Low birth weight is associated with accelerated brain aging in mid- and old-age: A large population-based cohort study in the UK Biobank.

BACKGROUND: Low birth weight has been linked to cognitive decline and neurological disorders in adults. We aimed to investigate the association between low birth weight and brain aging and explore whether low-grade inflammation plays a mediating role in this association. METHODS: Within the UK Biobank cohort, 20,920 adults free of chronic neurological disorders who underwent brain magnetic resonance imaging scans an average of nine years after baseline were included. Self-reported birth weight was classified as low (<2500g), normal (2500-4000g), or high (≥4000g). Brain age was estimated using machine learning algorithms based on 1,079 magnetic resonance imaging phenotypes. Brain age gap (BAG) was calculated as the difference between brain age and chronological age. Low-grade inflammation was calculated using the inflammation score (white blood cell count, platelet count, neutrophil granulocyte-to-lymphocyte ratio, C-creative protein). Data were analyzed using linear regression and structural equation models. RESULTS: The association between birth weight and BAG was significantly nonlinear (Pnon-linear<0.001). Compared to participants with normal birth weight, those with low birth weight had significantly larger BAG (β=0.38, 95%CI=0.14, 0.63), across middle-aged (<60years; β=0.47, 95%CI=0.04, 0.89) and older adults (60+years; β=0.35, 95%CI=0.05, 0.66). Low-grade inflammation partially mediated the association between low birth weight and larger BAG, accounting for 5.54% of the total association (P<0.001). CONCLUSIONS: Low birth weight is associated with accelerated brain aging. Low-grade inflammation may partially mediate this association.