Dementia in Parkinson disease: functional imaging of cholinergic and dopaminergic pathways

Neurology. 2005 Dec 13;65(11):1716-22. doi: 10.1212/01.wnl.0000191154.78131.f6.

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates
  • Acetylcholine / deficiency*
  • Acetylcholine / metabolism
  • Acetylcholinesterase / metabolism
  • Aged
  • Atrophy / diagnosis
  • Atrophy / etiology
  • Atrophy / physiopathology
  • Binding, Competitive / physiology
  • Brain / diagnostic imaging
  • Brain / pathology
  • Brain / physiopathology*
  • Brain Mapping
  • Dihydroxyphenylalanine / analogs & derivatives
  • Dopamine / deficiency*
  • Dopamine / metabolism
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology*
  • Neuropsychological Tests
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / metabolism
  • Parkinson Disease / physiopathology*
  • Piperidines
  • Positron-Emission Tomography
  • Synaptic Transmission / physiology

Substances

  • Acetates
  • N-methyl-4-piperidyl acetate
  • Piperidines
  • fluorodopa F 18
  • Dihydroxyphenylalanine
  • Acetylcholinesterase
  • Acetylcholine
  • Dopamine