Sidra Minhas

Alzheimer’s disease (AD) is a progressive and fatal disease, due to the nonavailability of any permanent cure. Some treatments are under experimentation that can slow down and possibly pause the progression of the disease only if the disease is diagnosed earlier. The onset of AD can only be detected at the mild cognitive impairment (MCI) stage in which slight memory loss is observed but daily routine functions are intact. A small fraction of the patient progresses from MCI to AD. In this research, we have designed a cascaded deep neural network model to identify those MCI subjects who will progress to AD in the following year. The analysis and experimentation have been performed using twenty longitudinal neuropsychological measures (NMs) provided by Alzheimer’s Disease Neuroimaging Initiative (ADNI). After normalization and ranking of longitudinal data, the deep neural network regression model is trained and tuned to forecast the next in-sequence biomarker value using two previous follow-up readings for each marker. Then, the three time-domain window samples are fed into another deep neural network classifier model for the classification of MCI progressor (MCIp) and MCI stables (MCIs). Our model presented regression forecasting MAE of 0.13 and classification accuracy of 86.9% with AUC of 92.1% (Sensitivity: 67.7%, specificity: 92.3%) over 5-fold cross-validation. We conclude that time-domain measures of NM alone can deliver comparable MCI to AD conversion prediction performance without leveraging more expensive and invasive counterparts such as MR imaging, PET scans, and CSF measures. Middle and low-income countries will benefit from such cheap and effective solutions greatly.

In Alzheimer’s disease (AD) progression, it is imperative to identify the subjects with mild cognitive impairment before clinical symptoms of AD appear. This work proposes a technique for decision support in identifying subjects who will show transition from mild cognitive impairment (MCI) to Alzheimer’s disease (AD) in the future. We used robust predictors from multivariate MRI‐derived biomarkers and neuropsychological measures and tracked their longitudinal trajectories to predict signs of AD in the MCI population. Assuming piecewise linear progression of the disease, we designed a novel weighted gradient offset‐based technique to forecast the future marker value using readings from at least two previous follow‐up visits. Later, the complete predictor trajectories are used as features for a standard support vector machine classifier to identify MCI‐to‐AD progressors amongst the MCI patients enrolled in the Alzheimer’s disease neuroimaging initiative (ADNI) cohort. We explored the performance of both unimodal and multimodal models in a 5‐fold cross‐validation setup. The proposed technique resulted in a high classification AUC of 91.2% and 95.7% for 6‐month‐ and 1‐year‐ahead AD prediction, respectively, using multimodal markers. In the end, we discuss the efficacy of MRI markers as compared to NM for MCI‐to‐AD conversion prediction.

Mild cognitive impairment is a preclinical stage of Alzheimer's disease (AD). For effective treatment of AD, it is important to identify mild cognitive impairment (MCI) patients who are at a high risk of developing AD over the course of time. In this study, autoregressive modelling of multiple heterogeneous predictors of Alzheimer's disease is performed to capture their evolution over time. The models are trained using three different arrangements of longitudinal data. These models are then used to estimate future biomarker readings of individual test subjects. Finally, standard support vector machine classifier is employed for detecting MCI patients at risk of developing AD over the coming years. The proposed models are thoroughly evaluated for their predictive capability using both cognitive scores and MRI-derived measures. In a stratified five-fold cross validation setup, our proposed methodology delivered highest AUC of 88.93% (Accuracy = 84.29%) and 88.13% (Accuracy = 83.26%) for 1 year and 2 year ahead AD conversion prediction, respectively, on the most widely used Alzheimer's disease neuroimaging initiative data. The notable conclusions of this study are: 1) Clinical changes in MRI-derived measures can be better forecasted than cognitive scores, 2) Multiple predictor models deliver better conversion prediction than single biomarker models, 3) Cognitive score boosted by MRI-derived measures delivers better short-term ahead conversion prediction, and 4) Neuropsychological scores alone can deliver good accuracy for long-term conversion prediction.