Data-driven causal model discovery and personalized prediction in Alzheimer's disease

Area of Science:

• Computational biology
• Neuroscience
• Biostatistics

Background:

• Alzheimer's disease (AD) research generates vast biomarker data, necessitating robust modeling techniques.
• Existing mathematical models for AD biomarkers are often empirical or based on pre-existing hypotheses of disease pathophysiology.
• Deriving causal models and parameters purely from data, without hypothesis bias, remains a significant challenge in computational modeling.

Purpose of the Study:

• To develop and validate an innovative, data-driven approach for constructing and parameterizing causal models of Alzheimer's disease biomarker trajectories.
• To overcome limitations of hypothesis-driven and purely empirical modeling in computational causal modeling for AD.
• To enable personalized prediction of disease progression using learned causal relationships.

Main Methods:

• Developed an integrated computational approach combining causal model learning, population parameterization, and parameter sensitivity analysis.
• Applied the methodology to the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, a large multicenter collection of AD biomarker data.
• Incorporated personalized prediction capabilities for individual subject modeling.

Main Results:

• Successfully revealed several data-driven causal models characterizing biomarker trajectories across different stages of Alzheimer's disease.
• Demonstrated the calibration of personalized models for individual subjects within the study cohort.
• Achieved accurate predictions of future cognitive status based on the developed personalized models.

Conclusions:

• The proposed data-driven modeling approach effectively builds and parameterizes causal models for Alzheimer's disease biomarkers.
• This methodology facilitates a deeper understanding of AD pathophysiology and biomarker dynamics.
• Personalized models derived from this approach show promise for accurate prediction of cognitive decline in Alzheimer's disease patients.