Forecasting the Progression of Alzheimer's Disease Using Neural Networks and a Novel Pre-Processing Algorithm

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 created for this project involving the comparison of all possible pairs of temporal data points for each patient. This data was then used to train various machine learning models. Models were evaluated using 7-fold cross-validation on the training dataset and confirmed using data from a separate testing dataset (110 patients). A neural network model was effective (mAUC = 0.866) at predicting the progression of AD on a month-by-month basis, both in patients who were initially cognitively normal and in patients suffering from mild cognitive impairment. Such a model could be used to identify patients at early stages of AD and who are therefore good candidates for clinical trials for AD therapeutics.Comment: 10 pages; updated acknowledgement

Bidirectional Representation Learning from Transformers using Multimodal Electronic Health Record Data to Predict Depression

Advancements in machine learning algorithms have had a beneficial impact on representation learning, classification, and prediction models built using electronic health record (EHR) data. Effort has been put both on increasing models' overall performance as well as improving their interpretability, particularly regarding the decision-making process. In this study, we present a temporal deep learning model to perform bidirectional representation learning on EHR sequences with a transformer architecture to predict future diagnosis of depression. This model is able to aggregate five heterogenous and high-dimensional data sources from the EHR and process them in a temporal manner for chronic disease prediction at various prediction windows. We applied the current trend of pretraining and fine-tuning on EHR data to outperform the current state-of-the-art in chronic disease prediction, and to demonstrate the underlying relation between EHR codes in the sequence. The model generated the highest increases of precision-recall area under the curve (PRAUC) from 0.70 to 0.76 in depression prediction compared to the best baseline model. Furthermore, the self-attention weights in each sequence quantitatively demonstrated the inner relationship between various codes, which improved the model's interpretability. These results demonstrate the model's ability to utilize heterogeneous EHR data to predict depression while achieving high accuracy and interpretability, which may facilitate constructing clinical decision support systems in the future for chronic disease screening and early detection.Comment: in IEEE Journal of Biomedical and Health Informatics (2021