Dementia in Parkinson disease: functional imaging of cholinergic and dopaminergic pathways.
OBJECTIVE
To assess neurochemical deficits in patients with Parkinson disease (PD) associated dementia (PDD) in vivo.


METHODS
The authors performed combined PET with N-[11C]-methyl-4-piperidyl acetate (MP4A) and 18F-fluorodopa (FDOPA) for evaluation of cholinergic and dopaminergic transmitter changes in 17 non-demented patients with PD and 10 patients with PDD. Data were compared to 31 age-matched controls by a combined region-of-interest and voxel-based Statistical Parametric Mapping analysis.


RESULTS
The striatal FDOPA uptake was significantly decreased in PD and PDD without differences between the groups. The global cortical MP4A binding was severely reduced in PDD (29.7%, p < 0.001 vs controls) and moderately decreased in PD (10.7%, p < 0.01 vs controls). The PDD group had lower parietal MP4A uptake rates than did patients with PD. Frontal and temporo-parietal cortices showed a significant covariance of striatal FDOPA reduction and decreased MP4A binding in patients with PDD.


CONCLUSIONS
While non-demented patients with Parkinson disease had a moderate cholinergic dysfunction, subjects with Parkinson disease associated dementia (PDD) presented with a severe cholinergic deficit in various cortical regions. The finding of a closely associated striatal FDOPA and cortical MP4A binding reduction suggests a common disease process leading to a complex transmitter deficiency syndrome in PDD.
Hilker
R
R
Department of Neurology, University of Cologne, Cologne, Germany. hilker@pet.mpin-koeln.mpg.de
Thomas
A V
AV
Klein
J C
JC
Weisenbach
S
S
Kalbe
E
E
Burghaus
L
L
Jacobs
A H
AH
Herholz
K
K
Heiss
W D
WD
D000085:Acetates; D000109:Acetylcholine / Q000172:deficiency* / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000368:Aged; D001284:Atrophy / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D001667:Binding, Competitive / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives; D004298:Dopamine / Q000172:deficiency* / Q000378:metabolism; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D010880:Piperidines; D049268:Positron-Emission Tomography; D009435:Synaptic Transmission / Q000502:physiology
D000085:Acetates; C100518:N-methyl-4-piperidyl acetate; D010880:Piperidines; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D000110:Acetylcholinesterase; D000109:Acetylcholine; D004298:Dopamine