Baseline MRI predictors of conversion from MCI to probable AD in the ADNI cohort

IU Center for Neuroimaging, Division of Imaging Sciences, Department of Radiology, Indiana University School of Medicine, 950 W Walnut St, R2 E124, Indianapolis, IN 46202, USA.
Current Alzheimer research (Impact Factor: 3.89). 08/2009; 6(4):347-61. DOI: 10.2174/156720509788929273
Source: PubMed


The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a multi-center study assessing neuroimaging in diagnosis and longitudinal monitoring. Amnestic Mild Cognitive Impairment (MCI) often represents a prodromal form of dementia, conferring a 10-15% annual risk of converting to probable AD. We analyzed baseline 1.5T MRI scans in 693 participants from the ADNI cohort divided into four groups by baseline diagnosis and one year MCI to probable AD conversion status to identify neuroimaging phenotypes associated with MCI and AD and potential predictive markers of imminent conversion. MP-RAGE scans were analyzed using publicly available voxel-based morphometry (VBM) and automated parcellation methods. Measures included global and hippocampal grey matter (GM) density, hippocampal and amygdalar volumes, and cortical thickness values from entorhinal cortex and other temporal and parietal lobe regions. The overall pattern of structural MRI changes in MCI (n=339) and AD (n=148) compared to healthy controls (HC, n=206) was similar to prior findings in smaller samples. MCI-Converters (n=62) demonstrated a very similar pattern of atrophic changes to the AD group up to a year before meeting clinical criteria for AD. Finally, a comparison of effect sizes for contrasts between the MCI-Converters and MCI-Stable (n=277) groups on MRI metrics indicated that degree of neurodegeneration of medial temporal structures was the best antecedent MRI marker of imminent conversion, with decreased hippocampal volume (left > right) being the most robust. Validation of imaging biomarkers is important as they can help enrich clinical trials of disease modifying agents by identifying individuals at highest risk for progression to AD.

Download full-text


Available from: John D West
    • "The brain regions and correlations listed in Table 6 have been reported to have abnormal alterations in MCI and AD patients, as well as in AD conversion process, indicating our findings are consistent with previous publications, such as studies in following regions: parahippocampal gyri, lingual gyri and cingulum cortex [60] [61] [62] [63] [64], insula [65] [66], inferior temporal gyri and superior temporal gyri [63] [67] [68], cuneus, parietal lobule, precuneus cortex, postcentral gyri and cingulate cortex [33, 68–71], supramarginal gyri, angular gyri, temporal lobe, and occipital cortex [66] [68] [72]. In addition, the correlations mentioned above are located either in the same hemisphere, or widely spread over the whole brain, suggesting the abnormalities caused by MCI and dementia have affected the entire brain rather than certain areas. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Brain network occupies an important position in representing abnormalities in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Currently, most studies only focused on morphological features of regions of interest without exploring the interregional alterations. In order to investigate the potential discriminative power of a morphological network in AD diagnosis and to provide supportive evidence on the feasibility of an individual structural network study, we propose a novel approach of extracting the correlative features from magnetic resonance imaging, which consists of a two-step approach for constructing an individual thickness network with low computational complexity. Firstly, multi-distance combination is utilized for accurate evaluation of between-region dissimilarity; and then the dissimilarity is transformed to connectivity via calculation of correlation function. An evaluation of the proposed approach has been conducted with 189 normal controls, 198 MCI subjects, and 163 AD patients using machine learning techniques. Results show that the observed correlative feature suggests significant promotion in classification performance compared with cortical thickness, with accuracy of 89.88% and area of 0.9588 under receiver operating characteristic curve. We further improved the performance by integrating both thickness and apolipoprotein E ɛ4 allele information with correlative features. New achieved accuracies are 92.11% and 79.37% in separating AD from normal controls and AD converters from non-converters, respectively. Differences between using diverse distance measurements and various correlation transformation functions are also discussed to explore an optimal way for network establishment.
    No preview · Article · Oct 2015 · Journal of Alzheimer's disease: JAD
  • Source
    • "pdf . et al. 2008 ; Li et al. 2012 ; Misra et al. 2009; Risacher et al. 2009 ; Wang et al. 2011b ) , and used off the - shelf machine learning tools to discriminate MCI - C from MCI - NC . However , those methods were short of high performance for clinical use . "
    [Show abstract] [Hide abstract]
    ABSTRACT: As the early stage of Alzheimer's disease (AD), mild cognitive impairment (MCI) has high chance to convert to AD. Effective prediction of such conversion from MCI to AD is of great importance for early diagnosis of AD and also for evaluating AD risk pre-symptomatically. Unlike most previous methods that used only the samples from a target domain to train a classifier, in this paper, we propose a novel multimodal manifold-regularized transfer learning (M2TL) method that jointly utilizes samples from another domain (e.g., AD vs. normal controls (NC)) as well as unlabeled samples to boost the performance of the MCI conversion prediction. Specifically, the proposed M2TL method includes two key components. The first one is a kernel-based maximum mean discrepancy criterion, which helps eliminate the potential negative effect induced by the distributional difference between the auxiliary domain (i.e., AD and NC) and the target domain (i.e., MCI converters (MCI-C) and MCI non-converters (MCI-NC)). The second one is a semi-supervised multimodal manifold-regularized least squares classification method, where the target-domain samples, the auxiliary-domain samples, and the unlabeled samples can be jointly used for training our classifier. Furthermore, with the integration of a group sparsity constraint into our objective function, the proposed M2TL has a capability of selecting the informative samples to build a robust classifier. Experimental results on the Alzheimer's Disease Neuroimaging Initiative (ADNI) database validate the effectiveness of the proposed method by significantly improving the classification accuracy of 80.1 % for MCI conversion prediction, and also outperforming the state-of-the-art methods.
    Full-text · Article · Feb 2015 · Brain Imaging and Behavior
    • "Neuropsychiatric symptoms collectively increase the level of caregiver burden in MCI [7], and our review has found that delusional symptoms significantly increase the level of functional impairment and caregiver burden in AD patients [8]. Previous research has shown there are significant neural correlates of conversion from MCI to AD, with degeneration in the temporal, hippocampal and cingulate cortices [9] and this has been analyzed in the Alzheimer's Disease Neuroimaging Initiative (ADNI) [10] [11]. Along these lines, persistent neuroanatomical changes may accompany the development of delusions in patients with "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: Grey matter atrophy in the right hemisphere has been shown to be more severe in dementia patients with delusions, suggesting a neuroanatomical localization that may be pertinent to impending neurodegeneration. Delusional symptoms may arise when atrophy in these areas reduces the regulatory functions of the right hemisphere, in tandem with asymmetric neuropathology in the left hemisphere. We hypothesized that delusional patients with either amnestic mild cognitive impairment (MCI) or early Alzheimer Disease (AD) would experience more pronounced grey matter atrophy in the right frontal lobe compared with matched patients without delusions. Methods: We used neuroimaging and clinical data obtained from the Alzheimer's Disease Neuroimaging Initiative. A comparison group of twenty-nine nondelusional MCI/early AD participants were compared with twenty-nine delusional participants using voxel-based morphometry, matched at baseline by age, sex, education, and Mini-Mental State Exam score. All included participants were diagnosed with amnestic MCI at study baseline. Results: Fifteen voxel clusters of decreased grey matter in participants with delusions were detected. Prominent grey matter decrease was observed in the right precentral gyrus, right inferior frontal gyrus, right insula, and left middle occipital gyrus, areas that may be involved in control of thought and emotions. Conclusion: Greater right fronto-temporal grey matter atrophy was observed in MCI or early AD participants with delusions compared to matched patients without delusions. Consistent with our predictions, asymmetric grey matter atrophy in the right hemisphere may contribute to development of delusions through loss of executive inhibition.
    No preview · Article · Feb 2015 · Current Alzheimer Research
Show more