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Spatial Covariance of Cholinergic Muscarinic M 1 / M 4 Receptors in Parkinson's Disease
Author(s) -
Colloby Sean J.,
Nathan Pradeep J.,
Bakker Geor,
Lawson Rachael A.,
Yarnall Alison J.,
Burn David J.,
O'Brien John T.,
Taylor JohnPaul
Publication year - 2021
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.28564
Subject(s) - basal forebrain , neuroscience , cholinergic , muscarinic acetylcholine receptor , psychology , cognitive decline , cholinergic neuron , medicine , endocrinology , receptor , biology , disease , dementia
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 M 1 /M 4 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) (M 1 /M 4 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 M 1 /M 4 spatial covariance patterns associated with PD. Results A cholinergic M 1 /M 4 pattern that converged onto key hubs of the default, auditory–visual, salience, and sensorimotor networks fully discriminated PD patients from controls (F 1,41 = 135.4, P < 0.001). In PD, we derived M 1 /M 4 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 M 1 /M 4 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 M 1 /M 4 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 M 1 /M 4 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