Spatial Covariance of Cholinergic Muscarinic M1/M4 Receptors in Parkinson's Disease. Issue 8 (11th May 2021)

• Record Type: Journal Article
• Authors: Colloby, Sean J.; Nathan, Pradeep J.; Bakker, Geor; Lawson, Rachael A.; Yarnall, Alison J.; Burn, David J.; O'Brien, John T.; Taylor, John‐Paul
• Is Part Of: Movement disorders. Volume 36:Issue 8(2021)
• Page Start: 1879
• Page End: 1888
• Publication Date: 2021-05-11
• Subjects: Parkinson's disease -- muscarinic receptors -- SPECT -- spatial covariance -- cholinergic M1/M4 receptors -- networks; Movement disorders -- Periodicals; 610
• DOI: 10.1002/mds.28564
• Languages: English
• ISSNs: 0885-3185

Abstract

ABSTRACT: Background: Parkinson's disease (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: Some 19 PD and 24 older adult controls underwent 123 I‐iodo‐quinuclidinyl‐benzilate (QNB) (M1 /M4 receptor) and 99m Tc‐exametazime (perfusion) single‐photon emission computed tomography (SPECT) 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. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society