Abstract Body: Introduction: Atrial fibrillation (AF) has been linked to cognitive impairment and dementia (CID) even among patients without clinically obvious stroke, but the mechanism is not established. In this study, we aim to clarify the relationship between the burden of AF and CID in a cohort of AF patients without any history of stroke. We hypothesized that a higher AF burden would be associated with CID, possibly through more pronounced cerebral hypoperfusion and covert infarcts.
Methods: We included 843 patients with AF and without a history of clinical stroke or neurodegenerative disease, who underwent brain MRI at a tertiary center. Clinical data were collected through chart review, assisted with natural language processing algorithms to improve accuracy. Patients with a diagnosis of mild cognitive impairment or dementia were classified as having CID. AF load was categorized as low-burden (paroxysmal/persistent AF) or high-burden (longstanding persistent/permanent AF). A vascular neurologist extracted data on the brain atrophy score, Fazekas score, the presence of embolic and lacunar infarcts, cerebral microbleeds (CMB), and cortical superficial siderosis (cSS) from brain MRIs (FIGURE).
Results: In total, 114 patients (13.7%) had CID, and they were older (78.4±7.6 vs 72.4±9.5 years, p < 0.001), and more likely to have a higher AF burden (44.7% vs 15.3%, p<0.001), Fazekas score, atrophy score, CHA₂DS_2-VASC score, presence of embolic infarct on imaging, lacunar infarct, and anticoagulant use. In multivariate analysis, higher AF burden (OR=3.33, C.I=2.08-5.36, p<0.001), brain atrophy score (p=0.005), Fazekas score (p=0.001), and presence of embolic infarct (p=0.045) remained associated with CID, while age, sex, CHA₂DS_2-VASC score, and lacunar infarct were not. AF burden was independently associated with higher brain atrophy scores (p=0.022) in a separate multivariate model, adjusted for age, CHA₂DS_2-VASC and Fazekas scores, anticoagulant use, and embolic and lacunar infarcts.
Conclusion: A higher AF burden is a contributing factor to the development of CID and brain atrophy. Brain atrophy and embolic infarcts are likely mechanisms for the effects of AF burden on cognition. White matter hyperintensities, which are mainly related to cerebral small vessel diseases, also contribute to CID in this population. Whether early and rigorous rhythm control can decrease the risk of cognitive impairment in patients with AF should be tested in randomized controlled trials.