Hyperhomocysteinemia in L-dopa treated patients with Parkinson's disease: potential implications in cognitive dysfunction and dementia?

BACKGROUND: Hyperhomocysteinemia has been associated with cognitive dysfunction and dementia. The incidence of dementia in Parkinson's Disease (PD) patients is higher than in the general population and plasma Homocysteine concentrations are increased in L-dopa treated PD patients. OBJECTIVE: We evaluated the possible correlations between L-Dopa related hyperhomocysteinemia and cognitive dysfunction in PD. METHODS: A Medline literature search was performed to identify all published studies on Homocysteine and cognitive dysfunction and dementia during the course of PD from 1966 to 31/03/2010. RESULTS: Sixteen studies were found for review; ten studies focused on homocysteine and cognitive dysfunction in PD patients, five on homocysteine and PD dementia and two on homocysteine and markers of neurodegeneration in PD. The design of the study was retrospective in 14 studies, while 2 had a prospective design, with a variable follow-up period (from 24-weeks to 2 years). In most of the studies plasma homocysteine levels significantly correlated with cognitive functions, dementia and markers of neurodegeneration in PD patients. However, some studies did not confirm these findings. Several factors may concur to explain these partially conflicting results, including the retrospective design of the studies, their small sample size, their high percentage of excluded patients, and the use of a wide range of neuropsychological tasks in assessment of cognitive dysfunctions across the available studies. CONCLUSIONS: Available data seem to indicate a potential role of L-dopa related hyperhomocysteinemia on cognitive impairment and dementia during the course of PD.

Hyperhomocysteinemia in L-dopa treated Parkinson's disease patients: effect of cobalamin and folate administration.

Homocysteine (Hcy) is a risk factor for vascular diseases, cognitive impairment and dementia. L-dopa treatment may represent an acquired cause of hyperhomocysteinemia (HHcy), as evidenced by studies in rats as well as in Parkinson's disease (PD) patients. Folate and cobalamin status also seems to influence the effects of L-dopa on plasma Hcy levels; therefore B-vitamins supplementation has been proposed to reduce the HHcy in L-dopa treated PD patients. Plasma Hcy, folate, and cobalamin levels were evaluated in 20 PD patients treated with L-dopa in the baseline condition and following a 5-week period of treatment with cobalamin and folate; results were compared with 35 controls. Analysis of data revealed that Hcy levels were higher in L-dopa treated PD patients when compared with age- and sex-matched controls and that supplementation of the diet with cobalamin and folate is effective in reducing Hcy concentrations; these findings may have important implications in the treatment of PD patients who are potentially at risk for vascular diseases and cognitive impairment or dementia.

Plasma homocysteine levels in Parkinson's disease: role of antiparkinsonian medications.

Elevated plasma homocysteine (Hcy) concentrations have been reported in L-dopa treated Parkinson's disease (PD) patients, suggesting that L-dopa treatment is an acquired cause of hyperhomocysteinemia. Aim of this study is to evaluate the effects of different antiparkinsonian drugs on Hcy concentrations. We compared Hcy, B(12) and folate levels in 45 PD patients (15 treated with dopamine-agonists, 15 with L-dopa and 15 with L-dopa plus a catechol-O-methyltransferase-inhibitor (COMT-I) and in 15 controls. Analysis of data revealed that L-dopa administration significantly increases Hcy concentrations and that the addition of COMT-I effectively reduces the homocysteinemia.