Pathogenetic mechanisms of cognitive impairment in cerebrovascular pathology and prospects for their correction using nootropic and neuroprotective agents

Abstract

The article presents modern ideas about the pathogenesis of cognitive disorders in cerebrovascular pathology at the cellular level. Dysfunction of neurovascular units is associated with impaired microcirculation, hypoxia, deficiency of energy resources, development of neuroinflammation, increased nitric oxide synthesis and oxidative stress, glutamate excitotoxicity, intracellular calcium accumulation, endothelial dysfunction, impaired circulation of cerebrovascular fluid, venous outflow from the cranial cavity and utilization of brain metabolic products, including misshaped proteins. The above determines the possibility of the combined development of cerebrovascular and neurodegenerative diseases, primarily Alzheimer’s disease. Currently, mixed (vascularneurodegenerative) brain damage is considered as the  main cause of  cognitive disorders, which is confirmed by the  data of post-mortem studies. Pathogenetic therapy of dementia with cholinesterase inhibitors and memantine does not eliminate the cognitive defect, but only slows down its progression. The impossibility of restoring the premorbid level of daily activity of the patient in the treatment of cognitive impairment at the stage of dementia dictates the need for the use of adjuvant nootropic and neuroprotective agents until the breakdown of the functional reserve, that is, at the stage of moderate cognitive impairment. Nicotinoyl gamma-aminobutyric acid has nootropic, tranquilizing, psychostimulant and antioxidant properties. Studies of the last decade have proven the ability of nicotinoyl gamma-aminobutyric acid to suppress neuroinflammation and apoptosis of  cells of  the central nervous system, increase the  expression of  angiogenic and cytoskeletal proteins, normalize the  permeability of  the blood-brain barrier, which can be used to improve the  function of  neurovascular units and correct vascular-neurodegenerative cognitive impairment. A small number of drug interactions with nicotinoyl gamma-aminobutyric acid allows it to be included in the complex therapy of comorbid patients.