Cerebellar aging is spatially heterogeneous and supports cognitive resilience in later life

Abstract

The cerebellum contains most of the brain’s neurons and supports many functions, yet how it changes with age remains unclear. Here we used three brain imaging studies spanning 47,000 adults and examined how different parts of the cerebellum age and their relation to cognition. We characterized cerebellar aging using volumetry and the T1-weighted/T2-weighted ratio, and corroborated these findings with quantitative magnetic resonance imaging in an independent sample. We show a spatially heterogeneous pattern of aging in which specific association and motor-related regions show steeper relationships with age than other lobules. Greater cerebellar volume was associated with higher cognitive scores with increasing age, suggesting that cerebellar structure may provide brain reserve that helps maintain function despite aging. In patients with Alzheimer’s disease, cerebellar volume was linked to cognition in individuals with lower amyloid burden, especially in those carrying two copies of the APOE-ε4 risk gene. This supports a threshold-reserve model, in which the cerebellum helps sustain cognition until pathology becomes widespread. These results show that the cerebellum has an active role in healthy cognitive aging and resilience.