Anatomical MRI and DTI in the Diagnosis of Alzheimer's Disease: A European Multicenter Study

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: Teipel, Stefan J.^{a; b; *} | Wegrzyn, Martin^b | Meindl, Thomas^c | Frisoni, Giovanni^d | Bokde, Arun L.W.^{e; f} | Fellgiebel, Andreas^g | Filippi, Massimo^h | Hampel, Haraldⁱ | Klöppel, Stefan^j | Hauenstein, Karlheinz^k | Ewers, Michael^{l; m} | the EDSD study group

Affiliations: [a] Department of Psychiatry, University of Rostock, Rostock, Germany | [b] DZNE, German Center for Neurodegenerative Diseases, Rostock, Germany | [c] Institute for Clinical Radiology, Department of MRI, Ludwig Maximilian University Munich, Munich, Germany | [d] LENITEM Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS Centro San Giovanni di Dio, FBF, Brescia, Italy | [e] Cognitive Systems Group, Discipline of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland | [f] Trinity College Institute of Neuroscience (TCIN), Trinity College Dublin, Dublin, Ireland | [g] Department of Psychiatry, University Medical Center of Mainz, Mainz, Germany | [h] Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy | [i] Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University, Frankfurt, Germany | [j] Department of Psychiatry and Psychotherapy, Freiburg Brain Imaging, University Clinic Freiburg, Freiburg, Germany | [k] Department of Radiology, University of Rostock, Rostock, Germany | [l] Department of Radiology, University of California, San Francisco, USA | [m] VA Medical Center, San Francisco, USA

Correspondence: [*] Correspondence to: Stefan J. Teipel, M.D., Department of Psychiatry and Psychotherapy, University Rostock, Gehlsheimer Str. 20, 18147 Rostock, Germany. Tel.: +01149 381 494 9470; Fax: +01149 381 494 9682; E-mail: stefan.teipel@med.uni-rostock.de.

Abstract: Diffusion tensor imaging (DTI) detects microstructural changes of the cerebral white matter in Alzheimer's disease (AD). The use of DTI for the diagnosis of AD in a multicenter setting has not yet been investigated. We used voxel-based analysis of fractional anisotropy, mean diffusivity, and grey matter volumes from multimodal magnetic resonance imaging data of 137 AD patients and 143 healthy elderly controls collected across 9 different scanners. We compared different univariate analysis approaches to model the effect of scanner, including a linear model across all scans with a scanner covariate, a random effects model with scanner as a random variable as well as a voxel-based meta-analysis. We found significant reduction of fractional anisotropy and significant increase of mean diffusivity in core areas of AD pathology including corpus callosum, medial and lateral temporal lobes, as well as fornix, cingulate gyrus, precuneus, and prefrontal lobe white matter. Grey matter atrophy was most pronounced in medial and lateral temporal lobe as well as parietal and prefrontal association cortex. The effects of group were spatially more restricted with random effects modeling of scanner effects compared to simple pooled analysis. All three analysis approaches yielded similar accuracy of group separation in block-wise cross-validated logistic regression. Our results suggest similar effects of center on group separation based on different analysis approaches and confirm a typical pattern of cortical and subcortical microstructural changes in AD using a large multimodal multicenter data set.

Keywords: Atrophy, cortical connectivity, early diagnosis, imaging biomarker, white matter

DOI: 10.3233/JAD-2012-112118

Journal: Journal of Alzheimer's Disease, vol. 31, no. s3, pp. S33-S47, 2012