Abstract

Aging is the predominant risk factor for a wide spectrum of degenerative disorders that collectively affect millions worldwide, including Alzheimer’s disease (AD), cerebrovascular disease, cardiac arrhythmias, cancer, and type 2 diabetes mellitus (DM2). In the United States alone, over six million individuals are affected by dementia—most commonly AD— while more than ten million live with atrial fibrillation (AFib), the most prevalent form of cardiac arrhythmia. Emerging epidemiological and clinical evidence indicates that AFib confers an increased risk of cognitive decline and dementia, particularly when diagnosed before the age of 65. Reported estimates suggest that AFib increases the risk of dementia in particular AD by 13% to over 65%, depending on age and other contributing factors. Conversely, individuals with AD exhibit a significantly higher prevalence of AFib (13.0%) compared with those without cognitive impairment (2.1%). The mechanistic underpinnings of this association remain incompletely understood. While cerebral microinfarcts and vascular injury have traditionally been implicated, several studies have demonstrated that the relationship persists even among individuals without overt stroke or cerebrovascular disease, implicating additional non-vascular pathways. Proposed mechanisms include systemic chronic inflammation, oxidative stress, and infectious processes. Notably, less attention has been directed toward shared aging-related mechanisms such as disruptions in proteostasis, cellular senescence, and common genetic susceptibilities. This review examines the converging biological pathways linking AD and AFib, with particular emphasis on their potential mechanistic intersections and translational relevance. We further discuss the therapeutic implications of these insights in the context of a rapidly evolving landscape-characterized by the advent of disease-modifying therapies for AD and innovative interventional strategies for AFib, including catheter ablation. Finally, we highlight the importance of considering the bidirectional dynamics of the brain–heart axis as a fundamental framework for understanding the pathophysiology and management of these interrelated disorders

Keywords

pathophysiology, alzheimer’s disease, fibrillation