Article

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

Department of Psychiatry, University of Rostock, Rostock, Germany DZNE, German Center for Neurodegenerative Diseases, Rostock, Germany.
Journal of Alzheimer's disease: JAD (Impact Factor: 4.15). 09/2012; 31:S33-47. DOI: 10.3233/JAD-2012-112118
Source: PubMed

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.

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Available from: Harald J Hampel, Feb 14, 2015
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    • "The absolute FA values are sensitive to fiber coherence, myelination levels, and axonal integrity, and have been widely used as an index of white matter integrity (Thomason and Thompson, 2011). FA has emerged as a sensitive index of diffuse abnormalities in many brain disorders including Alzheimer's disease (AD) (Clerx et al., 2012; Teipel et al., 2012); in many studies, it is related to cognitive performance (Penke et al., 2010a, 2010b) and is altered in numerous psychiatric disorders including major depressive disorder (Carballedo et al., 2012) and bipolar disorder (Barysheva et al., 2012; Sprooten et al., 2011). Patient-control differences in FA values are also among the most replicable and consistent neuroimaging findings in schizophrenia (Alba-Ferrara and de Erausquin, 2013; Friedman et al., 2008; Kochunov et al., 2012a; Mandl et al., 2012; Nazeri et al., 2013; Perez-Iglesias et al., 2011). "
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    ABSTRACT: The degree to which genetic factors influence brain connectivity is beginning to be understood. Large-scale efforts are underway to map the profile of genetic effects in various brain regions. The NIH-funded Human Connectome Project (HCP) is providing data valuable for analyzing the degree of genetic influence underlying brain connectivity revealed by state-of-the-art neuroimaging methods. We calculated the heritability of the fractional anisotropy (FA) measure derived from diffusion tensor imaging (DTI) reconstruction in 481 HCP subjects (194/287M/F) consisting of 57/60 pairs of mono- and dizygotic twins, and 246 siblings. FA measurements were derived using (Enhancing NeuroImaging Genetics through Meta-Analysis) ENIGMA DTI protocols and heritability estimates were calculated using the SOLAR-Eclipse imaging genetic analysis package. We compared heritability estimates derived from HCP data to those publicly available through the ENIGMA-DTI consortium, which were pooled together from five-family based studies across the US, Europe, and Australia. FA measurements from the HCP cohort for eleven major white matter tracts were highly heritable (h(2)=0.53-0.90, p<10(-5)), and were significantly correlated with the joint-analytical estimates from the ENIGMA cohort on the tract and voxel-wise levels. The similarity in regional heritability suggests that the additive genetic contribution to white matter microstructure is consistent across populations and imaging acquisition parameters. It also suggests the overarching genetic influence provides an opportunity to define a common genetic search space for future gene-discovery studies. Uniquely, the measurements of additive genetic contribution performed in this study can be repeated using online genetic analysis tools provided by the HCP ConnectomeDB web application. Copyright © 2015 Elsevier Inc. All rights reserved.
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    • "Data were obtained from ten different MRI scanners, including seven 3.0 Tesla and three 1.5 Tesla scanners . Acquisition parameters for the DTI sequences can be obtained from [22]. The number of gradient directions varied between 6 and 61 across the different scanners. "
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    • "Recent DTI studies confirmed a significant reduction of FA in the cingulate gyrus in patients with MCI and AD (Teipel et al. 2012; Alves et al. 2012). Other studies further demonstrated that this reduction primarily occurred in the posterior segment of the CB (Zimny et al. 2011; Catheline et al. 2010). "
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