Gradient Patterns of Age-Related Diffusivity Changes in Cerebral White Matter

The current concept of brain aging proposes three gradient patterns of changes in white matter that occur during healthy brain aging: antero-posterior, supero-inferior, and the myelodegeneration-retrogenesis (or the “last-in-first-out”) concept. The aim of this study was to correlate white matter diffusivity measures (fractional anisotropy-FA, mean diffusivity-MD, radial diffusivity-RD, and axial diffusivity-AD) in healthy volunteers with chronological age and education level, in order to potentially incorporate the findings with proposed patterns of physiological brain aging. The study was performed on 75 healthy participants of both sexes, with an average age of 37.32 ± 11.91 years underwent brain magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI). DTI was performed using tract-based spatial statistics (TBSS), with the analysis of four parameters: FA, MD, RD, and AD. Skeletonized measures were averaged in 29 regions of interest in white matter. Correlations between age and DTI measures and between education-level and DTI measures were performed using Pearson's correlation test. To correct for multiple comparisons, we applied a Bonferroni correction to the p-values. Significance was set at p ≤ 0.001. A significant negative correlation of FA with age was observed in posterior thalamic radiation (PTR) (p< 0.001). A significant positive correlation between age and MD was observed in sagittal stratum (SS) (p< 0.001), between age and RD in PTR, SS, and retrolenticular internal capsule (p< 0.001), and between age and AD in the body of the corpus callosum (p< 0.001). There were no significant correlations of DTI parameters with educational level. According to our study, RD showed the richest correlations with age, out of all DTI metrics. FA, MD, and RD showed significant changes in the diffusivity of projection fibers, while AD presented diffusivity changes in the commissural fibers. The observed heterogeneity in diffusivity changes across the brain cannot be explained by a single aging gradient pattern, since it seems that different patterns of degradation are true for different fiber tracts that no currently available theory can globally explain age-related changes in the brain. Additional factors, such as the effect of somatosensory decline, should be included as one of the important covariables to the existing patterns.