Neurosurg Rev. 2025 Dec 26;49(1):89. doi: 10.1007/s10143-025-04024-9.
ABSTRACT
Intracerebral hemorrhage (ICH) significantly threatens human health, and educational attainment (EA) may influence the burden of ICH. We aim to explore the relationship between EA levels and ICH by Mendelian randomization (MR) and Global Burden of Disease (GBD). We conducted bidirectional univariate MR (UVMR) analyses to evaluate the causal relationship between EA levels and ICH, and multivariate MR (MVMR) analyses to control for confounders. A two-step MR analyses were employed to assess the mediating effects of brain image-derived phenotypes (IDPs) and gut microbiota. Subsequently, MVMR and MR Bayesian model averaging (MR-BMA) were utilized to identify the optimal mediators. Multiple sensitivity analyses enhanced the robustness of the results. Finally, the GBD database was used to analyze the temporal trend and health inequality of ICH. UVMR and MVMR indicated that higher levels of EA significantly decreased the risk of ICH (OR=0.281, 95%CI: 0.156-0.507, P=2.42E-05), including nonlobar ICH (OR=0.312, 95%CI: 0.155-0.628, P=1.11E-03) and lobar ICH (OR=0.220, 95%CI: 0.101-0.478, P=1.33E-04). Mediation analysis found eight types of IDPs and one gut microbiota served as mediators between EA levels and ICH (nonlobar ICH and lobar ICH). Specifically, for EA levels and ICH, five types of IDPs and one type of gut microbiota acted as mediators, including IDP diffusion magnetic resonance imaging (dMRI) tract-based spatial statistics (TBSS) fractional anisotropy (FA) Superior cerebellar peduncle L (mediation percentage=3.67%), IDP dMRI TBSS orientation dispersion index (OD) Pontine crossing tract (mediation percentage=2.92%), aparc-Desikan lh volume middletemporal (mediation percentage=9.19%), aparc-Desikan lh volume insula (mediation percentage=4.92%), aparc-Desikan lh area bankssts (mediation percentage=5.70%), and Dialister_invisus (mediation percentage=10.22%). When considering the sites of ICH, aparc-Desikan lh area bankssts (mediation percentage=6.79%) and Dialister_invisus (mediation percentage=12.74%) mediated the causal relationship between EA levels and nonlobar ICH, while IDP dMRI TBSS OD Pontine crossing tract (mediation percentage=3.68%) and aparc-Desikan lh volume middletemporal (mediation percentage=8.05%) acted as mediators in the protective effect of EA levels against lobar ICH. Another three types of IDPs mediated the causal relationship between EA levels and nonlobar ICH, including IDP dMRI TBSS isotropic or free water volume fraction (ISOVF) Inferior cerebellar peduncle R (mediation percentage=7.61%), aparc-Desikan lh area TotalSurface (mediation percentage=5.06%), and aparc-Desikan rh area inferiorparietal (mediation percentage=7.84%). After mediation analysis, MVMR and MR-BMA, aparc-Desikan lh volume middletemporal was the optimal mediator for EA levels and ICH, specifically for lobar ICH. GBD statistical analyses showed a declining trend of ICH and provided evidence of health inequality. This study identified higher EA levels as protective against ICH and explored the potential mediating effects of IDPs and gut microbiota, indicating that more efforts are needed to improve EA levels to decrease the burden of ICH.
PMID:41452476 | DOI:10.1007/s10143-025-04024-9