Brain muscarinic receptors in progressive supranuclear palsy and Parkinson’s disease: a positron emission tomographic study

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 65; no. 2; pp. 155 - 163
• Main Authors: Asahina, Masato, Suhara, Tetsuya, Shinotoh, Hitoshi, Inoue, Osamu, Suzuki, Kazutoshi, Hattori, Takamichi
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.08.1998; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: Age; Aged; Alzheimer's disease; Benzilates; Biological and medical sciences; Brain - diagnostic imaging; Brain - physiopathology; Brain Mapping; Brain research; Carbon Radioisotopes; Cholinergic Fibers - diagnostic imaging; Cholinergic Fibers - physiology; cognitive dysfunction; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia; Female; Humans; Male; Medical sciences; Middle Aged; muscarinic receptor; Neurology; Neuropsychological Tests; Parasympatholytics; Parkinson Disease - diagnostic imaging; Parkinson Disease - physiopathology; Parkinson's disease; Piperidines; positron emission tomography; progressive supranuclear palsy; Receptors, Cholinergic - physiology; Receptors, Muscarinic - physiology; Supranuclear Palsy, Progressive - diagnostic imaging; Supranuclear Palsy, Progressive - physiopathology; Tomography, Emission-Computed; Womens health; Human; Radionuclide study; Nervous system diseases; Cognitive disorder; Pathogenesis; Supranuclear ophthalmoplegia; Parkinson disease; Psychometrics; Cerebral disorder; Progressive; Eye disease; Cholinergic receptor; Central nervous system disease; Distribution; Adult; Degenerative disease; Muscarinic receptor; Oculomotor syndrome; Brain stem syndrome; Comparative study; Extrapyramidal syndrome; Positron; Emission tomography
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp.65.2.155

OBJECTIVES 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.