Bakker G

Burn DJ

Colloby SJ

Lawson RA

Nathan P

OBrien JT

Taylor JP

Yarnall AJ

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&lt;&lt;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

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Spatial covariance of cholinergic muscarinic M<sub>1</sub>/M<sub>4</sub> receptors in Parkinson’s disease

Spatial covariance of cholinergic muscarinic M<sub>1</sub>/M<sub>4</sub> receptors in Parkinson’s disease

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