Is There the Preventive Effect of COMT-inhibitor on Parkinson's Disease Associated with Dementia?

Abstract

Background: Elevated homocysteine (hcy) levels are associated with dementia, which is a frequent nonmotor symptom of Parkinson's disease (PD). High levels of hcy in PD patients treated with levodopa are thought to result from increased synthesis during the metabolism of levodopa by COMT, and that use of a COMT-inhibitor may reduce hcy levels. In this study, we sought to clarify the effects of COMT-inhibitors on dementia in PD patients. Methods: Thirty-eight PD patients without dementia (PDwoD), 35 PD patients with dementia (PDD), and 48 controls were enrolled in this study. All subjects underwent neuropsychological testing and a neurological examination. The hcy levels were measured in all subjects, and the relationship between hcy levels and dementia was evaluated in two PD groups (those that underwent treatment with levodopa-alone versus treatment with levodopa plus a COMT-inhibitor). Results: Patients in the PDD group showed higher hcy levels than patients in the PDwoD group, though there was no significant difference in the hcy level between PDwoD patients and healthy controls. Regarding the effects of a COMT-inhibitor, there was no correlation between hcy levels in the 2 PD subgroups, indicating that there were no significant effects of the COMT-inhibitor on PDD. In addition, the odds ratio for PDD with the use of a COMT-inhibitor was 0.864 (95% CI= 0.342-2.180). Conclusions: These results are in agreement with previous studies in that levodopa treatment in PD patients leads to elevated hcy concentrations. COMT-inhibitors, on the other hand, had no preventive effect on cognitive impairment in PD patients.

Homocysteine levels, genetic background, and cognitive impairment in Parkinson’s disease

“…However, the literature on Hcy levels and cognitive impairment in PD is mixed. Some reports have found impaired cognition in PD patients with hyperhomocysteinemia [7,[11][12][13][14][15][16][17][18], while others found no relationship between Hcy levels and cognitive impairment in PD [19,20]. The discrepancies in the literature can be attributed to the sample size, the comprehensiveness of cognitive tests, or the interindividual genetic variability.…”