Brain muscarinic receptors in progressive supranuclear palsy andParkinson's disease: a positron emission tomographic study

OBJECTIVES—To assessmuscarinic acetylcholine receptors (mAChRs) in the brains of patientswith progressive supranuclear palsy and Parkinson's disease, and tocorrelate the cholinergic system with cognitive function in progressivesupranuclear palsy and Parkinson's disease.
METHODS— Positronemission tomography (PET) and [¹¹C]N-methyl-4-piperidylbenzilate ([¹¹C]NMPB) was used to measure mAChRs in thebrain of seven patients with progressive supranuclear palsy, 12 patients with Parkinson's disease, and eight healthy controls. All ofthe patients with progressive supranuclear palsy were demented. TheParkinson's disease group consisted of 11 non-demented patients andone demented patient. The mini mental state examination (MMSE) was usedto 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 withParkinson's disease and controls.
RESULTS—The meanK₃ value, an index of mAChR binding, was significantlyhigher for the frontal cortex in the patients with Parkinson's diseasethan in the controls (p<0.01). By contrast, the patients withprogressive supranuclear palsy had no significant changes in theK₃ values of any cerebral cortical regions. The mean score of the MMSE in the progressive supranuclear palsy group wassignificantly lower than that in the control group. Although there wasno difference between the Parkinson's disease and control groups inthe MMSE, the non-demented patients with Parkinson's disease showedsignificant frontal lobe dysfunction in the WCST.
CONCLUSIONS—Theincreased mAChR binding in the frontal cortex of the patients withParkinson's disease may reflect denervation hypersensitivity caused byloss of the ascending cholinergic input to that region from the basalforebrain and may be related to frontal lobe dysfunction inParkinson's disease. The cerebral cortical cholinergic system may nothave a major role in cognitive dysfunction in progressive supranuclear palsy.