Decoding Parkinson’s Disease through Behavioral Profiling and Plasma Biomarkers: A Clinical Approach to Differential Diagnosis and Prognosis

Objectives: Parkinson’s disease (PD) is a heterogeneous neurodegenerative condition characterized by both motor and systemic non-motor features. Engaging peripheral immune signatures in pathophysiology has recently gained attention; however, their prognostic and diagnostic roles remain to be better defined. This study investigatedlongitudinal behavioral and cognitive performance in PD alongside neuroinflammatory plasma signatures, with an emphasis on differentiating PD from Stiff-person syndrome (SPS) based on immune and clinical parameters. Material and Methods: One hundred and thirty-three PD participants were prospectively enrolled from Guru Gobind Singh Medical College, Faridkot. Standardized evaluations, including unified PD rating scale (UPDRS) motor and non-motor subscales and the PD-cognitive functional rating scale, were administered at baseline and on routine clinic follow-up. Plasma concentrations of Clusterin (CLU), glutamic acid decarboxylase (anti-GAD) antibody, and cyclic citrullinated peptide (anti-CCP) antibody were quantified by enzyme-linked immunosorbent assay. Relationships among biomarkers and clinical indices were examined through Pearson’s correlation coefficients, while hierarchical regression modeling served to elucidate independent prognostic trajectories. Distinction from SPS relied on stratigraphy of anti-GAD antibody titers in conjunction with divergent clinical and demographic features. Results: Follow-up assessments revealed marked reductions across all evaluated clinical domains (UPDRS-I: P < 0.001; UPDRS-II: P < 0.001; UPDRS-CF: P < 0.001; and PD cognition functional rating scale [PD-CFRS]: P < 0.001). Biomarker profiling demonstrated reliable declines in CLU concentration (from 125.68 ± 7.32 to 115.16 ± 7.69 µg/mL; P < 0.001) and anti-CCP antibody titers (from 36.47 ± 9.91 to 30.64 ± 9.66 EU/mL; P < 0.001). In contrast, anti-GAD antibody levels remained unchanged. Correlation analysis indicated a moderate positive relationship between anti-CCP concentrations and UPDRS-CF scores (r = 0.30). Hierarchical multiple regression revealed that baseline UPDRS-I (β = 0.256, P = 0.003) and UPDRS-II (β = 0.190, P = 0.029) independently predicted post-treatment with standard anti-Parkinson’s therapy UPDRS-CF levels. None of the enrolled subjects fulfilled clinical or serological criteria for SPS. Conclusion: These findings extend the current understanding of the interplay between plasma CLU, anti-CCP antibodies, and cognitive-behavioral deterioration in PD. The degree of motor and non-motor symptomatology at baseline emerges as a robust determinant of subsequent cognitive decline. Anti-GAD antibody screening retains its diagnostic value in differentiating Parkinson’s disease from SPS in ambiguous presentations. Cumulative use of plasma markers alongside clinical scoring systems strengthens both diagnostic accuracy and prognostic stratification in PD.