The Effect of Hyperhomocysteinemia on Motor Symptoms, Cognitive Status, and Vascular Risk in Patients with Parkinson’s Disease

Hindawi Publishing Corporation Parkinson’s Disease Volume 2016, Article ID 1589747, 7 pages http://dx.doi.org/10.1155/2016/1589747 Research Article The Effect of Hyperhomocysteinemia on Motor Symptoms, Cognitive Status, and Vascular Risk in Patients with Parkinson’s Disease Bilge Kocer,1 Hayat Guven,1 Isik Conkbayir,2 Selim Selcuk Comoglu,1 and Sennur Delibas1 1 Department of Neurology, Diskapi Yildirim Beyazit Training and Research Hospital, 06110 Ankara, Turkey Department of Radiology, Diskapi Yildirim Beyazit Training and Research Hospital, 06110 Ankara, Turkey 2 Correspondence should be addressed to Bilge Kocer; Received 7 February 2016; Accepted 2 August 2016 Academic Editor: Ivan Bodis-Wollner Copyright © 2016 Bilge Kocer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Factors related with hyperhomocysteinemia (HHcy) and the impact of HHcy in Parkinson’s disease (PD) are not well understood. We investigated the factors associated with increased levels of homocysteine (Hcy) and the relationship between HHcy and motor symptoms, cognitive status, and vascular risk in patients with Parkinson’s disease. Among 60 patients (29 males, 48.3%) with PD, the stage of the disease, the severity of clinical symptoms, and the patients’ cognitive status were measured using a modified Hoehn and Yahr Staging Scale (mHY), Unified Parkinson’s Disease Rating Scale (UPDRS) II and III, and Mini-Mental State Examination (MMSE), respectively. Patients were also noted for having dyskinesia and hallucinations. Serum vitamin B12, folic acid, and plasma Hcy levels were measured. Furthermore, the presence of vascular risk factors was recorded. Finally, we investigated carotid artery intima-media thickening and stenosis using colour Doppler ultrasonography as well as the presence of ischemic lesions using brain imaging techniques. Plasma Hcy levels were higher with advanced age and in males. In addition, there was an inverse relationship between Hcy and vitamin B12 levels. There was no correlation between HHcy and the stage of the disease, severity of motor symptoms, cognitive status as assessed by the MMSE, vascular risk factors, carotid artery atherosclerotic findings, and ischemic brain lesions. Plasma Hcy levels may rise due to several factors in PD. However, the resulting HHcy has no significant effect on the clinical picture in terms of motor features, cognitive status, and vascular diseases. 1. Introduction Hyperhomocysteinemia (HHcy) is an established risk factor for cardiovascular, cerebrovascular, and peripheral vascular diseases [1–3]. In Parkinson’s disease (PD) patients undergoing levodopa (LD) therapy, plasma homocysteine (Hcy) levels are elevated as a result of the transmethylation of LD via catechol O-methyl transferase (COMT) [4, 5]. The effect of this HHcy on vascular diseases in PD patients is unclear; HHcy could potentially cause vascular pathologies or the worsening of motor features. Experimental studies have demonstrated that Hcy can be neurotoxic and excitotoxic to the substantia nigra. Furthermore, Hcy may be associated with dyskinesias, which is an indicator of possible neurodegeneration due to the disruption of the balance of striatal activity [6, 7]. The prevalence of neuropsychiatric symptoms, such as depression and dementia, is increased in PD [8, 9]. Among the elderly, HHcy is a well-known risk factor for dementia [10]. HHcy has been proposed to also be a risk factor for the neuropsychiatric disorders, cognitive deterioration, dementia, and depression that are seen in PD, but some studies have not confirmed these results [11–15]. Therefore, we examined the relationship between plasma Hcy levels and the severity of PD-related motor features and cognitive status. We also determined the risk of vascular disease in PD patients by using vascular risk factors, previous vascular diseases, atherosclerotic findings detected by 2 carotid artery colour Doppler ultrasonography, and ischemic changes in brain imaging studies. 2. Materials and Methods 2.1. Study Design. This prospective study included 60 patients (29 males, 48.3%) randomly selected from patients diagnosed with idiopathic PD according to the UK Brain Bank criteria [16]. Patients with vascular parkinsonism and severe metabolic disorders or those who used vitamin supplements were excluded from the study. For all patients, the duration of the disease, on-going treatments, and dosage and duration of levodopa therapy were recorded. In addition, patients were also examined for the presence of vascular risk factors, such as hypertension, diabetes mellitus, and hyperlipidemia and for vascular diseases, such as coronary artery disease and stroke. The stage of PD and the severity of disease findings were determined by the “modified Hoehn and Yahr (mHY) Staging Scale” and “Unified Parkinson’s Disease Rating Scale” (UPDRS) II and III, respectively [17, 18]. The dominant motor features of PD were determined by using the subscores calculated from questions about tremor (20, 21), rigidity (22), bradykinesia (23, 24, 25, 26, 31), and balance/postural instability (27, 28, 29, and 30) in the UPDRS III. In addition, the presence of dyskinesia was also noted. The assessment of global cognitive status was conducted with the standardised “Mini-Mental State Examination” (MMSE). We also noted the presence of visual hallucinations. Blood samples were collected from peripheral veins into vacuum tubes containing EDTA in the early morning after 12 hours of fasting and 12-hour drug-free periods. Plasma Hcy levels were measured by high-performance liquid chromatography with fluorescence detection (HPLCFLD). Serum vitamin B12 and folic acid levels were measured by an immunoassay. The carotid arteries of patients and control subjects were investigated using carotid colour Doppler ultrasonography with a 6 to 11 MHz linear probe performed by the same physician in the Radiology Department who was blinded from the clinical history of 50 subjects. The common carotid arteries and extracranial internal carotid arteries were investigated on the axial and longitudinal planes using the B mode and colour Doppler methods, starting at the origin and including the bifurcation point; intimal thickening, plaques, and stenosis were noted. The frequency levels, gain adjustments, and grey scale and Doppler parameters were manually adjusted to optimise visualisation of stenosis [19]. Among 45 patients, ischemic lesions at the lacunar and specific arterial irrigation areas were recorded by brain computed tomography (CT) and magnetic resonance imaging (MRI) examinations. The study was carried out according to the Helsinki Declaration and was approved by the Institutional Ethics Committee. 2.2. Statistical Analysis. All statistical data analyses were performed with SPSS Statistics (ver (...truncated)