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Nonlinear Progression of Parkinson Disease as Determined by Serial Positron Emission Tomographic Imaging of Striatal Fluorodopa F 18 Activity
Hilker F, Schweitzer K, Coburger S, Ghaemi M, Weisenbach S, Jacobs AH, Rudolf J, Herholz KG, Heiss WD
Archives of Neurology. 2005;62 (3):378-382.
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Abstract
Department of Neurology, University of Cologne, Cologne, Germany. hilker@pet.mpin-koeln.mpg.deBACKGROUND: 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.PMID: 15767502 [PubMed - indexed for MEDLINE]