Nonlinear progression of Parkinson disease as determined by serial positron emission tomographic imaging of striatal fluorodopa F 18 activity

Arch Neurol. 2005 Mar;62(3):378-82. doi: 10.1001/archneur.62.3.378.


Background: The investigation of disease progression provides important information on the dynamics of cell death in Parkinson disease (PD).

Objective: To determine the progression of dopaminergic impairment in PD with the use of positron emission tomography (PET).

Design: Longitudinal prospective cohort study with a follow-up period of 64.5 +/- 22.6 months (mean +/- SD).

Setting: University hospital.

Patients: A consecutive sample of patients with PD (N = 31; age at symptom onset, 53.6 +/- 11.3 years) with a wide range of symptom duration and severity at the time of study entry.

Interventions: Investigation by serial fluorodopa F 18 ([(18)F]fluorodopa) PET as a marker for striatal dopaminergic function.

Main outcome measures: Changes in caudate and putaminal [(18)F]fluorodopa influx constant (K(i)) values.

Results: In patients with PD, the decline rate of putaminal [(18)F]fluorodopa K(i) correlated inversely with disease duration before study inclusion (r = -0.46, P = .01) and positively with baseline K(i) values (r = 0.44, P = .01), indicating a negative exponential loss of dopamine neurons. Annual disease progression rates ranged from 4.4% in the caudate nucleus to 6.3% in the putamen. A mean preclinical period of 5.6 +/- 3.2 years was calculated with symptom onset at a putaminal K(i) threshold of 69% from controls. Assuming nonlinear progression kinetics, the required sample size to prove neuroprotection with the use of [(18)F]fluorodopa PET was found to increase strongly with the preceding symptom duration of study subjects.

Conclusion: These data suggest that the neurodegenerative process in PD follows a negative exponential course and slows down with increasing symptom duration, contradicting the long-latency hypothesis of PD.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology*
  • Dihydroxyphenylalanine / analogs & derivatives*
  • Dihydroxyphenylalanine / metabolism*
  • Disease Progression
  • Female
  • Fluorine Radioisotopes / metabolism
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Nonlinear Dynamics*
  • Parkinson Disease / diagnosis
  • Parkinson Disease / etiology*
  • Parkinson Disease / pathology*
  • Positron-Emission Tomography / methods
  • Positron-Emission Tomography / statistics & numerical data*
  • Severity of Illness Index
  • Statistics, Nonparametric


  • Fluorine Radioisotopes
  • fluorodopa F 18
  • Dihydroxyphenylalanine