Kraft, J. N. | Search bioRxiv

bioRxiv2025

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

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.

neuroscience↗

bioRxiv2023

Differential effects of aging on regional corpus callosum microstructure and the modifying influence of pulse pressure

The corpus callosum is composed of several subregions, distinct in cellular and functional organization. This organization scheme may render these subregions differentially vulnerable to the aging process. Callosal integrity may be further compromised by vascular risk factors, which negatively influence white matter health. Here, we test for heterochronicity of aging, hypothesizing an anterior-to-posterior gradient of vulnerability to aging that may be altered by effects of vascular health. In 174 healthy adults across the adult lifespan (mean age=53.56 {+/-} 18.90, range=20-94 years old, 58.62% women), measures of pulse pressure and diffusion-weighted imaging were conducted. A deterministic tractography approach was utilized to extract fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) from each of five callosal subregions, serving as estimates of microstructural health. General linear models tested effects of age, hypertension, and pulse pressure on these metrics. We observed no significant effect of hypertensive diagnosis on callosal microstructure. We found a significant main effect of age and an age x pulse pressure interaction whereby older age and elevated pulse pressure were associated with poorer FA, AD, and RD. Age effects revealed non-linear components and occurred along an anterior-posterior gradient of severity in the callosum. This gradient disappeared when pulse pressure was considered. These results indicate that age-related deterioration across the callosum is regionally variable, and that pulse pressure, a proxy of arterial stiffness, alters this aging pattern. Significance StatementAging is associated with microstructural changes in the corpus callosum, the largest white matter tract in the brain. Additionally, vascular factors, such as hypertension and pulse pressure, affect corpus callosum microstructure. However, it is unclear whether these factors uniformly impact the corpus callosum throughout aging. The current study aimed to characterize patterns of aging and assess the role of hypertension and pulse pressure across different subregions of the corpus callosum. We found an age-related gradient on corpus callosum microstructure, with the most pronounced impact on anterior regions. However, this gradient was not found when pulse pressure was considered. These findings suggest that subregions are differentially sensitive to age-related decline, and pulse pressure modifies and exacerbates these declines.

neuroscience↗