Journal of Neurology

, Volume 253, Supplement 7, pp vii2–vii6

The natural history of Parkinson’s disease

Article

Abstract

Although Parkinson’s disease (PD) is the only chronic neurodegenerative disorder for which there are effective symptomatic therapies no treatment has yet been identified that would significantly slow its natural progression. Studies into the natural history of Parkinson’s disease have been complicated by issues of diagnostic accuracy, heterogeneity of different forms of the disease as well as confounding effects of age related comorbidities.

Only recently results from placebo-controlled clinical trials have helped to define the rates of progression of motor dysfunction as assessed by the UPDRS in early PD. Studies in treated patients suggest that there may be different rates of progression in different phases of the disease with faster decline in earlier versus later stages.

Measuring progression of motor symptoms, however, alone is insufficient to describe the natural history of PD and may also be inadequate to define clinically meaningful disease modification in intervention trials. Progression of global disability as captured in the Hoehn and Yahr scale is important to consider and progression to stage III with beginning postural impairment defines a major milestone in the natural history of this illness. In addition, non-motor symptoms have major impact on the natural history of PD. Dementia, sleep-wake cycle dysregulation and autonomic failure were present in 50–80% of patients in one recent 15 year-follow up study. Dementia and psychosis are also major risk factors for nursing home placement in PD.

A prerequisite for effective interventions that would modify disease progression in Parkinson’s disease is the identification of the earliest preclinical stages of illness. This is now become a realistic possibility with screening tests of olfactory function and subsequent functional imaging. Subjects at risk for Parkinson’s disease should be the future focus of neuroprotective trials.

Key words

Natural History pre-clinical PD non-motor symptoms disease-modification 

References

  1. 1.
    Poewe WH, Lees AJ, Stern GM (1986) Low-dose L-dopa therapy in Parkinson’s disease: a 6-year follow-up study. Neurology 36:1528–1530PubMedGoogle Scholar
  2. 2.
    Schrag A, Quinn N (2000) Dyskinesias and motor fluctuations in Parkinson’s disease. A community-based study. Brain 123 (Pt 11):2297–2305PubMedCrossRefGoogle Scholar
  3. 3.
    Goetz CG, Tanner CM, Shannon KM (1987) Progression of Parkinson’s disease without levodopa. Neurology 37:695–698PubMedGoogle Scholar
  4. 4.
    Muller J, Wenning GK, Verny M, McKee A, Chaudhuri KR, Jellinger K, Poewe W, Litvan I (2001) Progression of dysarthria and dysphagia in postmortem-confirmed parkinsonian disorders. Arch Neurol 58:259–264PubMedCrossRefGoogle Scholar
  5. 5.
    Hoehn MM, Yahr MD (1967) Parkinsonism: onset, progression and mortality. Neurology 17:427–442PubMedCrossRefGoogle Scholar
  6. 6.
    Muller J, Wenning GK, Verny M, McKee A, Chaudhuri KR, Jellinger K, Poewe W, Litvan I (2001) Progression of dysarthria and dysphagia in postmortem-confirmed parkinsonian disorders. Arch Neurol 58:259–264PubMedCrossRefGoogle Scholar
  7. 7.
    The Parkinson Study Group (1993) Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 328:176–183CrossRefGoogle Scholar
  8. 8.
    Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J,Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M (2002) Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 59:1541–1550PubMedCrossRefGoogle Scholar
  9. 9.
    Parkinson Study Group (2004) A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol 61:561–566CrossRefGoogle Scholar
  10. 10.
    Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J,Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M (2002) Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 59:1541–1550PubMedCrossRefGoogle Scholar
  11. 11.
    Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, Olanow CW, Tanner C, Marek K (2004) Levodopa and the progression of Parkinson’s disease. N Engl J Med 351:2498–2508PubMedCrossRefGoogle Scholar
  12. 12.
    The Parkinson Study Group (1996) Effect of lazabemide on the progression of disability in early Parkinson’s disease. Ann Neurol 40:99–107CrossRefGoogle Scholar
  13. 13.
    Marttila RJ, Rinne UK, Siirtola T, Sonninen V (1977) Mortality of Patients with Parkinson’s Disease Treated with Levodopa. J Neurol 216:147–153PubMedCrossRefGoogle Scholar
  14. 14.
    Hely MA, Morris JGL, Traficante R, Reid WG, O’Sullivan DJ, Williamson PM (1999) The Sydney multicentre study of Parkinson’s disease: progression and mortality at 10 years. J Neurol Neurosurg Psychiatry 67:300–307PubMedGoogle Scholar
  15. 15.
    Lucking CB, Durr A, Bonifati V, Vaughan J, De Michele G, Gasser T, Harhangi BS, Meco G, Denefle P, Wood NW, Agid Y, Brice A (2000) Association between early-onset Parkinson’s disease and mutations in the parkin gene. N Engl J Med 342:1560–1567PubMedCrossRefGoogle Scholar
  16. 16.
    Fearnley JM, Lees AJ (1994) Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain 114 (Pt 5):2283–2301Google Scholar
  17. 17.
    Lee CS, Schulzer M, Mak EK, Snow BJ, Tsui JK, Calne S, Hammerstad J, Calne DB (1994) Clinical observations on the rate of progression of idiopathic parkinsonism. Brain 117:501–507PubMedGoogle Scholar
  18. 18.
    Bonnet AM, Loria Y, Saint Hilaire MH, Lhermitte F, Agid Y (1987) Does long-term aggravation of Parkinson’s disease result from nondopaminergic lesions? Neurology 37:1539–1542PubMedGoogle Scholar
  19. 19.
    Schrag A, Quinn N (200) Dyskinesias and motor fluctuations in Parkinson’s disease. A community-based study. Brain 123 (Pt 11):2297–2305CrossRefGoogle Scholar
  20. 20.
    Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211PubMedCrossRefGoogle Scholar
  21. 21.
    Hely MA, Morris JG, Reid WG, Trafficante R (2005) Sydney Multicenter Study of Parkinson’s disease: non-L-dopa-responsive problems dominate at 15 years. Mov Disord 20:190–199PubMedCrossRefGoogle Scholar
  22. 22.
    Aarsland D, Zaccai J, Brayne C (1993) A systematic review of prevalence studies of dementia in Parkinson’s disease. Mov Disord 20:1255–1263CrossRefGoogle Scholar
  23. 23.
    Goetz CG, Stebbins GT (1993) Risk factors for nursing home placement in advanced Parkinson’s disease. Neurology 43:2227–2229PubMedGoogle Scholar
  24. 24.
    Abbott RD, Petrovitch H, White LR, Masaki KH, Tanner CM, Curb JD, Grandinetti A, Blanchette PL, Popper JS, Ross GW (2001) Frequency of bowel movements and the future risk of Parkinson’s disease. Neurology 57:456–462PubMedGoogle Scholar
  25. 25.
    Ponsen MM, Stoffers D, Booij J, Eck-Smit BL, Wolters EC, Berendse HW (2004) Idiopathic hyposmia as a preclinical sign of Parkinson’s disease. Ann Neurol 56:173–181PubMedCrossRefGoogle Scholar
  26. 26.
    Schenck CH, Bundlie SR, Mahowald MW (1996) Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology 46:388–393PubMedGoogle Scholar
  27. 27.
    Jellinger KA, Seppi K, Wenning GK, Poewe W (2002) Impact of coexistent Alzheimer pathology on the natural history of Parkinson’s disease. J Neural Transm 109:329–339PubMedCrossRefGoogle Scholar
  28. 28.
    Beyer MK, Herlofson K, Arsland D, Larsen JP (2001) Causes of death in a community-based study of Parkinson’s disease. Acta Neurol Scand 103:7–11PubMedCrossRefGoogle Scholar
  29. 29.
    Muller J, Wenning GK, Verny M, McKee A, Chaudhuri KR, Jellinger K, Poewe W, Litvan I (2001) Progression of dysarthria and dysphagia in postmortem-confirmed parkinsonian disorders. Arch Neurol 58:259–264PubMedCrossRefGoogle Scholar
  30. 30.
    Goetz CG, Poewe W, Rascol O, Sampaio C, Stebbins GT, Counsell C, Giladi N, Holloway RG, Moore CG, Wenning GK, Yahr MD, Seidl L (2004) Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations. Mov Disord 19:1020–1028PubMedCrossRefGoogle Scholar
  31. 31.
    Louis ED, Marder K, Cote L, Tang M, Mayeux R (1997) Mortality from Parkinson disease. Arch Neurol 54:260–264PubMedGoogle Scholar
  32. 32.
    Ben Shlomo Y, Churchyard A, Head J, Hurwitz B, Overstall P, Ockelford J, Lees AJ (1998) Investigation by Parkinson’s Disease Research Group of United Kingdom into excess mortality seen with combined levodopa and selegiline treatment in patients with early, mild Parkinson’s disease: further results of randomised trial and confidential inquiry. BMJ 316:1191–1196PubMedGoogle Scholar
  33. 33.
    Hely MA, Morris JG, Traficante R, Reid WG, O’Sullivan DJ, Williamson PM (1999) The sydney multicentre study of Parkinson’s disease: progression and mortality at 10 years. J Neurol Neurosurg Psychiatry 67:300–307PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff-Verlag 2006

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of InnsbruckInnsbruckAustria

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