Early life factors and individual differences in the brain through the human lifespan – association of intercept or change?

Abstract

AbstractBackgroundHuman fetal development has been associated with brain health at later stages. In this presentation, I review results of analyses by the center for Lifespan Changes in Brain and cognition (LCBC), on whether and how consistently factors present in utero, including genetics (APOE4; polygenic risk for Alzheimer´s Disease; AD), prenatal drug exposure and, especially, growth in utero, as indexed by birth weight (BW), relates to lifespan brain characteristics and changes.MethodWe investigated associations between BW and cortical surface area, thickness and volume as derived from MRIs, across and within developmental, aging and lifespan longitudinal samples (N = 5794, 4‐82 years of age, w/ 386 monozygotic (MZ) twins, followed for up to 8.3 years w/12,088 brain MRIs).ResultsAssociations of BW and structural brain characteristics appear to be identifiable through the lifespan, with largely topographically consistent effects across samples of varying age. In developmental (ABCD), older adult and aging (UKB) and lifespan (LCBC) longitudinal samples, positive associations between BW and cortical surface area and volume were remarkably stable within and across samples of different age and origin, with spatial correlations in the range r = .51‐.79. In contrast, there was modest and no consistent effect of BW on brain changes. Effects of BW discordance in the twin subsample indicated the effects were partly environmental. This stable effect of an early life factor (BW), is similar to effects through the lifespan of genetic risk for AD, and persistent effects of prenatal opioid and ‐polydrug exposure in childhood and young adulthood.ConclusionThe influence of these early life factors, as here shown for BW, on brain topography, appear in part stable through the lifespan, being reliably seen in development, adulthood, and aging, as an intercept effect. These findings support early life influence on the brain through the lifespan according to a threshold model of brain reserve, rather than a maintenance model. To test experimentally whether early life factors may still influence slopes of brain and cognitive change, a navigation training neuroimaging study of twins with known extent of discordance in BW has been conducted, preliminary data from which is also presented.