85 -3 (89) 2026 - Ismatov A.N., Tolibov D.S. - CLINICAL, NEUROIMAGING, AND IMMUNOGENETIC PREDICTORS OF DEMENTIA IN CADASIL PATIENTS

CLINICAL, NEUROIMAGING, AND IMMUNOGENETIC PREDICTORS OF DEMENTIA IN CADASIL PATIENTS

Ismatov A.N. - Tashkent State Medical University

Tolibov D.S. - Tashkent State Medical University

Resume

CADASIL belongs to the group of hereditary cerebral microangiopathies and is characterized by progressive cognitive decline and the development of vascular dementia. The aim of this study was to identify and evaluate clinical, neuroimaging, and immunogenetic markers associated with cognitive impairment in patients with CADASIL. Materials and Methods. A total of 106 participants were enrolled in the study, including 31 patients diagnosed with CADASIL, 45 patients with dyscirculatory encephalopathy, and 30 healthy control subjects. All participants underwent a comprehensive evaluation, which included clinical assessment, neuropsychological testing, brain MRI analysis, and genetic testing aimed at detecting mutations in the NOTCH3 gene as well as the TNF G308A polymorphism. Results. The CADASIL group demonstrated significantly lower SDMT scores compared to the control group (33.8 ± 7.1 vs. 48.6 ± 6.3; p < 0.001). White matter lesions of Fazekas grade ≥2 were observed in 74.2% of patients and showed a moderate negative correlation with SDMT scores (r = −0.52; p < 0.001). Carriers of the A allele of the TNF G308A polymorphism exhibited higher levels of inflammatory markers and poorer cognitive performance. The diagnostic model demonstrated high accuracy based on ROC analysis (AUC = 0.90). Conclusion. Cognitive impairment in patients with CADASIL is closely associated with structural changes in cerebral white matter as well as immunogenetic factors.

Keywords: CADASIL, cognitive impairment, NOTCH3, TNF G308A, Fazekas scale.

First page

522

Last page

528

For citation:Ismatov A.N., Tolibov D.S. - CLINICAL, NEUROIMAGING, AND IMMUNOGENETIC PREDICTORS OF DEMENTIA IN CADASIL PATIENTS//New Day in Medicine 3(89)2026 522-528 https://newdayworldmedicine.com/en/new_day_medicine/3-89-2026

List of References

  1. Luo W, Dai Z, Wu W, Li H, Zhang Y. White matter hyperintensities and the risk of vascular dementia: a systematic review and meta-analysis. PeerJ. 2025 Jun 16;13:e19460. doi:10.7717/peerj.19460
  2. Singh A, Bonnell G, De Prey J, Buchwald N, Eskander K, Kincaid KJ, et al. Small-vessel disease in the brain. Am Heart J Plus Cardiol Res Pract. 2023 Mar;27:100277. doi:10.1016/j.ahjo.2023.100277
  3. Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser MG. CADASIL. Lancet Neurol. 2009 Jul;8(7):643–53. doi:10.1016/S1474-4422(09)70127-9
  4. Yamamoto Y, Liao YC, Lee YC, Ihara M, Choi JC. Update on the epidemiology, pathogenesis, and biomarkers of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. J Clin Neurol. 2023;19(1):12. doi:10.3988/jcn.2023.19.1.12
  5. Choi JC. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: a genetic cause of cerebral small vessel disease. J Clin Neurol. 2010;6(1):1. doi:10.3988/jcn.2010.6.1.1
  6. Rutten JW, Dauwerse HG, Peters DJM, Goldfarb A, Venselaar H, Haffner C, et al. Therapeutic NOTCH3 cysteine correction in CADASIL using exon skipping: in vitro proof of concept. Brain. 2016 Apr;139(4):1123–35. doi:10.1093/brain/aww011
  7. O’Sullivan M, Jarosz JM, Martin RJ, Deasy N, Powell JF, Markus HS. MRI hyperintensities of the temporal lobe and external capsule in patients with CADASIL. Neurology. 2001 Mar 13;56(5):628–34. doi:10.1212/WNL.56.5.628
  8. Jokinen H, Laakso HM, Arola A, Paajanen TI, Virkkala J, Särkämö T, et al. Executive functions and processing speed in covert cerebral small vessel disease. Eur J Neurol. 2025 Jan;32(1):e16533. doi:10.1111/ene.16533
  9. Staszewski J, Skrobowska E, Piusińska-Macoch R, Brodacki B, Stępień A. IL-1α and IL-6 predict vascular events or death in patients with cerebral small vessel disease—data from the SHEF-CSVD study. Adv Med Sci. 2019 Sep;64(2):258–66. doi:10.1016/j.advms.2019.02.003
  10. Jokinen H, Kalska H, Ylikoski R, Madureira S, Verdelho A, Van Der Flier WM, et al. Longitudinal cognitive decline in subcortical ischemic vascular disease—the LADIS study. Cerebrovasc Dis. 2009;27(4):384–91. doi:10.1159/000207442
  11. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010 Jul;9(7):689–701. doi:10.1016/S1474-4422(10)70104-6
  12. Rutten JW, Van Eijsden BJ, Duering M, Jouvent E, Opherk C, Pantoni L, et al. The effect of NOTCH3 pathogenic variant position on CADASIL disease severity: NOTCH3 EGFr 1–6 pathogenic variant are associated with a more severe phenotype and lower survival compared with EGFr 7–34 pathogenic variant. Genet Med. 2019 Mar;21(3):676–82. doi:10.1038/s41436-018-0088-3
  13. Iadecola C. The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron. 2017 Sep;96(1):17–42. doi:10.1016/j.neuron.2017.07.030
  14. Толибов Д.С. Subkortikal infarkt va leyko ensefalopatiya bilan kechadigan autosomal dominant miya arteriopatiyasi (CADASIL sindromi). 2024.

    file

    download