Life course shaping of brain ageing: the SHARE blood biomarker study

Evidence from many countries shows that later life cognitive health is shaped by childhood poverty. However, whether it is associated with neurodegenerative biomarkers measured in population settings remains unclear. Methods We conducted a pooled analysis of 5,473 adults aged [&ge;]50 years from Denmark, Sweden and Germany participating in Wave 6 (2015) of the Survey of Health, Ageing and Retirement in Europe. Neurodegenerative biomarkers (neurofilament light chain, glial fibrillary acidic protein and phosphorylated tau) were assayed from dried blood spots. Childhood poverty was constructed as a latent variable from retrospective life histories. Weighted Poisson regression models estimated associations adjusting for age, sex, education, marital status and wealth in later life. Marginal predictions along age and across country were derived. Results Childhood poverty was strongly associated with higher NfL concentrations ({beta}=1.66, p<0.001), but not with GFAP or p-tau217. Predicted values indicated substantially elevated NfL among the childhood poor (10.3 pg/mL vs 2.0 pg/mL for the non-poor). Age profiles showed widening disparities: the childhood poor in midlife exhibited higher NfL levels than the oldest old who grew up not poor. No consistent differences were observed for GFAP or p-tau217. Findings were robust and similar across all three countries with different histories and health systems. Conclusions Childhood poverty is associated with markedly elevated levels of NfL in later life, suggesting long-term neuroaxonal injury consistent with life course shaping of brain health. Moreover, the evidence implies substantial acceleration of neurobiological ageing. These findings emphasise the importance of early-life interventions for brain health in ageing populations.