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The locus coeruleus shows a spatial pattern of structural disintegration in Parkinson's disease.

By Christopher Fugl Madelung, David Meder, Søren A Fuglsang, Marta M Marques, Vincent O Boer, Kristoffer H Madsen, Esben T Petersen, Anne-Mette Hejl, Annemette Løkkegaard, Hartwig R Siebner

Posted 03 Sep 2021
medRxiv DOI: 10.1101/2021.09.01.21262920

Background Parkinson's disease (PD) leads to a loss of neuromelanin positive, noradrenergic neurons in the locus coeruleus (LC) which has been implicated in non-motor dysfunction. "Neuromelanin sensitive" magnetic resonance imaging (MRI) has emerged as a promising tool for mapping the structural integrity of LC in vivo. Objectives To identify spatial patterns of structural LC disintegration in PD and regions in the LC where structural disintegration is associated with specific non-motor dysfunctions. Methods 42 patients with PD and 24 age-matched healthy volunteers underwent ultra-high field MRI of the LC using a "neuromelanin sensitive" magnetization transfer weighted (MTw) sequence. The contrast-to-noise ratio of the MTw signal (CNRMTw) served as an estimate of structural integrity, slice- and voxel-wise analyses of CNRMTw were performed to map the spatial pattern of structural disintegration, complemented by Principal Component Analysis (PCA). We also tested for correlations between CNRMTw and the severity of non-motor symptoms. Results Mean CNRMTw of LC was reduced in patients relative to controls. The attenuation of CNRMTw was not uniformly expressed in LC, but confined to the middle and caudal LC. CNRMTw attenuation in caudal LC scaled with the orthostatic drop in systolic blood pressure and apathy ratings. PCA identified a bilaterally expressed component that was more weakly expressed in patients. This component was characterized by a gradual change in CNRMTw along the rostro-caudal and dorso-ventral axes of the nucleus. The individual expression score of this component reflected the overall severity of non-motor symptoms. Conclusion PD related structural disintegration of LC mainly affects its caudal part and may determine the individual expression of specific non-motor symptoms such as orthostatic dysregulation or apathy.

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