Non-Motor Symptom Progression in Parkinson's Disease — Mechanisms and Biomarkers

SUMMARY

# Non-Motor Symptom Progression in Parkinson's Disease — Mechanisms and Biomarkers ## Background and Rationale Parkinson's disease (PD) is characterized not only by motor dysfunction but also by debilitating non-motor symptoms (NMS) that significantly impact quality of life and often precede motor manifestations by years. This longitudinal clinical study investigates the progression mechanisms of five key NMS: depression, anxiety, REM sleep behavior disorder (RBD), constipation, and hyposmia (lo

METHODOLOGY NOTES

Phase 1 (Months 1-6): Recruit 400 PD patients and 100 age-matched controls through movement disorder clinics. Inclusion criteria: diagnosed PD (UK Brain Bank criteria), Hoehn-Yahr stages 1-3, age 45-80. Exclusion: dementia (MoCA<24), major psychiatric disorders, significant comorbidities. Phase 2 (Baseline assessment): Comprehensive NMS evaluation using MDS-UPDRS Part I, NMSS, Beck Depression/Anxiety Inventories, UPSIT olfactory test, Rome IV constipation criteria, and video-polysomnography for RBD. Collect CSF (15mL) and blood samples (30mL) for alpha-synuclein, neurofilament light, inflammatory cytokines analysis using ELISA and electrochemiluminescence. Perform 3T MRI including T1/T2-weighted, DTI, neuromelanin-sensitive sequences, and DaTscan SPECT imaging. Phase 3 (Follow-up, every 6 months for 60 months): Repeat clinical assessments and biomarker collection. Annual neuroimaging studies. Polysomnography repeated at 18-month intervals. Phase 4 (Data analysis): Apply machine learnin