Insight into cerebral microvessel endothelial regulation of cognitive impairment: A systematic review of the causes and consequences

Abstract

Research on cognitive impairment (CI) has increasingly focused on the central nervous system, identifying numerous neuronal targets and circuits of relevance for CI pathogenesis and treatment. Brain microvascular endothelial cells (BMECs) form a barrier between the peripheral and central nervous systems, constituting the primary component of the blood-brain barrier (BBB) and playing a vital role in maintaining neural homeostasis. Stemming from the recognition of the close link between vascular dysfunction and CI, in recent years intense research has been devoted to characterize the pathological changes and molecular mechanisms underlying BMEC dysfunction both during normal aging and in disorders of cognition such as Alzheimer's disease and vascular dementia. In this review, keywords such as “dementia”, “cognitive impairment”, and “endothelium” were used to search PubMed and Web of Science. Based on the literature thus retrieved, we first review some common triggers of CI, i.e., amyloid beta and tau deposition, chronic cerebral hypoperfusion, hyperglycemia, viral infections, and neuroinflammation, and describe the specific mechanisms responsible for endothelial damage. Second, we review molecular aspects of endothelial damage leading to BBB disruption, neuronal injury, and myelin degeneration, which are crucial events underlying CI. Finally, we summarize the potential targets of endothelial damage in the development of cognitive dysfunction associated with Alzheimer's disease, vascular dementia, type 2 diabetes mellitus, and physiological aging. A thorough understanding of the induction mechanism and potential outcomes of microvascular endothelial damage is of great significance for the study of CI, to guide both diagnostic and therapeutic approaches for its prevention and treatment.