Skip to main content
NCBI home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1998 Mar;64(3):314–319. doi: 10.1136/jnnp.64.3.314

Measuring the rate of progression and estimating the preclinical period of Parkinson's disease with [18F]dopa PET

P Morrish 1, J Rakshi 1, D Bailey 1, G Sawle 1, D Brooks 1
PMCID: PMC2170010  PMID: 9527140

Abstract

OBJECTIVES—To measure the rate of progression in striatal [18F]dopa metabolism in a large group (n=32) of patients with Parkinson's disease, to estimate the average duration of preclinical period, and to examine the influence of the PET method on the assessment of rate of progression and preclinical period.
METHODS—Thirty two patients with Parkinson's disease (mean age 58 (SD 13) years, mean duration 39 (SD 33) months) were assessed with [18F]dopa PET and UPDRS scoring on two occasions a mean of 18 (SD 6) months apart. PET data were sampled with separate caudate and putamen and total striatal regions of interest, and both graphical (Ki) and ratio methods of analysis.
RESULTS—The mean annual rate of deterioration in [18F]dopa uptake varied according to structure and method of analysis, with putamen Ki showing the most rapid mean rate of progression (4.7% of normal mean per year). The group showed a significant deterioration (p<0.0004, paired two tailed t test) in UPDRS and in the putamen (p=0.008) and total striatal (p=0.012) [18F]dopa uptake measured using a graphical analysis, but no significant change in caudate or putamen uptake measured by a ratio approach. A study of sensitivity confirmed that putamen Ki was the most sensitive measure of disease progression, caudate ratio the least. Symptom onset in Parkinson's disease was estimated at a mean putamen [18F]dopa uptake (Ki) of 75% of normal and a mean caudate [18F]dopa uptake (Ki) of 91% of normal.
CONCLUSIONS—Estimation of mean rate of progression varies according to the sensitivity of a functional imaging method to clinical severity. Sensitivity and reproducibility of method must be considered when designing studies of disease progression and neuroprotection. The mean preclinical period in Parkinson's disease is unlikely to be longer than seven years.



Full Text

The Full Text of this article is available as a PDF (120.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bland J. M., Altman D. G. Calculating correlation coefficients with repeated observations: Part 2--Correlation between subjects. BMJ. 1995 Mar 11;310(6980):633–633. doi: 10.1136/bmj.310.6980.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brooks D. J., Salmon E. P., Mathias C. J., Quinn N., Leenders K. L., Bannister R., Marsden C. D., Frackowiak R. S. The relationship between locomotor disability, autonomic dysfunction, and the integrity of the striatal dopaminergic system in patients with multiple system atrophy, pure autonomic failure, and Parkinson's disease, studied with PET. Brain. 1990 Oct;113(Pt 5):1539–1552. doi: 10.1093/brain/113.5.1539. [DOI] [PubMed] [Google Scholar]
  3. Calne D. B., Langston J. W. Aetiology of Parkinson's disease. Lancet. 1983 Dec 24;2(8365-66):1457–1459. doi: 10.1016/s0140-6736(83)90802-4. [DOI] [PubMed] [Google Scholar]
  4. Fearnley J. M., Lees A. J. Ageing and Parkinson's disease: substantia nigra regional selectivity. Brain. 1991 Oct;114(Pt 5):2283–2301. doi: 10.1093/brain/114.5.2283. [DOI] [PubMed] [Google Scholar]
  5. Gibb W. R., Lees A. J. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry. 1988 Jun;51(6):745–752. doi: 10.1136/jnnp.51.6.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Guttman M., Burkholder J., Kish S. J., Hussey D., Wilson A., DaSilva J., Houle S. [11C]RTI-32 PET studies of the dopamine transporter in early dopa-naive Parkinson's disease: implications for the symptomatic threshold. Neurology. 1997 Jun;48(6):1578–1583. doi: 10.1212/wnl.48.6.1578. [DOI] [PubMed] [Google Scholar]
  7. Hoehn M. M., Yahr M. D. Parkinsonism: onset, progression and mortality. Neurology. 1967 May;17(5):427–442. doi: 10.1212/wnl.17.5.427. [DOI] [PubMed] [Google Scholar]
  8. Ichise M., Ballinger J. R. Physiologic modeling of PET data: quantitative conflict and challenge. J Nucl Med. 1997 Aug;38(8):1266–1267. [PubMed] [Google Scholar]
  9. Kish S. J., Shannak K., Hornykiewicz O. Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications. N Engl J Med. 1988 Apr 7;318(14):876–880. doi: 10.1056/NEJM198804073181402. [DOI] [PubMed] [Google Scholar]
  10. Koller W. C. When does Parkinson's disease begin? Neurology. 1992 Apr;42(4 Suppl 4):27–48. [PubMed] [Google Scholar]
  11. Leenders K. L. Pathophysiology of movement disorders studied using PET. J Neural Transm Suppl. 1997;50:39–46. doi: 10.1007/978-3-7091-6842-4_5. [DOI] [PubMed] [Google Scholar]
  12. Morrish P. K., Sawle G. V., Brooks D. J. An [18F]dopa-PET and clinical study of the rate of progression in Parkinson's disease. Brain. 1996 Apr;119(Pt 2):585–591. doi: 10.1093/brain/119.2.585. [DOI] [PubMed] [Google Scholar]
  13. Morrish P. K., Sawle G. V., Brooks D. J. Clinical and [18F] dopa PET findings in early Parkinson's disease. J Neurol Neurosurg Psychiatry. 1995 Dec;59(6):597–600. doi: 10.1136/jnnp.59.6.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Morrish P. K., Sawle G. V., Brooks D. J. Regional changes in [18F]dopa metabolism in the striatum in Parkinson's disease. Brain. 1996 Dec;119(Pt 6):2097–2103. doi: 10.1093/brain/119.6.2097. [DOI] [PubMed] [Google Scholar]
  15. Sawle G. V., Burn D. J., Morrish P. K., Lammertsma A. A., Snow B. J., Luthra S., Osman S., Brooks D. J. The effect of entacapone (OR-611) on brain [18F]-6-L-fluorodopa metabolism: implications for levodopa therapy of Parkinson's disease. Neurology. 1994 Jul;44(7):1292–1297. doi: 10.1212/wnl.44.7.1292. [DOI] [PubMed] [Google Scholar]
  16. Sawle G. V., Colebatch J. G., Shah A., Brooks D. J., Marsden C. D., Frackowiak R. S. Striatal function in normal aging: implications for Parkinson's disease. Ann Neurol. 1990 Dec;28(6):799–804. doi: 10.1002/ana.410280611. [DOI] [PubMed] [Google Scholar]
  17. Snow B. J., Tooyama I., McGeer E. G., Yamada T., Calne D. B., Takahashi H., Kimura H. Human positron emission tomographic [18F]fluorodopa studies correlate with dopamine cell counts and levels. Ann Neurol. 1993 Sep;34(3):324–330. doi: 10.1002/ana.410340304. [DOI] [PubMed] [Google Scholar]
  18. Takikawa S., Dhawan V., Chaly T., Robeson W., Dahl R., Zanzi I., Mandel F., Spetsieris P., Eidelberg D. Input functions for 6-[fluorine-18]fluorodopa quantitation in parkinsonism: comparative studies and clinical correlations. J Nucl Med. 1994 Jun;35(6):955–963. [PubMed] [Google Scholar]
  19. Vingerhoets F. J., Schulzer M., Ruth T. J., Holden J. E., Snow B. J. Reproducibility and discriminating ability of fluorine-18-6-fluoro-L-Dopa PET in Parkinson's disease. J Nucl Med. 1996 Mar;37(3):421–426. [PubMed] [Google Scholar]
  20. Vingerhoets F. J., Snow B. J., Lee C. S., Schulzer M., Mak E., Calne D. B. Longitudinal fluorodopa positron emission tomographic studies of the evolution of idiopathic parkinsonism. Ann Neurol. 1994 Nov;36(5):759–764. doi: 10.1002/ana.410360512. [DOI] [PubMed] [Google Scholar]
  21. Vingerhoets F. J., Snow B. J., Schulzer M., Morrison S., Ruth T. J., Holden J. E., Cooper S., Calne D. B. Reproducibility of fluorine-18-6-fluorodopa positron emission tomography in normal human subjects. J Nucl Med. 1994 Jan;35(1):18–24. [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES