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Spatial covariance of cholinergic muscarinic M1/M4 receptors in Parkinson’s disease

Lookup NU author(s): Dr Sean Colloby, Dr Rachael LawsonORCiD, Professor Alison Yarnall, Professor David Burn, Professor John O'Brien, Professor John-Paul TaylorORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Background: PD is associated with cholinergic dysfunction, although the role of M1 and M4 receptors remains unclear. Objective: To investigate spatial covariance patterns of cholinergic muscarinic M1/M4 receptors in PD and their relationship with cognition and motor symptoms. Methods: Nineteen PD and 24 older adult controls underwent 123I-iodo-quinuclidinyl-benzilate (QNB) (M1/M4 receptor) and 99mTc-exametazime (perfusion) single-photon emission computed tomography scanning. We implemented voxel principal components analysis, producing a series of images representing patterns of intercorrelated voxels across individuals. Linear regression analyses derived specific M1/M4 spatial covariance patterns associated with PD. Results: A cholinergic M1/M4 pattern that converged onto key hubs of the default, auditory-visual, salience and sensorimotor networks fully discriminated PD patients from controls (F1,41 = 135.4, p<<0.001). In PD, we derived M1/M4 patterns that correlated with global cognition (r = -0.62, p =0.008) and motor severity (r = 0.53, p =0.02). Both patterns emerged with a shared topography implicating the basal forebrain as well as visual, frontal executive and salience circuits. Further, we found a M1/M4 pattern that predicted global cognitive decline (r = 0.46, p = 0.04), comprising relative decreased binding within default and frontal executive networks. Conclusions: Cholinergic muscarinic M1/M4 modulation within key brain networks were apparent in PD. Cognition and motor severity were associated with a similar topography, inferring both phenotypes possibly rely on related cholinergic mechanisms. Relative decreased M1/M4 binding within default and frontal executive networks could be an indicator of future cognitive decline.

Publication metadata

Author(s): Colloby SJ, Nathan P, Bakker G, Lawson RA, Yarnall AJ, Burn DJ, OBrien JT, Taylor JP

Publication type: Article

Publication status: Published

Journal: Movement Disorders

Year: 2021

Volume: 36

Issue: 8

Pages: 1879-1888

Print publication date: 01/08/2021

Online publication date: 11/05/2021

Acceptance date: 01/03/2021

Date deposited: 17/03/2021

ISSN (print): 0885-3185

ISSN (electronic): 1531-8257

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/mds.28564


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Funder referenceFunder name
National Institute for Health Research Biomedical Research Centre in Ageing and Chronic Disease and Biomedical Research Unit in Lewy Body Dementia at Newcastle
National Institute for Health Research Dementia Biomedical Research Unit at Cambridge
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