Revealing the influences of sex hormones and sex differences in atrial fibrillation and vascular cognitive impairment

The impacts of sex differences on the biology of various organ systems and the influences of sex hormones on modulating health and disease have become increasingly relevant in clinical and biomedical research. A growing body of evidence has recently suggested fundamental sex differences in cardiovascular and cognitive function, including anatomy, pathophysiology, incidence and age of disease onset, symptoms affecting disease diagnosis, disease severity, progression, and treatment responses and outcomes. Atrial fibrillation (AF) is currently recognized as the most prevalent sustained arrhythmia and might contribute to the pathogenesis and progression of vascular cognitive impairment (VCI), including a range of cognitive deficits, from mild cognitive impairment to dementia. In this review, we describe sex-based differences and sex hormone functions in the physiology of the brain and vasculature and the pathophysiology of disorders therein, with special emphasis on AF and VCI. Deciphering how sex hormones and their receptor signaling (estrogen and androgen receptors) potentially impact on sex differences could help to reveal disease links between AF and VCI and identify therapeutic targets that may lead to potentially novel therapeutic interventions early in the disease course of AF and VCI.