Parkinson’s Disease

  • Nages Nagaratnam
  • Kujan Nagaratnam
  • Gary Cheuk
Reference work entry


Parkinson’s disease is a progressive disorder caused by degeneration of the dopaminergic neurons of the substantia nigra. Years before the substantia nigra compacta (SNc) and cortex are involved, there is pathological evidence of PD in the medulla oblongata, pontine tegmentum and olfactory bulb. The motor problems can be preceded by several years by subtle clinical symptoms such as rapid eye movement sleep behaviour and hyposmia during the prodromal period of PD. The striatonigral pathway plays a regulatory role in the system of positive and negative pathways that serve to modulate feedback from the thalamus to the motor cortex. This chapter reviews PD with emphasis on the age of onset. Parkinson’s disease usually begins in middle to late life (LOPD). In about 5–10%, PD begins before the age of 50 (EOPD). There are some distinguishing features between both.


Parkinson’s disease Glucocerebrosidase (GBA) gene mutations Late-onset Pompe disease (LOPD) Early-onset Pompe disease (EOPD) Lewy bodies Striatonigral pathway Secondary parkinsonism 


  1. 1.
    Obeso JA, Rodriguez-Oroz MC, Benitez-Temino B, Blesa FJ, Guridi J, Marin C, et al. Functional organisation of the basal ganglia: therapeutic implications for Parkinson’s disease. Mov Disord. 2008;23 Suppl 3:S548–59.CrossRefPubMedGoogle Scholar
  2. 2.
    Weinberge M, Hutchison WD, Lozano AM, Hodale M,Dostrovsky JO. Increased gamma oscillatory activity in the subthalamic nucleus during tremor in Parkinson’s disease patients. J Neurophysiol. 2009;101(2);789–02.CrossRefGoogle Scholar
  3. 3.
    Dickson DW. Parkinson’s disease and Parkinsonism: Neuropathology. Cold Spring Harbor Perspectives in Medicine. 2012.Cold Spring Laboratory Press. .Google Scholar
  4. 4.
    Thomas B, Beal MF. Parkinson’s disease Hum Mol Geriatr. 2007;16(Spec No2):R183–R194.CrossRefGoogle Scholar
  5. 5.
    Schapira AHV. Recent advances in neurology 2013–2014; Eur J Neurol 2014;21:1425–1434.CrossRefPubMedGoogle Scholar
  6. 6.
    Nakamura K, Edwards RH. Physiology versus pathology in Parkinson’s disease. Proc Nat Acad. Sci.
  7. 7.
    Chua CE, Tang BL. Alpha-synuclein and Parkinson’s disease: the first road block. J Cell Mol Med. 2006;10(4):837–s.CrossRefPubMedGoogle Scholar
  8. 8.
    Glasson BI, Lee VM-Y. Parkin and molecular pathways of Parkinson’s disease. Neuron. 2001;31(6):885–888.CrossRefGoogle Scholar
  9. 9.
    Dauer W, Przedborski S. Parkinson’s Disease. Neuron. 2003;39(6):889–909.CrossRefPubMedGoogle Scholar
  10. 10.
    Outeiro TF, Lopes LV. Synaptic dysfunction in Parkinson’s disease: From protein misfolding to functional alterations. Folding for the synapse. Andreas Wyttenbach, Vincent O’Connor. Springer US. 2011;257–267.CrossRefGoogle Scholar
  11. 11.
    Schapira AHV. Etiology of Parkinson’s disease. Neurology. 2006;66(10): suppl 4 S10–S23.CrossRefPubMedGoogle Scholar
  12. 12.
    Bergman H, Deuschl G, Pathophysiology of Parkinson’s disease: from clinical neurology to basic neuroscience and back. Mov Disord. 2002;17 Suppl 3:S28–40.CrossRefPubMedGoogle Scholar
  13. 13.
    Rivlin-Etzion M, Marmor O, Heimer G, Raz A, Nini A, Bergman H. Basal ganglia oscillations and pathophysiology of movement. Curr Opin Neurobiol. 2006;16(6):629–37.CrossRefPubMedGoogle Scholar
  14. 14.
    Hornykiewicz O. Dopamine (3 hydroxytyramine) and function. Pharmacol Rev. 1966;1892:825–64.Google Scholar
  15. 15.
    Bergman H, Wichmann T, Karmon R, De Long MR. The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. J Neurophysiol. 1994;72:507–20.CrossRefPubMedGoogle Scholar
  16. 16.
    Smith Y, Bevan MD, Shink E, Bolam JP. Microcircuitry of direct and indirect pathways of the basal ganglia. Neuroscience. 1998;86 (2):353–397.CrossRefPubMedGoogle Scholar
  17. 17.
    Braak H, Del Tredici K, Rub U, de os RN, Steur E, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003;24:197–211.CrossRefPubMedGoogle Scholar
  18. 18.
    Bostantjopulou S, Logothetis J, Katsarou Z, Mentenopoulos G. Clinical observations in early and late onset Parkinson’s disease. Funct Neurol. 1994;6(2):145–9.Google Scholar
  19. 19.
    Giovannini P, Piccolo I, Genitrini S, Soliveri P, Girotti F, Geminiani G, et al. Early-onset Parkinson’s disease. Mov Disord. 1991;6(1):36–42.CrossRefPubMedGoogle Scholar
  20. 20.
    Arevalo GG, Jorge R, Garcia O, Scipioni G, Gershaniko O. Clinical and pharmacological differences in early versus late-onset Parkinson’s disease. Mov Disord. 1997; 12:277–284.CrossRefGoogle Scholar
  21. 21.
    Friedman A. Old-onset Parkinson’s disease comparted with young-onset disease: clinical differences and similarities. Acta Neurol Scand. 1994; 89(4): 258–61.CrossRefPubMedGoogle Scholar
  22. 22.
    Hindle JV. Ageing neurodegeneration and Parkinson’s disease. Age and Ageing. 2010;39(2):156–161CrossRefPubMedGoogle Scholar
  23. 23.
    Tang H, Huang J, Nie K, Gan R,Wang L, Zhao J, et al. Cognitive profile of Parkinson’s disease patients: a comparative study between early onset and late onset Parkinson’s disease. Int J Neurosci.
  24. 24.
    Bertucci Fiho D, Teive HA, Werneck LC. Early-onset Parkinson’s disease and depression. Arg Neuropsiquiatr. 2007;65(1):5–10.CrossRefGoogle Scholar
  25. 25.
    Parkinson’s Disease Foundation. Parkinson’s Disease symptoms vary with age of disease onset. Accessed 27 October 2015.
  26. 26.
    Mehanna R, Moore S, Hou JG, Sarwar A, Lai EC. Comparing clinical features of young-onset, middle-onset and late-onset Parkinson’s Disease. Baylor College of Medicine.Google Scholar
  27. 27.
    Fereshtehnejad S-M, Hadizadeh H, Farhadi F, Shahidi GA, Delbari A, Lokk J. Comparison of the psychological symptoms and disease-specific quality of life between early and typical onset Parkinson’s disease patients. Parkinson’s Disease Vol 2014 (2014) Article ID 819260 7 pages.
  28. 28.
    Ramaker C, Marinus J, Stiggelbout AM, van Hilten BJ. Systematic evaluation of rating scales for impairment and disability in Parkinson’s Disease. Mov Disord. 2002;17(5):867–976.CrossRefPubMedGoogle Scholar
  29. 29.
    Rascol O, Lozano A, Stern M, Poewe W. Milestones in Parkinson’s disease therapeutics. Mov Disord. 2011;26(6):102–82.CrossRefGoogle Scholar
  30. 30.
    Lang AE, Lozano AM. Parkinson’s disease: first of two parts. N Engl J Med. 1998; 339(15):1044–53.CrossRefPubMedGoogle Scholar
  31. 31.
    Lang AE, Lozano AM. Parkinson’s disease: second of two parts. N Engl J Med. 1998; 339 (16)1130–43.CrossRefPubMedGoogle Scholar
  32. 32.
    Giladi N, Boroojerdi B, Korczyn AD, Burn DJ,Clarke CE,Schapira AH, SP513 Investigators. Rotigotine transdermal patch in early Parkinson’s disease: a randomized double-blind controlled study versus placebo and ropinirole. Mov Disord. 2007;22:2398–2404.CrossRefPubMedGoogle Scholar
  33. 33.
    Hauser RA, Schapira AH, Rascol O, Barone P, Mozuno Y, Salin L. et al. Randomized double-blind multicentre evaluation of pramipexole extended-release once daily in early Parkinson’s disease. Mov Disord. 2010;25:2542–2549.CrossRefPubMedGoogle Scholar
  34. 34.
    Fox SH. Non-dopamaminergic treatment for motor control in Parkinson’s disease. Drugs. 203;73(13):405–15.Google Scholar
  35. 35.
    Hughes A, Bishop DS, Kleedorfer B, Turjanski N, Fernandez W, Lees AJ, et al. Subcutaneous apomorphine in Parkinson’s disease: response to chronic administration for up to five years. Mov Disord. 1993;8:165–170.CrossRefPubMedGoogle Scholar
  36. 36.
    DeMaagd G, Philip A. Part 2. Introduction to the pharmacotherapy of Parkinson’s disease, with focus on the use of dopaminergic agents. PT 2015;40(9):590–600.Google Scholar
  37. 37.
    Chen JJ, Swope DM. Parkinson’s disease. In DiPiro JT, Talbert RL, Yee GC, et al., editors. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. New York, New York: McGraw-Hill; 2014.Google Scholar
  38. 38.
    Perez-Lloret S, Rascol O. Dopamine receptor agonists for the treatment of early or advanced Parkinson’s disease. CNS Drugs. 2010;24:941–968.CrossRefPubMedGoogle Scholar
  39. 39.
    Jenner P. Dopamine agonists, receptor selectivity and dyskinesia induction in Parkinson’s disease. Curr Opin Neurol. 2003;16(suppl 1):S3-S7.CrossRefPubMedGoogle Scholar
  40. 40.
    Wu L, Wang X, Cheng B. Parkinson’s disease. accessed 6 November 2015.
  41. 41.
    Chaudhuri RK, Healy DG, Schapira HV. Non-motor symptoms of Parkinson’s disease: diagnosis and management. The Lancet Neurol. 2006;5:235–245.CrossRefPubMedGoogle Scholar
  42. 42.
    Braak H, Braak E, Yilmazer D, Schultz C, De Vos RA, Jansen EN, et al. Nigral and extranigral pathology in Parkinson’s disease. J Neural Transmission Suppl 1995;46:15–3.Google Scholar
  43. 43.
    Ehrt U. Depressive symptom profile in Parkinson’s disease: a comparison with depression in elderly patients without Parkinson’s disease. Int J Geriatr Psychiatry. 2006; 21(3): 252–258.CrossRefPubMedGoogle Scholar
  44. 44.
    Dubois B, Pillon B. Cognitive deficits in Parkinson’s disease. J Neurol. 1996; 44 (1):2–8.CrossRefGoogle Scholar
  45. 45.
    Postuma RB, Gagnon JF, Vendite M, Charland K,Montplaisir J. Manifestations of Parkinson’s disease differ in associated with REM sleep disorder. Mov Disord. 2008; 25:1665–72.CrossRefGoogle Scholar
  46. 46.
    Simuni T, Sethi K. Nonmotor symptoms of Parkinson’s disease. Ann Neurol. 2000; 64: 565–80.Google Scholar
  47. 47.
    Truong DD, Bhidayasiri R, Wolters E. Management of non motor symptoms in advanced Parkinson’s disease. J Neurol Sci. 2008;266: 216–28.CrossRefPubMedGoogle Scholar
  48. 48.
    Long term effects. disorders-center/health/long-effects. Accessed on 28 October 2015.
  49. 49.
    Myalovitska O, Lobanova I. Generalized assessment of the impact of Parkinson’s disease on functional condition[version1:referees:2not approved]F1000Research 2013:2121 (
  50. 50.
    Gallagher DA, Schrg A. Impact of newer pharmacological treatments on quality of life in patients with Parkinson’s disease. CNS Drugs. 2008;22(7):563–86.CrossRefPubMedGoogle Scholar
  51. 51.
    Scheife RT, Schumock GT, Burstein A, Gottwald MD, Luer MS. Impact of Parkinson’s disease and its pharmacologic treatment on quality of life and economic outcomes. Am J Health Syst.Pharm. accessed 28 October 2015.
  52. 52.
    Dowding CH, Shenton CL, Salek SS. A review of the health-related quality of life and economic impact of Parkinson’s disease. Drugs Aging. 2006;23(9):693–721.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Nages Nagaratnam
    • 1
  • Kujan Nagaratnam
    • 1
  • Gary Cheuk
    • 2
  1. 1.The University of SydneyWestmead Clinical SchoolWestmeadAustralia
  2. 2.Rehabilitation and Aged Care ServiceBlacktown-Mt Druitt HospitalMount DruittAustralia

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