Chronology of Non-Motor Symptoms in 100 Patients with Advanced PD of 10 Years’ Duration: Pre- versus Post-Motor Period

BACKGROUND: Parkinson's disease (PD) is characterized by motor and non-motor symptoms (NMS) due to alpha-synuclein aggregation in the central and peripheral nervous system. There is limited data on the temporal evolution of NMS in patients with long-standing PD. OBJECTIVE: To elucidate the chronology of the evolution of NMS in patients with long-standing PD. METHODS: This single-centre cross-sectional study was conducted at a tertiary care centre from May 2023 to December 2024. Patients with clinically diagnosed idiopathic PD of at least 10 years" duration were recruited, and the chronology of the evolution of NMS was characterized. RESULTS: One hundred patients with PD (68% male) were recruited, with a mean age at assessment of 58.8 ± 9.7 years, an age at onset of 45.7 ± 10.1 years and a disease duration of 13.2 ± 3.3 years. Six percent of the patients did not develop any NMS despite the long duration of the illness. Rapid eye movement sleep behavioural disorder (RBD) (63%) was the most frequent NMS, followed by constipation (59%) and urinary dysfunction (55%). Pre-motor onset of NMS was present in 24% of the patients, with RBD (8%) and constipation (8%) being the most frequent. Post-motor onset was observed in 70% of cases. Based on the pre- or post-motor onset of RBD, patients were classified into two subtypes: body-first (8%) and brain-first (84%) PD subtypes. CONCLUSION: This study highlights the distinct trajectories of NMS evolution in PD. While the majority developed at least one NMS, the occurrence of pre-motor NMS was present in about one-fourth. The body-first subtype, characterized by pre-motor RBD, was distinctly uncommon.