Mapping the Structural Brain Changes in Alzheimer's Disease: The Independent Contribution of Two Imaging Modalities

Issue title: Imaging the Alzheimer Brain

Guest editors: J. Wesson Ashford, Allyson Rosen, Maheen Adamson, Peter Bayley, Osama Sabri, Ansgar Furst, Sandra E. Black and Michael Weiner

Article type: Research Article

Authors: Canu, Elisa^{a; 1} | McLaren, Donald G.^{b; c; d} | Fitzgerald, Michele E.^{b; d} | Bendlin, Barbara B.^{b; d} | Zoccatelli, Giada^e | Alessandrini, Franco^e | Pizzini, Francesca B.^e | Ricciardi, Giuseppe K.^e | Beltramello, Alberto^e | Johnson, Sterling C.^{b; d} | Frisoni, Giovanni B.^{a; *}

Affiliations: [a] LENITEM - Laboratory of Epidemiology Neuroimaging and Telemedicine, IRCCS Centro San Giovanni di Dio FBF, The National Centre for Research and Care of Alzheimer's and Mental Diseases, Brescia, Italy | [b] Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veteran's Hospital, Madison, WI, USA | [c] Neuroscience Training Program, University of Wisconsin, Madison, WI, USA | [d] Wisconsin Alzheimer's Disease Research Center, Department of Medicine, University of Wisconsin, Madison, WI, USA | [e] Service of Neuroradiology, Ospedale Maggiore, Borgo Trento, Verona, Italy

Correspondence: [*] Correspondence to: Giovanni B. Frisoni, LENITEM - Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS San Giovanni di Dio – FBF, Via Pilastroni 4, 25125 – Brescia, Italy. Tel.: +39 0303501361; Fax: +39 02 700435727; E-mail: [email protected].

Note: [1] current address: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Ospedale San Raffaele, Milan, Italy.

Abstract: The macrostructural atrophy of Alzheimer's disease (AD) has been fully described. Current literature reports that also microstructural alterations occur in AD since the early stages. However, whether the microstructural changes offer unique information independent from macrostructural atrophy is unclear. Aim of this study is to define the independent contribution of macrostructural atrophy and microstructural alterations on AD pathology. The study involved 17 moderate to severe AD patients and 13 healthy controls. All participants underwent conventional and non conventional MRI (respectively, T1-weighted and diffusion-weighted MR scanning). We processed the images in order to obtain gray and white matter volumes to assess macrostructural atrophy, and fractional anisotropy and mean diffusivity to assess the microstructural damage. Analyses of covariance between patients and controls were performed to investigate microstructural tissue damage independent of macrostructural tissue loss, and viceversa, voxel by voxel. We observed microstructural differences, independent of macrostructural atrophy, between patients and controls in temporal and retrosplenial regions, as well as in thalamus, corticopontine tracts, striatum and precentral gyrus. Volumetric differences, independent of microstructural alterations, were observed mainly in the entorhinal cortex, posterior cingulum, and splenium. Measures of microstructural damage provide unique information not obtainable with volumetric mapping in regions known to be pivotal in AD as well as in others thought to be spared. This work expands the understanding of the topography of pathological changes in AD that can be captured with imaging techniques.

Keywords: Diffusion Tensor Imaging (DTI), Alzheimer's disease (AD), Microstructure, Fractional Anisotropy (FA), Mean Diffusivity (MD)

DOI: 10.3233/JAD-2011-0040

Journal: Journal of Alzheimer's Disease, vol. 26, no. s3, pp. 263-274, 2011