Validity Gates Expose Limits of Longitudinal Multimodal Parkinson Disease Prediction
Validity Gates Expose Limits of Longitudinal Multimodal Parkinson Disease Prediction
Publication status: preprint
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Original abstract
Multimodal Parkinson disease models can improve internally while obscuring why patients differ and whether a gain is deployable. We separated clinical trajectories, dated biological sources, observation process and cohort-relative, age-weighted evidence for dopaminergic, injury/glial, cognitive co-pathology and lysosomal burden across 5,404 cutoffs in 1,058 Parkinson's Progression Markers Initiative participants. DaT-SPECT and MoCA history produced a small 12-month motor-change gain (Delta R^2=0.015; delta MAE=-0.060) that failed prespecified magnitude and strict-calendar criteria. Continuous evidence retained overlapping support but showed no detectable predictive increment beyond raw sources. Source-aware intervals achieved 90.6% simultaneous participant coverage yet failed selective prediction, yielding ABSTAIN. In 8,000 semisynthetic experiments, the gate limited null promotion to 0.35%, detected leakage and blocked 94.75% of calendar reversals; PDBP clinical transport and multimodal eligibility failed. The framework reveals state support, stale or missing evidence, and unjustified prognostic, uncertainty or transport claims.