White matter structural decline in normal ageing: A prospective longitudinal study using tract-based spatial statistics

Normal ageing is accompanied by a progressive decline in cognitive function but the mechanisms for this are not fully understood. Nevertheless, the importance of white matter degeneration is supported by diffusion tensor imaging (DTI) studies, although several important questions remain about the pattern and nature of age-related white matter degeneration. Firstly, there is a lack of longitudinal data determining the rate of change in DTI parameters with age, and whether this can be detected over short time periods. Secondly, it is unclear whether observed changes are uniform across the brain or whether accelerated white matter degeneration is localised to particular brain regions, as would support the frontal-ageing hypothesis. This study uses DTI techniques to quantify structural integrity change to determine whether regional differences are apparent in the rate of degeneration during longitudinal follow-up in a sample of healthy middle aged and older adults aged between 50 and 90years. Longitudinal differences in fractional anisotropy, axial and radial diffusivity are investigated using 1D coronal slice profiles, and 2D column maps in standard space, as well as using 3D tract-based spatial statistics (TBSS) to investigate local age-related structural changes on a voxel-by-voxel basis at baseline and two-year follow-up. Results indicate that DTI can detect age-related change in white matter structure over a relatively short follow-up period and that longitudinal analyses reveal significant changes in white matter integrity throughout the brain with no evidence of accelerated decline in the frontal lobe regions during a 2year period. Common changes across different diffusion characteristics are discussed.