Estrogen receptor involvement in vascular cognitive impairment and vascular dementia pathogenesis and treatment
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REVIEW
Estrogen receptor involvement in vascular cognitive impairment and vascular dementia pathogenesis and treatment Dianna H. Nguyen & J. Thomas Cunningham Nathalie Sumien
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Received: 18 June 2020 / Accepted: 2 September 2020 # American Aging Association 2020
Abstract 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. D. H. Nguyen : J. T. Cunningham (*) Department of Physiology and Anatomy, UNT Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA e-mail: [email protected] D. H. Nguyen Texas College of Osteopathic Medicine, UNT Health Science Center, Fort Worth, TX, USA N. Sumien Department of Pharmacology and Neuroscience, UNT Health Science Center, Fort Worth, TX, USA
Keywords Vascular cognitive impairment (VCI) . Vasculardementia(VaD) . Estrogenreceptor(ER) . Brain aging . Alzheimer’s disease (AD)
Introduction Increase in lifespan of the aging population worldwide is creating a greater demand for cardiovascular and neurobiology of aging research, particularly since prevalence of various pathologies (e.g., stroke and dementia) increases exponentially with age [1, 2]. Vascular cognitive impairment (VCI) is a term which encompasses a continuum of cognitive deficits with cerebrovascular pathology contribution, ranging from mild cognitive impairment to vascular dementia (VaD) [3, 4], and it represents an interesting intersection between cardiovascular disease and Alzheimer’s disease (AD). There is an expanding body of evidence indicating a greater prevalence of cardiovascular disease [5, 6] and AD [7, 8] in postmenopausal women, as well as differences in pathogenesis and response to treatment [9–12]. However, one important aspect that remains elusive in the literature is information on sex differences in VCI. Several studies have reported associations of estrogen receptor (ER) polymorphisms with VaD [13–15]; however, this has not been extensively reviewed in terms of sex differences in VCI epidemiology, pathogenesis, a
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