Deep Learning in Alzheimer's Disease: Diagnostic Classification and Prognostic Prediction Using Neuroimaging Data

Deep learning, a state-of-the-art machine learning approach, has shown outstanding performance over traditional machine learning in identifying intricate structures in complex high-dimensional data, especially in the domain of computer vision. The application of deep learning to early detection and automated classification of Alzheimer's disease (AD) has recently gained considerable attention, as rapid progress in neuroimaging techniques has generated large-scale multimodal neuroimaging data. A systematic review of publications using deep learning approaches and neuroimaging data for diagnostic classification of AD was performed. A PubMed and Google Scholar search was used to identify deep learning papers on AD published between January 2013 and July 2018. These papers were reviewed, evaluated, and classified by algorithm and neuroimaging type, and the findings were summarized. Of 16 studies meeting full inclusion criteria, 4 used a combination of deep learning and traditional machine learning approaches, and 12 used only deep learning approaches. The combination of traditional machine learning for classification and stacked auto-encoder (SAE) for feature selection produced accuracies of up to 98.8% for AD classification and 83.7% for prediction of conversion from mild cognitive impairment (MCI), a prodromal stage of AD, to AD. Deep learning approaches, such as convolutional neural network (CNN) or recurrent neural network (RNN), that use neuroimaging data without pre-processing for feature selection have yielded accuracies of up to 96.0% for AD classification and 84.2% for MCI conversion prediction. The best classification performance was obtained when multimodal neuroimaging and fluid biomarkers were combined. Deep learning approaches continue to improve in performance and appear to hold promise for diagnostic classification of AD using multimodal neuroimaging data. AD research that uses deep learning is still evolving, improving performance by incorporating additional hybrid data types, such as—omics data, increasing transparency with explainable approaches that add knowledge of specific disease-related features and mechanisms.

[1]  Tara N. Sainath,et al.  Deep Neural Networks for Acoustic Modeling in Speech Recognition , 2012 .

[2]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. , 2010, International journal of surgery.

[3]  Sidong Liu,et al.  Multimodal Neuroimaging Feature Learning for Multiclass Diagnosis of Alzheimer's Disease , 2015, IEEE Transactions on Biomedical Engineering.

[4]  Dinggang Shen,et al.  A Robust Deep Model for Improved Classification of AD/MCI Patients , 2015, IEEE Journal of Biomedical and Health Informatics.

[5]  Danni Cheng,et al.  Classification of Alzheimer’s Disease by Combination of Convolutional and Recurrent Neural Networks Using FDG-PET Images , 2018, Front. Neuroinform..

[6]  Yoshua Bengio,et al.  An empirical evaluation of deep architectures on problems with many factors of variation , 2007, ICML '07.

[7]  Bram van Ginneken,et al.  A survey on deep learning in medical image analysis , 2017, Medical Image Anal..

[8]  Yoshua Bengio,et al.  Deep Learning of Representations: Looking Forward , 2013, SLSP.

[9]  Danni Cheng,et al.  Classification of MR brain images by combination of multi-CNNs for AD diagnosis , 2017, International Conference on Digital Image Processing.

[10]  F ROSENBLATT,et al.  The perceptron: a probabilistic model for information storage and organization in the brain. , 1958, Psychological review.

[11]  Qihao Weng,et al.  A survey of image classification methods and techniques for improving classification performance , 2007 .

[12]  Dinggang Shen,et al.  Landmark‐based deep multi‐instance learning for brain disease diagnosis , 2018, Medical Image Anal..

[13]  Pascal Vincent,et al.  Stacked Denoising Autoencoders: Learning Useful Representations in a Deep Network with a Local Denoising Criterion , 2010, J. Mach. Learn. Res..

[14]  Yoshua Bengio,et al.  Deep Sparse Rectifier Neural Networks , 2011, AISTATS.

[15]  W S McCulloch,et al.  A logical calculus of the ideas immanent in nervous activity , 1990, The Philosophy of Artificial Intelligence.

[16]  Guigang Zhang,et al.  Deep Learning , 2016, Int. J. Semantic Comput..

[17]  Heekuck Oh,et al.  Neural Networks for Pattern Recognition , 1993, Adv. Comput..

[18]  Inke R. König,et al.  Validation in Genetic Association Studies , 2011, Briefings Bioinform..

[19]  P. Werbos Backwards Differentiation in AD and Neural Nets: Past Links and New Opportunities , 2006 .

[20]  Geoffrey E. Hinton,et al.  Reducing the Dimensionality of Data with Neural Networks , 2006, Science.

[21]  Hugo Larochelle,et al.  Efficient Learning of Deep Boltzmann Machines , 2010, AISTATS.

[22]  Danni Cheng,et al.  CNNs based multi-modality classification for AD diagnosis , 2017, 2017 10th International Congress on Image and Signal Processing, BioMedical Engineering and Informatics (CISP-BMEI).

[23]  Samy Bengio,et al.  Tensor2Tensor for Neural Machine Translation , 2018, AMTA.

[24]  Geoffrey E. Hinton,et al.  Learning representations by back-propagating errors , 1986, Nature.

[25]  Yoshua Bengio,et al.  Scaling learning algorithms towards AI , 2007 .

[26]  Geoffrey E. Hinton,et al.  Using very deep autoencoders for content-based image retrieval , 2011, ESANN.

[27]  J. Whitwell,et al.  Alzheimer's disease neuroimaging , 2018, Current opinion in neurology.

[28]  Jian Sun,et al.  Deep Residual Learning for Image Recognition , 2015, 2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).

[29]  Geoffrey E. Hinton,et al.  On the importance of initialization and momentum in deep learning , 2013, ICML.

[30]  Vince D. Calhoun,et al.  Deep learning for neuroimaging: a validation study , 2013, Front. Neurosci..

[31]  Adrian Preda,et al.  Multimodal and Multiscale Deep Neural Networks for the Early Diagnosis of Alzheimer’s Disease using structural MR and FDG-PET images , 2018, Scientific Reports.

[32]  Brendan J. Frey,et al.  k-Sparse Autoencoders , 2013, ICLR.

[33]  Hilla Peretz,et al.  The , 1966 .

[34]  Dinggang Shen,et al.  Deep Learning Based Imaging Data Completion for Improved Brain Disease Diagnosis , 2014, MICCAI.

[35]  Arthur W Toga,et al.  Global Data Sharing in Alzheimer Disease Research , 2016, Alzheimer disease and associated disorders.

[36]  Jason H. Moore,et al.  Chapter 11: Genome-Wide Association Studies , 2012, PLoS Comput. Biol..

[37]  Seong-Whan Lee,et al.  Hierarchical feature representation and multimodal fusion with deep learning for AD/MCI diagnosis , 2014, NeuroImage.

[38]  Tara N. Sainath,et al.  Deep Neural Networks for Acoustic Modeling in Speech Recognition: The Shared Views of Four Research Groups , 2012, IEEE Signal Processing Magazine.

[39]  Yulia Dodonova,et al.  Residual and plain convolutional neural networks for 3D brain MRI classification , 2017, 2017 IEEE 14th International Symposium on Biomedical Imaging (ISBI 2017).

[40]  Ninon Burgos,et al.  Reproducible evaluation of classification methods in Alzheimer's disease: Framework and application to MRI and PET data , 2018, NeuroImage.

[41]  J. Galvin,et al.  Prevention of Alzheimer's Disease: Lessons Learned and Applied , 2017, Journal of the American Geriatrics Society.

[42]  Subhashini Venugopalan,et al.  Development and Validation of a Deep Learning Algorithm for Detection of Diabetic Retinopathy in Retinal Fundus Photographs. , 2016, JAMA.

[43]  Seong-Whan Lee,et al.  Latent feature representation with stacked auto-encoder for AD/MCI diagnosis , 2013, Brain Structure and Function.

[44]  Dmitrij Frishman,et al.  Pitfalls of supervised feature selection , 2009, Bioinform..

[45]  H. Boezen,et al.  Genome-wide association studies: what do they teach us about asthma and chronic obstructive pulmonary disease? , 2009, Proceedings of the American Thoracic Society.

[46]  Geoffrey E. Hinton,et al.  ImageNet classification with deep convolutional neural networks , 2012, Commun. ACM.

[47]  Léon Bottou,et al.  Large-Scale Machine Learning with Stochastic Gradient Descent , 2010, COMPSTAT.

[48]  Sotirios A. Tsaftaris,et al.  Medical Image Computing and Computer Assisted Intervention , 2017 .

[49]  Geoffrey E. Hinton,et al.  Autoencoders, Minimum Description Length and Helmholtz Free Energy , 1993, NIPS.

[50]  Jenny Benois-Pineau,et al.  FuseMe: Classification of sMRI images by fusion of Deep CNNs in 2D+ε projections , 2017, CBMI.

[51]  Christos Davatzikos,et al.  A review on neuroimaging-based classification studies and associated feature extraction methods for Alzheimer's disease and its prodromal stages , 2017, NeuroImage.

[52]  M. Hutson Artificial intelligence faces reproducibility crisis. , 2018, Science.

[53]  Sterling C. Johnson,et al.  Multimodal and Multiscale Deep Neural Networks for the Early Diagnosis of Alzheimer's Disease using structural MR and FDG-PET images , 2017, ArXiv.

[54]  Yann Le Cun,et al.  A Theoretical Framework for Back-Propagation , 1988 .

[55]  Robert Krikorian,et al.  Mechanisms of Risk Reduction in the Clinical Practice of Alzheimer’s Disease Prevention , 2018, Front. Aging Neurosci..

[56]  Gary Marcus,et al.  Deep Learning: A Critical Appraisal , 2018, ArXiv.

[57]  M. Marazita,et al.  Genome-wide Association Studies , 2012, Journal of dental research.

[58]  Kyong Hwan Jin,et al.  Predicting cognitive decline with deep learning of brain metabolism and amyloid imaging , 2017, Behavioural Brain Research.

[59]  Dinggang Shen,et al.  Deep Learning-Based Feature Representation for AD/MCI Classification , 2013, MICCAI.

[60]  Michael S. Bernstein,et al.  ImageNet Large Scale Visual Recognition Challenge , 2014, International Journal of Computer Vision.

[61]  Pascal Vincent,et al.  Representation Learning: A Review and New Perspectives , 2012, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[62]  Paul M. Thompson,et al.  Uncovering Biologically Coherent Peripheral Signatures of Health and Risk for Alzheimer’s Disease in the Aging Brain , 2018, Front. Aging Neurosci..

[63]  Yoshua Bengio,et al.  Pattern Recognition and Neural Networks , 1995 .

[64]  Jürgen Schmidhuber,et al.  Multi-column deep neural networks for image classification , 2012, 2012 IEEE Conference on Computer Vision and Pattern Recognition.

[65]  Yoshua Bengio,et al.  Generative Adversarial Nets , 2014, NIPS.

[66]  Kunihiko Fukushima,et al.  Cognitron: A self-organizing multilayered neural network , 1975, Biological Cybernetics.

[67]  Sidong Liu,et al.  Early diagnosis of Alzheimer's disease with deep learning , 2014, 2014 IEEE 11th International Symposium on Biomedical Imaging (ISBI).

[68]  Hyung-Jeong Yang,et al.  Multimodal learning using convolution neural network and Sparse Autoencoder , 2017, 2017 IEEE International Conference on Big Data and Smart Computing (BigComp).

[69]  Honglak Lee,et al.  Convolutional deep belief networks for scalable unsupervised learning of hierarchical representations , 2009, ICML '09.

[70]  Paul J. Werbos,et al.  Applications of advances in nonlinear sensitivity analysis , 1982 .

[71]  Geoffrey E. Hinton,et al.  Deep Learning , 2015, Nature.

[72]  Juhan Nam,et al.  Multimodal Deep Learning , 2011, ICML.

[73]  Igor Kononenko,et al.  Machine learning for medical diagnosis: history, state of the art and perspective , 2001, Artif. Intell. Medicine.

[74]  Ye Zhang,et al.  A Sensitivity Analysis of (and Practitioners’ Guide to) Convolutional Neural Networks for Sentence Classification , 2015, IJCNLP.

[75]  Yee Whye Teh,et al.  A Fast Learning Algorithm for Deep Belief Nets , 2006, Neural Computation.

[76]  Alekseĭ Grigorʹevich Ivakhnenko,et al.  CYBERNETIC PREDICTING DEVICES , 1966 .

[77]  Richard S. Sutton,et al.  Reinforcement Learning: An Introduction , 1998, IEEE Trans. Neural Networks.

[78]  Yoshua. Bengio,et al.  Learning Deep Architectures for AI , 2007, Found. Trends Mach. Learn..

[79]  A. Roli Artificial Neural Networks , 2012, Lecture Notes in Computer Science.

[80]  Jean Ponce,et al.  A Theoretical Analysis of Feature Pooling in Visual Recognition , 2010, ICML.

[81]  J. Morris,et al.  Understanding disease progression and improving Alzheimer's disease clinical trials: Recent highlights from the Alzheimer's Disease Neuroimaging Initiative , 2018, Alzheimer's & Dementia.

[82]  A. G. Ivakhnenko,et al.  Polynomial Theory of Complex Systems , 1971, IEEE Trans. Syst. Man Cybern..

[83]  Ieee Xplore,et al.  IEEE Transactions on Pattern Analysis and Machine Intelligence Information for Authors , 2022, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[84]  Eric Karran,et al.  The Cellular Phase of Alzheimer’s Disease , 2016, Cell.

[85]  Jeffrey Dean,et al.  Distributed Representations of Words and Phrases and their Compositionality , 2013, NIPS.

[86]  S. Agatonovic-Kustrin,et al.  Basic concepts of artificial neural network (ANN) modeling and its application in pharmaceutical research. , 2000, Journal of pharmaceutical and biomedical analysis.

[87]  Kunihiko Fukushima,et al.  Neocognitron: A self-organizing neural network model for a mechanism of pattern recognition unaffected by shift in position , 1980, Biological Cybernetics.

[88]  Geoffrey E. Hinton,et al.  Rectified Linear Units Improve Restricted Boltzmann Machines , 2010, ICML.

[89]  Yoshua Bengio,et al.  Extracting and composing robust features with denoising autoencoders , 2008, ICML '08.

[90]  Jürgen Schmidhuber,et al.  Deep learning in neural networks: An overview , 2014, Neural Networks.

[91]  Camille Couprie,et al.  Learning Hierarchical Features for Scene Labeling , 2013, IEEE Transactions on Pattern Analysis and Machine Intelligence.