RT Journal Article SR Electronic T1 The neurobiology of life course socioeconomic conditions and associated cognitive performance in middle to late adulthood JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP e1231232024 DO 10.1523/JNEUROSCI.1231-23.2024 A1 Schrempft, Stephanie A1 Trofimova, Olga A1 Künzi, Morgane A1 Ramponi, Cristina A1 Lutti, Antoine A1 Kherif, Ferath A1 Latypova, Adeliya A1 Vollenweider, Peter A1 Marques-Vidal, Pedro A1 Preisig, Martin A1 Kliegel, Matthias A1 Stringhini, Silvia A1 Draganski, Bogdan YR 2024 UL http://www.jneurosci.org/content/early/2024/03/07/JNEUROSCI.1231-23.2024.abstract AB Despite major advances, our understanding of the neurobiology of life course socioeconomic conditions is still scarce. This study aimed to provide insight into the pathways linking socioeconomic exposures – household income, last-known occupational position, and life course socioeconomic trajectories – with brain microstructure and cognitive performance in middle to late adulthood. We assessed socioeconomic conditions alongside quantitative relaxometry and diffusion-weighted magnetic resonance imaging indicators of brain tissue microstructure, and cognitive performance in a sample of community-dwelling men and women (N=751, aged 50-91 years). We adjusted the applied regression analyses and structural equation models for the linear and non-linear effects of age, sex, education, cardiovascular risk factors, and presence of depressive, anxiety, and substance use disorders. Individuals from lower income households showed signs of advanced brain white matter aging with greater mean diffusivity, lower neurite density, lower myelination, and lower iron content. The association between household income and mean diffusivity was mediated by neurite density (B=0.084, p=0.003) and myelination (B=0.019, p=0.009); mean diffusivity partially mediated the association between household income and cognitive performance (B=0.017, p<0.05). Household income moderated the relation between white matter microstructure and cognitive performance, such that greater mean diffusivity, lower myelination, or lower neurite density was only associated with poorer cognitive performance among individuals from lower income households. Individuals from higher income households showed preserved cognitive performance even with greater mean diffusivity, lower myelination, or lower neurite density. These findings provide novel mechanistic insight into associations between socioeconomic conditions, brain anatomy, and cognitive performance in middle to late adulthood.Significance statement Pathways linking socioeconomic conditions, brain anatomy, and cognitive performance have rarely been investigated. Using multi-contrast imaging, we found that individuals from lower income households had markers of advanced brain white matter aging with lower neurite density, lower myelination, and lower iron content, alongside greater mean diffusivity. Greater mean diffusivity (reflecting myelin and neurite density) contributed to the association between household income and cognitive performance. Household income also buffered the observed white matter effects, such that greater mean diffusivity, lower index of myelin content, or lower neurite density was only associated with poorer cognitive performance among individuals from lower income households. These findings provide a detailed neurobiological understanding of socioeconomic differences in brain anatomy and associated cognitive performance.