Cortical Surface Area Profile Mediates Effects of Childhood Disadvantage on Later-Life General Cognitive Ability

Objectives: Abstract Childhood disadvantage is associated with lower general cognitive ability (GCA) and brain structural differences in midlife and older adulthood. However, the neuroanatomical mechanisms underlying childhood disadvantage effects on later-life GCA remain poorly understood. Although total surface area (SA) has been linked to lifespan GCA differences, total SA does not capture the nonuniform nature of childhood disadvantage effects on neuroanatomy, which varies across unimodal and transmodal cortices. Here, we examined whether cortical SA profile-the extent to which the spatial patterning of SA deviates from the normative unimodal-transmodal cortical organization-is a mediator of childhood disadvantage effects on later-life GCA. Methods: In 477 community-dwelling men aged 56-72 years old, childhood disadvantage index was derived from four indicators of disadvantages and GCA was assessed using a standardized test. Cortical SA was obtained from structural magnetic resonance imaging. For cortical SA profile, we calculated the spatial similarity between maps of individual cortical SA and MRI-derived principal gradient (i.e., unimodal-transmodal organization). Mediation analyses were conducted to examine the indirect effects of childhood disadvantage index through cortical SA profile on GCA. Results: Around 1.31% of childhood disadvantage index effects on later-life GCA were mediated by cortical SA profile, whereas total SA did not. Higher childhood disadvantage index was associated with more deviation of the cortical SA spatial patterning from the principal gradient, which in turn related to lower later-life GCA. Discussion: Childhood disadvantage may contribute to later-life GCA differences partly by influencing the spatial patterning of cortical SA in a way that deviates from the normative cortical organizational principle.