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.

Download full-text


Available from: Harald J Hampel, Feb 14, 2015
67 Reads
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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.
    Journal of Alzheimer's disease: JAD 02/2014; 41(1). DOI:10.3233/JAD-131829 · 4.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neuropathological correlates of Alzheimer's disease (AD) emerge years before dementia. Biomarkers preceding cognitive decline and reflecting the causative processes can potentially aid early intervention and diagnosis. Diffusion tensor imaging (DTI) indirectly reflects tissue microstructure. To answer whether DTI is an early biomarker for AD and to explore the relationship between DTI and the established biomarkers of medial temporal lobe atrophy and cerebrospinal fluid (CSF) Aβ42, T-tau, and P-tau, we longitudinally studied normal controls and patients with subjective (SCI) or mild (MCI) cognitive impairment. 21 controls and 64 SCI or MCI cases recruited from a university-hospital based memory clinic were re-examined after two to three years. FreeSurfer was used for longitudinal processing of morphometric data, and DTI derived fractional anisotropy, radial diffusivity, and mean diffusivity were analyzed in Tract-Based Spatial Statistics. Using regression models, we explored and compared the predictive powers of DTI and CSF biomarkers in regard to cognitive change and atrophy of the medial temporal lobe. Both DTI and CSF biomarkers significantly predicted cognitive decline and atrophy in the medial temporal lobe. In this population, however, DTI was a better predictor of dementia and AD-specific medial temporal lobe atrophy than the CSF biomarkers. The case for DTI as an early biomarker for AD is strengthened, but further studies are needed to confirm these results.
    Journal of Alzheimer's disease: JAD 11/2012; 33(3). DOI:10.3233/JAD-2012-121603 · 4.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction of diffusion tensor imaging (DTI) in the 1980th and its advancement in the last three decades offered the possibility to visualize and quantify changes in white matter. DTI allows the evaluation of the structural integrity in complex neurodegenerative diseases, such as Alzheimer's disease (AD). Progressive disintegration of functional and structural neural network coordination contributes to the cognitive dysfunction in AD. Therefore, detection of loss of cortico-cortical projections may support an early diagnosis at prodromal stages of disease which may prove essential for future preventive AD treatment trials. Moreover, structural integrity measured by DTI may help to distinguish between symptomatic and disease modifying effects of pharmacological interventions. This review gives a concise account on the physical basis of DTI acquisition and processing. We summarize DTI findings in normal aging and AD and regarding the effects of cognitive intervention and antidementive treatment on structural neural connectivity. Finally, we evaluate the promising future potential of DTI to become a surrogate endpoint in clinical AD trials.
    Current pharmaceutical design 02/2013; 19(36). DOI:10.2174/1381612811319360003 · 3.45 Impact Factor
Show more