Diffusion tensor imaging of superficial prefrontal white matter in healthy aging

The prefrontal cortex (PFC) is a heterogenous structure that is highly susceptible to the effects of aging. Few studies have investigated age effects on the superficial white matter (WM) contained within the PFC using in-vivo magnetic resonance imaging (MRI). This study used diffusion tensor imaging (DTI) tractography to examine the effects of age, sex, and intracranial volume (ICV) on superficial WM within specific PFC subregions, and to model the relationships with age using higher order polynomial regression modelling. PFC WM of 140 healthy individuals, aged 18-85, was segmented into medial and lateral orbitofrontal, medial prefrontal, and dorsolateral prefrontal subregions. Differences due to age in microstructural parameters such as fractional anisotropy (FA), axial and radial diffusivities, and macrostructural measures of tract volumes, fiber counts, average fiber lengths, and average number of fibers per voxel were examined. We found that most prefrontal subregions demonstrated age effects, with decreases in FA, tract volume, and fiber counts, and increases in all diffusivity measures. Age relationships were mostly non-linear, with higher order regressions chosen in most cases. Declines in PFC FA began at the onset of adulthood while the greatest changes in diffusivity and volume did not occur until middle age. The effects of age were most prominent in medial tracts while the lateral orbitofrontal tracts were less affected. Significant effects of sex and ICV were also observed in certain parameters. The patterns mostly followed myelination order, with late-myelinating prefrontal subregions experiencing earlier and more pronounced age effects, further supporting the frontal theory of aging.