Possible Retrogenesis Observed with Fiber Tracking: An Anteroposterior Pattern of White Matter Disintegrity in Normal Aging and Alzheimer's Disease

Retrogenesis refers to the phenomenon by which degenerative processes in aging reverse the sequence of acquisition in development. Although there has been some evidence for brain retrogenesis in abnormal aging, e. g., Alzheimer's disease (AD), it has not been explicitly addressed in the normal aging. Using diffusion tensor imaging and tractography, we explored the effects of normal and abnormal aging on the integrity of white matter (WM) in fifty participants, including 18 AD patients, 17 normal elderly, and 15 normal young adults. Compared with young adults, the traditional voxel-based analysis, and the quantitative fiber tracking methods revealed lower fractional anisotrophy (FA) for both normal elderly and AD patients, indicating WM disintegrity in the anterior part of the brain with developmentally late-myelinating fiber bundles. Furthermore, AD patients showed lower FA in the posterior part of the brain with relatively early-myelinating fiber bundles. Additional analysis on axial diffusion and radial diffusion measures suggest that demyelination may be the main mechanism underlying the observed microstructural impairments. Consistent with a proposal of retrogenesis, our results demonstrate an anteroposterior pattern of white matter disintegrity in both normal aging and AD, with the pattern being more salient in the latter than in the former.