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Shannon L. Risacher

Publications and source records attributed to Shannon L. Risacher.

3 recordsLinked to original sources

Cognitive Biomarker Prioritization in Alzheimer's Disease using Brain Morphometric Data

Background:Cognitive assessments represent the most common clinical routine for the diagnosis of Alzheimer's Disease (AD). Given a large number of cognitive assessment tools and time-limited office visits, it is important to determine a proper set of cognitive tests for different subjects. Most current studies create guidelines of cognitive test selection for a targeted population, but they are not customized for each individual subject. In this manuscript, we develop a machine learning paradigm enabling personalized cognitive assessments prioritization. Method: We adapt a newly developed learning-to-rank approach PLTR to implement our paradigm. This method learns the latent scoring function that pushes the most effective cognitive assessments onto the top of the prioritization list. We also extend PLTR to better separate the most effective cognitive assessments and the less effective ones. Results: Our empirical study on the ADNI data shows that the proposed paradigm outperforms the state-of-the-art baselines on identifying and prioritizing individual-specific cognitive biomarkers. We conduct experiments in cross validation and level-out validation settings. In the two settings, our paradigm significantly outperforms the best baselines with improvement as much as 22.1% and 19.7%, respectively, on prioritizing cognitive features. Conclusions: The proposed paradigm achieves superior performance on prioritizing cognitive biomarkers. The cognitive biomarkers prioritized on top have great potentials to facilitate personalized diagnosis, disease subtyping, and ultimately precision medicine in AD.

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Optimizing Differential Identifiability Improves Connectome Predictive Modeling of Cognitive Deficits in Alzheimer's Disease

Functional connectivity, as estimated using resting state fMRI, has shown potential in bridging the gap between pathophysiology and cognition. However, clinical use of functional connectivity biomarkers is impeded by unreliable estimates of individual functional connectomes and lack of generalizability of models predicting cognitive outcomes from connectivity. To address these issues, we combine the frameworks of connectome predictive modeling and differential identifiability. Using the combined framework, we show that enhancing the individual fingerprint of resting state functional connectomes leads to robust identification of functional networks associated to cognitive outcomes and also improves prediction of cognitive outcomes from functional connectomes. Using a comprehensive spectrum of cognitive outcomes associated to Alzheimer's disease, we identify and characterize functional networks associated to specific cognitive deficits exhibited in Alzheimer's disease. This combined framework is an important step in making individual level predictions of cognition from resting state functional connectomes and in understanding the relationship between cognition and connectivity.

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Towards Subject and Diagnostic Identifiability in the Alzheimer's Disease Spectrum based on Functional Connectomes

Alzheimer's disease (AD) is the only major cause of mortality in the world without an effective disease modifying treatment. Evidence supporting the so called disconnection hypothesis suggests that functional connectivity biomarkers may have clinical potential for early detection of AD. However, known issues with low test-retest reliability and signal to noise in functional connectivity may prevent accuracy and subsequent predictive capacity. We validate the utility of a novel principal component based diagnostic identifiability framework to increase separation in functional connectivity across the Alzheimer's spectrum by identifying and reconstructing FC using only AD sensitive components or connectivity modes. We show that this framework (1) increases test-retest correspondence and (2) allows for better separation, in functional connectivity, of diagnostic groups both at the whole brain and individual resting state network level. Finally, we evaluate a posteriori the association between connectivity mode weights with longitudinal neurocognitive outcomes.

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