Age-Associated Structural Decline is Linked to Arterial Flow Territories in the Brain: Insights from Lifespan Human Connectome Project in Aging

Abstract The effect of biological aging on brain structure is widespread and apparent. However, little is understood regarding which regions exhibit similarities in vulnerability, and what biological processes drive regional patterns of senescence-associated atrophy. Here, we investigated whether associations between age and brain structure exhibit distinct patterns of regional vulnerability, and if so, whether they are related to patterns of cerebral physiology which also show age-related decline. Using both data-driven and hypothesis-driven approaches, we identified recurring patterns of accelerated and delayed decline across the lifespan. Notably, the results mapped using unsupervised clustering methods mirrored the organization of major arterial flow territories, suggesting that vascular architecture may serve as a key organizing principle in brain aging. These results provide support for future research on aging and neurodegenerative disorders that aim to link patterns of structural deterioration to physiological processes that may be useful for identifying ‘at risk’ individuals and developing novel therapeutics.