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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

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These pathological pathways are probably mediated, at least in part, through NLRP3 inflammasome stimulation and mitochondrial disruption

Neuropathologic substrates of Parkinson disease dementia