Birth weight is associated with brain tissue volumes seven decades later, but not with age-associated changes to brain structure

Abstract

Birth weight, an indicator of fetal growth, is associated with cognitive outcomes in early life and risk of metabolic and cardiovascular disease across the life course. Cognitive ability in early life is predictive of cognitive ability in later life. Brain health in older age, defined by MRI features, is associated with cognitive performance. However, little is known about how variation in normal birth weight impacts on brain structure in later life. In a community dwelling cohort of participants in their early seventies we tested the hypothesis that birthweight is associated with the following MRI features: total brain (TB), grey matter (GM) and normal appearing white matter (NAWM) volumes; whiter matter hyperintensity (WMH) volume; a general factor of fractional anisotropy (gFA) and peak width skeletonised mean diffusivity (PSMD) across the white matter skeleton. We also investigated the associations of birthweight with cortical surface area, volume and thickness. Birthweight was positively associated with TB, GM and NAWM volumes in later life (β ≥ 0.194), and with regional cortical surface area but not gFA, PSMD, WMH volume, or cortical volume or thickness. These positive relationships appear to be explained by larger intracranial volume rather than by age-related tissue atrophy, and are independent of body height and weight in adulthood. This suggests that larger birthweight is linked to increased brain tissue reserve in older life, rather than a resilience to age-related changes in brain structure, such as tissue atrophy or WMH volume.Significance StatementCognitive brain ageing carries a high personal, societal and financial cost and understanding its developmental origins is important for identifying possible preventative strategies. In a sample of older participants from the Lothian Birth Cohort 1936 we were able to explore the neurobiological correlates of birth weight, which is indicative of the fetal experience. We find that higher birth weight is related to larger brain tissue volumes in later life, but does not modify the trajectory of age-related change. This suggests that early life growth confers preserved differentiation, rather than differential preservation with regards to brain reserve. That these effects are detectable into later life indicates that this variable may be valuable biomarker in the epidemiology of ageing.

Brain charts for the human lifespan

“…Centile scores also showed increased twin-based heritability in two independent studies (total N=913 twin-pairs) compared to non-centiled phenotypes (average increase of 11.8% points in h 2 across phenotypes; Fig.4D , SI13 ). In summary, centile normalisation of brain metrics reproducibly detected case-control differences and genetic effects on brain structure, as well as long-term sequelae of adverse birth outcomes even in the adult brain 10 .…”

“…3C, SI6). In summary, centile normalisation of brain metrics reproducibly detects case-control and genetic influences on brain structure, as well as long-term sequelae of adverse birth outcomes even in the adult brain 8 .…”

“…Note that age of diagnosis is significantly later than age of symptom onset for many disorders 6 . Developmental milestones were re-plotted from published work for brain resting metabolic rate (RMR) 8 , anthropometric variables 9 , and typical acquisition of the six gross motor capabilities 4 . Pubertal age ranges were taken from reported typical age ranges 10,11 .…”

“…The lack of brain reference standards is particularly relevant to psychiatric disorders that are increasingly considered to be disorders of neurodevelopment 2 and arguably represent the single highest current global health burden 3 . Furthermore, preterm infants and those born with congenital conditions – many with psychiatric sequelae – show marked morphological differences during early brain development 4–7 and even decades later during adulthood 7,8 . With ageing, neurodegeneration and accelerated overall reductions in brain tissue volume are hallmark signatures of Alzheimer’s disease 9 and other types of dementia.…”

“…The lack of tools for standardised assessment of brain development and aging is particularly relevant to research studies of psychiatric disorders, which are increasingly recognised as a consequence of atypical brain development 6 , and neurodegenerative diseases that cause pathological brain changes in the context of normative senescence 7 . Preterm birth and neurogenetic disorders are also associated with marked abnormalities of brain structure 8,9 that persist into adult life 9,10 and are associated with learning disabilities and mental health disorders. Mental illness and dementia collectively represent the single biggest global health burden 11 , highlighting the urgent need for normative brain charts as an anchorpoint for standardised quantification of brain structure over the lifespan 12 .…”