The heterogeneity of cerebrovascular diseases makes it difficult to find out neuropathological substrates and mechanisms of neurocognitive disorders in vascular encephalopathy. The aim of the study: to develop a mathematical model for predicting the risk of developing cognitive disorders and functional disability in patients with chronic vascular encephalopathy based on the analysis of polymorphic variants of the ACE, AT2R1, eNOS, ePON1, IL-1β, IL-10, TNF-α genes, as well as cofactors (gender, age category, catamnesis and presence/absence of somatic comorbidity). Materials and methods. To perform a clinical characterization of patients with vascular encephalopathy in chronic brain ischemia (chronic vascular encephalopathy), we conducted a retrospective analysis of 145 medical records. Molecular and genetic differentiation of the investigated gene variants was carried out by allele-specific polymerase chain reaction methods. Amplification of the studied gene regions was provided by oligonucleotide primers. The results. Analyzing polymorphic variants of ACE, AT2R1, eNOS, ePON1, IL-1β, IL-10, TNF-α genes, as well as cofactors — gender, age category, catamnesis and somatic comorbidity in the context of the development of cognitive disorders in patients with chronic vascular encephalopathy, the dominant role of somatic comorbidity was established (p<0.05). At the same time, carrying the D allele of the ACE gene is associated with a significant decrease in scores on the MoCA scale compared to a group of patients who are not carriers of this allele. In patients with chronic vascular encephalopathy carrying the A allele of the TNF-α gene, the probability of functional failure is 71.43%. At the same time, genotypes A/A and G/A of the TNF-α gene are characterized by probably lower Barthel index values compared to G/G homozygotes. Conclusion. Polymorphism of ACE and TNF-α genes, as well as somatic comorbidity in patients with chronic vascular encephalopathy increase the likelihood of functional failure.