To evaluate how aging affects functional connectivity of pivotal regions of the human brain connectome (i.e., hubs), which represent potential vulnerability ‘stations’ to aging, and whether such effects influence the functional and structural changes of the whole brain. 

Multifactorial models integrating brain variables at multiple scales are warranted to investigate aging and its relationship with neurodegeneration.

We enrolled 128 cognitively unimpaired participants that were divided into two groups according to age: 50 young adults (≤ 35 years old) and 78 older adults (> 35 years old). At study entry, both groups underwent brain MRI scan. We combined the information of the functional connectome vulnerability, studied through an innovative graph-analysis approach (stepwise functional connectivity), with brain cortical thinning in aging.

First, investigating the topological functional network organization in the optimal healthy condition (i.e., young adults), we observed that fronto-temporo-parietal hubs showed direct functional connectivity with themselves and among each other, while occipital hubs showed direct functional connectivity within occipital regions and sensorimotor areas. Then, modelling cortical thickness changes over lifespan, we observed that fronto-temporo-parietal hubs were among the brain regions that changed the most, whereas occipital hubs showed a quite spared cortical thickness across ages. Finally, cortical regions highly functionally linked to the fronto-temporo-parietal hubs in healthy adults were characterized by the greatest cortical thinning along the lifespan.

Our findings reveal a significant role of hub connectome topology and geometry in shaping the accumulation of biological damage and distribution of atrophy with aging, supporting the hypothesis that hub functional connectivity rearrangements appear to govern the region-specific structural alterations of the brain regions.