Alzheimer’s Disease Neuroimaging Initiative: A One-year Follow up Study Using Tensor-based Morphometry Correlating Degenerative Rates, Biomarkers and Cognition

Department Psychology and Evelyn F. McKnight Brain Institute, University of Arizona, Tucson, AZ, USA
NeuroImage (Impact Factor: 6.36). 02/2009; 45(3). DOI: 10.1016/j.neuroimage.2009.01.004
Source: PubMed


Tensor-based morphometry can recover three-dimensional longitudinal brain changes over time by nonlinearly registering baseline to follow-up MRI scans of the same subject. Here, we compared the anatomical distribution of longitudinal brain structural changes, over 12 months, using a subset of the ADNI dataset consisting of 20 patients with Alzheimer's disease (AD), 40 healthy elderly controls, and 40 individuals with mild cognitive impairment (MCI). Each individual longitudinal change map (Jacobian map) was created using an unbiased registration technique, and spatially normalized to a geometrically-centered average image based on healthy controls. Voxelwise statistical analyses revealed regional differences in atrophy rates, and these differences were correlated with clinical measures and biomarkers. Consistent with prior studies, we detected widespread cerebral atrophy in AD, and a more restricted atrophic pattern in MCI. In MCI, temporal lobe atrophy rates were correlated with changes in mini-mental status exam (MMSE) scores, clinical dementia rating (CDR), and logical/verbal learning memory scores. In AD, temporal atrophy rates were correlated with several biomarker indices, including a higher CSF level of p-tau protein, and a greater CSF tau/beta amyloid 1-42 (Abeta42) ratio. Temporal lobe atrophy was significantly faster in MCI subjects who converted to AD than in non-converters. Serial MRI scans can therefore be analyzed with nonlinear image registration to relate ongoing neurodegeneration to a variety of pathological biomarkers, cognitive changes, and conversion from MCI to AD, tracking disease progression in 3-dimensional detail.

Download full-text


Available from: Alex Leow,
  • Source
    • "These data are in agreement with previous studies, which observed that in the rate of progression of atrophy in these regions is about 2–4% per year [8] [34]. The additional tissue loss that we found in the orbitofrontal, inferior frontal regions, and basal ganglia over time is also in keeping with previous studies [6] [8] [35] and well reflects the trajectory of the neurofibrillary pathology which typically occurs later in these areas [36] [37]. This study revealed that AD patients experienced distributed DT MRI changes of the corpus callosum , cingulum, fronto-parietal and temporo-occipital connections bilaterally over the period of follow up. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Longitudinal MRI studies in Alzheimer's disease (AD) are one of the most reliable way to track brain changes along the course of the disease. Objective: To investigate the evolution of grey matter (GM) atrophy and white matter (WM) damage in AD patients, and to assess the relationships of MRI changes with baseline clinical and cognitive variables and their evolution over time. Methods: Clinical, neuropsychological, and MRI assessments (T1-weighted and diffusion tensor [DT]-MRI) were obtained from 14 patients with AD at baseline and after a 16 ± 3 month period. Lumbar puncture was obtained at study entry. At baseline, AD patients were compared to 37 controls. GM atrophy progression was assessed with tensor-based morphometry and GM volumes of interest, and WM damage progression using tract-based spatial statistics and tractography. Results: At baseline, patients showed cortical atrophy in the medial temporal and parietal regions and a widespread pattern of WM damage involving the corpus callosum, cingulum, and temporo-occipital, parietal, and frontal WM tracts. During follow up, AD patients showed total GM atrophy, while total WM volume did not change. GM tissue loss was found in frontal, temporal, and parietal regions. In addition, AD patients showed a progression of WM microstructural damage to the corpus callosum, cingulum, fronto-parietal and temporo-occipital connections bilaterally. Patients with higher baseline cerebrospinal fluid total tau showed greater WM integrity loss at follow up. GM and WM changes over time did not correlate with each other nor with cognitive evolution. Conclusion: In AD, GM atrophy and WM tract damage are likely to progress, at least partially, independently. This study suggests that a multimodal imaging approach, which includes both T1-weighted and DT MR imaging, may provide additional markers to monitor disease progression.
    Journal of Alzheimer's disease: JAD 09/2015; 47(4):995-1007. DOI:10.3233/JAD-150196 · 4.15 Impact Factor
  • Source
    • "ADNI began in 2005, after testing the feasibility and reproducibility of a range of scanning protocols. This led to standardized scanning methods implemented at 58 sites across North America (Leow et al. 2009; Jahanshad et al. 2010; Jack 2012; Zhan et al. 2012). Many other neuroimaging consortia have been established, including the functional Brain Imaging Research Network (FBIRN) (Potkin and Ford 2009) which has developed standardized methods for multi-center functional MRI studies (Glover et al. 2012) and the Mind Clinical Imaging Consortium (Gollub et al. 2013) focusing on schizophrenia, as well as research networks focusing on pediatric imaging (Evans 2006), autism (Ecker et al. 2013), HIV/AIDS (Cohen et al. 2010) and many others. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This article reviews work published by the ENIGMA Consortium and its Working Groups ( It was written collaboratively; P.T. wrote the first draft and all listed authors revised and edited the document for important intellectual content, using Google Docs for parallel editing, and approved it. Some ENIGMA investigators contributed to the design and implementation of ENIGMA or provided data but did not participate in the analysis or writing of this report. A complete listing of ENIGMA investigators is available at For ADNI, some investigators contributed to the design and implementation of ADNI or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators is available at ADNI_Acknowledgement_List.pdf The work reviewed here was funded by a large number of federal and private agencies worldwide, listed in Stein et al. (2012); the funding for listed consortia is also itemized in Stein et al. (2012).
    Brain Imaging and Behavior 01/2014; 8(2). DOI:10.1007/s11682-013-9269-5 · 4.60 Impact Factor
  • Source
    • "Proposed models of AD progression (Jack et al., 2010) suggest a strong relationship between tau and atrophy, especially in MCI. However published results from ADNI show mixed findings, with some studies demonstrating evidence of an association between baseline tau and atrophy rates (Fjell et al., 2010; Tosun et al., 2010) and others not finding such relationships (Leow et al., 2009; Schuff et al., 2009). These discrepancies, although potentially explained in part by the differing methodologies used, demonstrate that the relationship between baseline tau and subsequent atrophy is complex. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This study assessed relationships among white matter hyperintensities (WMH), cerebrospinal fluid (CSF), Alzheimer's disease (AD) pathology markers, and brain volume loss. Subjects included 197 controls, 331 individuals with mild cognitive impairment (MCI), and 146 individuals with AD with serial volumetric 1.5-T MRI. CSF Aβ1-42 (n = 351) and tau (n = 346) were measured. Brain volume change was quantified using the boundary shift integral (BSI). We assessed the association between baseline WMH volume and annualized BSI, adjusting for intracranial volume. We also performed multiple regression analyses in the CSF subset, assessing the relationships of WMH and Aβ1-42 and/or tau with BSI. WMH burden was positively associated with BSI in controls (p = 0.02) but not MCI or AD. In multivariable models, WMH (p = 0.003) and Aβ1-42 (p = 0.001) were independently associated with BSI in controls; in MCI Aβ1-42 (p < 0.001) and tau (p = 0.04) were associated with BSI. There was no evidence of independent effects of WMH or CSF measures on BSI in AD. These data support findings that vascular damage is associated with increased brain atrophy in the context of AD pathology in pre-dementia stages.
    Neurobiology of aging 03/2013; 34(8). DOI:10.1016/j.neurobiolaging.2013.02.003 · 5.01 Impact Factor
Show more