Alzheimer's Disease (AD) is a neurodegenerative disease that affects subjects in a broad range of severity and is assessed in clinical trials with multiple cognitive and functional instruments. As clinical trials in AD increasingly focus on earlier stages of the disease, especially Mild Cognitive Impairment (MCI), the ability to model subject outcomes across the disease spectrum is extremely important. We use unsupervised machine learning models called Conditional Restricted Boltzmann Machines (CRBMs) to create Digital Twins of AD subjects. Digital Twins are simulated clinical records that share baseline data with actual subjects and comprehensively model their outcomes under standard-of-care. The CRBMs are trained on a large set of records from subjects in observational studies and the placebo arms of clinical trials across the AD spectrum. These data exhibit a challenging, but common, patchwork of measured and missing observations across subjects in the dataset, and we present a novel model architecture designed to learn effectively from it. We evaluate performance against a held-out test dataset and show how Digital Twins simultaneously capture the progression of a number of key endpoints in clinical trials across a broad spectrum of disease severity, including MCI and mild-to-moderate AD.
Alzheimer's Disease (AD), as the most devastating neurodegenerative disease worldwide, has reached nearly 10 million new cases annually. Current technology provides unprecedented opportunities to study the progression and etiology of this disease with the advanced in imaging techniques. With the recent emergence of a society driven by big data and machine learning (ML), researchers have exerted considerable effort to summarize recent advances in ML-based AD diagnosis. Here, we outline some of the most prevalent and recent ML models for assessing the progression of AD and provide insights on th…
University of Illinois at Urbana-Champaign（伊利诺伊大学厄巴纳-香槟分校）；National Institutes of Health（美国国立卫生研究院）
Alzheimer's disease (AD) is a degenerative brain disease impairing a person's ability to perform day to day activities. The clinical manifestations of Alzheimer's disease are characterized by heterogeneity in age, disease span, progression rate, impairment of memory and cognitive abilities. Due to these variabilities, personalized care and treatment planning, as well as patient counseling about their individual progression is limited. Recent developments in machine learning to detect hidden patterns in complex, multi-dimensional datasets provides significant opportunities to address this criti…
Most approaches to machine learning from electronic health data can only predict a single endpoint. Here, we present an alternative that uses unsupervised deep learning to simulate detailed patient trajectories. We use data comprising 18-month trajectories of 44 clinical variables from 1908 patients with Mild Cognitive Impairment or Alzheimer's Disease to train a model for personalized forecasting of disease progression. We simulate synthetic patient data including the evolution of each sub-component of cognitive exams, laboratory tests, and their associations with baseline clinical characteri…
Instituto Superior Técnico, Universidade de Lisboa（里斯本大学高等技术学院）
Most machine learning classifiers give predictions for new examples accurately, yet without indicating how trustworthy predictions are. In the medical domain, this hampers their integration in decision support systems, which could be useful in the clinical practice. We use a supervised learning approach that combines Ensemble learning with Conformal Predictors to predict conversion from Mild Cognitive Impairment to Alzheimer's Disease. Our goal is to enhance the classification performance (Ensemble learning) and complement each prediction with a measure of credibility (Conformal Predictors). O…
Massachusetts Institute of Technology（麻省理工学院）；Imperial College London（伦敦帝国学院）
In this paper, we introduce the use of a personalized Gaussian Process model (pGP) to predict the key metrics of Alzheimer's Disease progression (MMSE, ADAS-Cog13, CDRSB and CS) based on each patient's previous visits. We start by learning a population-level model using multi-modal data from previously seen patients using the base Gaussian Process (GP) regression. Then, this model is adapted sequentially over time to a new patient using domain adaptive GPs to form the patient's pGP. We show that this new approach, together with an auto-regressive formulation, leads to significant improvements …
Washington University School of Medicine（华盛顿大学医学院）
Objective Alzheimer disease (AD) is the most common cause of dementia, a syndrome characterized by cognitive impairment severe enough to interfere with activities of daily life. We aimed to conduct a systematic literature review (SLR) of studies that applied machine learning (ML) methods to clinical data derived from electronic health records in order to model risk for progression of AD dementia. Materials and Methods: We searched for articles published between January 1, 2010, and May 31, 2020, in PubMed, Scopus, ScienceDirect, IEEE Explore Digital Library, Association for Computing Machinery…
A comprehensive interpretable machine learning framework for Mild Cognitive Impairment and Alzheimer's disease diagnosis
Faculty of Electrical and Computer Engineering, National Technical University of Athens（雅典国立技术大学电气与计算机工程学院）；Center for Biomedical Image Computing and Analytics, University of Pennsylvania（宾夕法尼亚大学生物医学图像计算与分析中心）
Alzheimer's disease (AD) is the most common neurodegenerative disease in older people. Despite considerable efforts to find a cure for AD, there is a 99.6% failure rate of clinical trials for AD drugs, likely because AD patients cannot easily be identified at early stages. This project investigated machine learning approaches to predict the clinical state of patients in future years to benefit AD research. Clinical data from 1737 patients was obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and was processed using the "All-Pairs" technique, a novel methodology crea…
Deep Learning Approaches with Explainable AI for Differentiating Alzheimer Disease and Mild Cognitive Impairment
School of Mathematical and Natural Sciences（数学与自然科学学院）；Arizona State University（亚利桑那州立大学）；Department of Mathematics（数学系）；Florida Gulf Coast University（佛罗里达海岸大学）；Department of Public Health（公共卫生系）；Julia Jones Matthews School of Population and Public Health（朱莉亚·琼斯·马修斯人口与公共卫生学院）；Texas Tech University Health Sciences Center（德克萨斯农工大学健康科学中心）
Longitudinal Progression Prediction of Alzheimer's Disease with Tabular Foundation Model
Department of Computer Science Emory University Atlanta GA USA（埃默里大学计算机科学系）；Center for Data Science Nell Hodgson Woodruff School of Nursing Emory University Atlanta GA USA（埃默里大学数据科学中心）；Department of Computer Science Georgia State University Atlanta GA USA（佐治亚州立大学计算机科学系）；Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS) Atlanta GA USA（神经影像与数据科学转化研究三机构中心（TReNDS））
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) an…
Erasmus MC, University Medical Center Rotterdam（鹿特丹伊拉斯姆斯医学中心（鹿特丹大学医学中心））；Delft University of Technology（代尔夫特理工大学）
Alzheimer's Disease (AD) is characterized by a cascade of biomarkers becoming abnormal, the pathophysiology of which is very complex and largely unknown. Event-based modeling (EBM) is a data-driven technique to estimate the sequence in which biomarkers for a disease become abnormal based on cross-sectional data. It can help in understanding the dynamics of disease progression and facilitate early diagnosis and prognosis. In this work we propose a novel discriminative approach to EBM, which is shown to be more accurate than existing state-of-the-art EBM methods. The method first estimates for e…
In this thesis the aim is to work on optimizing the modern machine learning models for personalized forecasting of Alzheimer Disease (AD) Progression from clinical trial data. The data comes from the TADPOLE challenge, which is one of the largest publicly available datasets for AD research (ADNI dataset). The goal of the project is to develop machine learning models that can be used to perform personalized forecasts of the participants cognitive changes (e.g., ADAS-Cog13 scores) over the time period of 6,12, 18 and 24 months in the future and the change in Clinical Status (CS) i.e., whether a …
The Mind Research Network（心智研究网络）；University of New Mexico（新墨西哥大学）；Microsoft Research（微软研究院）；Montreal Institute for Learning Algorithms（蒙特利尔学习算法研究所）；University of Montreal（蒙特利尔大学）；Shanxi University（山西大学）
Arguably, unsupervised learning plays a crucial role in the majority of algorithms for processing brain imaging. A recently introduced unsupervised approach Deep InfoMax (DIM) is a promising tool for exploring brain structure in a flexible non-linear way. In this paper, we investigate the use of variants of DIM in a setting of progression to Alzheimer's disease in comparison with supervised AlexNet and ResNet inspired convolutional neural networks. As a benchmark, we use a classification task between four groups: patients with stable, and progressive mild cognitive impairment (MCI), with Alzhe…
Unifying Interpretability and Explainability for Alzheimer's Disease Progression Prediction
Kansas State University（堪萨斯州立大学）；Carnegie Mellon University（卡内基梅隆大学）；University of Kansas Medical Center（堪萨斯大学医学中心）；Alzheimer’s Disease Research Center（阿尔茨海默病研究中心）
Queen Mary University of London（伦敦玛丽女王大学）；Jožef Stefan Institute（约热夫·斯特凡研究所）
This paper is a submission to the Alzheimer's Dementia Recognition through Spontaneous Speech (ADReSS) challenge, which aims to develop methods that can assist in the automated prediction of severity of Alzheimer's Disease from speech data. We focus on acoustic and natural language features for cognitive impairment detection in spontaneous speech in the context of Alzheimer's Disease Diagnosis and the mini-mental state examination (MMSE) score prediction. We proposed a model that obtains unimodal decisions from different LSTMs, one for each modality of text and audio, and then combines them us…
Multi-Scale Graph Theoretical Analysis of Resting-State fMRI for Classification of Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls
University of Bojnord（博季努尔德大学）；Munster Technological University（芒斯特理工大学）
DeepTokenEEG Enhancing Mild Cognitive Impairment and Alzheimers Classification via Tokenized EEG Features
Hanoi University of Science and Technology（河内科学与技术大学）；VNU University of Engineering and Technology（越南工程与技术大学）；Central Military Hospital 108（第108中心军医院）；University of California, Irvine（加州大学尔湾分校）
McGovern Institute for Brain Research, Massachusetts Institute of Technology（麻省理工学院麦戈文脑研究所）；Complutense University of Madrid（马德里康普顿斯大学）；Harvard Medical School（哈佛医学院）
Characterizing the subtle changes of functional brain networks associated with the pathological cascade of Alzheimer's disease (AD) is important for early diagnosis and prediction of disease progression prior to clinical symptoms. We developed a new deep learning method, termed multiple graph Gaussian embedding model (MG2G), which can learn highly informative network features by mapping high-dimensional resting-state brain networks into a low-dimensional latent space. These latent distribution-based embeddings enable a quantitative characterization of subtle and heterogeneous brain connectivit…
Northwestern University（西北大学）；University of Florida（佛罗里达大学）；Weill Cornell Medicine（威尔康奈尔医学院）；Mayo Clinic（梅奥诊所）
Objective: We develop a deep learning framework based on the pre-trained Bidirectional Encoder Representations from Transformers (BERT) model using unstructured clinical notes from electronic health records (EHRs) to predict the risk of disease progression from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD). Materials and Methods: We identified 3657 patients diagnosed with MCI together with their progress notes from Northwestern Medicine Enterprise Data Warehouse (NMEDW) between 2000-2020. The progress notes no later than the first MCI diagnosis were used for the prediction. We fi…
University of Texas at Arlington（德克萨斯大学阿灵顿分校）；The University of Georgia（佐治亚大学）
For decades, a variety of predictive approaches have been proposed and evaluated in terms of their prediction capability for Alzheimer's Disease (AD) and its precursor - mild cognitive impairment (MCI). Most of them focused on prediction or identification of statistical differences among different clinical groups or phases (e.g., longitudinal studies). The continuous nature of AD development and transition states between successive AD related stages have been overlooked, especially in binary or multi-class classification. Though a few progression models of AD have been studied recently, they w…
Erasmus MC, University Medical Center Rotterdam（鹿特丹大学医学中心伊拉斯谟医学中心）；Delft University of Technology（代尔夫特理工大学）
Alzheimer's disease (AD) is the most common form of dementia and is phenotypically heterogeneous. APOE is a triallelic gene which correlates with phenotypic heterogeneity in AD. In this work, we determined the effect of APOE alleles on the disease progression timeline of AD using a discriminative event-based model (DEBM). Since DEBM is a data-driven model, stratification into smaller disease subgroups would lead to more inaccurate models as compared to fitting the model on the entire dataset. Hence our secondary aim is to propose and evaluate novel approaches in which we split the different st…
Kharkevich Institute for Information Transmission Problems（哈尔克维奇信息传输问题研究所）；Skolkovo Institute of Science and Technology（斯科尔科沃科学技术研究所）
Nowadays, a lot of scientific efforts are concentrated on the diagnosis of Alzheimer's Disease (AD) applying deep learning methods to neuroimaging data. Even for 2017, there were published more than a hundred papers dedicated to AD diagnosis, whereas only a few works considered a problem of mild cognitive impairments (MCI) conversion to the AD. However, the conversion prediction is an important problem since approximately 15% of patients with MCI converges to the AD every year. In the current work, we are focusing on the conversion prediction using brain Magnetic Resonance Imaging and clinical…
Institute of Smart Systems and Artificial Intelligence, Nazarbayev University（纳扎尔巴耶夫大学智能系统与人工智能研究所）
Alzheimer's disease (AD) is a progressive brain disorder that causes memory and functional impairments. The advances in machine learning and publicly available medical datasets initiated multiple studies in AD diagnosis. In this work, we utilize a multi-modal deep learning approach in classifying normal cognition, mild cognitive impairment and AD classes on the basis of structural MRI and diffusion tensor imaging (DTI) scans from the OASIS-3 dataset. In addition to a conventional multi-modal network, we also present an input agnostic architecture that allows diagnosis with either sMRI or DTI s…
PROMISE-AD: Progression-aware Multi-horizon Survival Estimation for Alzheimer's Disease Progression and Dynamic Tracking
Department of Radiology and Biomedical Imaging, Yale School of Medicine（放射科与生物医学成像系，耶鲁医学院）；Department of Radiology Oncology, Wake Forest University School of Medicine（放射肿瘤科，沃杰福大学医学院）；Department of Applied Mathematics & Statistics and Department of Computer Science, Stony Brook University（应用数学与统计系和计算机科学系，史泰文布鲁克大学）
Flexible Multimodal Neuroimaging Fusion for Alzheimer's Disease Progression Prediction
Department of Computer Science and Engineering（计算机科学与工程系）；Department of Biomedical Informatics（生物医学信息学系）；Department of Neurology（神经病学系）；Translational Data Analytics Institute（转化数据分析研究所）
Linguistic and Audio Embedding-Based Machine Learning for Alzheimer's Dementia and Mild Cognitive Impairment Detection: Insights from the PROCESS Challenge
Singapore University of Technology and Design（新加坡科技设计大学）；Hochschule für Musik Detmold（音乐学院Detmold）
Isik University（伊希克大学）；Istanbul Technical University（伊斯坦布尔技术大学）
Retinal optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) are promising tools for the (early) diagnosis of Alzheimer's disease (AD). These non-invasive imaging techniques are cost-effective and more accessible than alternative neuroimaging tools. However, interpreting and classifying multi-slice scans produced by OCT devices is time-consuming and challenging even for trained practitioners. There are surveys on machine learning and deep learning approaches concerning the automated analysis of OCT scans for various diseases such as glaucoma. However, the curr…
Longitudinal Bayesian Learning of Continuous Disease Position across the Alzheimer's Disease Continuum
University of Texas Rio Grande Valley（德克萨斯大学里奥格兰德河谷分校）；University of Pittsburgh（匹兹堡大学）；Eli and Lilly Company（礼来公司）；Washington University in St. Louis（圣路易斯华盛顿大学）
Alzheimer's disease (AD) is known as one of the major causes of dementia and is characterized by slow progression over several years, with no treatments or available medicines. In this regard, there have been efforts to identify the risk of developing AD in its earliest time. While many of the previous works considered cross-sectional analysis, more recent studies have focused on the diagnosis and prognosis of AD with longitudinal or time series data in a way of disease progression modeling (DPM). Under the same problem settings, in this work, we propose a novel computational framework that ca…
Multi-Task Learning with Feature-Similarity Laplacian Graphs for Predicting Alzheimer's Disease Progression
School of Software（软件学院）；Yunnan University（云南大学）；Department of Computer Science（计算机科学系）；The University of Sheffield（谢菲尔德大学）；Department of Computing（计算系）；Xi’an JiaoTong-Liverpool University（西安交通大学利物浦大学）；School of Medical Technology（医学技术学院）；Beijing Institute of Technology（北京理工大学）
Identification of Causal Relationship between Amyloid-beta Accumulation and Alzheimer's Disease Progression via Counterfactual Inference
University of Georgia（佐治亚大学）；Beijing Normal University（北京师范大学）；The University of Texas at Arlington（德克萨斯大学阿灵顿分校）；Massachusetts General Hospital（麻省总医院）；Harvard Medical School（哈佛医学院）；Brigham and Women’s Hospital（布莱根妇女医院）；Shanghai Jiao Tong University（上海交通大学）；The University of Virginia（弗吉尼亚大学）
Indian Institute of Technology Patna（印度理工学院巴特那分校）；Indian Institute of Technology Madras（印度理工学院马德拉斯分校）；University of Cambridge（剑桥大学）
Reliable detection of the prodromal stages of Alzheimer's disease (AD) remains difficult even today because, unlike other neurocognitive impairments, there is no definitive diagnosis of AD in vivo. In this context, existing research has shown that patients often develop language impairment even in mild AD conditions. We propose a multimodal deep learning method that utilizes speech and the corresponding transcript simultaneously to detect AD. For audio signals, the proposed audio-based network, a convolutional neural network (CNN) based model, predicts the diagnosis for multiple speech segment…
Intense debate in the Neurology community before 2010 culminated in hypothetical models of Alzheimer's disease progression: a pathophysiological cascade of biomarkers, each dynamic for only a segment of the full disease timeline. Inspired by this, data-driven disease progression modelling emerged from the computer science community with the aim to reconstruct neurodegenerative disease timelines using data from large cohorts of patients, healthy controls, and prodromal/at-risk individuals. This chapter describes selected highlights from the field, with a focus on utility for understanding and f…
Forecasting Medium-Horizon Alzheimer's Disease Progression: Residual Gap-Aware Transformers for 24-Month CDR-SB Change from ADNI Clinical and Biomarker Histories
Department of Mathematical Sciences, University of Texas at Dallas（德克萨斯大学达拉斯分校数学科学系）；Department of Plant Science and Landscape Architecture, University of Connecticut（康奈尔大学植物科学与景观建筑系）；Naveen Jindal School of Management, University of Texas at Dallas（德克萨斯大学达拉斯分校纳文·金达管理学院）；Zhejiang Provincial People’s Hospital（浙江省人民医院）
University of Pennsylvania（宾夕法尼亚大学）；University of Texas San Antonio Health Science Center（德克萨斯大学圣安东尼奥健康科学中心）；National Institute on Aging（美国国家老龄化研究所）
Heterogeneity of brain diseases is a challenge for precision diagnosis/prognosis. We describe and validate Smile-GAN (SeMI-supervised cLustEring-Generative Adversarial Network), a novel semi-supervised deep-clustering method, which dissects neuroanatomical heterogeneity, enabling identification of disease subtypes via their imaging signatures relative to controls. When applied to MRIs (2 studies; 2,832 participants; 8,146 scans) including cognitively normal individuals and those with cognitive impairment and dementia, Smile-GAN identified 4 neurodegenerative patterns/axes: P1, normal anatomy a…
University of Vic – Central University of Catalonia（维克大学-加泰罗尼亚中央大学）
Dementia, and specially Alzheimer s disease (AD) and Mild Cognitive Impairment (MCI) are one of the most important diseases suffered by elderly population. Music therapy is one of the most widely used non-pharmacological treatment in the field of cognitive impairments, given that music influences their mood, behavior, the decrease of anxiety, as well as facilitating reminiscence, emotional expressions and movement. In this work we present HAIDA, a multi-platform support system for Musical Therapy oriented to cognitive impairment, which includes not only therapy tools but also non-invasive biom…
Biomediq A/S（Biomediq公司）；Cerebriu A/S（Cerebriu公司）；University of Copenhagen（哥本哈根大学）；University College London（伦敦大学学院）；King’s College London（伦敦国王学院）
Disease progression modeling (DPM) using longitudinal data is a challenging machine learning task. Existing DPM algorithms neglect temporal dependencies among measurements, make parametric assumptions about biomarker trajectories, do not model multiple biomarkers jointly, and need an alignment of subjects' trajectories. In this paper, recurrent neural networks (RNNs) are utilized to address these issues. However, in many cases, longitudinal cohorts contain incomplete data, which hinders the application of standard RNNs and requires a pre-processing step such as imputation of the missing values…
