Disease progression and phenotypes of non‐motor symptoms in Parkinson’s disease

Background Motor symptoms, non‐motor symptoms, and treatment‐related motor complications appear during the course of Parkinson's disease. Aim To observe the progression of all symptoms related to Parkinson's disease including prodromal non‐motor symptoms, motor symptoms, treatment‐related motor complications, and non‐motor symptoms. Methods We assessed 201 patients with Parkinson's disease. The reviewed symptoms included all of the motor and non‐motor symptoms listed in the Movement Disorder Society‐Parkinson's disease criteria and other non‐motor symptoms such as pain, fatigue, and apathy. According to established criteria, the presence of each symptom was coded. If present, latencies were calculated by months. To identify representative non‐motor symptoms, we performed non‐hierarchical and hierarchical cluster analyses. Results We observed the presence of prodromal non‐motor symptoms and the progression of motor symptoms, treatment‐related complications, and non‐motor symptoms. Regarding the non‐motor symptoms, a comparison of the results from the two sets of cluster analysis led to the identification of six subgroups: “pain,” “constipation,” “depression and insomnia,” “hyposmia,” “daytime urinary urgency and symptomatic orthostatic hypotension,” and “excessive daytime somnolence, rapid eye movement sleep behavioral disorder, hallucinations, and dementia.” Conclusions In some patients, Parkinson's disease starts from the extra‐striatonigral pathway. Apart from the motor symptoms and treatment‐related complications, the non‐motor symptoms progress independently in several directions, as a result of non‐dopaminergic dysfunction, outside the nigrostriatal pathway.