Structural Medicine v2.0: Neurodegeneration as a Potential Critical Structural Transition with Predictive Signatures

This study presents Structural Medicine v2.0, a time-dependent framework for analyzing neurodegenerative progression as a potential critical structural transition. Using longitudinal cognitive data, we define structural persistence F(t) and derive a local structural decay rate λ(t). We introduce directional asymmetry A as a structural indicator and demonstrate its association with time to conversion, conversion-free probability, and hazard risk. We further identify pre-conversion dynamical signatures, including variance instability and rising lag-1 autocorrelation, consistent with early-warning signals observed in complex systems approaching critical transitions. A schematic potential-landscape model is proposed to provide a possible mechanistic interpretation of directional asymmetry, linking structural fluctuations to asymmetric collapse dynamics. Sensitivity analyses show that predictive performance is robust to MMSE ceiling effects, supporting the validity of the structural indicators. Overall, the results suggest that neurodegeneration may be interpreted as a potential critical structural transition with measurable predictive signatures, offering a foundation for time-dependent risk prediction and predictive structural medicine. All figures are included, and a Python script is provided to generate schematic reproductions for illustration purposes.