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Alzheimers 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 steps of DEBM into group-aspecific and group-specific parts, where the entire dataset is used to train the group-aspecific parts and only the data from a specific group is used to train the group-specific parts of the DEBM. We performed simulation experiments to benchmark the accuracy of the proposed approaches and to select the optimal approach. Subsequently, the chosen approach was applied to the baseline data of 417 cognitively normal, 235 mild cognitively impaired who convert to AD within 3 years, and 342 AD patients from the Alzheimers Disease Neuroimaging Initiative (ADNI) dataset to gain new insights into the effect of APOE carriership on the disease progression timeline of AD. The presented models could aid understanding of the disease, and in selecting homogeneous group of presymptomatic subjects at-risk of developing symptoms for clinical trials.
We model Alzheimers 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 rela
Alzheimers 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
Early detection is crucial to prevent the progression of Alzheimers disease (AD). Thus, specialists can begin preventive treatment as soon as possible. They demand fast and precise assessment in the diagnosis of AD in the earliest and hardest to dete
In order to find effective treatments for Alzheimers disease (AD), we need to identify subjects at risk of AD as early as possible. To this end, recently developed disease progression models can be used to perform early diagnosis, as well as predict
Modeling a systems temporal behaviour in reaction to external stimuli is a fundamental problem in many areas. Pure Machine Learning (ML) approaches often fail in the small sample regime and cannot provide actionable insights beyond predictions. A pro