Neuropsychiatric Disease and Treatment (May 2019)

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

  • Parfenov VA,
  • Ostroumova OD,
  • Ostroumova TM,
  • Kochetkov AI,
  • Fateeva VV,
  • Khacheva KK,
  • Khakimova GR,
  • Epstein OI

Journal volume & issue
Vol. Volume 15
pp. 1381 – 1402

Abstract

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Vladimir A Parfenov,1 Olga D Ostroumova,2,3 Tatiana M Ostroumova,1 Alexey I Kochetkov,2 Victoria V Fateeva,4 Kristina K Khacheva,4 Gulnara R Khakimova,5 Oleg I Epstein61Department of Neurology, Federal State Autonomous Educational Institution of Higher Education, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russian Federation; 2Laboratory of Clinical Pharmacology and therapy, Federal State Budgetary Educational Institution of Higher Education “N.I. Pirogov Russian National Research Medical University” of the Ministry of Health of the Russian Federation, Russian Clinical and Research Center of Gerontology, Moscow, Russia; 3Department of Clinical Pharmacology, Internal Medicine and Propaedeutics I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; 4Medical Information Department, OOO NPF Materia Medica Holding, Moscow, Russian Federation; 5Research and Analytical Division of Scientific Research and Development Department, Moscow, Russian Federation; 6Laboratory of Physiologicaly Active Substances, Department of Molecular and Cellular Pathophysiology, Research Institute of General Pathology and Pathophysiology, Moscow, Russian FederationAbstract: 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.Keywords: vascular cognitive impairment, cerebrovascular disease, neurovascular unit, endothelial dysfunction, S100 protein

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