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


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.
    Full-text · Article · Mar 2015 · NeuroImage
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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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    ABSTRACT: Diffusion tensor imaging (DTI) allows the simultaneously measurement of several diffusion indices that provide complementary information on the substrate of white matter alterations in neurodegenerative diseases. These indices include fractional anisotropy (FA) as measure of fiber tract integrity, and the mode of anisotropy (Mode) reflecting differences in the shape of the diffusion tensor. We used a multivariate approach based on joint independent component analysis of FA and Mode in a large sample of 138 subjects with Alzheimer's disease (AD) dementia, 37 subjects with cerebrospinal fluid biomarker positive mild cognitive impairment (MCI-AD), and 153 healthy elderly controls from the European DTI Study on Dementia to comprehensively study alterations of microstructural white matter integrity in AD dementia and predementia AD. We found a parallel decrease of FA and Mode in intracortically projecting fiber tracts, and a parallel increase of FA and Mode in the corticospinal tract in AD patients compared to controls. Subjects with MCI-AD showed a similar, but spatially more restricted pattern of diffusion changes. Our findings suggest an early axonal degeneration in intracortical projecting fiber tracts in dementia and predementia stages of AD. An increase of Mode, parallel to an increase of FA, in the corticospinal tract suggests a more linear shape of diffusion due to loss of crossing fibers along relatively preserved cortico-petal and cortico-fugal fiber tracts in AD. Supporting this interpretation, we found three populations of fiber tracts, namely cortico-petal and cortico-fugal, commissural, and intrahemispherically projecting fiber tracts, in the peak area of parallel FA and Mode increase.
    Full-text · Article · Feb 2014 · Journal of Alzheimer's disease: JAD
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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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    ABSTRACT: Diffusion spectrum imaging (DSI) of MRI can detect neural fiber tract changes. We investigated integrity of cingulum bundle (CB) in patients with mild cognitive impairment (MCI) and early Alzheimer's disease (EAD) using DSI tractography and explored its relationship with cognitive functions. We recruited 8 patients with MCI, 9 with EAD and 15 healthy controls (HC). All subjects received a battery of neuropsychological tests to access their executive, memory and language functions. We used a 3.0-tesla MRI scanner to obtain T1- and T2-weighted images for anatomy and used a pulsed gradient twice-refocused spin-echo diffusion echo-planar imaging sequence to acquire DSI. Patients with EAD performed significantly poorer than the HC on most tests in executive and memory functions. Significantly smaller general fractional anisotropy (GFA) values were found in the posterior and inferior segments of left CB and of the anterior segment of right CB of the EAD compared with those of the HC. Spearman's correlation on the patient groups showed that GFA values of the posterior segment of the left CB were significantly negatively associated with the time used to complete Color Trails Test Part II and positively correlated with performance of the logical memory and visual reproduction. GFA values of inferior segment of bilateral CB were positively associated with the performance of visual recognition. DSI tractography demonstrates significant preferential degeneration of the CB on the left side in patients with EAD. The location-specific degeneration is associated with corresponding declines in both executive and memory functions.
    Full-text · Article · Jan 2014 · Brain Topography
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