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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 Lawson, Dr Alison Yarnall, Professor David Burn, Professor John O'Brien, Professor John-Paul Taylor



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

Issue: ePub ahead of Print

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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