Childhood Adiposity and Midlife Cognitive performance: Investigating Socioeconomic and Biological Pathways Using Causal Inference

Childhood obesity has traditionally been linked to short-term comorbidities, with its long-term consequences primarily attributed to progression into adult obesity. However, recent observational studies report associations between childhood obesity-independent of adult obesity-and later-life cognitive performance. These findings may be influenced by unmeasured or poorly captured confounding factors. If early-life obesity does causally impact cognitive performance, the growing prevalence of childhood obesity could contribute to increasing adverse cognitive outcomes. This highlights the need for robust evidence to determine whether early-life body size directly affects cognitive performance.

Study 1 will aim to investigate whether childhood BMI mediates the association between early-life socioeconomic position and mid-life cognitive performance. Using harmonised data from three UK longitudinal birth cohorts, this study will apply mediation analysis to test whether childhood BMI explains part of the pathway between early disadvantage and later cognitive performance. Understanding this mechanism could help identify intervention points to reduce cognitive health disparities.

Study 2 will aim to examine whether early-life body size has a direct causal effect on adult cognitive performance, independent of adult body size. Using multivariable Mendelian randomisation (MVMR) in the UK Biobank, this study will leverage genetic instruments to disentangle the effects of body size across the life course. This approach will help address confounding and reverse causation, enabling stronger causal conclusions than observational designs.

Study 3 will incorporate findings from Studies 1 and 2 to further elucidate the biological pathways linking early-life adiposity to mid-life cognitive performance, with a focus on potential mechanisms underlying these associations.

Together, these studies will aim to clarify life-course determinants of cognitive performance, informing early interventions and public health strategies.