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

Abstract

The cerebellum supports higher-order cognition, such as working memory and executive function (EF) both directly and through connection with prefrontal areas via cortical loops. Thus, age-related degradation to white matter connectivity comprising cerebello-thalamo-cortical (CTC) loops may underlie age-related differences in EF. In 190 healthy adults (aged 20-94 years) we collected diffusion tensor imaging scans and multiple tests of working memory and EF. Deterministic tractography was used to generate CTC tracts from which white matter metrics (mean, radial, axial diffusivities) were extracted. General linear model results indicated that reduced white matter integrity (i.e., higher diffusivity) was associated with significantly poorer EF performance in an age-dependent fashion. Higher mean, radial, and axial diffusivities in fronto-cerebellar white matter was associated with lower EF scores in older, but not younger, adults. These findings suggest CTC white matter connectivity is important for executive function performance and lend mechanistic evidence to the role of the cerebellum in age-related differences in higher-order cognitive operations.