Impairment of Motor Function Correlates with Neurometabolite and Brain Iron Alterations in Parkinson's Disease

• Type of Material: Article
• Authors: Beate Pesch, Institute of the Ruhr University Bochum; Swaantje Casjens, Institute of the Ruhr University Bochum; Dirk Woitalla, Ruhr University Bochum; Shalmali Dharmadhikari, Emory University; David A. Edmondson, Purdue University; Maria Angela Samis Zella, Katholische Kliniken Ruhrhalbinsel; Martin Lehnert, Institute of the Ruhr University Bochum; Anne Lotz, Institute of the Ruhr University Bochum; Lennard Herrmann, Ruhr University Bochum; Siegfried Muhlack, Ruhr University Bochum; Peter Kraus, Ruhr University Bochum; Chien-Lin Yeh, Purdue University; Benjamin Glaubitz, Ruhr University Bochum; Tobias Schmidt-Wilcke, St Mauritius Therapieklin; Talf Gold, Ruhr University Bochum; Christoph van Thriel, TU Dortmund; Thomas Bruening, Institute of the Ruhr University Bochum; Lars Toenges, Ruhr University Bochum; Ulrike Dydak, Purdue University
• Language: English
• Date: 2019-02-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2019 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/cells8020096
• Title of Journal or Parent Work: Cells
• ISSN: 2073-4409
• Volume: 8
• Issue: 2
• Grant/Funding Information: U.D., S.D., D.A.E., and C.-L.Y. were supported through NIH grant R01ES020529.; The WELDOX II study was supported by a grant from the Employer’s Liability Insurance Association for Wood and Metals (Berufsgenossenschaft Holz und Metall).
• Keywords: MAGNETIC-RESONANCE-SPECTROSCOPY; PROTON MR SPECTROSCOPY; spectroscopy; motor dysfunction; GABA; METABOLISM; MANGANESE; Cell Biology; brain iron; Parkinson's disease; BASAL GANGLIA; DIAGNOSIS; ASSOCIATION; neurometabolites; magnetic resonance imaging; magnetic resonance spectroscopy; Science & Technology; Life Sciences & Biomedicine; EXPOSURE; THALAMIC GABA; SUBSTANTIA-NIGRA
• Research Categories: Health Sciences, Radiology; Biology, Neuroscience; Psychology, Clinical

Abstract

We took advantage of magnetic resonance imaging (MRI) and spectroscopy (MRS) as non-invasive methods to quantify brain iron and neurometabolites, which were analyzed along with other predictors of motor dysfunction in Parkinson’s disease (PD). Tapping hits, tremor amplitude, and the scores derived from part III of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS-UPDRS3 scores) were determined in 35 male PD patients and 35 controls. The iron-sensitive MRI relaxation rate R2* was measured in the globus pallidus and substantia nigra. γ-aminobutyric acid (GABA)-edited and short echo-time MRS was used for the quantification of neurometabolites in the striatum and thalamus. Associations of R2*, neurometabolites, and other factors with motor function were estimated with Spearman correlations and mixed regression models to account for repeated measurements (hands, hemispheres). In PD patients, R2* and striatal GABA correlated with MDS-UPDRS3 scores if not adjusted for age. Patients with akinetic-rigid PD subtype (N = 19) presented with lower creatine and striatal glutamate and glutamine (Glx) but elevated thalamic GABA compared to controls or mixed PD subtype. In PD patients, Glx correlated with an impaired dexterity when adjusted for covariates. Elevated myo-inositol was associated with more tapping hits and lower MDS-UPDRS3 scores. Our neuroimaging study provides evidence that motor dysfunction in PD correlates with alterations in brain iron and neurometabolites.