Multimodal Imaging Evidence for Axonal and Myelin Deterioration in Amnestic Mild Cognitive Impairment

Issue title: Predictive Biomarkers for Alzheimer's Disease using State-of-the-Art Brain Imaging Techniques

Guest editors: Pravat K. Mandal

Article type: Research Article

Authors: Gold, Brian T.^{a; c; e; *} | Jiang, Yang^{b; c; e} | Powell, David K.^e | Smith, Charles D.^{c; d; e}

Affiliations: [a] Department of Anatomy and Neurobiology, Chandler Medical Center, University of Kentucky, Lexington, KY, USA | [b] Department of Behavioral Sciences, Chandler Medical Center, University of Kentucky, Lexington, KY, USA | [c] Sanders-Brown Center on Aging, Alzheimer's Disease Center, Chandler Medical Center, University of Kentucky, Lexington, KY, USA | [d] Neurology, Chandler Medical Center, University of Kentucky, Lexington, KY, USA | [e] Magnetic Resonance Imaging and Spectroscopy Center, Chandler Medical Center, University of Kentucky, Lexington, KY, USA

Correspondence: [*] Correspondence to: Brian T. Gold, Department of Anatomy and Neurobiology, University of Kentucky School of Medicine, Lexington, KY, USA. Tel.: +1 859 323 4813; Fax: +1 859 257 6700; E-mail: brian.gold@uky.edu.

Abstract: White matter (WM) microstructural declines have been demonstrated in Alzheimer's disease and amnestic mild cognitive impairment (aMCI). However, the pattern of WM microstructural changes in aMCI after controlling for WM atrophy is unknown. Here, we address this issue through joint consideration of aMCI alterations in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, as well as macrostructural volume in WM and gray matter compartments. Participants were 18 individuals with aMCI and 24 healthy seniors. Voxelwise analyses of diffusion tensor imaging data was carried out using tract-based spatial statistics (TBSS) and voxelwise analyses of high-resolution structural data was conducted using voxel based morphometry. After controlling for WM atrophy, the main pattern of TBSS findings indicated reduced fractional anisotropy with only small alterations in mean diffusivity/radial diffusivity/axial diffusivity. These WM microstructural declines bordered and/or were connected to gray matter structures showing volumetric declines. However, none of the potential relationships between WM integrity and volume in connected gray matter structures was significant, and adding fractional anisotropy information improved the classificatory accuracy of aMCI compared to the use of hippocampal atrophy alone. These results suggest that WM microstructural declines provide unique information not captured by atrophy measures that may aid the magnetic resonance imaging contribution to aMCI detection.

Keywords: Alzheimer's disease, atrophy, diffusion tensor imaging, mild cognitive impairment

DOI: 10.3233/JAD-2012-112165

Journal: Journal of Alzheimer's Disease, vol. 31, no. s3, pp. S19-S31, 2012