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Journal of Zhejiang University SCIENCE B 2011 Vol.12 No.9 P.694-703


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

Author(s):  Ping Liu, Tao Feng, Yong-jun Wang, Xuan Zhang, Biao Chen

Affiliation(s):  Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China, Department of Neurology, Beijing Xuanwu Hospital, Capital Medical University, Beijing 100053, China

Corresponding email(s):   happyft@sina.com

Key Words:  Parkinson’, s disease, Heterogeneity, Subtype, Cluster analysis

Ping Liu, Tao Feng, Yong-jun Wang, Xuan Zhang, Biao Chen. Clinical heterogeneity in patients with early-stage Parkinson’s disease: a cluster analysis[J]. Journal of Zhejiang University Science B, 2011, 12(9): 694-703.

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%T Clinical heterogeneity in patients with early-stage Parkinson’s disease: a cluster analysis
%A Ping Liu
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%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1100069

T1 - Clinical heterogeneity in patients with early-stage Parkinson’s disease: a cluster analysis
A1 - Ping Liu
A1 - Tao Feng
A1 - Yong-jun Wang
A1 - Xuan Zhang
A1 - Biao Chen
J0 - Journal of Zhejiang University Science B
VL - 12
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SP - 694
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B1100069

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.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Chaudhuri, K.R., Naidu, Y., 2008. Early Parkinson’s disease and non-motor issues. J. Neurol., 255(s5):33-38.

[2]Chaudhuri, K.R., Healy, D.G., Schapira, A.H., 2006. Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol., 5(3):235-245.

[3]Everitt, B.S., Landau, S., Leese, M., 2001. Cluster Analysis, 4th Ed. Hodder Headline Group, London.

[4]Fahn, S., Elton, R.L., Members of the UPDRS Development Committee, 1987. Unified Parkinson’s Disease Rating Scale. In: Fahn, S., Marsden, C.D., Calne, D.B., Goldstein, M., (Eds.), Recent Developments in Parkinson’s Disease. Vol. 2, McMillan Health Care Information, Florham Park, New Jersey, p.153-163.

[5]Folstein, M.F., Folstein, S.E., McHugh, P.R., 1975. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res., 12(3):189-198.

[6]Foltynie, T., Brayne, C., Barker, R.A., 2002. The heterogeneity of idiopathic Parkinson’s disease. J. Neurol., 249(2):138-145.

[7]Gibb, W.R., Lees, A.J., 1988. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry, 51(6):745-752.

[8]Giovannini, P., Piccolo, I., Genitrini, S., Soliveri, P., Girotti, F., Geminiani, G., Scigliano, G., Caraceni, T., 1991. Early-onset Parkinson’s disease. Mov. Disord., 6(1):36-42.

[9]Golbe, L.I., 1993. Risk factors in young-onset Parkinson’s disease. Neurology, 43(9):1641-1643.

[10]Graham, J.M., Sagar, H.J., 1999. A data-driven approach to the study of heterogeneity in idiopathic Parkinson’s disease: identification of three distinct subtypes. Mov. Disord., 14(1):10-20.

[11]Hamilton, M., 1960. A rating scale for depression. J. Neurol. Neurosurg. Psychiatry, 23(1):56-62.

[12]Harrison, M.B., Wylie, S.A., Frysinger, R.C., Patrie, J.T., Huss, D.S., Currie, L.J., Wooten, G.F., 2009. UPDRS activity of daily living score as a marker of Parkinson’s disease progression. Mov. Disord., 24(2):224-230.

[13]Hoehn, M.M., Yahr, M.D., 1967. Parkinsonism: onset, progression and mortality. Neurology, 17(5):427-442.

[14]Hughes, A.J., Daniel, S.E., Blankson, S., Lees, A.J., 1993. A clinicopathologic study of 100 cases of Parkinson’s disease. Adv. Neurol., 50(2):140-148.

[15]Jankovic, J., McDermott, M., Carter, J., Gauthier, S., Goetz, C., Golbe, L., Huber, S., Koller, W., Olanow, C., Shoulson, I., et al., 1990. Variable expression of Parkinson’s disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group. Neurology, 40(10):1529-1534.

[16]Jellinger, K.A., 2002. Recent developments in the pathology of Parkinson’s disease. J. Neural Transm. Suppl., (62):347-376.

[17]Krupp, L.B., LaRocca, N.G., Muir-Nash, J., Steinberg, A.D., 1989. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch. Neurol., 46(10):1121-1123.

[18]Lewis, S.J., Dove, A., Robbins, T.W., Barker, R.A., Owen, A.M., 2003. Cognitive impairments in early Parkinson’s disease are accompanied by reductions in activity in frontostriatal neural circuitry. J. Neurosci., 23(15):6351-6356.

[19]Lewis, S.J., Foltynie, T., Blackwell, A.D., Robbins, T.W., Owen, A.M., Barker, R.A., 2005. Heterogeneity of Parkinson’s disease in the early clinical stages using a data driven approach. J. Neurol. Neurosurg. Psychiatry, 76(3):343-348.

[20]Li, G., Shen, Y.C., Chen, C.H., Li, S.R., Zhao, Y.W., Liu, M., Xu, L., Wang, L.X., Wang, Q., 1988. Preliminary application of MMSE in the aged of urban population in Beijing. Chin. Mental Health J., 2(1):13-18 (in Chinese).

[21]Nazem, S., Siderowf, A.D., Duda, J.E., Have, T.T., Colcher, A., Horn, S.S., Moberg, P.J., Wilkinson, J.R., Hurtig, H.I., Stern, M.B., et al., 2009. Montreal cognitive assessment performance in patients with Parkinson’s disease with “normal” global cognition according to mini-mental state examination score. J. Am. Geriatr. Soc., 57(2):304-308.

[22]Post, B., Speelman, J.D., de Haan, R.J., 2008. Clinical heterogeneity in newly diagnosed Parkinson’s disease, J. Neurol., 255(5):716-722.

[23]Reijnders, J.S., Ehrt, U., Lousberg, R., Aarsland, D., Leentjens, A.F., 2009. The association between motor subtypes and psychopathology in Parkinson’s disease. Parkinsonism Relat. Disord., 15(5):379-382.

[24]Selikhova, M., Williams, D.R., Kempster, P.A., Holton, J.L., Revesz, T., Lees, A.J., 2009. A clinico-pathological study of subtypes in Parkinson’s disease. Brain, 132(Pt 11):2947-2957.

[25]Smyth, C., 2003. The pittsburgh sleep quality index. Dermatol. Nurs., 15(2):195-196.

[26]Thompson, W.G., Longstreth, G.F., Drossman, D.A., Heaton, K.W., Irvine, E.J., Muller-Lissner, S.A., 1999. Functional bowel disorders and functional abdominal pain. Gut, 45(Suppl. 2):II43-II47.

[27]van Rooden, S.M., Visser, M., Verbaan, D., Marinus, J., van Hilten, J.J., 2009a. Motor patterns in Parkinson’s disease: a data-driven approach. Mov. Disord., 24(7):1042-1047.

[28]van Rooden, S.M., Visser, M., Verbaan, D., Marinus, J., van Hilten, J.J., 2009b. Patterns of motor and non-motor features in Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry, 80(8):846-850.

[29]van Rooden, S.M., Heiser, W.J., Kok, J.N., Verbaan, D., van Hilten, J.J., Marinus, J., 2010. The identification of Parkinson’s disease subtypes using cluster analysis: a systematic review. Mov. Disord., 25(8):969-978.

[30]Williams, L.N., Seignourel, P., Crucian, G.P., Okun, M.S., Rodriguez, R.L., Skidmore, F.M., Foster, P.S., Jacobson, C.E.4th, Romrell, J., Bowers, D., et al., 2007. Laterality, region, and type of motor dysfunction correlate with cognitive impairment in Parkinson’s disease. Mov. Disord., 22(1):141-145.

[31]Zetusky, W.J., Jankovic, J., Pirozzolo, F.J., 1985. The heterogeneity of Parkinson’s disease: clinical and prognostic implications. Neurology, 35(4):522-526.

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