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Early-onset vs. Late-onset Parkinson’s disease: A Clinical-pathological Study

  • Leslie Wayne Ferguson (a1), Ali H. Rajput (a1) and Alexander Rajput (a1)


Background: Several studies have compared early-onset Parkinson disease (EOPD) and late-onset Parkinson disease (LOPD) but most are not based on autopsy confirmed cases. Methods: We compared clinical and pharmacological profiles, time to reach irreversible Hoehn and Yahr (H&Y) Stage 3 and levodopa motor complications in autopsy confirmed EOPD and LOPD cases. Results: At first clinic visit EOPD cases were younger but had longer disease duration and they died at a younger age (all p<0.0001). Anti-Parkinsonian drug use, including levodopa, was significantly delayed in EOPD. Lifetime use of amantadine (p<0.05) and dopamine agonists (p<0.01) were higher in EOPD. While lifetime use of levodopa was similar in the two groups, levodopa was used for a significantly longer period by EOPD (p< 0.0001). EOPD had a higher cumulative incidence of dyskinesias (p<0.01), wearing-off (p<0.01), and on-off (p<0.01). However, the time to dyskinesia onset was similar in the two groups. The threshold to wearing-off was much longer in EOPD (p<0.01). H&Y stage profile at first visit was similar in the two groups. The duration from disease onset to reach irreversible H&Y stage 3 was significantly longer in EOPD. Conclusions: Our observations indicate that progression of PD is slower in EOPD and suggest that the pre-clinical interval in this group is longer. These findings can be used for case selection for drug trials and studies of the pathogenesis of PD.

Maladie de Parkinson à début précoce et à début tardif : étude anatomo-clinique. Contexte: Plusieurs études ont comparé la maladie de Parkinson à début précoce (MPDP) et la maladie de Parkinson à début tardif (MPDT), mais la plupart de ces études ne reposent pas sur des cas dont le diagnostic a été confirmé en anatomopathologie. Méthode : Nous avons comparé les profiles cliniques et pharmacologiques, le délai pour atteindre le stade 3 irréversible à l’échelle de Hoehn and Yahr (H&Y) et les complications motrices du traitement par la lévodopa chez des cas de MPDP et de MPDT confirmés à l’autopsie. Résultats : Au moment de la première consultation, les cas de MPDP étaient plus jeunes, mais leur maladie durait depuis plus longtemps et ils sont morts plus jeunes (p<0,0001). L’utilisation de médicaments antiparkinsoniens, incluant la lévodopa, était significativement plus tardive chez les cas de MPDP. L’utilisation de l’amantadine au cours de la vie (p<0,05) et d’agonistes de la dopamine (p<0,01) étaient plus élevée chez les patients atteints de MPDP. Bien que la prise de lévodopa était similaire dans les deux groupes, la lévodopa avait été utilisée pendant plus longtemps par les patients atteints de MPDP (p<0,0001). L’incidence cumulative de dyskinésies était plus élevée chez les cas de MPDP (p<0,01), ainsi que les signes de l’épuisement de l’effet thérapeutique en fin de dose (p<0,01) et les fluctuations de la motricité, phénomène « on-off », (p<0,01). Cependant, le temps écoulé avant le début des dyskinésies était similaire dans les deux groupes. Le seuil de l’épuisement de l’effet thérapeutique était beaucoup plus long chez les patients atteints de la MPDP (p<0,01). Le profile du stade de H&Y à la première consultation était similaire dans les deux groupes. Le temps écoulé depuis le début de la maladie jusqu’au stade 3 irréversible de H&Y était significativement plus long chez les patients atteints de MPDP. Conclusions : Nos observations indiquent que la progression de la MP est plus lente chez les patients atteints de la MPDP ce qui suggère que l’intervalle préclinique est plus long chez ce groupe de patients. Ces observations peuvent être utilisées pour sélectionner les patients à inclure dans les essais thérapeutiques et les études sur la pathogenèse de la MP.

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This is an Open Access article, distributed under the terms of the creative commons attribution licence (, which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

Correspondence to Alexander Rajput, Division of Neurology, University of Saskatchewan, Room 1663, Royal University Hospital, 103 Hospital Drive, Saskatoon, Saskatchewan, Canada S7N 0W8. E-mail:


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1. Rajput, AH. Early onset parkinsonism. Adv Clin Neurosci. 1996;6:27-35.
2. Rajput, AH. Frequency and cause of Parkinson's disease. Can J Neurol Sci. 1992;19:103-107.
3. de Lau, LM, Breteler, MM. Epidemiology of Parkinson's disease. Lancet Neurol. 2006;5:525-535.
4. Quinn, N, Critchley, P, Marsden, C. Young onset Parkinson's disease. Mov Disord. 1987;2:73-91.
5. Schrag, A, Schott, JM. Epidemiological, clinical, and genetic characteristics of early-onset parkinsonism. Lancet Neurol. 2006;5:355-363.
6. Giovannini, P, Piccolo, I, Genitrini, S, et al. Early-onset Parkinson's disease. Mov Disord. 1991;6:36-42.
7. Gershanik, OS. Early onset parkinsonism. Front Biosci. 2003;8:s568-s578.
8. Gomez Arevalo, G, Jorge, R, Garcia, S, Scipioni, O, Gershanik, O. Clinical and pharmacological differences in early- versus late-onset Parkinson's disease. Mov Disord. 1997;12:277-284.
9. Golbe, L. Young-onset Parkinson's disease: a clinical review. Neurology. 1991;41:168-173.
10. Gibb, WRG, Lees, AJ. A comparison of clinical and pathological features of young- and old-onset Parkinson's disease. Neurology. 1988;38:1402-1406.
11. Bostantjopoulou, S, Logothetis, J, Katsarou, Z, Mentenopoulos, G. Clinical observations in early and late onset Parkinson's disease. Funct Neurol. 1991;6:145-149.
12. Friedman, A. Old-onset Parkinson's disease compared with young-onset disease: clinical differences and similarities. Acta Neurol Scand. 1994;89:258-261.
13. Wickremaratchi, MM, Ben-Shlomo, Y, Morris, HR. The effect of onset age on the clinical features of Parkinson's disease. Eur J Neurol. 2009;16:450-456.
14. Schrag, A, Ben-Shlomo, Y, Quinn, N. Cross sectional prevalence survey of idiopathic Parkinson's disease and parkinsonism in London. BMJ. 2000;321:21-22.
15. Selikhova, M, Williams, DR, Kempster, PA, Holton, JL, Revesz, T, Lees, AJ. A Clinico-pathological study of subtypes in Parkinson's disease. Brain. 2009;132:2947-2957.
16. Pantelatos, A, Fornadi, F. Clinical features and medical treatment of Parkinson's disease in patient groups selected in accordance with age at onset. Adv Neurol. 1993;60:690-697.
17. Rajput, AH, Rozdilsky, B, Rajput, A, Ang, L. Levodopa efficacy and pathological basis of Parkinson syndrome. Clin Neuropharmacol. 1990;13(6):553-558.
18. Kempster, PA, Williams, DR, Selikhova, M, Holton, J, Revesz, T, Lees, AJ. Patterns of levodopa response in Parkinson's disease: A clinico-pathological study. Brain. 2007;130:2123-2128.
19. Rajput, AH, Fenton, ME, Birdi, S, et al. Clinical-pathological study of levodopa complications. Mov Disord. 2002;17:289-296.
20. Kostic, V, Przedborski, S, Flaster, E, Sternic, N. Early development of levodopa-induced dyskinesias and response fluctuations in young-onset Parkinson's disease. Neurology. 1991;41:202-205.
21. Hughes, AJ, Daniel, SE, Kilford, L, Lees, AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: A clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992;55:181-184.
22. Rajput, AH, Rozdilsky, B, Rajput, A. Accuracy of clinical diagnosis in Parkinsonism - A prospective study. Can J Neurol Sci. 1991;18:275-278.
23. Hoehn, MM, Yahr, MD. Parkinsonism: onset, progression and mortality. Neurology. 1967;17:427-442.
24. Jankovic, J, Kapadia, AS. Functional decline in Parkinson disease. Arch Neurol. 2001;58:1611-1615.
25. Rajput, AH, Stern, W, Laverty, WH. Chronic low-dose levodopa therapy in Parkinson's disease: an argument for delaying levodopa therapy. Neurology. 1984;34:991-996.
26. Markham, CH, Diamond, SG. Evidence to support early levodopa therapy in Parkinson's disease. Neurology. 1981;31:121-131.
27. Webster, DD. Critical analysis of the disability in Parkinson's disease. Mod Treat. 1968;5:257-282.
28. Fahn, S, Elton, RL, UPDRSDevelopmentCommittee. Unified Parkinson's disease rating scale. In: Fahn S, Marsden CD, Calne D, Goldstein M, editors. Recent Developments in Parkinson's Disease. Florham Park, NJ: MacMillan Healthcare Information; 1987:153-305.
29. Rajput, AH, Uitti, RJ, Offord, KP. Timely levodopa (LD) administration prolongs survival in Parkinson's disease. Parkinsonism Relat Disord. 1997;3:159-165.
30. Goetz, CG, Poewe, W, Rascol, O, et al. Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations. Mov Disord. 2004;19:1020-1028.
31. Rajput, AH, Voll, A, Rajput, ML, Robinson, CA, Rajput, A. Course in Parkinson disease subtypes: A 39-year clinicopathologic study. Neurology. 2009;73:206-212.
32. Jellinger, K. The pathology of Parkinsonism. In: Marsden CD, Fahn S editors. Movement Disorders 2. London: Butterworth and Co,; 1987:124-165.
33. Gelb, DJ, Oliver, E, Gilman, S. Diagnostic criteria for Parkinson disease. Arch Neurol. 1999;56:33-39.
34. Duvoisin, R, Goble, LI. Toward a definition of Parkinson's disease. Neurology. 1989;39:746.
35. Gustavsson, EK, Trinh, J, Guella, I, et al. DNAJC13 genetic variants in parkinsonism. Mov Disord. 2015;30:273-278.
36. Dickson, DW, Braak, H, Duda, JE, et al. Neuropathological assessment of Parkinson's disease: Refining the diagnostic criteria. Lancet Neurol. 2009;8:1150-1157.
37. Foltynie, T, Brayne, C, Barker, RA. The heterogeneity of idiopathic Parkinson's disease. J Neurol. 2002;249:138-145.
38. Schrag, A, Ben-Shlomo, Y, Brown, R, Marsden, CD, Quinn, N. Young-onset Parkinson's disease revisited--clinical features, natural history, and mortality. Mov Disord. 1998;13:885-894.
39. Lewis, SJG, Foltynie, T, Blackwell, AD, Robbins, TW, Owen, AM, Barker, RA. Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry. 2005;76:343-348.
40. Marder, K, Levy, G, Louis, ED, et al. Familial aggregation of early- and late-onset Parkinson's disease. Ann Neurol. 2003;54:507-513.
41. Ferguson, LW, Rajput, ML, Muhajarine, N, Shah, SM, Rajput, A. Clinical features at first visit and rapid disease progression in Parkinson's disease. Parkinsonism Relat Disord. 2008;14:431-435.
42. Liu, P, Feng, T, Wang, YJ, Zhang, X, Chen, B. Clinical heterogeneity in patients with early-stage Parkinson's disease: a cluster analysis. J Zhejiang Univ Sci B. 2011;12:694-703.
43. Schrag, A, Quinn, NP, Ben-Shlomo, Y. Heterogeneity of Parkinson's disease. J Neurol Neurosurg Psychiatry. 2006;77:275-276.
44. Dauer, W, Przedborski, S. Parkinson's disease: mechanisms and models. Neuron. 2003;39:889-909.
45. Hindle, JV. Ageing, neurodegeneration and Parkinson's disease. Age Ageing. 2010;39:156-161.
46. Rajput, A, Uitti, RJ, Lang, AE, Rajput, AH. Amantadine (Amd) ameliorates levodopa (LD) induced dyskinesias (DK). Neurology. 1997;48:A328.
47. Uitti, RJ, Rajput, AH, Ahlskog, JE, et al. Amantadine treatment is an independent predictor of improved survival in Parkinson's disease. Neurology. 1996;46:1551-1556.
48. Spica, V, Pekmezovic, T, Svetel, M, Kostic, VS. Prevalence of non-motor symptoms in young-onset versus late-onset Parkinson's disease. J Neurol. 2013;260:131-137.
49. Reijnders, JS, Ehrt, U, Lousberg, R, Aarsland, D, Leentjens, AF. The association between motor subtypes and psychopathology in Parkinson's disease. Parkinsonism Relat Disord. 2009;15:379-382.
50. Jankovic, J. Motor fluctuations and dyskinesias in Parkinson's disease: clinical manifestations. Mov Disord. 2005;20 (Suppl 11):S11-S16.
51. Ku, S, Glass, GA. Age of Parkinson's disease onset as a predictor for the development of dyskinesia. Mov Disord. 2010;25:1177-1182.
52. Kumar, N, Van Gerpen, JA, Bower, JH, Ahlskog, JE. Levodopa-dyskinesia incidence by age of Parkinson's disease onset. Mov Disord. 2005;20(3):342-344.
53. Sato, K, Hatano, T, Yamashiro, K, et al. Prognosis of Parkinson's disease: Time to Stage III, IV, V and to motor fluctuations. Mov Disord. 2006;21:1384-1395.
54. Alves, G, Wentzel-Larsen, T, Aarsland, D, Larsen, JP. Progression of motor impairment and disability in Parkinson disease: a population-based study. Neurology. 2005;65:1436-1441.
55. Hely, MA, Morris, JG, Traficante, R, Reid, WG, O'Sullivan, DJ, Williamson, PM. The Sydney multicentre study of Parkinson's disease: progression and mortality at 10 years. J Neurol Neurosurg Psychiatry. 1999;67:300-307.
56. Kostic, VS, Marinkovic, J, Svetel, M, Stefanova, E, Przedborski, S. The effect of stage of Parkinson's disease at the onset of levodopa therapy on development of motor complications. Eur J Neurol. 2002;9:9-14.
57. Muller, J, Wenning, GK, Jellinger, K, McKee, A, Poewe, W, Litvan, I. Progression of Hoehn and Yahr stages in Parkinsonian disorders: a clinicopathologic study. Neurology. 2000;55:888-891.


Early-onset vs. Late-onset Parkinson’s disease: A Clinical-pathological Study

  • Leslie Wayne Ferguson (a1), Ali H. Rajput (a1) and Alexander Rajput (a1)


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