Validation Study of the Official Korean Version of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale

Background@#and Purpose: The Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) is widely used for estimating the symptoms of Parkinson’s disease. Translation and validation of the MDS-UPDRS is necessary for non-English speaking countries and regions. The aim of this study was to validate the Korean version of the MDS-UPDRS. @*Methods@#Altogether, 362 patients in 19 centers were recruited for this study. We translated the MDS-UPDRS to Korean using the translation-back translation method and cognitive pretesting. We performed both confirmatory and exploratory factor analyses to validate the scale.We calculated the comparative fit index (CFI) for confirmatory factor analysis, and used unweighted least squares for exploratory factor analysis. @*Results@#The CFI was higher than 0.90 for all parts of the scale. Exploratory factor analysis also showed that the Korean MDS-UPDRS has the same number of factors in each part as the English version. @*Conclusions@#The Korean MDS-UPDRS has the same overall structure as the English MDSUPDRS. Our translated scale can be designated as the official Korean MDS-UPDRS.

Clinical Utility of Seoul Neuropsychological Screening Battery-Core for Dementia Management Project in the Community

BACKGROUND: The increasing number of dementia patients is increasing the importance of identifying them and also those at a high risk of dementia. The early diagnosis and management of dementia can slow the progression of the disease and reduce the socioeconomic burden. For these purposes, the Local Dementia Centers established in all regions of Korea are working on the early detection of dementia using neuropsychological batteries. This study investigated the utility of the Seoul Neuropsychological Screening Battery-Core (SNSB-C) in a dementia management project performed in the local community. METHODS: This study was conducted in two parts. The first part used data from the Local Dementia Centers to investigate the accuracy of detecting cognitive impairment in SNSB-C compared with the Seoul Neuropsychological Screening Battery-Second Edition (SNSB-II). The second part of this study which data from hospital examined the accuracy of diagnosing dementia using SNSB-C. RESULTS: Data were collected from 508 participants at the Local Dementia Centers in Daejeon and 50 participants at a hospital. SNSB-C had a high sensitivity and specificity for detecting cognitive impairment, and also a high sensitivity, high specificity, and positive predictive value for diagnosing dementia. CONCLUSIONS: The sensitivity in diagnosing dementia was as high for SNSB-C as for SNSB-II while taking less time. SNSB-C could therefore be a good diagnostic evaluation tool for use in local dementia centers.

Characteristics of Cerebral Microbleeds

Cerebral microbleeds (CMBs) are increasingly recognized neuroimaging findings, occurring with cerebrovascular disease, dementia, and aging. CMBs are associated with subsequent hemorrhagic and ischemic stroke, and also with an increased risk of cognitive deterioration and dementia. They occur in the setting of impaired small vessel integrity due to hypertension or cerebral amyloid angiopathy. This review summarizes the concepts, cause or risk factors, histopathological mechanisms, and clinical consequences of CMBs.

Orthostatic Hypotension and Cognitive Function in Parkinson's Disease

BACKGROUND: Although orthostatic hypotension (OH) and cognitive impairment (CI) are common non-motor symptoms of Parkinson's disease (PD), the relationship between OH and CI remains to be clarified. This study was aimed to investigate the relationship between OH and CI in PD. METHODS: We recruited 192 patients who were diagnosed as PD based on the UK Brain Bank diagnostic criteria. The Hoehn & Yahr stages were ranged I to III and patients underwent extensive clinical evaluation, including brain magnetic resonance imaging (MRI) for cerebral white matter hyperintensity (WMH), tilt table test, the Korean version of Montreal Cognitive Assessments and the Korean version of Mini-Mental Status Examination in one month from the first clinic visit. The participants were divided into two groups according to the presence of OH (OH+ vs. OH−) and cognitive function (cognitive normal, CN vs. CI), respectively. RESULTS: Significant relationship between OH and cognitive function (p=0.04) was found in our patients. The patients with OH+ had higher risk of CI by 2.6 times than that of OH+ patients. Maximum heart rate change during tilt table test was correlated with cognitive function and white matter changes, whereas blood pressure change during tilt table test showed no correlation with those parameters. CONCLUSIONS: There was significant relationship between OH and CI in PD. Therefore, PD patients with either symptom may need periodic evaluation and proper management for OH and cognitive functions.

Correlation of Driving-related Cognition and Cognitive Impairment in Drivers over the Age of 60

BACKGROUND: A rate of traffic accidents by elderly drivers increased by 70% between 2011 and 2015 in Korea. Elderly drivers with cognitive impairment are more susceptible to be involved traffic accidents than cognitively normal individuals. This study aimed to evaluate the correlation of driving-related cognition and cognitive impairment in drivers over the age of 60 using the standardized program developed by the Road Traffic Authority (RTA). METHODS: Current drivers older than 60 years were recruited for the study. All participants were tested using the Mini-Mental Status Examination (MMSE), Rey Complex Figure Test (RCFT)-copy, and Digit Symbol Substitution Test (DSST) for cognitive function assessments. The driving aptitude test (DAT) for the elderly developed by RTA consists of 4 different tasks including speed and distance driving tests (SD), visuospatial memory driving tests (VM), sustained attention driving tests (SA), and divided attention driving tests (DA). The participants were divided into two groups by their MMSE score (normal cognition, CN; cognitive impairment, CI). RESULTS: One hundred fourteen participants were enrolled in the study and 57 of them were assigned to the CI group. In comparison, drivers in CI showed worse scores at DSST, SD, VM, and DA than those in CN. DSST and DA were worsened with increasing age. DSST was the best predictive assessment to be the risk or caution grade in DAT. CONCLUSIONS: We could find a correlation between DAT and cognitive function in drivers over the age 60. These results could be used as the basis of investigating optimal tools for decreasing driving risks in the cognitive impaired elderly.

Validity and Reliability Study of the Korean Tinetti Mobility Test for Parkinson's Disease

OBJECTIVE: Postural instability and gait disturbance are the cardinal symptoms associated with falling among patients with Parkinson’s disease (PD). The Tinetti mobility test (TMT) is a well-established measurement tool used to predict falls among elderly people. However, the TMT has not been established or widely used among PD patients in Korea. The purpose of this study was to evaluate the reliability and validity of the Korean version of the TMT for PD patients. METHODS: Twenty-four patients diagnosed with PD were enrolled in this study. For the interrater reliability test, thirteen clinicians scored the TMT after watching a video clip. We also used the test-retest method to determine intrarater reliability. For concurrent validation, the unified Parkinson’s disease rating scale, Hoehn and Yahr staging, Berg Balance Scale, Timed-Up and Go test, 10-m walk test, and gait analysis by three-dimensional motion capture were also used. We analyzed receiver operating characteristic curve to predict falling. RESULTS: The interrater reliability and intrarater reliability of the Korean Tinetti balance scale were 0.97 and 0.98, respectively. The interrater reliability and intra-rater reliability of the Korean Tinetti gait scale were 0.94 and 0.96, respectively. The Korean TMT scores were significantly correlated with the other clinical scales and three-dimensional motion capture. The cutoff values for predicting falling were 14 points (balance subscale) and 10 points (gait subscale). CONCLUSION: We found that the Korean version of the TMT showed excellent validity and reliability for gait and balance and had high sensitivity and specificity for predicting falls among patients with PD.

A High-fat Diet Induces a Loss of Midbrain Dopaminergic Neuronal Function That Underlies Motor Abnormalities

Movement defects in obesity are associated with peripheral muscle defects, arthritis, and dysfunction of motor control by the brain. Although movement functionality is negatively correlated with obesity, the brain regions and downstream signaling pathways associated with movement defects in obesity are unclear. A dopaminergic neuronal pathway from the substantia nigra (SN) to the striatum is responsible for regulating grip strength and motor initiation through tyrosine hydroxylase (TH) activity-dependent dopamine release. We found that mice fed a high-fat diet exhibited decreased movement in open-field tests and an increase in missteps in a vertical grid test compared with normally fed mice. This motor abnormality was associated with a significant reduction of TH in the SN and striatum. We further found that phosphorylation of c-Jun N-terminal kinase (JNK), which modulates TH expression in the SN and striatum, was decreased under excess-energy conditions. Our findings suggest that high calorie intake impairs motor function through JNK-dependent dysregulation of TH in the SN and striatum.

Factors Affecting Cognitive Impairment and Depression in the Elderly Who Live Alone: Cases in Daejeon Metropolitan City

BACKGROUND AND PURPOSE: With the rapid increase in the number of elderly people in Korea, multiple socio-economic problems have emerged. In 2015, 6.4 million people accounting for about 13% of the total population in Korea were aged 65 years and over. As the elderly population continues to grow, the elderly who live alone are also increasing. They have potential risks in medical and neuropsychological aspects. The purpose of this study was to investigate the association between cognition and socio-environmental status in the elderly who live alone. METHODS: This study was conducted on 512 people who live alone (equivalent to 1% of the total elderly people) in Daejeon Metropolitan City between April and November 2015. Structured questionnaires were used to investigate the general characteristics, socio-economic status, physical status, and mood for participants. Simple tests using Mini-Mental Status Examination-Demetia Screening, Geriatric Depression Scale and Korean-instrumental activities of daily living were also performed. RESULTS: Among the 512 participants, 109 participants (21.3%) had cognitive impairment, and 128 participants (25.0%) had depression. The number of daily meals, frequency of meeting with family, and depression were independent risk factors for cognitive impairment. Factors including the duration of living alone, cognitive impairment, poor self-perceived health status, frequency of meeting with family and duration of education were considered an independent risk factor for depression. CONCLUSIONS: This study showed that the elderly who live alone are susceptible to cognitive impairment and depression, and factors including the number of daily meals, social contact, and self-perceived health status may affect cognition and depressive mood. Thus, physicians need to pay attention to management of major factors that may cause cognition impairment and depression in the elderly who live alone; in addition, they require ongoing community interest and support.

Mild Cognitive Impairment

Mild cognitive impairment (MCI) is an intermediate cognitive state between normal aging and dementia. It has disparate features in activities of daily life which is interfered notably in dementia. Recently, there have been consistent reports of MCI which is predementia, however significant controversy exist. In this review, we make out the diagnostic criteria, classification, risk factor, prevalence, diagnostic test including neuroimaging and biomarkers, management, and prognosis of MCI. This review will cover current knowledge and future directions on MCI.

Treatment of Alzheimer's Disease with Repetitive Transcranial Magnetic Stimulation Combined with Cognitive Training: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) has been examined as a potential treatment for many neurological disorders. High-frequency rTMS in particular improves cognitive functions such as verbal fluency and memory. This study explored the effect of rTMS combined with cognitive training (rTMS-COG) on patients with Alzheimer's disease (AD). METHODS: A prospective, randomized, double-blind, placebo-controlled study was performed with 27 AD patients (18 and 8 in the treatment and sham groups, respectively, and 1 drop-out). The participants were categorized into mild [Mini-Mental State Examination (MMSE) score=21-26] and moderate (MMSE score=18-20) AD groups. The rTMS protocols were configured for six cortical areas (both dorsolateral prefrontal and parietal somatosensory associated cortices and Broca's and Wernicke's areas; 10 Hz, 90-110% intensity, and 5 days/week for 6 weeks). Neuropsychological assessments were performed using the AD Assessment Scale-cognitive subscale (ADAS-cog), Clinical Global Impression of Change (CGIC), and MMSE before, immediately after, and 6 weeks after the end of rTMS-COG treatment. RESULTS: Data from 26 AD patients were analyzed in this study. There was no significant interactive effect of time between the groups. The ADAS-cog score in the treatment group was significantly improved compared to the sham group (4.28 and 5.39 in the treatment group vs. 1.75 and 2.88 in the sham group at immediately and 6 weeks after treatment, respectively). The MMSE and CGIC scores were also improved in the treatment group. Based on subgroup analysis, the effect of rTMS-COG was superior for the mild group compared to the total patients, especially in the domains of memory and language. CONCLUSIONS: The present results suggest that rTMS-COG represents a useful adjuvant therapy with cholinesterase inhibitors, particularly during the mild stage of AD. The effect of rTMS-COG was remarkable in the memory and language domains, which are severely affected by AD.

High Frequency Repetitive Transcranial Magnetic Stimulation for Freezing of Gait and Nonmotor Symptoms in Parkinson's Disease

BACKGROUND: To investigate the effect of high frequency repetitive transcranial magnetic stimulation (rTMS) on motor symptoms especially freezing of gait (FoG), and nonmotor symptoms in Parkinson disease (PD). METHODS: In this randomized, double-blind, sham-controlled study, fifteen PD patients were enrolled. For 10 days, 5 Hz, both motor cortices and dorsolateral prefrontal cortex (DLPFC) were stimulated. The motor symptoms and FoG were evaluated by the Unified Parkinson's Disease Rating Scale (UPDRS) part III, FoG questionnaire (FoG-Q), variable parameters of FoG, and kinematic gait analysis. Nonmotor symptoms were evaluated by the Korean version of non-Motor Symptoms Scale (K-NMSS), 39-item Parkinson disease questionnaire (K-PDQ39), Mini-Mental Status examination (K-MMSE), Montreal Cognitive Assessment (K-MoCA), and Frontal assessment battery (FAB). RESULTS: Finally, 12 patients (real:8, sham:4) data were analyzed. FoG-Q and UPDRS part III were improved (p=0.002, 0.022) and variable parameters of FoG was improved after 10 days stimulation in real treatment group. In addition, their effects maintained until 6 weeks from the baseline. In nonmotor symptoms, K-NMSS and K-PDQ 39 were improved until 6 weeks in real treatment group (p=0.002, 0.002), however no changes were shown in cognitive function test. CONCLUSIONS: The high frequency rTMS was effective for FoG, in addition to motor and a few nonmotor symptoms in PD.

A novel mutation of CACNA1A gene in episodic ataxia type 2 family in Korea

Episodic ataxia type 2 (EA-2) is a rare disorder presenting with paroxysmal vertigo and cerebellar dysfunction. EA-2 is known to be caused by mutations of the CACNA1A gene on chromosome 19q13. We examined a family of EA-2 with a novel mutation of the CACNA1A gene showing characteristic ocular symptoms. A-36-year woman visited our hospital with paroxysmal vertigo. When she experienced vertigo attack, she also suffered from gait disturbance, dysarthria, and ataxia. She complained that she could not ride in a car or a train that moved fast, because she could not visually follow the moving objects. Her mother, grandmother, and uncle also complained of similar symptoms. Video nystagmographic findings showed loss of optokinetic nystagmus. We found a novel missense mutation, R279C (c.835C>T), on exon 6 in the CACNAIA gene. This is the first report of a family with new mutation of EA-2 in Korea.

Reversible Cerebellar Leukoencephalopathy Associated With Oral Methotrexate

Methotrexate (MTX)-induced leukoencephalopathy is the most often reported leukoencephalopathy following intrathecal or intravenous administration. A 72-year-old woman developed leukoencephalopathy localized to the cerebellum after treatment with oral MTX at a dose of 15 mg/week for 3 years. She complained of subtle imbalance during walking and reported having fallen. Her symptoms improved after discontinuation of MTX, and the leukoencephalopathy resolved. This is therefore a case report of selective cerebellar reversible leukoencephalopathy associated with oral MTX.

Sleep Disorders Associated With Movement Disorders and Dementia

Sleep disorders are common, occurring in both healthy elderly people and in association with neurodegenerative diseases, sometimes preceding other clinical manifestations of those diseases. The sleep disorders of neurodegenerative diseases include insomnia, hypersomnia, parasomnia, excessive nocturnal motor activity, circadian sleep-wake rhythm disturbances, and sleep breathing disorders. This review addresses the neuroanatomical basis of sleep, the associated regulatory mechanisms and neurotransmitters, and the relationship between cognitive function and sleep. Furthermore, the clinical features of sleep disorders in a wide variety of neurodegenerative diseases are reviewed, including movement disorders and dementia.