Problem solving, working memory, and motor correlates of association and commissural fiber bundles in normal aging: a quantitative fiber tracking study.

Normal aging is accompanied by decline in selective cognitive and motor functions. A concurrent decline in regional white matter integrity, detectable with diffusion tensor imaging (DTI), potentially contributes to waning function. DTI analysis of white matter loci indicates an anterior-to-posterior gradient distribution of declining fractional anisotropy (FA) and increasing diffusivity with age. Quantitative fiber tracking can be used to determine regional patterns of normal aging of fiber systems and test the functional ramifications of the DTI metrics. Here, we used quantitative fiber tracking to examine age effects on commissural (genu and splenium), bilateral association (cingulate, inferior longitudinal fasciculus and uncinate), and fornix fibers in 12 young and 12 elderly healthy men and women and tested functional correlates with concurrent assessment of a wide range of neuropsychological abilities. Principal component analysis of cognitive and motor tests on which the elderly achieved significantly lower scores than the young group was used for data reduction and yielded three factors: Problem Solving, Working Memory, and Motor. Age effects--lower FA or higher diffusivity--in the elderly were prominent in anterior tracts, specifically, genu, fornix, and uncinate fibers. Differential correlations between FA or diffusivity in fiber tracts and scores on Problem Solving, Working Memory, or Motor factors provide convergent validity to the biological meaningfulness of the integrity of the fibers tracked. The observed pattern of relations supports the possibility that regional degradation of white matter fiber integrity is a biological source of age-related functional compromise and may have the potential to limit accessibility to alternative neural systems to compensate for compromised function.