Pathways Explaining Racial/ethnic and Socio-economic Disparities in Brain White Matter Integrity Outcomes in the UK Biobank Study

Pathways explaining racial/ethnic and socio-economic status (SES) disparities in white matter integrity (WMI) reflecting brain health, remain underexplored, particularly in the UK population. We examined racial/ethnic and SES disparities in diffusion tensor brain magnetic resonance imaging (dMRI) markers, namely global and tract-specific mean fractional anisotropy (FA), and tested total, direct and indirect effects through lifestyle, health-related and cognition factors using a structural equations modeling approach among 36,184 UK Biobank participants aged 40-70 y at baseline assessment (47% men). Multiple linear regression models were conducted, testing independent associations of race/ethnicity, socio-economic and other downstream factors in relation to global mean FA, while stratifying by Alzheimer's Disease polygenic Risk Score (AD PRS) tertiles. Race (Non-White vs. White) and lower SES predicted poorer WMI (i.e. lower global mean FA) at follow-up, with racial/ethnic disparities in FA involving multiple pathways and SES playing a central role in those pathways. Mediational patterns differed across tract-specific FA outcomes, with SES-FA total effect being partially mediated (41% of total effect = indirect effect). Furthermore, the association of poor cognition with FA was markedly stronger in the two uppermost AD PRS tertiles compared to the lower tertile (T and T: β±SE: -0.0009 ± 0.0001 vs. T: β±SE: -0.0005 ± 0.0001,  < 0.001), independently of potentially confounding factors. Race and lower SES were generally important determinants of adverse WMI outcomes, with partial mediation of socio-economic disparities in global mean FA through lifestyle, health-related and cognition factors. The association of poor cognition with lower global mean FA was stronger at higher AD polygenic risk.