Reinforcement Learning based Disease Progression Model for Alzheimer's Disease

We model Alzheimer’s disease (AD) progression by combining differential equations (DEs) and reinforcement learning (RL) with domain knowledge. DEs provide relationships between some, but not all, factors relevant to AD. We assume that the missing relationships must satisfy general criteria about the working of the brain, for e.g., maximizing cognition while minimizing the cost of supporting cognition. This allows us to extract the missing relationships by using RL to optimize an objective (reward) function that captures the above criteria. We use our model consisting of DEs (as a simulator) and the trained RL agent to predict individualized 10-year AD progression using baseline (year 0) features on synthetic and real data. The model was comparable or better at predicting 10-year cognition trajectories than state-of-the-art learning-based models. Our interpretable model demonstrated, and provided insights into, "recovery/compensatory" processes that mitigate the effect of AD, even though those processes were not explicitly encoded in the model. Our framework combines DEs with RL for modelling AD progression and has broad applicability for understanding other neurological disorders.

[1]  Malek Adjouadi,et al.  Profile-Specific Regression Model for Progression Prediction of Alzheimer's Disease Using Longitudinal Data , 2018, 2018 17th IEEE International Conference on Machine Learning and Applications (ICMLA).

[2]  Frank G. Hillary,et al.  Injured Brains and Adaptive Networks: The Benefits and Costs of Hyperconnectivity , 2017, Trends in Cognitive Sciences.

[3]  Michael Weiner,et al.  Network Diffusion Model of Progression Predicts Longitudinal Patterns of Atrophy and Metabolism in Alzheimer's Disease. , 2015, Cell reports.

[4]  Yiannis Ventikos,et al.  Modelling of the physiological response of the brain to ischaemic stroke , 2013, Interface Focus.

[5]  Joelle Pineau,et al.  Treating Epilepsy via Adaptive Neurostimulation: a Reinforcement Learning Approach , 2009, Int. J. Neural Syst..

[6]  Joachim M. Buhmann,et al.  A generative model of whole-brain effective connectivity , 2018, NeuroImage.

[7]  Paul Schrater,et al.  Cognitive cost as dynamic allocation of energetic resources , 2015, Front. Neurosci..

[8]  Alec Radford,et al.  Proximal Policy Optimization Algorithms , 2017, ArXiv.

[9]  D. Brooks,et al.  Cortical hypermetabolism in MCI subjects: a compensatory mechanism? , 2015, European Journal of Nuclear Medicine and Molecular Imaging.

[10]  Christoforos Hadjichrysanthou,et al.  Why do so many clinical trials of therapies for Alzheimer's disease fail? , 2017, The Lancet.

[11]  C. Jack,et al.  Evidence for ordering of Alzheimer disease biomarkers. , 2011, Archives of neurology.

[12]  B. T. Thomas Yeo,et al.  Predicting Alzheimer’s disease progression using deep recurrent neural networks , 2019, NeuroImage.

[13]  S. Laughlin,et al.  Fly Photoreceptors Demonstrate Energy-Information Trade-Offs in Neural Coding , 2007, PLoS biology.

[14]  Clifford R. Jack,et al.  Tau, amyloid, and cascading network failure across the Alzheimer's disease spectrum , 2017, Cortex.

[15]  Hugo Geerts,et al.  Challenges in Alzheimer's Disease Drug Discovery and Development: The Role of Modeling, Simulation, and Open Data , 2020, Clinical pharmacology and therapeutics.

[16]  Yaakov Stern,et al.  Task difficulty modulates young–old differences in network expression , 2012, Brain Research.

[17]  K. Kieburtz,et al.  A review of disease progression models of Parkinson's disease and applications in clinical trials , 2016, Movement disorders : official journal of the Movement Disorder Society.

[18]  R. Karaman,et al.  Comprehensive Review on Alzheimer’s Disease: Causes and Treatment , 2020, Molecules.

[19]  R Gieschke,et al.  Modeling Alzheimer's Disease Progression Using Disease Onset Time and Disease Trajectory Concepts Applied to CDR-SOB Scores From ADNI , 2013, CPT: pharmacometrics & systems pharmacology.

[20]  Emily L. Dennis,et al.  Functional Brain Connectivity Using fMRI in Aging and Alzheimer’s Disease , 2014, Neuropsychology Review.

[21]  H. Braak,et al.  Vulnerability of Select Neuronal Types to Alzheimer's Disease , 2000, Annals of the New York Academy of Sciences.

[22]  Daniel C Alexander,et al.  Data-driven models of dominantly-inherited Alzheimer’s disease progression , 2018, bioRxiv.

[23]  R. Cabeza,et al.  Que PASA? The posterior-anterior shift in aging. , 2008, Cerebral cortex.

[24]  Olaf Sporns,et al.  Network structure of cerebral cortex shapes functional connectivity on multiple time scales , 2007, Proceedings of the National Academy of Sciences.

[25]  M. Weiner,et al.  A Network Diffusion Model of Disease Progression in Dementia , 2012, Neuron.

[26]  Di Guo,et al.  Convolutional Neural Networks-Based MRI Image Analysis for the Alzheimer’s Disease Prediction From Mild Cognitive Impairment , 2018, Front. Neurosci..

[27]  Yogatheesan Varatharajah,et al.  Predicting Longitudinal Cognitive Scores Using Baseline Imaging and Clinical Variables , 2020, 2020 IEEE 17th International Symposium on Biomedical Imaging (ISBI).

[28]  Michael Cole,et al.  Cognitive task information is transferred between brain regions via resting-state network topology , 2017 .

[29]  Lars Lau Raket,et al.  Statistical Disease Progression Modeling in Alzheimer Disease , 2020, Frontiers in Big Data.

[30]  S. Laughlin,et al.  An Energy Budget for Signaling in the Grey Matter of the Brain , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[31]  Romain Laroche,et al.  Reinforcement Learning Framework for Deep Brain Stimulation Study , 2020, IJCAI.

[32]  Mary Mittelman,et al.  World Alzheimer Report 2012: Overcoming the Stigma of Dementia , 2012 .

[33]  Michael W. Weiner,et al.  Impact of the Alzheimer's Disease Neuroimaging Initiative, 2004 to 2014 , 2015, Alzheimer's & Dementia.

[34]  C. Jack,et al.  Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade , 2010, The Lancet Neurology.

[35]  Stephen J. Roberts,et al.  Bayesian deep neural networks for low-cost neurophysiological markers of Alzheimer's disease severity , 2018, ArXiv.

[36]  Danielle S Bassett,et al.  Cognitive fitness of cost-efficient brain functional networks , 2009, Proceedings of the National Academy of Sciences.

[37]  Steven Mennerick,et al.  Synaptic Activity Regulates Interstitial Fluid Amyloid-β Levels In Vivo , 2005, Neuron.

[38]  Polina Golland,et al.  TADPOLE Challenge: Accurate Alzheimer's Disease Prediction Through Crowdsourced Forecasting of Future Data , 2019, PRIME@MICCAI.

[39]  O Sporns,et al.  Predicting human resting-state functional connectivity from structural connectivity , 2009, Proceedings of the National Academy of Sciences.

[40]  Sébastien Ourselin,et al.  An event-based model for disease progression and its application in familial Alzheimer's disease and Huntington's disease , 2012, NeuroImage.

[41]  Sergey Levine,et al.  Trust Region Policy Optimization , 2015, ICML.

[42]  Xi Chen,et al.  Simulating the Evolution of Functional Brain Networks in Alzheimer’s Disease: Exploring Disease Dynamics from the Perspective of Global Activity , 2016, Scientific Reports.

[43]  A. Cohen,et al.  Predictors of Heterogeneity in Cognitive Function: APOE-e4, Sex, Education, Depression, and Vascular Risk. , 2020, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[44]  E. Kuhl,et al.  Multiphysics of Prionlike Diseases: Progression and Atrophy. , 2018, Physical review letters.

[45]  J. Rapoport,et al.  Simple models of human brain functional networks , 2012, Proceedings of the National Academy of Sciences.

[46]  Nick C. Fox,et al.  Data-driven models of dominantly-inherited Alzheimer’s disease progression , 2018 .