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Muscarinic acetylcholine receptor status in Alzheimer's disease assessed using (R, R) 123I-QNB SPECT

Lookup NU author(s): Dr Sanjeet Pakrasi, Dr Sean Colloby, Dr Michael FirbankORCiD, Emeritus Professor Elaine Perry, Professor Ian McKeith, Professor David Williams, Professor John O'Brien


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Background: One of the most characteristic changes in Alzheimer's disease (AD) is a deficit in cortical cholinergic neurotransmission and associated receptor changes. Objective: To investigate differences in the distribution of M1/M4 receptors using (R, R) 123I-iodo-quinuclidinyl-benzilate (QNB) and single photon emission computed tomography (SPECT) in patients with mild/moderate AD and agematched controls. Also, to compare 123I-QNB uptake to the corresponding changes in regional cerebral blood flow (rCBF) in the same subjects. Methods: Forty two subjects (18 AD and 24 healthy elderly controls) underwent 123IQNB and perfusion 99mTc- exametazime SPECT scanning. Image analysis was performed using statistical parametric mapping (SPM99) following intensity normalisation of each image to its corresponding mean whole brain uptake. Group differences and correlations were assessed using two sample t-tests and linear regression respectively. Results: Significant reductions in 123I-QNB uptake were observed in regions of the frontal rectal gyrus, right parahippocampal gyrus, left hippocampus and areas of the left temporal lobe in AD compared to controls (height threshold of p ≤ 0.001 uncorrected). Such regions were also associated with marked deficits in rCBF. No significant correlations were identified between imaging data and clinical variables. Conclusion: Functional impairment as measured by rCBF is more widespread than changes in M1/M4 receptor density in mild/moderate AD, where there was little or no selective loss of M1/M4 receptors in these patients that was greater than the general functional deficits shown on rCBF scans. © 2007 Steinkopff-Verlag.

Publication metadata

Author(s): Pakrasi S, Colloby SJ, Firbank MJ, Perry EK, Wyper DJ, Owens J, McKeith IG, Williams ED, O'Brien JT

Publication type: Article

Publication status: Published

Journal: Journal of Neurology

Year: 2007

Volume: 254

Issue: 7

Pages: 907-913

Print publication date: 01/07/2007

ISSN (print): 0340-5354

ISSN (electronic): 1432-1459

Publisher: Dr. Dietrich Steinkopff Verlag


DOI: 10.1007/s00415-006-0473-8

PubMed id: 17361343


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Funder referenceFunder name
G0400074Medical Research Council
G0502157Medical Research Council