Estrogen receptor involvement in vascular cognitive impairment and vascular dementia pathogenesis and treatment

Vascular cognitive impairment (VCI) is a term that encompasses a continuum of cognitive disorders with cerebrovascular pathology contribution, ranging from mild cognitive impairment to vascular dementia (VaD). VCI and VaD, thus, represent an interesting intersection between cardiovascular disease and neurodegenerative disorders such as Alzheimer's disease (AD) and a rising area of research in recent years. Although VCI and VaD research has identified various causes and explanations for disease development, many aspects remain unclear, particularly sex differences in VCI (e.g., epidemiology), unlike those available for cardiovascular disease and AD. Despite limited information in the literature, several studies have observed an association of estrogen receptor (ER) polymorphisms and VaD. If further explored, this association could provide valuable insights for novel therapeutic approaches. This review aims to provide a brief epidemiological overview and subsequent discussion exploring concepts of brain aging and involvement of estrogen receptors in potential mechanisms of VCI/VaD pathogenesis and treatment development.