Elevated plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with dyskinesias

Abstract

Elevated plasma homocysteine (Hcy) concentrations are associated with increased risk of systemic vascular diseases, Alzheimer's disease and vascular dementia. Several cross-sectional reports and two prospective clinical studies have recently reported elevated plasma Hcy levels in L-dopa-treated Parkinson's disease (PD) patients and Hcy has been proposed as a possible mediator for the development of long-term L-dopa motor complications (such as wearing off and on-off phenomena, and dyskinesias). The aim of the study was to elucidate a possible role of L-dopa-related hyperhomocysteinemia in the development of dyskinesias. In this cross-sectional study we compared Hcy, B(12) and folate levels in 53 PD patients treated with L-dopa (29 with dyskinesias, 24 without dyskinesias). Mean plasma Hcy levels were higher in the group of PD patients with dyskinesias (19 vs. 15.4 micromol/L; T: 2.12; p=0.04). After taking into account potential confounding factors, analysis of the data revealed that the occurrence of dyskinesias progressively increased with plasma Hcy levels (relative risk 1.2, 95% CI 1.015-1.4; p=0.03). Our results raise the possibility that Hcy plays a role in the development of dyskinesias, through its toxic effects on both dopaminergic neurons and non-substantia nigra, non-dopaminergic neurons.