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

Article type: Research Article

Authors: Gao, Junling^a | Cheung, Raymond Tak-Fai^{a; b; *} | Lee, Tatia M.C.^{c; d} | Chu, Leung-Wing^{a; b; e} | Chan, Ying-Shing^{b; f} | Mak, Henry Ka-Fung^{b; e; g} | Zhang, John X.^h | Qiu, Deqiang^{g; i} | Fung, Germaine^j | Cheung, Charlton^j

Affiliations: [a] Department of Medicine, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong SAR | [b] Research Centre of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR | [c] Neuropsychology Laboratory, Department of Psychology, The University of Hong Kong, Hong Kong SAR | [d] Institute of Clinical Neuropsychology, MacLehose Medical Rehabilitation Centre, Hong Kong SAR | [e] HKU Alzheimer's Disease Research Network, SRT Healthy Aging, The University of Hong Kong, Hong Kong SAR | [f] Department of Physiology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR | [g] Department of Radiology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR | [h] Department of Psychology, Chinese University of Hong Kong, Hong Kong SAR | [i] Lucas Center for MR Imaging, Department of Radiology, Stanford University, CA, USA | [j] Department of Psychiatry, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR

Correspondence: [*] Correspondence to: Raymond Tak-Fai Cheung, Rm. 805, Administration Block, Department of Medicine, Queen Mary Hospital, Pokfulam Road, Hong Kong. Tel.: +852 22554049; Fax: +852 28186474; E-mail: [email protected].

Abstract: 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.

Keywords: Aging, Alzheimer's disease, diffusion tensor imaging, fiber tracking, retrogenesis, white matter integrity

DOI: 10.3233/JAD-2011-101788

Journal: Journal of Alzheimer's Disease, vol. 26, no. 1, pp. 47-58, 2011