Brain Imaging and Behavior

, Volume 9, Issue 4, pp 913–926 | Cite as

Multimodal manifold-regularized transfer learning for MCI conversion prediction

  • Bo Cheng
  • Mingxia Liu
  • Heung-Il Suk
  • Dinggang ShenEmail author
  • Daoqiang ZhangEmail author
  • Alzheimer’s Disease Neuroimaging Initiative
Original Research


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.


Mild cognitive impairment conversion Manifold regularization Transfer learning Semi-supervised learning Multimodal classification Sample selection 



Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., as well as non-profit partners the Alzheimer’s Association and Alzheimer’s Drug Discovery Foundation, with participation from the U.S. Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health ( The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuron Imaging at the University of California, Los Angeles. This work was supported by the National Natural Science Foundation of China (Nos. 61422204, 61473149, 61473190, 1401271, 81471733), the Jiangsu Natural Science Foundation for Distinguished Young Scholar (No. BK20130034), the Specialized Research Fund for the Doctoral Program of Higher Education (No. 20123218110009), the NUAA Fundamental Research Funds (No. NE2013105), and also by the NIH grant (EB006733, EB008374, EB009634, MH100217, AG041721, AG042599).

Conflict of Interest

Matthew Bo Cheng, Mingxia Liu, Heung-Il Suk, Dinggang Shen, and Daoqiang Zhang declare that they have no conflicts of interest.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Bo Cheng
    • 1
    • 2
    • 3
  • Mingxia Liu
    • 1
    • 4
  • Heung-Il Suk
    • 5
  • Dinggang Shen
    • 2
    • 5
    Email author
  • Daoqiang Zhang
    • 1
    Email author
  • Alzheimer’s Disease Neuroimaging Initiative
  1. 1.College of Computer Science and TechnologyNanjing University of Aeronautics and AstronauticsNanjingChina
  2. 2.Department of Radiology and BRICUniversity of North CarolinaChapel HillUSA
  3. 3.School of Computer Science and EngineeringChongqing Three Gorges UniversityChongqingChina
  4. 4.School of Information Science and TechnologyTaishan UniversityTaianChina
  5. 5.Department of Brain and Cognitive EngineeringKorea UniversitySeoulRepublic of Korea

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