Vascular cognitive impairment: pathophysiological mechanisms, insights into structural basis, and perspectives in specific treatments

Vascular cognitive impairment (VCI) and vascular dementia are the most common forms of cognitive disorder associated with cerebrovascular disease and related to increased morbidity and mortality among the older population. Growing evidence suggests the contribution of blood-pressure variability, cardiac arrhythmia, hyperactivation of the renin-angiotensin-aldosterone system, endothelial dysfunction, vascular remodeling and stiffness, different angiopathies, neural tissue homeostasis, and systemic metabolic disorders to the pathophysiology of VCI. In this review, we focus on factors contributing to cerebrovascular disease, neurovascular unit alterations, and novel approaches to cognitive improvement in patients with cognitive decline. One of the important factors associated with the neuronal causes of VCI is the S100B protein, which can affect the expression of cytokines in the brain, support homeostasis, and regulate processes of differentiation, repair, and apoptosis of the nervous tissue. Since the pathological basis of VCI is complex and diverse, treatment affecting the mechanisms of cognitive disorders should be developed. The prospective role of a novel complex drug consisting of released-active antibodies to S100 and to endothelial NO synthase in VCI treatment is highlighted.