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Dementia in Parkinson disease: functional imaging of cholinergic and dopaminergic pathways.
Hilker R, Thomas A, Klein J, Weisenbach S, Kalbe E, Burghaus L, Jacobs A, Herholz KG, Heiss W
Neurology. 2005;65( 11):1716-22.
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Abstract
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.
Keyword(s)
Aged; Brain Mapping; Comparative Study; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Research Support, Non-U.S. Gov't; analogs & derivatives: Dihydroxyphenylalanine; deficiency: Acetylcholine; deficiency: Dopamine; diagnosis: Atrophy; diagnostic use: Acetates; diagnostic use: Piperidines; metabolism: Acetylcholinesterase; metabolism: Neural Pathways; metabolism: Parkinson Disease; pathology: Brain; physiology: Binding, Competitive; physiology: Synaptic Transmission