Uncovering mediational pathways behind racial and socioeconomic disparities in brain volumes: insights from the UK Biobank study

Mediation pathways explaining racial/ethnic and socioeconomic (SES) disparities in structural MRI markers of brain health remain underexplored. We examined racial/ethnic and SES disparities in sMRI markers 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 years at baseline assessment (47% men). Race (non-White vs. White) and lower SES-predicted poorer brain sMRI volumetric outcomes at follow-up, with racial/ethnic disparities in sMRI outcomes involving multiple pathways and SES playing a central role in those pathways. Mediational patterns differed across outcomes, with the SES-sMRI total effect being partially mediated for all outcomes. Over 20% of the total effect (TE) of race/ethnicity on WMH was explained by the indirect effect (IE), by a combination of different pathways going through SES, lifestyle, health-related, and cognition factors. This is in contrast to < 10% for total brain, gray matter (GM), white matter (WM), and frontal GM left/right. Another significant finding is that around 57% of the total effect for SES and the normalized white matter hyperintensity (WMH) was attributed to an indirect effect. This effect encompasses many pathways that involve lifestyle, health-related, and cognitive aspects. Aside from WMH, the percent of TE of SES mediated through various pathways ranged from ~ 5% for WM to > 15% up to 36% for most of the remaining sMRI outcomes, which are composed mainly of GM phenotypes. Race and SES were important determinants of brain volumetric outcomes, with partial mediation of racial/ethnic disparities through SES, lifestyle, health-related, and cognition factors.