Brain muscarinic receptors in progressive supranuclear palsy and Parkinson's disease: a positron emission tomographic study.
OBJECTIVE
To assess muscarinic acetylcholine receptors (mAChRs) in the brains of patients with progressive supranuclear palsy and Parkinson's disease, and to correlate the cholinergic system with cognitive function in progressive supranuclear palsy and Parkinson's disease.


METHODS
Positron emission tomography (PET) and [11C]N-methyl-4-piperidyl benzilate ([11C]NMPB) was used to measure mAChRs in the brain of seven patients with progressive supranuclear palsy, 12 patients with Parkinson's disease, and eight healthy controls. All of the patients with progressive supranuclear palsy were demented. The Parkinson's disease group consisted of 11 non-demented patients and one demented patient. The mini mental state examination (MMSE) was used to assess the severity of cognitive dysfunction in all of the subjects. The modified Wisconsin card sorting test (WCST) was used to evaluate frontal cognitive function in the non-demented patients with Parkinson's disease and controls.


RESULTS
The mean K3 value, an index of mAChR binding, was significantly higher for the frontal cortex in the patients with Parkinson's disease than in the controls (p<0.01). By contrast, the patients with progressive supranuclear palsy had no significant changes in the K3 values of any cerebral cortical regions. The mean score of the MMSE in the progressive supranuclear palsy group was significantly lower than that in the control group. Although there was no difference between the Parkinson's disease and control groups in the MMSE, the non-demented patients with Parkinson's disease showed significant frontal lobe dysfunction in the WCST.


CONCLUSIONS
The increased mAChR binding in the frontal cortex of the patients with Parkinson's disease may reflect denervation hypersensitivity caused by loss of the ascending cholinergic input to that region from the basal forebrain and may be related to frontal lobe dysfunction in Parkinson's disease. The cerebral cortical cholinergic system may not have a major role in cognitive dysfunction in progressive supranuclear palsy.
Division of Clinical Research and Radiation Health, National Institute of Radiological Science, Chiba, Japan. masatoasahina@msn.com
M
M
Asahina
T
T
Suhara
H
H
Shinotoh
O
O
Inoue
K
K
Suzuki
T
T
Hattori
D000368:Aged; D001561:Benzilates; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D002799:Cholinergic Fibers / Q000000981:diagnostic imaging / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010276:Parasympatholytics; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology; D010880:Piperidines; D011950:Receptors, Cholinergic / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D013494:Supranuclear Palsy, Progressive / Q000000981:diagnostic imaging* / Q000503:physiopathology; D014055:Tomography, Emission-Computed
D001561:Benzilates; D002250:Carbon Radioisotopes; D010276:Parasympatholytics; D010880:Piperidines; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; C020407:enpiperate