An atlas of age- and sex-related volumetric alterations of grey matter in subcortical regions: The case of 46,111 UK Biobank participants

Ageing is commonly associated with neuroanatomical changes in brain structure, underscoring the importance of distinguishing normal age-related alterations from those linked to pathological neurodegeneration. Despite this critical need, a standardized benchmark for identifying brain volumetric signatures of ageing remains lacking, and the influence of biological sex on age-related changes in brain volume is not yet fully understood. To address the above-mentioned gaps, we employed T1-weighted MRI images of 46,111 cognitively healthy individuals aged 44-83 from the UK Biobank cohort, and generated comprehensive maps of all the linear and non-linear trajectories of alterations in the grey matter volumes (GMVs) of subcortical regions across males and females. According to our findings, Brainstem, bilateral Amygdala and Hippocampus are the most susceptible subcortical regions to age-related atrophy, with males being generally more prone to such alterations. However, ageing proves to have a dual function as we also observed age-related inflammation in GMVs of Pallidum and Caudate which accelerates during older age and remains consistent across males and females. Our findings guide regenerative strategies and therapeutic interventions by locating subcortical regions most vulnerable to age-related atrophy and inflammation and establish a benchmark for sex-specific typical patterns of subcortical grey matter alterations due to ageing.