3D-Deep Learning Based Automatic Diagnosis of Alzheimer’s Disease with Joint MMSE Prediction Using Resting-State fMRI

  • Nguyen Thanh Duc
  • Seungjun Ryu
  • Muhammad Naveed Iqbal Qureshi
  • Min Choi
  • Kun Ho LeeEmail author
  • Boreom LeeEmail author
Original Article


We performed this research to 1) evaluate a novel deep learning method for the diagnosis of Alzheimer’s disease (AD) and 2) jointly predict the Mini Mental State Examination (MMSE) scores of South Korean patients with AD. Using resting-state functional Magnetic Resonance Imaging (rs-fMRI) scans of 331 participants, we obtained functional 3-dimensional (3-D) independent component spatial maps for use as features in classification and regression tasks. A 3-D convolutional neural network (CNN) architecture was developed for the classification task. MMSE scores were predicted using: linear least square regression (LLSR), support vector regression, bagging-based ensemble regression, and tree regression with group independent component analysis (gICA) features. To improve MMSE regression performance, we applied feature optimization methods including least absolute shrinkage and selection operator and support vector machine-based recursive feature elimination (SVM-RFE). The mean balanced test accuracy was 85.27% for the classification of AD versus healthy controls. The medial visual, default mode, dorsal attention, executive, and auditory related networks were mainly associated with AD. The maximum clinical MMSE score prediction accuracy with the LLSR method applied on gICA combined with SVM-RFE features had the lowest root mean square error (3.27 ± 0.58) and the highest R2 value (0.63 ± 0.02). Classification of AD and healthy controls can be successfully achieved using only rs-fMRI and MMSE scores can be accurately predicted using functional independent component features. In the absence of trained clinicians, AD disease status and clinical MMSE scores can be jointly predicted using 3-D deep learning and regression learning approaches with rs-fMRI data.


Alzheimer’s disease Mini mental state examination Group ICA 3-D CNN LASSO Recursive feature elimination 



This work was supported by a GIST Research Institute (GRI) grant funded by the GIST in 2019. This work was also supported by the Bio & Medical Technology Development Program of the NRF funded by the Korean government, MSIT (NRF-2016M3A9E9941946), and the Original Technology Research Program for Brain Science of the NRF funded by the Korean government, MSIT (NRF-2014M3C7A1046041).

Compliance with Ethical Standards

Declaration of Interest



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Authors and Affiliations

  1. 1.Department of Biomedical Science and Engineering (BMSE), Institute of Integrated Technology (IIT)Gwangju Institute of Science and Technology (GIST)GwangjuSouth Korea
  2. 2.Translational Neuroimaging Laboratory, The McGill University Research Center for Studies in Aging (MCSA)McGill UniversityMontrealCanada
  3. 3.Alzheimer’s Disease Research Unit, Douglas Mental Health University InstituteMcGill UniversityMontrealCanada
  4. 4.Department of PsychiatryMcGill UniversityMontrealCanada
  5. 5.National Research Center for DementiaChosun UniversityGwangjuSouth Korea
  6. 6.Department of Biomedical ScienceChosun UniversityGwangjuSouth Korea

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