Skip to Main content Skip to Navigation
Master Thesis

Impact des variants génétiques à risque de la maladie des petites artères cérébrales sur la microstructure de la substance blanche et les fonctions exécutives chez le sujet jeune. À partir des données de l’étude i-Share

Abstract : Context: Small vessels disease (SVD) is an important risk factor for stroke, cognitive impairment and dementia. Epidemiological studies suggest that pathological processes leading to dementia start many years before the onset of clinical symptoms. In order to improve our understanding of the underlying the mechanisms and time-courses of structural brain changes throughout a lifetime, we are interested in the association of genetic determinants of white matter hyperintensities with an early marker of integrity of the white matter microstructure in MRI-DTI, peak-width of skeletonized mean diffusivity (PSMD), and the impact of these early structural changes on cognitive performance in the i-Share study, cohort of students. Methods: We included ~ 1,700 individuals, from i-Share cohort. Linear multivariable regressions have been used to study, firstly, the association between genetic risk score (GRS) of variants associated with white matter hyperintensities (WMH) at a genome-wide significance threshold (p<5x10-8) and a new MRI marker, PSMD. And secondly, between GRS and PSMD on processing speed information of Stroop test. Results: after adjustment, GRS of WMH was significantly associated with PSMD (β: 0.001, 95% CI: 0.0003, 0.0024, p = 0.0087). Although GRS of WMH and PSMD was not significantly associated with the processing speed in young adults, an association trend was observed between higher PSMD and slower processing speed. This association was significant for the upper quartile of the PSMD. Conclusion: The associations between PSMD, cognition function and GRS of WMH in this study, add insights in favor of the hypothesis on microstructural changes of the white matter in young subjects could be an early phase of SVD, or reflecting a process of brain maturation that would share genetic loci at risk with WMH; still additional studies are needed to confirm these exploratory findings
Document type :
Master Thesis
Complete list of metadatas

Cited literature [79 references]  Display  Hide  Download

https://dumas.ccsd.cnrs.fr/dumas-02435123
Contributor : Isped Ub <>
Submitted on : Friday, January 10, 2020 - 3:20:41 PM
Last modification on : Saturday, January 11, 2020 - 1:28:58 AM

File

M2EPI_2019_BORDES.pdf
Files produced by the author(s)

Identifiers

  • HAL Id : dumas-02435123, version 1

Collections

Citation

Constance Bordes. Impact des variants génétiques à risque de la maladie des petites artères cérébrales sur la microstructure de la substance blanche et les fonctions exécutives chez le sujet jeune. À partir des données de l’étude i-Share. Santé publique et épidémiologie. 2019. ⟨dumas-02435123⟩

Share

Metrics

Record views

86

Files downloads

80