Age and severity of nigrostriatal damage at onset of Parkinson's disease.
The clinical evolution of Parkinson's disease (PD) is known to be partly dependent on the age of onset. For example, motor complications associated with chronic dopaminomimetic treatment occur more often in younger patients. However, few attempts have been made to characterize the functional pathological differences underlying this age effect. We investigated the relationship between age and severity of nigrostriatal damage at onset of PD. Twenty patients with early PD (symptom duration <or=5 years) with onset before age 50 (n = 10) and with onset after age 50 (n = 10) were studied. The two groups were compared with respect to severity of nigrostriatal damage as evaluated by positron emission tomography (PET) scanning with 6-[(18)F]fluoro-L-dopa ([(18)F]-dopa), (+/-)-alpha-[(11)C]dihydrotetrabenazine ([(11)C]DTBZ), and d-threo-[(11)C]methylphenidate ([(11)C]MP). We found no significant differences between younger- and older-onset PD patients with regard to any of the three presynaptic markers. For putamen, the P-values corresponding to the different PET measurements ranged from P = 0.34 ([(18)F]-dopa) to P = 0.79 ([(11)C]DTBZ). However, after adjusting for treatment and PD duration, regression analysis showed that [(18)F]-dopa uptake correlated positively with age of onset (r = 0.59; P = 0.010). No correlation was found between [(11)C]DTBZ and [(11)C]MP binding potentials and age of onset (P = 0.26 and P = 0.90, respectively). These data suggest that age-of-onset-dependent differences in clinical evolution are not likely to reflect early differences in nigrostriatal pathology in PD. Age-related differences in [(18)F]-dopa uptake may be related to changes in dopamine turnover.
De La Fuente-Fernández
Raúl
R
Pacific Parkinson's Research Centre, and TRIUMF, University of British Columbia, Vancouver, BC, Canada V6T 2B5.
Lim
Andrew S
AS
Sossi
Vesna
V
Adam
Michael J
MJ
Ruth
Thomas J
TJ
Calne
Donald B
DB
Stoessl
A Jon
AJ
Lee
Chong S
CS
D017668:Age of Onset; D002250:Carbon Radioisotopes; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000378:metabolism / Q000473:pathology*; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D014055:Tomography, Emission-Computed; D050492:Vesicular Biogenic Amine Transport Proteins
D002250:Carbon Radioisotopes; D050483:Dopamine Plasma Membrane Transport Proteins; D005462:Fluorine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D050492:Vesicular Biogenic Amine Transport Proteins; D004298:Dopamine