Hypersensitivity of cortical muscarinic receptors in Parkinson's disease demonstrated by PET

The status of muscarinic receptors (mAChRs) is not clear in Parkinson's disease (PD). We measured mAChR binding in the brain of eight patients with PD and eight, age-matched, healthy controls by positron emission tomography (PET) and [¹¹ C]N-methyl-4-piperidyl benzilate ([¹¹ C]NMPB). PD patients were not demented according to DSM III criteria but showed significant frontal lobe dysfunction in the Modified Wisconsin Card Sorting Test. A mean K₃ value, which is an index of mAChR binding calculated by a graphical method, was 20% higher in the frontal cortex of PD patients than controls (p<0.05). Hypersensitivity of mAChRs in the frontal cortex of PD patients may be a response to a loss of ascending cholinergic input to that region, and may relate to frontal lobe dysfunction in PD.