Submitted:
14 January 2026
Posted:
14 January 2026
You are already at the latest version
Abstract
Background: Atrial fibrillation (AF) is independently associated with cognitive impairment and dementia through mechanisms extending far beyond traditional cardioembolic stroke risk. However, the relative contribution of distinct pathophysiological pathways and the efficacy of emerging therapeutic interventions for cognitive protection remain incompletely characterized. Objectives: This comprehensive review synthesizes current evidence on the epidemiology, pathophysiological mechanisms, therapeutic interventions (pharmacological, rhythm-control, and digital health), and research priorities addressing the AF–dementia relationship. Methods: A narrative review integrating evidence from observational studies, mechanistic research, randomized controlled trials, systematic reviews, and meta-analyses published through January 2026. Literature sources included MEDLINE/PubMed, major cardiology and neurology journals, and expert consensus statements. Searches used combinations of keywords: "atrial fibrillation," "cognitive decline," "dementia," "silent cerebral infarction," "cerebral hypoperfusion," "direct oral anticoagulants," "catheter ablation," and "digital health." Inclusion criteria encompassed studies examining the AF–cognition association, mechanistic pathways, therapeutic interventions with cognitive outcomes, and digital health technologies in AF management. Heterogeneous study designs prevented quantitative meta-analysis; qualitative synthesis focused on effect sizes, strength of evidence, and clinical implications. Results: Strong epidemiological evidence demonstrates that AF increases relative risk of dementia by 1.4–2.2 fold independently of clinical stroke, with silent cerebral infarction present in 25–40% of AF patients. Multiple interacting pathophysiological mechanisms account for AF-associated cognitive decline: cerebral microembolism (meta-analysis: OR 2.30 for silent infarction on MRI), chronic cerebral hypoperfusion (15–20% reduction in total cerebral blood flow in persistent AF), neuroinflammation, cerebral small vessel disease, and structural brain atrophy. Emerging therapeutic strategies offer complementary neuroprotective mechanisms: direct oral anticoagulants (DOACs)—particularly apixaban and rivaroxaban—reduce dementia risk by approximately 30% compared to warfarin (RR 0.69); rhythm control strategies and catheter ablation demonstrate dementia risk reduction (HR 0.52–0.69); and comprehensive digital health platforms implementing the ABC pathway reduce adverse cardiovascular events by 61% while optimizing adherence and enabling early AF detection. However, evidence-specific to cognitive endpoints remains limited, with the landmark BRAIN-AF trial showing no benefit of low-dose rivaroxaban in low-stroke-risk AF patients—suggesting that non-embolic mechanisms predominate in this population. Conclusions: AF represents a multifaceted threat to brain health requiring a paradigm shift from isolated stroke prevention toward comprehensive heart–brain health optimization. Integration of pharmacological neuroprotection (preferring DOACs), hemodynamic optimization (rhythm control in selected patients), cardiovascular risk factor management, and digital health technologies provides unprecedented opportunity for cognitive preservation. However, critical knowledge gaps persist regarding AF burden thresholds, the relative contribution of competing pathophysiological mechanisms, optimal anticoagulation strategies in low-risk populations, and the long-term cognitive benefits of emerging digital technologies. Prospective randomized clinical trials with cognitive impairment as a primary endpoint, serial neuroimaging, and diverse population representation are urgently needed to validate preventive strategies and refine therapeutic decision-making.
