Objective: The objective of this study was the identification of biochemical markers of cognitive impairment in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) by focusing on cerebrospinal fluid (CSF) and serum levels of various monoaminergic neurotransmitters across different stages of cognitive decline.

Methods: The study population comprised 154 subjects in total, of which 43 healthy control subjects, 28 patients with PD, 27 patients with PD and mild cognitive impairment (PD-MCI), 18 patients with PD dementia (PDD), and, 38 patients with DLB. Matched serum and CSF levels of a variety of eight monoamines and metabolites were analyzed applying RP-HPLC-ECD, i.e. dopamine (DA), serotonin (5-HT), (nor)adrenaline ((N)A) and their respective metabolites, i.e. 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), 5-hydroxy-3-indoleacetic acid (5-HIAA), and, 3-methoxy-4-hydroxyphenylglycol (MHPG). Furthermore, MMSE scores were obtained as a parameter of cognitive performance and the administered psychotropic medication was documented.

Results: CSF and serum levels of both NA and MHPG were found to be significantly higher in patients with PD compared to healthy control subjects. In addition, in PD patients, CSF MHPG levels were higher in patients with PDD compared to cognitively normal PD patients. Furthermore, we observed higher CSF and serum 5-HIAA levels in healthy controls compared to all PD groups and DLB patients. As for the patient groups, CSF 5-HIAA levels were lower especially in patients with cognitive decline. More specifically, CSF 5-HIAA levels of PD-MCI, PDD and DLB patients differed significantly from those of healthy controls as well as PD patients without cognitive impairment. Finally, serum DA levels were significantly lower in DLB patients compared to controls whereas CSF and serum levels of HVA and DOPAC had the highest values for PD groups.

Conclusions: Monoaminergic neurotransmitter and metabolite levels in serum and CSF not only differed between healthy controls, PD and DLB patients, but also across different stages of cognitive impairment in PD. Our data suggests an important correlation between cognitive deterioration in PD and a dysfunctioning of especially the noradrenergic and serotonergic neurotransmission. This study therefore hypothesizes that these monoamines and metabolites could prove to be potential biomarkers for the cognitive decline in PD and DLB.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/monoaminergic-biomarkers-of-cognitive-decline-in-parkinsons-disease-and-lewy-body-dementia/