were 0.003, 0.26, and 0.03, respectively). Thus, in this community-based sample of elderly individuals, those with an AF burden of 100% (persistent AF), but not 1% to 6% (paroxysmal AF), had lower executive and verbal cognitive test scores than those without AF. As hypothesized, these associations remained significant after adjustment for prevalent clinical stroke. However, contrary to our expectation, these associations persisted even after further adjustment for SCIs, refuting our hypothesis that SCIs can explain the relationship between higher AF burden and lower cognitive function.
Our findings are hypothesis-generating because of several limitations. First, this study was a small cross-sectional trial that included mostly white participants and evaluated cognitive scores at a single point in time. Second, because of the numerous comparisons, positive findings could be due to chance. Third, because the AF burden distribution was bimodal, we could not evaluate the full spectrum of AF burden.
In conclusion, persistent but not paroxysmal AF was associated with lower cognitive function in community-dwelling elderly individuals. Further prospective research is needed to confirm an association of higher AF burden with greater cognitive decline and higher risk of incident dementia. In addition, further investigation is warranted to elucidate the underlying mechanisms to facilitate discovery of prevention strategies.
Please note: The Atherosclerosis Risk in Communities Study is conducted as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). Neurocognitive data are collected by U01 HL096812, HL096814, HL096899, HL096902, and HL096917. The funder had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. The authors thank the staff and participants of the ARIC study for their important contributions. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. P.K. Shah, MD, served as Guest Editor for this paper.
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- Lopez F.L.,
- Gottesman R.F.,
- et al.
- Knopman D.S.,
- Griswold M.E.,
- Lirette S.T.,
- et al.
- Turakhia M.P.,
- Hoang D.D.,
- Zimetbaum P.,
- et al.