Abstract
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.
Similar content being viewed by others
References
Chaudhuri, K.R., Naidu, Y., 2008. Early Parkinson’s disease and non-motor issues. J. Neurol., 255(s5):33–38. [doi: 10.1007/s00415-008-5006-1]
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. [doi:10.1016/S1474-4422(06)70373-8]
Everitt, B.S., Landau, S., Leese, M., 2001. Cluster Analysis, 4th Ed. Hodder Headline Group, London.
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.
Folstein, M.F., Folstein, S.E., McHugh, P.R., 1975. “Minimental state”. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res., 12(3):189–198. [doi:10.1016/0022-3956(75)90026-6]
Foltynie, T., Brayne, C., Barker, R.A., 2002. The heterogeneity of idiopathic Parkinson’s disease. J. Neurol., 249(2): 138–145. [doi:10.1007/PL00007856]
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. [doi:10.1136/jnnp.51.6.745]
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. [doi: 10.1002/mds.870060107]
Golbe, L.I., 1993. Risk factors in young-onset Parkinson’s disease. Neurology, 43(9):1641–1643.
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. [doi:10.1002/1531-8257(199901)14:1〈10::AID-MDS1005〉3.0.CO;2-4]
Hamilton, M., 1960. A rating scale for depression. J. Neurol. Neurosurg. Psychiatry, 23(1):56–62. [doi:10.1136/jnnp.23.1.56]
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. [doi:10.1002/mds.22335]
Hoehn, M.M., Yahr, M.D., 1967. Parkinsonism: onset, progression and mortality. Neurology, 17(5):427–442.
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.
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.
Jellinger, K.A., 2002. Recent developments in the pathology of Parkinson’s disease. J. Neural Transm. Suppl., (62): 347–376.
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.
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.
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. [doi:10.1136/jnnp.2003.033530]
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).
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. [doi:10.1111/j.1532-5415.2008.02096.x]
Post, B., Speelman, J.D., de Haan, R.J., 2008. Clinical heterogeneity in newly diagnosed Parkinson’s disease, J. Neurol., 255(5):716–722. [doi:10.1007/s00415-008-0782-1]
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. [doi:10.1016/j.parkreldis.2008.09.003]
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. [doi:10.1093/brain/awp234]
Smyth, C., 2003. The pittsburgh sleep quality index. Dermatol. Nurs., 15(2):195–196.
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. [doi:10.1136/gut.45.2008.ii43]
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. [doi:10.1002/mds.22512]
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. [doi:10.1136/jnnp.2008.166629]
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. [doi: 10.1002/mds.23116]
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. [doi:10.1002/mds.21220]
Zetusky, W.J., Jankovic, J., Pirozzolo, F.J., 1985. The heterogeneity of Parkinson’s disease: clinical and prognostic implications. Neurology, 35(4):522–526.
Author information
Authors and Affiliations
Corresponding author
Additional information
Project (No. 2006AA02A408) supported by the National High-Tech R & D Program (863) of China
Rights and permissions
About this article
Cite this article
Liu, P., Feng, T., Wang, Yj. et al. Clinical heterogeneity in patients with early-stage Parkinson’s disease: a cluster analysis. J. Zhejiang Univ. Sci. B 12, 694–703 (2011). https://doi.org/10.1631/jzus.B1100069
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1631/jzus.B1100069