Fractional anisotropy shows differential reduction in frontal-subcortical fiber bundles—A longitudinal MRI study of 76 middle-aged and older adults

Motivated by the frontal- and white matter (WM) retrogenesis hypotheses and the assumptions that fronto-striatal circuits are especially vulnerable in normal aging, the goal of the present study was to identify fiber bundles connecting subcortical nuclei and frontal areas and obtain site-specific information about age related fractional anisotropy (FA) changes. Multimodal magnetic resonance image acquisitions [3D T1-weighted and diffusion weighted imaging (DWI)] were obtained from healthy older adults (N = 76, range 49–80 years at inclusion) at two time points, 3 years apart. A subset of the participants (N = 24) was included at a third time-point. In addition to the frontal-subcortical fibers, the anterior callosal fiber (ACF) and the corticospinal tract (CST) was investigated by its mean FA together with tract parameterization analysis. Our results demonstrated fronto-striatal structural connectivity decline (reduced FA) in normal aging with substantial inter-individual differences. The tract parameterization analysis showed that the along tract FA profiles were characterized by piece-wise differential changes along their extension rather than being uniformly affected. To the best of our knowledge, this is the first longitudinal study detecting age-related changes in frontal-subcortical WM connections in normal aging.