Clinical heterogeneity in patients with early-stage Parkinson’s disease:a cluster analysis

The aim of this study was to investigate the clinical heterogeneity of Parkinson's disease(PD) among a cohort of Chinese patients in early stages.Clinical data on demographics,motor variables,motor phenotypes,disease progression,global cognitive function,depression,apathy,sleep quality,constipation,fatigue,and L-dopa complications were collected from 138 Chinese PD subjects in early stages(Hoehn and Yahr stages 1-3).The PD subject subtypes were classified using k-means cluster analysis according to the clinical data from five-to three-cluster consecutively.Kappa statistical analysis was performed to evaluate the consistency among different subtype solutions.The cluster analysis indicated four main subtypes:the non-tremor dominant subtype(NTD,n=28,20.3%),rapid disease progression subtype(RDP,n=7,5.1%),young-onset subtype(YO,n=50,36.2%),and tremor dominant subtype(TD,n=53,38.4%).Overall,78.3%(108/138) of subjects were always classified between the same three groups(52 always in TD,7 in RDP,and 49 in NTD),and 98.6%(136/138) between five-and four-cluster solutions.However,subjects classified as NTD in the four-cluster analysis were dispersed into different subtypes in the three-cluster analysis,with low concordance between four-and three-cluster solutions(kappa value= 0.139,P=0.001).This study defines clinical heterogeneity of PD patients in early stages using a data-driven approach.The subtypes generated by the four-cluster solution appear to exhibit ideal internal cohesion and external isolation.