Temporal patterns of motor and nonmotor symptom emergence in Parkinson's disease: a cluster analysis.

Background: Parkinson's disease is a heterogeneous disorder characterized by a broad spectrum of motor and nonmotor symptoms. Recent studies suggest that the order of motor and nonmotor symptom development may indicate different subtypes of Parkinson's disease. However, the temporal occurrence patterns of these symptoms remain unclear. Objectives: This study aims to identify progression patterns of nonmotor symptoms and assess their relationships with the clinical characteristics of Parkinson's disease. Methods: We evaluated the prevalence and onset time of motor and nonmotor symptoms in 78 non-demented patients with Parkinson's disease with a disease duration of less than 10 years, all of whom completed questionnaires regarding the presence of these symptoms and the timing of their appearance. We performed a hierarchical cluster analysis based on onset age and the relative onset times of motor and nonmotor symptoms. We then compared clinical characteristics, and cortical morphological changes among the resulting subgroups. Cortical morphology was analyzed in a subset of patients with available brain imaging and was treated as a sub-analysis. Results: We identified three core clusters that exhibited different temporal patterns of symptom emergence in Parkinson's disease. Cluster 1 was an older-onset group with early sleep problems, poor cognitive function. Cluster 2 was a younger-onset group with typical prodromal nonmotor symptom, mostly constipation. Cluster 3 was another older-onset group with poor cognitive function and many nonmotor symptoms present after the onset of motor symptoms. Structural brain imaging was available for most participants (58/78), and a subset of Cluster 1 showed more pronounced cortical atrophy. Conclusions: Temporal patterns of nonmotor symptom emergence are heterogeneous and are highly influenced by onset age. Older-onset patients showed a higher burden of nonmotor symptoms and worse cognitive function, with symptom emergence occurring either before or after motor symptom onset. Characterizing these symptom-emergence patterns may help refine the clinical classification of Parkinson's disease and support more individualized evaluation and management.