CSF Monoamine Metabolites and Cognitive Trajectory in Early Parkinson's Disease

Imaging and postmortem studies indicate that abnormalities in monoaminergic neurotransmission contribute to cognitive impairment in Parkinson's disease (PD). However, it remains uncertain if cerebrospinal fluid (CSF) monoamine metabolites can serve as biomarkers of cognitive decline in early PD.

We therefore examined associations of CSF 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3,4-dihydroxyphenylglycol (DOPEG), and 5-hydroxyindoleacetic acid (5-HIAA) with baseline Montreal Cognitive Assessment (MoCA) scores and with longitudinal rates of change.

Ninety-five patients with early PD and fifty-six demographically matched healthy controls (HCs) were included from the Parkinson's Progression Markers Initiative cohort. Baseline CSF concentrations of monoamine metabolites were measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). In PD patients, multivariable linear regression and linear mixed-effects models were used to evaluate the cross-sectional and longitudinal associations, respectively, between baseline CSF metabolites and MoCA scores. To facilitate comparison, the levels of monoamine metabolites were converted into Z-scores to attain standardized β coefficients.

Compared with HCs, PD patients had lower baseline CSF concentrations of DOPAC, HVA, and 5-HIAA. After adjustment for relevant covariates, any standardized CSF metabolite was not associated with baseline MoCA scores. Lower baseline CSF DOPAC and HVA were significantly associated with more rapid cognitive decline over time (z-DOPAC: β = 0.17, p < 0.001; z-HVA: β = 0.14, p = 0.009). Neither DOPEG nor 5-HIAA was associated with longitudinal cognitive decline.

Taken together, our results indicated that baseline CSF DOPAC and HVA may serve as promising longitudinal predictors of cognitive decline in patients with PD.