Abstract
Objective
To determine clinical heterogeneity in newly diagnosed Parkinson’s disease using cluster analysis and to describe the subgroups in terms of impairment, disability, perceived quality of life, and use of dopaminergic therapy.
Methods
We conducted a k-means cluster analysis in a prospective hospital based cohort of 133 patients with newly diagnosed Parkinson’s disease. Variables selected for the cluster analysis were age of disease onset, age at the moment of examination, rate of disease progression, levodopa responsive PD symptoms and levodopa non-responsive PD symptoms, cognition (mini-mental state examination) and emotional functioning (hospital anxiety depression scale). In addition, the homogeneous subgroups identified were clinically validated using descriptive statistics.
Results
Cluster analysis with a two-cluster solution identified a younger and older age group. The three-cluster solution identified an intermediate group with respect to age. In both cluster solutions the older the onset group, the higher the progression rate and the level of motor impairments. The intermediate older onset group in the three cluster solution was characterized by more anxiety and depressive symptoms. Increasing age at disease onset was significantly associated with higher Hoehn and Yahr stages, level of disability and lower perceived quality of life.
Conclusions
We hypothesize there are three distinct subgroups in patients with newly diagnosed PD: a younger onset group, an intermediate older onset group with more anxiety and depressive symptoms and an oldest onset group with more motor impairment and higher rate of progression.
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References
Aaronson NK, Muller M, Cohen PD, Essink-Bot ML, Fekkes M, Sanderman R, Sprangers MA, te VA, Verrips E (1998) Translation, validation, and norming of the Dutch language version of the SF-36 Health Survey in community and chronic disease populations. J Clin Epidemiol 51:1055–1068
Bjelland I, Dahl AA, Haug TT, Neckelmann D (2002) The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res 52:69–77
Bosboom JL, Stoffers D, Wolters EC (2004) Cognitive dysfunction and dementia in Parkinson’s disease. J Neural Transm 111:1303–1315
Bostantjopoulou S, Logothetis J, Katsarou Z, Mentenopoulos G (1991) Clinical observations in early and late onset Parkinson’s disease. Funct Neurol 6:145–149
Cockrell JR, Folstein MF (1988) Mini- Mental State Examination (MMSE). Psychopharmacol Bull 24:689–692
Defer GL, Widner H, Marie RM, Remy P, Levivier M (1999) Core assessment program for surgical interventional therapies in Parkinson’s disease (CAPSIT-PD). Mov Disord 14:572–584
Esselink RA, de Bie RM, de Haan RJ, Lenders MW, Nijssen PC, Staal MJ, Smeding HM, Schuurman PR, Bosch DA, Speelman JD (2004) Unilateral pallidotomy versus bilateral subthalamic nucleus stimulation in PD: a randomized trial. Neurology 62:201–207
Everitt BS (1995) Commentary: classification and cluster analysis. BMJ 311:535–536
Fahn S, Elton RL, Members of the UPDRS Development Committee (1987) Unified Parkinson’s Disease Rating Scale. In: Fahn S, Marsden CD, Calne DB (eds) Recent developments in Parkinson’s disease. Macmillan Healthcare Information, Florham Park, NJ, pp 153, 163, 293, 304
Foltynie T, Brayne C, Barker RA (2002) The heterogeneity of idiopathic Parkinson’s disease. J Neurol 249:138–145
Gelb DJ, Oliver E, Gilman S (1999) Diagnostic criteria for Parkinson disease. Arch Neurol 56:33–39
Goetz Cc (2006) New MDS-UPDRS working document. Presented at the first International World Parkinson’s disease Congress Washington
Graham JM, Sagar HJ (1999) A data-driven approach to the study of heterogeneity in idiopathic Parkinson’s disease: identification of three distinct subtypes. Mov Disord 14:10–20
Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442
Holman R, Weisscher N, Glas CA, Dijkgraaf MG, Vermeulen M, de Haan RJ, Lindeboom R (2005) The Academic Medical Center Linear Disability Score (ALDS) item bank: item response theory analysis in a mixed patient population. Health Qual Life Outcomes 3:83
Levy G, Tang MX, Cote LJ, Louis ED, Alfaro B, Mejia H, Stern Y, Marder K (2000) Motor impairment in PD: relationship to incident dementia and age. Neurology 55:539–544
Lewis SJ, Foltynie T, Blackwell AD, Robbins TW, Owen AM, Barker RA (2005) Heterogeneity of Parkinson’s disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry 76:343–348
Lindeboom R, Vermeulen M, Holman R, de Haan RJ (2003) Activities of daily living instruments: optimizing scales for neurologic assessments. Neurology 60:738–742
Marinus J, Leentjens AF, Visser M, Stiggelbout AM, van Hilten JJ (2002) Evaluation of the hospital anxiety and depression scale in patients with Parkinson’s disease. Clin Neuropharmacol 25:318–324
Marras C, Rochon P, Lang AE (2002) Predicting motor decline and disability in Parkinson disease: a systematic review. Arch Neurol 59:1724–1728
McHorney CA, Ware JE Jr, Raczek AE (1993) The MOS 36-Item Short-Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care 31:247–263
Post B, Merkus MP, de Haan RJ, Speelman JD (2007) Prognostic factors for the progression of Parkinson’s disease: A systematic review. Mov Disord 22(13):1839–1851
Reider CR, Halter CA, Castelluccio PF, Oakes D, Nichols WC, Foroud T (2003) Reliability of reported age at onset for Parkinson’s disease. Mov Disord 18:275–279
Samii A, Nutt JG, Ransom BR (2004) Parkinson’s disease. Lancet 363:1783–1793
Schrag A, Quinn NP, Ben-Shlomo Y (2006) Heterogeneity of Parkinson’s disease. J Neurol Neurosurg Psychiatry 77:275–276
Suchowersky O, Reich S, Perlmutter J, Zesiewicz T, Gronseth G, Weiner WJ (2006) Practice Parameter: diagnosis and prognosis of new onset Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 66:968–975
Zetusky WJ, Jankovic J, Pirozzolo FJ (1985) The heterogeneity of Parkinson’s disease: clinical and prognostic implications. Neurology 35:522–526
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Participants in the CARPA study group: Janneke M. Stolwijk-Swuste, Anita Beelen, Frans Nollet, Gaby M. van Dijk, C.H.M. van den Ende, Bart Post, Rob J. de Haan, Johannes D. Speelman, J. Dekker and Guus J. Lankhorst
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Post, B., Speelman, J.D., de Haan, R.J. et al. Clinical heterogeneity in newly diagnosed Parkinson’s disease. J Neurol 255, 716–722 (2008). https://doi.org/10.1007/s00415-008-0782-1
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DOI: https://doi.org/10.1007/s00415-008-0782-1