McNeil, C. J. | Search bioRxiv

bioRxiv2023

The influence of birthweight, socioeconomic status, and adult health on brain volumes during aging

Preserved late-life brain volume is associated with resilience to dementia. We examined relationships between birthweight, socioeconomic status and adult health with late-life brain volumes. We hypothesised that early-life factors have direct and indirect effects on the aging brain. Neurotypical adults aged 61-67y underwent MRI and brain volumes measured. Birthweight, health and socioeconomic status were assessed by historical data or contemporary assessment. Measures of health and socioeconomic status were extracted using principal component analysis. Relationships between variables were explored by linear regression and structural equation models. Birthweight ({beta}=0.095, p=0.017, n=280) and childhood socioeconomic status ({beta}=0.091, p=0.033, n=280) were directly associated with late-life brain volume. Childhood socioeconomic status was associated with additional increase in grey matter volume ({beta}=0.04, p=0.047, n=280). Better adult health was linked to increased late-life brain volume ({beta}=0.15, p=0.003, n=280). Birthweight and childhood socioeconomic status are associated with whole and regional brain volume through direct and indirect mechanisms. Optimal fetal development, good adult health and reduced poverty, may prevent brain atrophy and decrease dementia risk in late-life.

neuroscience↗

bioRxiv2023

Associations between sex, systemic iron and inflammatory status and subcortical brain iron

Key PointsO_LIDifferences in subcortical brain iron levels were observed between males and females C_LIO_LIFemales exhibited more associations between brain iron and systemic markers for iron than males. C_LIO_LIMales exhibited more associations between brain iron and systemic markers for inflammation than females. C_LI BackgroundBrain iron is increased in several neurodegenerative diseases, with studies demonstrating relationships between increased subcortical iron and disease progression. However, the causes of increased brain iron remain unclear. This study investigates relationships between subcortical iron and systemic iron and inflammatory status to improve our understanding of brain iron accumulation. MethodsBrain MRI scans and blood plasma samples were collected from cognitively healthy females (n=176, mean age = 61.4 {+/-} 4.5 y, age range = 28 - 72 y) andmales (n=152, mean age = 62.0 {+/-} 5.1 y, age range = 32 - 74 y). Quantitative susceptibility mapping was used to quantify regional brain iron. To assess systemic iron, haematocrit, plasma ferritin and plasma soluble transferrin receptor (sTfR) were measured and total body iron index (TBI) was calculated. To assess systemic inflammation, C-reactive protein (CRP), Neutrophil/Lymphocyte ratio (NLR), plasma macrophage colony stimulating factor 1 (MCSF), plasma interleukin 6 (IL6) and plasma interleukin 1{beta} (IL1{beta}) were measured. ResultsFemales exhibited associations between TBI and iron levels in the left and right caudate and right pallidum. Females also exhibited associations between haematocrit and iron levels in the right pallidum and left putamen. However, in males, the only association between brain iron and iron status was a positive correlation between iron in the right caudate and ferritin. In males, positive associations were observed between CRP levels and iron in the right thalamus and between IL6 levels and iron in the right amygdala and right pallidum. Males also exhibited a negative association between IL6 levels and iron in the left caudate. Positive associations between iron in the left thalamus and NLR were observed in both sexes. ConclusionsThis study demonstrates differential relationships between systemic iron and inflammation markers and brain iron in females and males. These results suggest differing iron regulation mechanisms in older age between sexes which could lead towards an understanding of the differences in neurodegenerative disease prevalence in males and females.

neuroscience↗