Monoaminergic Markers Across the Cognitive Spectrum of Lewy Body Disease

Article type: Research Article

Authors: van der Zee, Sygrid^{a; 1} | Vermeiren, Yannick^{a; b; 1} | Fransen, Erik^c | Van Dam, Debby^{a; b} | Aerts, Tony^b | Gerritsen, Marleen J.^a | Spikman, Jacoba M.^{a; d} | van Laar, Teus^a | De Deyn, Peter P.^{a; b; e; *}

Affiliations: [a] Department of Neurology, Alzheimer Research Center, University of Groningen and University Medical Center Groningen (UMCG), Groningen, Netherlands | [b] Department of Biomedical Sciences, Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Wilrijk (Antwerp), Belgium | [c] StatUa Center for Statistics, University of Antwerp, Wilrijk (Antwerp), Belgium | [d] Department of Clinical and Developmental Neuropsychology, Faculty of Behavioral and Social Sciences, University of Groningen, Groningen, Netherlands | [e] Department of Neurology, Memory Clinic of Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium

Correspondence: [*] Correspondence to: Prof. Dr. Peter P. De Deyn, Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, BE-2610 Wilrijk (Antwerp), Belgium. Tel.: +32 3 265 2620; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:Lewy body disorders, including Parkinson’s disease (PD), Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB), are characterized by profound central and peripheral monoaminergic dysfunction. Objective:To investigate whether these alterations depend on dementia status, we measured cerebrospinal fluid (CSF) and serum monoamine and metabolite levels across subgroups of the cognitive spectrum, and evaluated their marker potential afterwards. Methods:In total, 153 subjects were included, of which 43 healthy controls (HC), 28 PD patients with normal cognition (PD-NC), 26 patients with PD and mild cognitive impairment (PD-MCI), 18 PDD patients, and 38 DLB patients. The levels of monoamines and metabolites in paired CSF and serum samples were analyzed applying reversed-phase high-performance liquid chromatography with electrochemical detection. Results:Firstly, when comparing subgroups, CSF 3-methoxy-4-hydroxyphenylglycol (MHPG) levels were found lowest in HC and PD-NC groups and significantly higher in PDD/DLB patients. In addition, CSF 5-hydroxyindoleacetic acid (5-HIAA) levels differed significantly between HC and PD-MCI/PDD, and DLB patients (P≤0.001), but not between HC and PD-NC patients. Secondly, when performing logistic regression, it was shown that particularly CSF/serum MHPG levels and the serum MHPG to noradrenaline (NA) ratio effectively differentiated between HC and (non-)pooled PD subgroups (AUC = 0.914–0.956), and PDD and DLB patients (AUC = 0.822), respectively. Furthermore, CSF 5-HIAA was the most discriminative parameter to differentiate between PD-NC and PD-MCI (AUC = 0.808), and, PD-NC and PDD subgroups (AUC = 0.916). Conclusions:Our data revealed that especially alterations of the noradrenergic neurotransmitter system could distinguish between Lewy body disorder subtypes, pinpointing CSF/serum MHPG and NA as potential stage markers across the cognitive spectrum.

Keywords: 3-methoxy-4-hydroxyphenylglycol, noradrenaline, 5-hydroxyindoleacetic acid, dementia with Lewy bodies, Parkinson’s disease, Parkinson’s disease dementia, monoamines, biomarkers, RP-HPLC-ECD

DOI: 10.3233/JPD-171228

Journal: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 71-84, 2018