Monoaminergic biomarkers of cognitive decline in Parkinson's disease and Lewy body dementia

Objective: The objective of this study was the identification of biochemicalmarkers of cognitive impairment in Parkinson’s disease (PD)and dementia with Lewy bodies (DLB) by focusing on cerebrospinalfluid (CSF) and serum levels of various monoaminergic neurotransmittersacross different stages of cognitive decline. Methods: The study population comprised 154 subjects in total, ofwhich 43 healthy control subjects, 28 patients with PD, 27 patients withPD and mild cognitive impairment (PD-MCI), 18 patients with PDdementia (PDD), and, 38 patients with DLB. Matched serum and CSFlevels of a variety of eight monoamines and metabolites were analyzedapplying RP-HPLC-ECD, i.e. dopamine (DA), serotonin (5-HT), (nor)-adrenaline ((N)A) and their respective metabolites, i.e. 3,4-dihydroxyphenylaceticacid (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 ofcognitive performance and the administered psychotropic medicationwas documented. Results: CSF and serum levels of both NA and MHPG were foundto be significantly higher in patients with PD compared to healthy controlsubjects. In addition, in PD patients, CSF MHPG levels were higherin patients with PDD compared to cognitively normal PD patients. Furthermore,we observed higher CSF and serum 5-HIAA levels in healthycontrols compared to all PD groups and DLB patients. As for the patientgroups, CSF 5-HIAA levels were lower especially in patients with cognitivedecline. More specifically, CSF 5-HIAA levels of PD-MCI, PDDand DLB patients differed significantly from those of healthy controls aswell as PD patients without cognitive impairment. Finally, serum DAlevels were significantly lower in DLB patients compared to controlswhereas CSF and serum levels of HVA and DOPAC had the highest valuesfor PD groups. Conclusions: Monoaminergic neurotransmitter and metabolite levelsin serum and CSF not only differed between healthy controls, PD andDLB patients, but also across different stages of cognitive impairment inPD. Our data suggests an important correlation between cognitive deteriorationin PD and a dysfunctioning of especially the noradrenergic andserotonergic neurotransmission. This study therefore hypothesizes thatthese monoamines and metabolites could prove to be potential biomarkersfor the cognitive decline in PD and DLB