Krystyna Honczarenko

Rotigotine Effects on Early Morning Motor Function and Sleep in Parkinson's Disease: A Double-Blind, Randomized, pLacebo-Controlled Study (RECOVER)

In a multinational, double‐blind, placebo‐controlled trial (NCT00474058), 287 subjects with Parkinsons disease (PD) and unsatisfactory early‐morning motor symptom control were randomized 2:1 to receive rotigotine (2–16 mg/24 hr [n = 190]) or placebo (n = 97). Treatment was titrated to optimal dose over 1–8 weeks with subsequent dose maintenance for 4 weeks. Early‐morning motor function and nocturnal sleep disturbance were assessed as coprimary efficacy endpoints using the Unified Parkinsons Disease Rating Scale (UPDRS) Part III (Motor Examination) measured in the early morning prior to any medication intake and the modified Parkinsons Disease Sleep Scale (PDSS‐2) (mean change from baseline to end of maintenance [EOM], last observation carried forward). At EOM, mean UPDRS Part III score had decreased by −7.0 points with rotigotine (from a baseline of 29.6 [standard deviation (SD) 12.3] and by −3.9 points with placebo (baseline 32.0 [13.3]). Mean PDSS‐2 total score had decreased by −5.9 points with rotigotine (from a baseline of 19.3 [SD 9.3]) and by −1.9 points with placebo (baseline 20.5 [10.4]). This represented a significantly greater improvement with rotigotine compared with placebo on both the UPDRS Part III (treatment difference: −3.55 [95% confidence interval (CI) −5.37, −1.73]; P = 0.0002) and PDSS‐2 (treatment difference: −4.26 [95% CI −6.08, −2.45]; P < 0.0001). The most frequently reported adverse events were nausea (placebo, 9%; rotigotine, 21%), application site reactions (placebo, 4%; rotigotine, 15%), and dizziness (placebo, 6%; rotigotine 10%). Twenty‐four‐hour transdermal delivery of rotigotine to PD patients with early‐morning motor dysfunction resulted in significant benefits in control of both motor function and nocturnal sleep disturbances.

The effect of monoamine oxidase B (MAOB) and catechol-O-methyltransferase (COMT) polymorphisms on levodopa therapy in patients with sporadic Parkinson's disease

Objectives –  The etiology of sporadic idiopathic Parkinsons disease (PD) is considered multifactorial with both genetic and environmental factors modifying the disease expression. Recent studies suggest that polymorphism in monoamine oxidase B (MAOB) and catechol‐O‐methyltransferase (COMT) might influence the risk and treatment of PD. The aim of the study was to evaluate the effect of MAOB and COMT genetic polymorphism on effective daily dose of levodopa applied during the first 5 years of treatment, and to find out if a relationship exists between MAOB and COMT haplotypes and motor disturbances onset in PD patients treated with levodopa preparations.

Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson's disease.

Introduction Elevated plasma homocysteine (Hcy) concentration is an independent risk factor for cardiovascular disease, and its involvement in endothelial cell dysfunction is well established. However, the role of Hcy and folate in the pathogenesis of Parkinson’s disease (PD) remains controversial. Objectives The study was aimed at evaluating the relationships between Hcy, vitamin B12, and folic acid levels in the blood and cognitive status in PD patients with the genetic polymorphisms of MTHFR (rs1801133: C>T-677C>T, rs1801131: A>C-1298A>C), COMT (rs4680: A>G-Val158Met, rs6269: A>G, rs4633: C>T, rs4818: C>G), or SLC19A1 (rs1051266: G>A-80G>A). Methods A total of 502 participants (248 with PD and 254 age-matched and sex-matched controls) were included in the study. The Unified Parkinson’s Disease Rating Scale score, Hoehn–Yahr staging, and the Schwab–England scale were used to assess motor abilities and activity during daily life. Complex psychological examination with a battery of tests was used to classify patients into groups with (PDD) and without (nPDD) dementia. Blood samples were examined for Hcy, vitamin B12, and folic acid levels, as well as polymorphisms in genes related to Hcy metabolism, such as COMT, MTHFR, and SLC19A1(RFC-1). Results The frequency of homozygous COMT rs4680G and rs4633C allele carriers was significantly decreased in PD patients in comparison with the controls (P=0.015; odds ratio=0.60; 95% confidence interval 0.41–0.90 and P=0.020; odds ratio=0.619; 95% confidence interval 0.42–0.92, respectively). No significant differences in the distribution of MTHFR 677C>T, 1298A>C, and SLC19A1 80G>A alleles and genotypes between PD patients and the controls were found. Hcy levels were significantly increased in PD patients (18±7.8 &mgr;mol/l) as compared with the controls (14.0±9.6 &mgr;mol/l, P=10–8) and were significantly associated with the MTHFR 677C>T polymorphism both in PD patients and controls, in which T allele carriers were characterized by markedly elevated Hcy plasma concentrations. No association was observed between Hcy plasma level and COMT and SLC19A polymorphisms. The results of multivariate logistic regression analysis revealed age (P=0.0003) and Hcy plasma levels (P=0.07) as independent risk factors predisposing individuals to PD dementia. The studied polymorphisms were not associated with cognitive status in PD patients. Conclusion The genetic factors studied were not associated with cognitive status in PD patients. Only age and Hcy plasma levels were found to be independent risk factors predisposing individuals to PD dementia. However, COMT: rs4680: A>G and rs4633: C>T polymorphisms were found to significantly affect PD risk, and the MTHFR 677C>T polymorphism helped determine plasma Hcy concentrations.

Ophthalmological Features of Parkinson Disease

Background The aim of this study was to determine the type and frequency of ophthalmologic changes occurring in patients with Parkinson disease (PD). Material/Methods One hundred consecutive patients (196 eyes) with idiopathic PD and a control group consisting of 100 healthy patients (196 eyes) matched for age and sex underwent a complete ophthalmological examination of both eyes, including assessment of patient medical history, dry eye questionare, and visual hallucinations questionnaire, distance and near best corrected visual acuity (DBCVA, NBCVA), color vision, distance photopic contrast sensitivity, near point of convergence, slit lamp examination of the eye anterior segment, tear film osmolarity and breakup time, aqueous tear production, and intraocular pressure, as well as fundus examination and evaluation of the perimacular retinal thickness (RT) and peripapillary retinal nerve fiber layer (RNFL) thickness. Results In the eyes of PD patients DBCVA, NBCVA, contrast sensitivity, and color discrimination were significantly reduced. We also detected increased frequency of convergence insufficiency, seborrhoic blepharitis, meibomian gland disease (MGD), dry eye syndrome, nuclear and posterior subcapsular cataract, and glaucoma (p<0.05). However, intraocular pressure (IOP) was significantly lower in the PD group compared to controls. The frequency of visual hallucinations, age-related macular degeneration (ARMD), and other ophthalmological diseases, as well as RT and RNFL thickness, did not significantly differ between investigated groups. Conclusions Clinicians need to be aware of the association between PD and ophthalmological changes. Restoration of good-quality vision has a great impact on PD patients’ quality of life, reduction of costs of treatment and care, and rehabilitation.

The impact of MRI white matter hyperintensities on dementia in Parkinson's disease in relation to the homocysteine level and other vascular risk factors.

Background: The role of white matter hyperintensities (WMH) and homocysteine (Hcy) and other vascular risk factors in the pathogenesis of Parkinsons disease (PD) dementia (PDD) remains unclear. Objective: The aim of the study was to assess the impact of WMH, Hcy and other biochemical and vascular risk factors on PDD. Methods: A total of 192 patients with PD and 184 age- and sex-matched healthy controls were included. A semistructured interview was used to assess demographic and clinical variables with respect to vascular risk factors (arterial hypertension, diabetes mellitus, atrial fibrillation, ischemic heart disease, obliterative atherosclerosis, hypercholesterolemia, smoking, alcohol intake). Unified Parkinsons Disease Rating Scale score, Hoehn-Yahr staging and the Schwab-England activities of daily living scale were used to assess motor abilities and activities of daily living. A complex neuropsychological examination with a battery of tests was used to classify patients into a group with dementia (PDD) and a group without dementia (PD). Neuroradiological examination of MRI scans included visual rating scales for WMH (according to the Wahlund and Erkinjunntti rating scales) and the Scheltens scale for hippocampal atrophy. Blood samples for Hcy, folate, vitamin B12, fibrinogen, lipids, glucose, creatinine, transaminases and thyroid stimulating hormone (TSH) were examined. Results: Among all patients, 57 (29.7%) fulfilled the diagnostic criteria for dementia. Significantly higher Hcy plasma levels were noted in PD and PDD groups compared to controls (p < 0.05) and in PDD when compared to PD (p < 0.05). According to multivariate regression analysis, WMH (Erkinjuntti scale), high Hcy, low vitamin B12 and folate plasma levels were independent risk factors for PDD. Vascular risk factors did not play any role in the pathogenesis of PDD and WMH. Conclusions: WMH along with Hcy, folate and vitamin B12 may impact cognition in PD. Therapy with vitamin B12, folate and catechol-O-methyltransferase inhibitors may play a potential protective role against PDD.

BDNF G196A (Val66Met) polymorphism associated with cognitive impairment in Parkinson's disease

Brain-derived neurotrophic factor (BDNF) is a neurotrophin widely expressed in the mammalian brain, regulating neuronal survival and known to influence dopaminergic neurons and cognitive processes. The present study investigated the BDNF Val66Met polymorphism associations with PD risk, and cognitive impairment in PD. A total of 486 study subjects (244 PD and 242 age and sex matched controls) were included in the study. UPDRS score, Hoehn-Yahr staging and the Schwab-England scale were used to assess motor abilities and activity during daily life. The patients were classified into groups with dementia (PDD, n=69) and without it (nPDD, n=166) on the basis of neuropsychological assessment. The most common functional polymorphism in BDNF Val66Met (rs6265, G196A) gene was determined using TaqMan real-time PCR assay. Frequencies of evaluated BDNF alleles and genotypes were similar in PD and the controls. The mean age of disease onset among BDNF Met/Met carriers was later (65.00±6.13) in comparison to Val/Val (57.45±10.68) and Val/Met (56.33±10.91) subjects (p=0.077). The studied BDNF polymorphism was not associated with cognitive status in PD patients. However, patients with Met/Met alleles demonstrated better delayed recall of information than patients with Val/Val alleles. The results of multivariate logistic regression analysis revealed age (p=0.0003) and the disease stage (p=0.002) as independent risk factors predisposing to PD dementia.

Catechol-O-Methyltransferase and Monoamine Oxidase B Genes and Susceptibility to Sporadic Parkinson’s Disease in a Polish Population

Recent reports have proved that genetic factors play a role in the pathogenesis of sporadic Parkinson’s disease (PD). It has been suggested that polymorphisms in monoamine oxidase B (MAOB) and catechol-O-methyltransferase (COMT) might increase the risk of PD. A total of 210 Polish patients with sporadic PD and 152 healthy controls were studied. The MAOB and COMT polymorphisms were identified using the polymerase chain reaction-restriction fragment length polymorphism method. The MAOB allele and genotype frequencies in PD patients did not differ significantly from the controls. A statistically lower frequency of the COMTLL genotype in patients with parkinsonism was found. The combined haplotype of the MAOB G (G/G) and COMTHL genotype showed a fourfold increase (p < 0.05) in the risk of PD in female patients in this Polish population.

Articulation disorders and duration, severity and L-dopa dosage in idiopathic Parkinson's disease.

BACKGROUND Parkinsons disease (PD) is one of the most common diseases of the central nervous system (CNS). It is frequently heralded by speech disturbances, which are one of its first symptoms. AIM The aim of this paper is to share our own experience concerning the correlation between the severity of speech disorders and the PD duration, its severity and the intake of L-dopa. MATERIAL AND METHODS The research included 93 patients with idiopathic PD, aged 26-86 years (mean age 65.1 years). Participants were examined neurologically according to the Unified Parkinsons Disease Rating Scale (UPDRS) and the Hoehn and Yahr Scale. They were also assessed by Frenchay Dysarthria Assessment. RESULTS Considerable and severe disorders were concurrent with impairments in the mobility of the tongue, lips, the jaw as well as the pitch and loudness of the voice. The strongest correlation but at a moderate level was found to exist between the severity of labial impairment, voice loudness and the length of the disease. There was also a positive correlation between lip movement while the motions were being diversified, lip arrangement while speaking and the intake of L-dopa. CONCLUSIONS As PD progresses a significant decline in vocal articulation can be observed, which is due to reduced mobility within the lips and the jaw. Exacerbation of articulation disorders resulting from progression of the disease does not materially influence the UPDRSS scores. L-dopa has been found to positively affect the mobility of the lips while the patient is speaking and their arrangement at rest.

Is there an effect of folic acid supplementation on the coagulation factors and C-reactive protein concentrations in subjects with atherosclerosis risk factors?

INTRODUCTION Folic acid (FA) may delay the formation of atherosclerotic lesions. Increased plasma levels of von Willebrand factor (VWF) are observed in cardiovascular disease, which leads to higher risk of thrombosis. Fibrinogen (Fb) is a well-documented risk factor of cardiovascular disease. The aim of this study was to analyze the effect of FA supplementation on the Fb, VWF and C-reactive protein (CRP) plasma concentrations in subjects with atherosclerosis risk factors. MATERIAL/METHODS The study enrolled 124 Caucasian individuals (60 M, 64 F) with atherosclerosis risk factors--family history of premature ischaemic stroke, arterial hypertension, dyslipidaemia, overweight and obesity, cigarette smoking and low physical activity. The participants were asked to take FA in the low dose of 0.4 mg/24 h for three months. RESULTS After FA supplementation a significant reduction of the VWF concentrations in females (76.6 vs 72.3%; p=0.028) and in males (75.5 vs 66.9%; p=0.001) was observed. Among women and men with dyslipidaemia concentrations of VWF decreased after FA supplementation (76.8% vs 69.6%; p=0.003 and 76.7% vs 67.8%; p=0.001 respectively). Among females and males with BMI ≥25 kg/m² concentrations of VWF decreased only in men (77.6% vs 66.5%; p=0.001). In female and male smokers supplementation of FA decreased VWF concentrations (82.5% vs 74.4%; p=0.012 and 76.6% vs 69.5%; p=0.036 respectively). DISCUSSION The results of our study suggest that there is an effect of FA supplementation on VWF concentrations in subjects with atherosclerosis risk factors.

Risk Factors of Fatigue in Idiopathic Parkinson's Disease in a Polish Population

Introduction. Fatigue syndrome is one of the nonmotor symptoms in Parkinsons disease (PD). The aim of the study was assessment of prevalence of fatigue syndrome in PD and answering the question what are the independent risk factors connected with intensity of fatigue in PD. Methods. 114 patients with idiopathic PD (mean age 62.2 + 10.8 years) were enrolled. The fatigue was assessed according to the Fatigue Severity Scale (FSS). We analyzed associations between fatigue and sex, age, education, duration and severity of the disease, everyday activity, intensity of the main symptoms, treatment, presence of dyskinesias and fluctuations, depression and excessive sleep during the day, and presence of pain and nycturia. Results. The fatigue syndrome was detected in 57.9% of patients. The score in the FSS was 1 to 7 points, 4.3 average. Greater fatigue intensity correlated with higher total daily levodopa equivalent dose. Patients with moderate depression had significantly greater fatigue. Conclusions. Fatigue syndrome affects 57.9% of patients with PD. Use of higher LED and presence of moderate depression are independent risk factors of greater intensity of fatigue.