Background: An elevated plasma homocysteine (Hcy) level has been prospectively associated with an increased risk of vascular and degenerative dementias. An Hcy elevation is prevalent in patients with Parkinson disease (PD) in part because levodopa metabolism produces Hcy. The clinical relevance of an elevated Hcy level in patients with PD is unknown. Objective: To determine if hyperhomocysteinemia in patients with PD is associated with depression or with cognitive or physical impairments. Design: Ninety-seven people with a mean (SD) PD duration of 3.6 (1.6) years completed the Beck Depression Inventory, a battery of 11 cognitive tests, and the motor and function components of the Unified Parkinson's Disease Rating Scale. Normalized scores for the affective, cognitive, and physical measures were compared between those with a normal Hcy level (n= 66) and those with hyperhomocysteinemia (n=31) (Hcy level, >1.89 mg/L [>14 μmol/L]), controlling for age, sex, disease duration, and treatment. Results: Subjects with an elevated Hcy level were slightly older (68 vs 62 years), but had similar plasma concentrations of vitamin B12 and folate. Hyperhomocysteinemic patients were more depressed (P=.02) and had worse cognition (P<.01), but the physical measure did not differ. Conclusions: Patients with PD and hyperhomocysteinemia are more likely to be depressed and to perform worse on neuropsychometric tasks compared with normohomocysteinemic patients. Further research is warranted to see if hyperhomocysteinemia is a reversible risk factor for neuropsychiatric burden in patients with PD.