Pathways explaining racial/ethnic and socio-economic disparities in brain white matter integrity outcomes in the UK Biobank study

Abstract

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_mean involving multiple pathways and SES playing a central role in those pathways. Mediational patterns differed across tract-specific FA outcomes, with SES-FA_mean total effect being partially mediated (41% of total effect = indirect effect). Furthermore, the association of poor cognition with FA_mean was markedly stronger in the two uppermost AD PRS tertiles compared to the lower tertile (T₂ and T₃: β±SE: -0.0009 ± 0.0001 vs. T₁: β±SE: -0.0005 ± 0.0001, P < 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.

Keywords: Aging; Magnetic resonance imaging; Racial disparities; Socio-economic status; White matter integrity.

Fig. 1

Consort diagram. Abbreviations: AD = Alzheimer’s Disease; dMRI = Diffusion-weighted magnetic resonance imaging; PRS=Polygenic Risk Score; sMRI=Structural magnetic resonance imaging; UK=United Kingdom.

Fig. 2

Conceptual Framework. Abbreviations: ALCOHOL = Alcohol consumption z-score; COGN=Poor cognitive performance z-score; DIET = Diet quality z-score; dMRI = Diffusion-weighted magnetic resonance imaging; FA=Fractional Anisotropy; HEALTH=Poor cardio-metabolic and general health z-score; PA=Physical Activity z-score; NUTR=Nutritional biomarker z-score; SEM= Structural Equations Model; SES=Socio-economic status z-score; SMOKING=Smoking z-score; SS=Social Support z-score. Notes: Plain arrows are statistically significant associations (p < 0.05) within the hypothesized pathway; Dashed arrows are statistically significant associations (p < 0.05) outside the hypothesized pathway.

Fig. 3

Main findings from SEM models on standard brain images and heat maps for race/ethnic (Non-White vs. White) and SES total, indirect and direct effects on dMRI outcomes: global mean and tract-specific fractional anisotropy (z-scored)^a,b. Abbreviations: DE = Direct Effect; IE=Indirect Effect; SEM= Structural Equations Model; SES=Socio-Economic Status; TE = Total Effect; ^a Mediational patterns plotted on standard brain images pertain only to subcortical structures, and are based on statistical significance of TE, IE and DE. Dark blue color is for significant TE reflecting an inverse association with the subcortical structure. Light blue color is used when TE is non-significant but IE is significant reflecting an inverse association with the subcortical structure through a series of mediators. Dark red is for a positive association based on a significant, positive TE. Yellow is used for significant positive IE, when TE is not statistically significant at type I error of 0.05. Brain image visualization used a standard MNI 152 brain template and FSLEYES software: https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/FSLeyes. ^b Heat map shows the associations of race and SES with all dMRI outcomes, focusing on standardized associations (TE, IE and DE) and percent mediated. For TE, DE and IE, blueish colors are for inverse associations and brownish colors are for positive associations. Size of the circle pertains to p-values associated with TE, IE and DE. Pink/purple colors are for proportion mediated, irrespective of the direction of the IE or TE. However, those were left empty when p-values associated with TE were >0.05. Heatmaps were generated using R Software. FA_mean is unitless and entered in this analysis as a standardized z-score. 1 SD of FA_mean is equivalent to 0.020. The same applied to tract-specific FA, though with varying SDs. See Table 3, Table 4 for details and abbreviations. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

SEM findings for key dMRI outcomes: Fractional Anisotropy (FA)^a,b. Abbreviations: ALCOHOL = Alcohol consumption z-score; COGN=Poor cognitive performance z-score; DIET = Diet quality z-score; dMRI = Diffusion-weighted magnetic resonance imaging; FA=Fractional Anisotropy; HEALTH=Poor cardio-metabolic and general health z-score; PA=Physical Activity z-score; NUTR=Nutritional biomarker z-score; SD=Standard Deviation; SEM= Structural Equations Model; SES=Socio-economic status z-score; SMOKING=Smoking z-score; SS=Social Support z-score. ^a Arrows indicate statistically significant direct effects from SEM models. Blue arrows stand for inverse relationships (β < 0, p < 0.05), red arrow stand for positive relationships (β > 0, p < 0.05), solid lines are for direct effects that are part of the hypothesized pathway; dashed lines are direct effects outside the hypothesized pathway. FA_mean is unitless and entered in this analysis as a standardized z-score. 1 SD of FA_mean is equivalent to 0.020. ^b See Methods section for a full list of exogenous variables entered into the SEM model. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)