Identifying the clusters within nonmotor manifestations in early Parkinson's disease by using unsupervised cluster analysis

Background: Classical and data-driven classifications of Parkinson's disease (PD) are based primarily on motor symptoms, with little attention being paid to the clustering of nonmotor manifestations. Methods: Clinical data on demographic, motor and nonmotor features, including the Korean version of the sniffin' stick (KVSS) test results, and responses to the screening questionnaire of the nonmotor features were collected from 56 PD patients with disease onset within 3 years. Nonmotor subgroups were classified using unsupervised hierarchical cluster analysis (HCA). In addition to unsupervised HCA, we performed a cross-sectional analysis comparing the performance on the KVSS olfactory test with other nonmotor manifestations of the patients. Results: Forty-nine patients (87.5%) had hyposmia based on the KVSS test. HCA suggested three nonmotor clusters for all PD patients and two nonmotor clusters in de novo PD patients, without a priori assumptions about the relatedness. In the cross-sectional analysis, drem-enactment behavior was more prevalent in patients with lower olfactory scores, implying impaired olfactory function (P = 0.029 for all PD patients; P = 0.046 for de novo PD patients). Conclusion: We propose the existence of different clusters of nonmotor manifestations in early PD by using unsupervised hierarchical clustering. To our knowledge, this study is the first to report the identification of nonmotor subgroups based on unsupervised HCA of multiple nonmotor manifestations in the early stage of the disease.