Quantitative Magnetization Transfer of White Matter Tracts Correlates with Diffusion Tensor Imaging Indices in Predicting the Conversion from Mild Cognitive Impairment to Alzheimer’s Disease

Article type: Research Article

Authors: Makovac, Elena^a | Serra, Laura^a | Di Domenico, Carlotta^a | Marra, Camillo^b | Caltagirone, Carlo^{c; d} | Cercignani, Mara^{a; e} | Bozzali, Marco^{a; e; *}

Affiliations: [a] Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome | [b] Institute of Neurology, Catholic University, Rome | [c] Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome | [d] Department of Systems Medicine, University of Rome ‘Tor Vergata’, Rome | [e] Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, UK

Correspondence: [*] Correspondence to: Dr. Marco Bozzali, Department of Neuroscience, Brighton and Sussex Medical School, University of Sussex, Brighton, East Sussex, BN1 9RH, UK. Tel.: +44 0 1273 873509; Fax: +44 0 1273 876721; E-mail: [email protected].

Abstract: Patients with amnestic mild cognitive impairment (aMCI) have higher probability to develop Alzheimer’s disease (AD) than elderly controls. The detection of subtle changes in brain structure associated with disease progression and the development of tools to identify patients at high risk for dementia in a short time is crucial. Here, we used probabilistic white matter (WM) tractography to explore microstructural alterations within the main association, limbic, and commissural pathways in aMCI patients who converted to AD after 1 year follow-up (MCIconverters) and those who remained stable (MCIstable). Both diffusion tensor imaging (DTI) and quantitative magnetization transfer (qMT) parameters have been considered for a comprehensive pathophysiological characterization of the WM damage. Overall, tract-specific parameters derived from qMT and DTI at baseline were able to differentiate aMCI patients who converted to AD from those who remained stable in time. In particular, the qMT exchange rate, RMB0, of the right uncinate fasciculus was significantly decreased in MCIconverters, whereas fractional anisotropy was significantly decreased in the bilateral superior cingulum in MCIconverters compared to MCIstable. These results confirm the involvement of WM and particularly of association fibers in the progression of AD, highlighting disconnection as a potential mechanism.

Keywords: Diffusion tensor imaging, mild cognitive impairment, probabilistic tractography, quantitative magnetization transfer, white matter

DOI: 10.3233/JAD-170995

Journal: Journal of Alzheimer's Disease, vol. 63, no. 2, pp. 561-575, 2018