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Objectives: The pathogenesis of isolated rapid eye movement sleep behavior disorders (iRBD) is poorly understood. The severity of RBD may reflect its pathogenesis., Methods: We compared motor function and non-motor symptoms (NMSs) between iRBD patients and healthy volunteers. We correlated motor function, NMSs, and striatal dopaminergic activity with RBD severity using video-polysomnography., Results: Twenty-one iRBD patients and 17 controls participated. The Unified Parkinson's Disease Rating Scale part III scores were higher in patients compared to controls ( p  < 0.001). There was no difference in upper extremity function between patients and controls (right, p  = 0.220; left, p  = 0.209), but gait was slower in iRBD patients (walking time, p  < 0.001; number of steps, p  < 0.001). The mean value of the Korean version of the Mini-Mental State Exam and Clinical Dementia Rating were lower in patients ( p  = 0.006, p  = 0.003, respectively). Patients with were also more depressed ( p  = 0.002), had decreased olfactory function ( p  < 0.001), reported more frequent sleep/fatigue episodes ( p  < 0.001), worse attention/memory capacity ( p  < 0.001), gastrointestinal problems ( p  = 0.009), urinary problems ( p  = 0.007), and pain ( p  = 0.083). Further, iRBD patients reported more frequent sleep-related disturbances ( p  = 0.004), but no difference in daytime sleepiness ( p  = 0.663). Disease severity was correlated with pain ( r  = 0.686, p  = 0.002) and visuospatial function ( r = -0.507, p  = 0.038). There were no correlations between RBD severity and striatal dopaminergic activities ( p  > 0.09)., Conclusions: iRBD is a multisystem neurodegenerative disorder, and gait abnormalities may be a disease characteristic, possibly related to the akinetic-rigid phenotype of Parkinson's disease. The correlation between pain/visuospatial dysfunction and RBD severity may be related to its pathogenesis.

Aside from the glucocerebrosidase gene, the genetic risk factors for cognitive decline in Parkinson's disease (PD) are controversial. We investigated whether the G2385R polymorphism in leucine-rich repeat kinase 2 gene (LRRK2), a risk variant for the development of PD in East Asians, is associated with cognitive dysfunction in PD. We recruited 299 PD patients, consisting of 23 carriers and 276 non-carriers of LRRK2 G2385R, from 14 centers. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA). PD with cognitive dysfunction was defined as an MMSE Z score that, adjusting for age at study entry and years of education, was below -1.0 standard deviations. In multivariate analysis, PD duration, age at study entry and depression were significant risk factors for cognitive dysfunction as assessed by MMSE performance or the MoCA. In linear regression analysis of the association between MMSE Z scores and PD duration, there was no significant difference associated with the LRRK2 G2385R genotype. The interaction terms between PD duration and the LRRK2 G2385R genotype were not significant for the MMSE Z score but were significant for the MoCA. In conclusion, the LRRK2 G2385R genotype may not be associated with cognitive dysfunction in PD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Visual hallucination (VH) is closely associated with cognitive impairment in Parkinson's disease (PD). The aim of this study is to analyze the domain of cognitive impairment related to the VH by analyzing cognition in PD., Method: Twenty-six of 58 patients had VH (PD-VH), whereas 32 patients had no hallucinations (PD-NH); patients assigned to the PD-VH on the basis of having at least one VH per week for one month before participation in the study. All of the patients were administered the Montreal Cognitive Assessment-Korean test (MoCA-K). We analyzed the differences in cognition between PD-VH and PD-NH., Results: The Hoehn-Yahr (HY) stage and the Beck Depression Inventory version I (BDI) scores in PD-VH were significantly different from those in PD-NH. After adjusting for the HY stage and BDI, the language domain of the MoCA-K cognitive domains presents a significant difference between PD-VH and PD-NH., Conclusion: Sentence processing and naming as the composition of the language domain in the MoCA-K have been associated in common with posterior cortical dysfunction. Although our result shows that the language domain of MoCA-K is sensitive to cognitive deficit in PD-VH patients, it needs further neuroimaging analysis for certifying the relationship between language impairment and posterior cortical deficit as the pathophysiology of PD-VH., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: To analyze the characteristics of neuropsychological profiles and gray matter volume in de novo, drug-naïve Parkinson's disease with mild cognitive impairment (PD-MCI)., Methods: Fifty-two newly diagnosed PD patients were assessed with neuropsychological testing, and PD-MCI was defined in patients with at least one or more abnormal cognitive test domains. PD with normal cognition (PD-NC) did not meet the criteria for PD-MCI or PD with dementia. Brain MRI scans was acquired from the patients and healthy controls (HC). The imaging processing and analysis of the gray matter (GM) volume were performed platform to determine the difference between PD-MCI and PD-NC., Results: There were no differences of motor subscores between PD-MCI and PD-NC. The clinical dementia rating, global deterioration scale, and verbal memory were significantly worse in PD-MCI than in PD-NC. GM volume loss was observed in the right hippocampus, right cuneus, and right precuneus in PD-NC compared to in the HC. PD-MCI had significantly decreased GM volume in the bilateral temporal and frontal areas compared with that of the HC. The GM volume was significantly decreased in the right temporal pole, left precuneus, medial frontal and posterior cingulated gyrus in PD-MCI compared with PD-NC., Conclusions: Clinical dementia ratings and global deterioration scales could differentiate PD-MCI from PD-NC. Verbal memory impairment is characterized as a cognitive deficit of de novo PD-MCI and is associated with the posterior cortical area., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) can be divided into the akinetic-rigid (ART), mixed (MT), and tremor-dominant (TDT) subtypes according to the clinically dominant symptoms. We analyzed the correlations between (123)I-meta-iodobenzylguanidine (MIBG) uptake and the clinical features of patients with various PD subtypes. In addition, we evaluated the relationship between MIBG uptake and the severity of the cardinal motor symptoms among patients with PD subtypes. The mean Unified Parkinson's Disease Rating Scale motor scores differed significantly among patients with different PD subtypes (± standard deviation [SD]) (ART, 34.6 ± 18.28; MT, 24.63 ± 7.78; TDT, 16.22 ± 4.15, p=0.002), especially between the ART and TDT subtypes (p=0.022). The mean MIBG uptake (± SD) was decreased in the TDT (1.69 ± 0.39), MT (1.35 ± 0.32), and ART (1.35 ± 0.22) subtypes (p=0.049). The MIBG uptake values differed significantly between the ART and TDT subtypes (p=0.02). The MIBG uptake was inversely correlated with the severity of hypokinesia in the ART subtype (r=-0.75; p=0.01) and the MT subtype (r=-0.8; p=0.02), but it was not correlated with the severity of any of the parkinsonian motor symptoms in the TDT subtype. These results imply that hypokinesia is strongly associated with sympathetic myocardial degeneration and that sympathetic myocardial degeneration can reflect the progression of the disease in patients with the ART and mixed MT subtypes of PD., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Parkinson's disease (PD) with autonomic dysfunction is difficult to differentiate from Parkinsonism-predominant multiple system atrophy (MSA-p). This study aimed to analyze the validity of MIBG scintigraphy for PD with autonomic dysfunction and MSA-p. Thirty-nine patients (PD: 27 patients, MSA-p type: 12) and 12 age-matched controls were prospectively enrolled and underwent MIBG scintigraphy and autonomic function test (AFT). We separately calculated early and delayed heart-to-mediastinal (H/M) ratio and washout rates (WRs). AFT was composed of sympathetic skin reflex and parasympathetic tests based on heart rate variability. Abnormal AFT was observed in 17 (63%) of PD and 10 (83%) of MSA-p. On comparing PD with abnormal AFT with MSA-p, either the early or delayed H/M ratio in PD was not different from that in MSA-p (P > 0.05). Only the WR could differentiate PD with abnormal AFT from MSA-p (47.07 +/- 57.48 vs. 31.39 +/- 31.52, respectively) (P = 0.026). According to the results, WR may be more useful than the early and delayed H/M ratio to distinguish MSA-p from PD with abnormal AFT. Furthermore, the MIBG uptake did not reflect the disease duration or severity., (2009 Movement Disorder Society.)

Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential therapeutic tool in Parkinson's disease (PD). However, the therapeutic value and/or the placebo effect of rTMS on PD remain to be elucidated. To investigate the therapeutic value and/or placebo effect of rTMS in PD, we compared the motor section of unified PD rating scale (UPDRS III) and the amount of extracellular dopamine concentration using [(11)C] raclopride PET before and after two sessions of rTMS in 9 PD patients. During a consecutive 2 days while off-medication, two series of 15 trains of 5 Hz-frequency rTMS (intensity, 90% of the resting motor threshold) were applied to the hand area of more severely symptomatic motor cortex (MC). After unilateral rTMS of MC, mean raclopride binding potentials (BPs) were reduced not only in putaminal and caudate areas on the stimulated side (-4.9% and -6.5%, respectively) (P > 0.05) but also in putaminal and caudate areas of nonstimulated hemispheres (-6.6%, P > 0.05 and -12.1%, P = 0.049, respectively). UPDRS III scores were significantly decreased (35.0 +/- 14.1 to 32.0 +/- 13.4, P = 0.049). A reduction of raclopride BP in nonstimulated ventral striatum by unilateral rTMS supports the placebo response during rTMS., (2007 Movement Disorder Society)

Olfactory deficit is known to occur frequently in Parkinson's disease (PD). This study aimed to explore olfactory deficit in PD and to investigate its possible correlation with the disease severity or the depth of the olfactory sulcus. Fifty-nine PD patients and 25 normal controls were examined by the odor identification test with the crosscultural smell identification test (CC-SIT). Among these subjects, the depth of the olfactory sulcus of 42 PD patients and 8 controls was measured in the plane of the posterior tangent through the eyeballs using the coronal view brain MRI. The CC-SIT scores of the PD patients were significantly lower than those of the normal control (P<0.001). However, CC-SIT did not correlate with the disease duration, H-Y stage, score of UPDRS Part III, or the depth of either side of the olfactory sulcus (P>0.05). Our study confirms that CC-SIT is a helpful test in detecting the olfactory deficit in Korean PD patients. The absence of correlation of olfactory deficit with the disease severity or the depth of olfactory sulcus may suggest that olfactory loss precede the development of motor signs and not be a primary consequence of damage to the olfactory sulcus., (Copyright (c) 2007 Movement Disorder Society.)

Valvular heart disease, associated with ergot derivative dopamine agonists, has been reported in patients with Parkinson's disease (PD). There are few comparative studies on the frequency, severity, and dose dependency of valvular disease associated with ergot derivatives. We analyzed these factors in 58 PD patients who were taking ergot derivatives (22 were taking bromocriptine and 36 were taking pergolide) and compared them with 20 age-matched controls based on the two-dimensional echocardiographic findings. Aortic, mitral, and tricuspid valvular thicknesses, as well as tenting areas and tenting distance of the mitral valve were measured. We also assessed the correlation between the cumulative or daily doses of ergot derivatives and each valvular parameter. There was no significant increase in the frequency of valvulopathy in the PD patients taking bromocriptine or pergolide. We identified a positive correlation between the daily dose of pergolide and the tenting area of the mitral valve (r = 0.385; P = 0.020). However, other valvular parameters were not found to correlate with the age, disease duration, treatment duration, or dosage of medication. Our study failed to uncover definitive harmful effects of ergot derivative dopamine agonists on cardiac valves; this is considering the relatively lower daily doses than other reported cases. To establish a dosage dependency with valvulopathy, a more detailed study with higher doses of ergot derivatives for longer duration of treatment may be needed., ((c) 2006 Movement Disorder Society)

Background: Systematic analysis of clinical features and gene mutations has not been performed in Korean patients with early-onset Parkinson disease (PD)., Objective: To investigate the clinical characteristics and genetic background of Korean patients with early-onset PD., Design: Clinical and genetic study., Setting: University hospital., Patients: Ninety-four patients with early-onset PD (mean +/- SD age at onset, 39.8 +/- 7.3 years) of 1100 patients with PD., Interventions: Analysis of clinical characteristics and mutation analysis of the parkin and PTEN-induced kinase (PINK1) genes by direct sequencing and gene-dosage analysis using the multiplex ligation-dependent probe amplification technique., Main Outcome Measures: The correlation between age at onset and clinical characteristics and the clinical features of patients with onset before age 30 years vs patients with onset after age 30 years., Results: Because age at onset was younger, levodopa-induced dyskinesia and off-dystonia were more frequently observed (P=.008). Patients affected before age 30 years showed more frequent levodopa-induced dyskinesia and off-dystonia (P=.002). We identified 3 patients (5%) with parkin gene mutations but none with the PINK1 mutation., Conclusions: Earlier onset of levodopa-induced dyskinesia and off-dystonia were characteristic features of early-onset PD, especially before an onset age of 30 years. However, parkin gene mutations were less frequent in these patients than in Japanese groups reported elsewhere.