Age-related cerebello-thalamo-cortical white matter degradation and executive function performance across the lifespan.

White matter diffusivity in cerebello-thalamo-cortical tracts increased with age in an accelerated, non-linear fashion across the adult lifespan.

• Study included 190 healthy adults aged 20–94 years
• Diffusion tensor imaging and deterministic tractography were used to generate CTC tracts
• White matter metrics extracted included mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD)
• Results indicated an accelerated rate of increased diffusivity with increasing age, suggesting non-linear age-related degradation

Higher mean, radial, and axial diffusivities in fronto-cerebellar white matter tracts were associated with lower executive function scores in older but not younger adults.

• The relationship between white matter integrity and EF performance was age-dependent
• Higher MD, RD, and AD were linked to poorer EF performance specifically in older adults
• No significant association between diffusivity and EF was observed in younger adults
• This age-dependent pattern was identified using general linear model analyses

Reduced white matter integrity in cerebello-thalamo-cortical loops was significantly associated with poorer executive function performance.

• General linear model results indicated that higher diffusivity (indicating reduced white matter integrity) was associated with significantly poorer EF performance
• EF was assessed using multiple tests of working memory and executive function
• The association was characterized as age-dependent, with the effect manifesting more strongly with increasing age
• Fronto-cerebellar white matter tracts were the specific focus of the connectivity analysis

The cerebellum contributes to higher-order cognition through cerebello-thalamo-cortical loops connecting to prefrontal areas, providing a structural basis for cerebellar involvement in executive function.

• CTC loops were identified as the mechanistic pathway linking cerebellar function to prefrontal-dependent cognitive operations
• Deterministic tractography was used to isolate CTC tracts specifically
• The findings were interpreted as providing 'mechanistic evidence to the role of the cerebellum in age-related differences in higher-order cognitive operations'
• Working memory and executive function were the cognitive domains examined as supported by these loops