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

Ping LIU 1,Tao FENG 1,Yong-jun WANG 1,Xuan ZHANG 1,Biao CHEN 2(1 Department of Neurology,Beijing Tiantan Hospital,Capital Medical University,Beijing 100050,China)(2 Department of Neurology,Beijing Xuanwu Hospital,Capital Medical University,Beijing 100053,China)  
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.
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