Regional Brain Volume Variation Across Adulthood: A Cross-Sectional MRI Analysis of Age, Sex, and Hemispheric Asymmetry

Distinguishing normative cross-sectional structural age differences from early neurodegeneration requires region-specific characterisation of cross-sectional age-related variation, yet findings remain sensitive to modelling strategy and intracranial volume (ICV) correction. T1-weighted MRI from 187 healthy adults (97 female, 90 male; aged 16.22–81.48 years) in the AgeRisk dataset were segmented using Vol2Brain. Multiple regression models applied to 19 predefined brain regions tested linear and quadratic age, sex, ICV, and signal-to-noise ratio (FDR-corrected within predictor families); hemispheric asymmetry indices were Bonferroni-corrected. Three hypothesis domains were preregistered: age associations, sex differences, and hemispheric asymmetry. Negative cross-sectional age associations were observed in subcortical (hippocampus, amygdala, caudate, putamen, and nucleus accumbens) and cortical regions (insula, temporal and occipital lobes; all pFDR<0.05). The parietal lobe showed significant quadratic curvature (pFDR=0.008); total cortical grey matter showed no age effect. White matter exhibited a positive linear rather than the hypothesised inverted-U relationship. After ICV adjustment, females showed greater grey-matter-dominant volumes and males greater cerebrospinal fluid volume (both pFDR<0.05). Sex-by-age interactions in four subcortical regions indicated shallower negative cross-sectional age associations in females (all pFDR≤0.034). Age was associated with reduced parietal and temporal hemispheric asymmetry (both p<0.001). Findings confirm regionally heterogeneous ageing, ICV-adjusted sex differences, and a selective negative cross-sectional association between age and hemispheric asymmetry, consistent with the broader lifespan literature.