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These models significantly improve diagnostic accuracy yet still face challenges in interpretability [198]

The MDS-UPDRS and CDR-SB cannot cleanly separate symptomatic relief from disease modification, and EVOKE showed the converse failure mode, biomarker movement without clinical benefit, so future trials should anchor on objective measures such as dopamine-transporter SPECT, neurofilament light chain, and tau, amyloid, and neuroinflammation PET