Relationship between Apathy and Subjective Poor Night-time Sleep in de novo, Untreated Parkinson's Disease.

BACKGROUND: Sleep disturbance is one of the most common non-motor symptoms of Parkinson's disease (PD). However, the confounding effects of dopaminergic medication on sleep are a major challenge in understanding the impact of sleep disturbance in PD. We investigated the sleep disturbance and associated clinical features in patients with de novo, untreated PD. METHODS: One-hundred-eight patients with de novo, untreated PD were included. Night sleep disturbance was evaluated using the night sleep subscale of the Scales for Outcomes in Parkinson's Disease (SCOPA-Sleep). Depression, anxiety, and apathy were assessed using the Geriatric Depression Scale (GDS), Beck Anxiety Inventory (BAI), and Apathy Evaluation Scale (AES), respectively. Early perfusion and dopamine transporter imaging of F-18 FP-CIT PET/CT were performed together with statistical parametric mapping analysis. RESULTS: The night sleep SCOPA-Sleep sub-score was correlated with the AES (p = 0.014), BAI (p = 0.014), and GDS (p = 0.023) scores. Patients with poor night sleep were more apathetic (p = 0.013). Additionally, there was increased perfusion in the left posterior cingulate in patients with sleep disturbance and apathy compared to those with sleep disturbance only. CONCLUSIONS: Night sleep disturbance was related to mood disorders, particularly apathy, in patients with de novo, untreated PD.

Brain F-18 FDG and F-18 FP-CIT PET/CT Findings of c.856_860delCTCTA Mutation McLeod Syndrome.

McLeod syndrome is a rare X-linked recessive genetic disorder that is caused by mutations of the XK gene. It is one of the core neuroacanthocytosis syndromes. We report the case of a 67-year-old man who presented to Kyungpook National University Hospital in the Republic of Korea with progressive worsening of generalized chorea and dystonia. He had no recognized family history of neurologic illness. A peripheral blood smear showed increased acanthocytes. His serum creatine kinase levels were 894 U/L. A brain MRI showed atrophy of the bilateral striatal nuclei. An F-18 F-N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane PET/CT showed moderately decreased dopamine transporter uptake in the putamen and severely decreased uptake in the caudate nucleus. An F-18 fludeoxyglucose PET/CT demonstrated markedly decreased metabolism at the caudate nucleus and the putamen. Whole exome sequencing revealed hemizygous pathogenic mutations of the XK gene (c.856_860delCTCTA;p.Leu286TyrfsTer16). We believe that these findings provide useful information regarding the clinical features of individuals with McLeod syndrome.

Alpha-synuclein in gastric and colonic mucosa in Parkinson's disease: Limited role as a biomarker.

BACKGROUND: Gastric and colonic alpha-synuclein immunoreactivity has been reported in patients with Parkinson's disease (PD). However, enteric alpha-synuclein also has been reported in healthy individuals. OBJECTIVES: We aimed to investigate the utility of alpha-synuclein immunoreactivity from gastric and colonic mucosal tissues obtained by routine endoscopy to detect PD, and to correlate the pathological burden of alpha-synuclein with motor and nonmotor features of PD. METHODS: We recruited 104 study subjects, consisting of 38 patients with PD, 13 patients with probable multiple system atrophy (MSA), and 53 healthy controls. Gastric and colonic mucosal tissues obtained by endoscopic gastroduodenoscopy and colonoscopy were assessed using alpha-synuclein immunohistochemistry. Detailed motor and nonmotor features of PD were correlated with enteric alpha-synuclein immunoreactivity. RESULTS: No difference was seen in the enteric α-SYN immunoreactivity among patients with PD (31.6% for stomach and 10.4% for colon), patients with MSA (40.0% for stomach and 8.0% for colon), and healthy controls (33.3% for stomach and 18.5% for colon). The frequency of positive alpha-synuclein immunoreactivity was higher in gastric biopsy tissues than in colonic biopsy tissues in all of the study groups (P < 0.05). No significant correlation was found between the presence of alpha-synuclein immunoreactivity and the motor and nonmotor features of PD. CONCLUSIONS: The presence of alpha-synuclein immunoreactivity in gastric and colonic mucosa was detected in a similar manner in patients with PD, patients with MSA, and controls, thus suggesting a limited role of enteric mucosal alpha-synuclein as a diagnostic biomarker for PD. Future studies are warranted to detect pathological alpha-synuclein strains.

Linking a genome-wide association study signal to a LRRK2 coding variant in Parkinson's disease.

BACKGROUND: Genome-wide association studies have identified several loci associated with Parkinson's disease (PD). Whole-exome sequencing detects rare coding variants, but their links with PD genome-wide association study loci are unknown. Our objective was to investigate whether nonsynonymous variants in LRRK2 can explain associations at the PD-associated locus tagged by rs1994090. METHODS: We sequenced all coding exons of LRRK2 in 453 East Asian samples and evaluated linkage disequilibrium between each nonsynonymous variant and rs1994090. We then tested selected variants and haplotypes for association with PD in 13,581 East Asian samples. RESULTS: Of all the nonsynonymous variants, only p.Gly2385Arg was in moderate linkage disequilibrium with rs1994090 and was observed on haplotypes tagged by the rs1994090-C risk allele. Conditional analyses showed that associations at these 2 variants are not independent. CONCLUSIONS: LRRK2 p.Gly2385Arg can explain most if not all of the PD association at rs1994090 in East Asians, but other nonsynonymous variants are independent. © 2015 International Parkinson and Movement Disorder Society.

The first reported case of West Nile encephalitis in Korea.

West Nile encephalitis was first identified in 1937, but until now, it was never diagnosed in Korea. A 58-yr-old Korean man was admitted with headache and cognitive dysfunction. The patient had been on a business trip in Guinea. Cerebrospinal fluid (CSF) showed pleocytosis. The patient complained of both leg weakness,and arachnoiditis and myelitis were observed on lumbar magnetic resonance imaging (MRI). A specific neutralizing antibody for West Nile virus was positive in serum. After a treatment with interferon-α 3mu, follow up CSF findings recovered completely after 3 months later. The first case of West Nile encephalitis in Korea was imported from Guinea, and was cured successfully.

Gender differences in the effect of comorbid insomnia symptom on depression, anxiety, fatigue, and daytime sleepiness in patients with obstructive sleep apnea.

PURPOSE: This study investigated gender differences in the effect of comorbid insomnia symptom on depression, anxiety, fatigue, daytime sleepiness, and quality of life in patients with obstructive sleep apnea. There are gender differences in the presentation of obstructive sleep apnea. However, the influence of gender on the presentation of comorbid insomnia symptom and obstructive sleep apnea is not known. METHODS: Allparticipantsperformed overnightpolysomnography and completed a battery of questionnaires including Beck Depression Inventory, State-Trait Anxiety Inventory, Multidimensional Fatigue Inventory, Epworth Sleepiness Scale, and Short Form-36 Health Survey. Insomnia symptom was defined as present if a patient had any insomnia complaints longer than 1 month and at least one time per week. RESULTS: Six hundred fifty-five adult patients with obstructive sleep apnea were enrolled; 233 (35.5 %) reported comorbid insomnia symptom with obstructive sleep apnea. The severity of obstructive sleep apnea was not related to comorbid insomnia symptom. Based on linear regression, women had higher depression, fatigue, and daytime sleepiness and lower health-related quality of life than men (all, p<0.05). The presence of insomnia symptom had negative effects on fatigue (p=0.005) and quality of life only (p=0.015) in men but not in women when taking gender-by-insomnia interaction into consideration. There were significant differences in polysomnography-based sleep architecture between the obstructive sleep apnea-only and obstructive sleep apnea-insomnia groups, but only in the subgroup of men. CONCLUSIONS: Men are more prone to the negative impact of comorbid insomnia symptom and obstructive sleep apnea on their level of fatigue and quality of life than women.

Clinical and Genetic Characteristics Associated With Survival Outcome in Late-Onset Huntington's Disease in South Korea.

BACKGROUND AND PURPOSE: The onset of Huntington's disease (HD) usually occurs before the age of 50 years, and the median survival time from onset is 15 years. We investigated survival in patients with late-onset HD (LoHD) (age at onset ≥60 years) and the associations of the number of mutant CAG repeats and age at onset (AAO) with survival in patients with HD. METHODS: Patients with genetically confirmed HD at six referral centers in South Korea between 2000 and 2020 were analyzed retrospectively. Baseline demographic, clinical, and genetic characteristics and the survival status as at December 2020 were collected. RESULTS: Eighty-seven patients were included, comprising 26 with LoHD (AAO=68.77±5.91 years, mean±standard deviation; 40.54±1.53 mutant CAG repeats) and 61 with common-onset HD (CoHD) (AAO=44.12±8.61 years, 44.72±4.27 mutant CAG repeats). The ages at death were 77.78±7.46 and 53.72±10.86 years in patients with LoHD and CoHD, respectively (p<0.001). The estimated survival time was 15.21±2.49 years for all HD patients, and 10.74±1.95 and 16.15±2.82 years in patients with LoHD and CoHD, respectively. More mutant CAG repeats and higher AAO were associated with shorter survival (hazard ratio [HR]=1.05, 95% confidence interval [CI]=1.01-1.09, p=0.019; and HR=1.17, 95% CI=1.03-1.31, p=0.013; respectively) for all HD patients. The LoHD group showed no significant factors associated with survival after disease onset, whereas the number of mutant CAG repeats had a significant effect (HR=1.12, 95% CI=1.01-1.23, p=0.034) in the CoHD group. CONCLUSIONS: Survival after disease onset was shorter in patients with LoHD than in those with CoHD. More mutant CAG repeats and higher AAO were associated with shorter survival in patients with HD.

Ethnicity- and sex-specific genome wide association study on Parkinson's disease.

Most previous genome-wide association studies (GWASs) on Parkinson's disease (PD) focus on the European population. There are several sex-specific clinical differences in PD, but little is known about its genetic background. We aimed to perform an ethnicity-specific and sex-specific GWAS on PD in the Korean population. A total of 1050 PD patients and 5000 controls were included. For primary analysis, we performed a GWAS using a logistic additive model adjusted for age and sex. The same statistical models were applied to sex-specific analyses. Genotyping was performed using a customized microarray chip optimized for the Korean population. Nine single nucleotide polymorphisms (SNPs) including four in the SNCA locus and three from the PARK16 locus were associated with PD in Koreans. The rs34778348 in the LRRK2 locus showed a strong association, though failed to pass cluster quality control. There were no notable genome-wide significant markers near the MAPT or GBA1 loci. In the female-only analysis, rs34778348 in LRRK2 and the four other SNPs in the SNCA showed a strong association with PD. In the male-only analysis, no SNP surpassed the genome-wide significance threshold under Bonferroni correction; however, the most significant signal was rs708726 in the PARK16 locus. This ethnicity- and sex-specific GWAS on PD implicate the pan-ethnic effect of SNCA, the universal but East-Asian inclined effect of PARK16, the East Asian-specific role of LRRK2 G2385R variants, and the possible disproportionate effect of SNCA and PARK16 between sexes for PD susceptibility. These findings suggest the different genetic contributions to sporadic PD in terms of ethnicity and sex.

Discovery of levodopa-induced dyskinesia-associated genes using genomic studies in patients and Drosophila behavioral analyses.

Although levodopa is the most effective medication for Parkinson's disease, long-term levodopa treatment is largely compromised due to late motor complications, including levodopa-induced dyskinesia (LID). However, the genetic basis of LID pathogenesis has not been fully understood. Here, we discover genes pathogenic for LID using Drosophila genetics and behavioral analyses combined with genome-wide association studies on 578 patients clinically diagnosed with LID. Similar to the therapeutic effect of levodopa in patients, acute levodopa treatments restore the motor defect of Parkinson's disease model flies, while prolonged treatments cause LID-related symptoms, such as increased yawing, freezing and abrupt acceleration of locomotion. These symptoms require dopamine 1-like receptor 1 and are induced by neuronal overexpression of the receptor. Among genes selected from our analyses in the patient genome, neuronal knockdown of adenylyl cyclase 2 suppresses the levodopa-induced phenotypes and the receptor overexpression-induced symptoms in Drosophila. Together, our study provides genetic insights for LID pathogenesis through the D1-like receptor-adenylyl cyclase 2 signaling axis.

Simple Quantification of Surface Uptake in F-18 Florapronol PET/CT Imaging for the Validation of Alzheimer's Disease.

We developed a novel quantification method named shape feature using F-18 florapronol positron emission tomography-computed tomography (PET/CT) and evaluated its sensitivity and specificity for discriminating between patients with Alzheimer's disease (AD) and patients with mild cognitive impairment or other precursors dementia (non-AD). We calculated the cerebral amyloid smoothing score (CASS) and brain atrophy index (BAI) using the surface area and volume of the region of interest in PET images. We calculated gray and white matter from trained CT data, prepared using U-net. Shape feature was calculated by multiplying CASS with BAI scores. We measured region-based standard uptake values (SUVr) and performed receiver operating characteristic (ROC) analysis to compare SUVr, shape feature, CASS, and BAI score. We investigated the relationship between shape feature and neuropsychological tests. Fifty subjects (23 with AD and 27 with non-AD) were evaluated. SUVr, shape feature, CASS, and BAI score were significantly higher in patients with AD than in those with non-AD. There was no statistically significant difference between shape feature and SUVr in ROC analysis. Shape feature correlated well with mini-mental state examination scores. Shape feature can effectively quantify beta-amyloid deposition and atrophic changes in the brain. These results suggest that shape feature is useful in the diagnosis of AD.

Movement Disorders Associated With Cerebral Artery Stenosis: A Nationwide Study.

Background: Studies of secondary movement disorder (MD) caused by cerebrovascular diseases have primarily focused on post-stroke MD. However, MD can also result from cerebral artery stenosis (CAS) without clinical manifestations of stroke. In this study, we aimed to investigate the clinical characteristics of MD associated with CAS. Materials and Methods: A nationwide multicenter retrospective analysis was performed based on the data from patients with CAS-associated MDs from 16 MD specialized clinics in South Korea, available between January 1999 and September 2019. CAS was defined as the >50% luminal stenosis of the major cerebral arteries. The association between MD and CAS was determined by MD specialists using pre-defined clinical criteria. The collected clinical information included baseline demographics, features of MD, characteristics of CAS, treatment, and MD outcomes. Statistical analyses were performed to identify factors associated with the MD outcomes. Results: The data from a total of 81 patients with CAS-associated MD were analyzed. The mean age of MD onset was 60.5 ± 19.7 years. Chorea was the most common MD (57%), followed by tremor/limb-shaking, myoclonus, and dystonia. Atherosclerosis was the most common etiology of CAS (78%), with the remaining cases attributed to moyamoya disease (MMD). Relative to patients with atherosclerosis, those with MMD developed MD at a younger age (p < 0.001) and had a more chronic mode of onset (p = 0.001) and less acute ischemic lesion (p = 0.021). Eight patients who underwent surgical treatment for CAS showed positive outcomes. Patients with acute MD onset had a better outcome than those with subacute-to-chronic MD onset (p = 0.008). Conclusions: This study highlights the spectrum of CAS-associated with MD across the country. A progressive, age-dependent functional neuronal modulation in the basal ganglia due to CAS may underlie this condition.

Microarray Genotyping Identifies New Loci Associated with Dementia in Parkinson's Disease.

Dementia is one of the most disabling nonmotor symptoms of Parkinson's disease (PD). However, the risk factors contributing to its development remain unclear. To investigate genetic variants associated with dementia in PD, we performed microarray genotyping based on a customized platform utilizing variants identified in previous genetic studies. Microarray genotyping was performed in 313 PD patients with dementia, 321 PD patients without dementia, and 635 healthy controls. The primary analysis was performed using a multiple logistic regression model adjusted for age and sex. SNCA single nucleotide polymorphism (SNP) rs11931074 was determined to be most significantly associated with PD (odds ratio = 0.66, 95% confidence interval = 0.56-0.78, p = 7.75 × 10-7). In the analysis performed for patients with PD only, MUL1 SNP rs3738128 (odds ratio = 2.52, 95% confidence interval = 1.68-3.79, p = 8.75 × 10-6) was found to be most significantly associated with dementia in PD. SNPs in ZHX2 and ERP29 were also associated with dementia in PD. This microarray genomic study identified new loci of MUL1 associated with dementia in PD, suggesting an essential role of mitochondrial dysfunction in the development of dementia in patients with PD.

Nocturnal stridor in multiple system atrophy: Video-polysomnography and clinical features.

INTRODUCTION: Nocturnal stridor, a life-threatening condition linked to respiratory failure and sudden death during sleep, is a serious issue in patients with multiple system atrophy (MSA). However, little is known about polysomnographic findings and clinical features of MSA patients with nocturnal stridor. Hence, we investigated video-polysomnography (VPSG) findings and clinical features associated with nocturnal stridor in patients with MSA. METHODS: We retrospectively analyzed the clinical data of patients with MSA (n = 49) who underwent overnight VPSG for the evaluation of sleep-disordered breathing. The presence of nocturnal stridor was confirmed based on overnight VPSG findings. Clinical data, including VPSG findings and clinical features, were compared between MSA patients with and without nocturnal stridor. RESULTS: Nocturnal stridor was present in 31 (63.3%) patients with MSA. Patients with stridor showed significantly higher apnea-hypopnea, respiratory disturbance, and oxygen desaturation indices than those without stridor (P = 0.024, P = 0.049, and P = 0.006, respectively). Patients with stridor had more severe axial motor features, more impaired activities of daily living, and longer disease duration than those without stridor (P = 0.012, P = 0.036, and P = 0.003, respectively). However, there were no significant between-group differences in sex, age at disease onset, MSA subtype, parkinsonian features, cerebellar ataxia, residual urine volume, or systolic and diastolic blood pressure change. CONCLUSIONS: MSA with nocturnal stridor is related to higher apnea indices in conjunction with higher O2 desaturation index, more severe axial motor features, more impaired activities of daily living, and longer disease duration.

Prognostic Factors of COVID-19 Infection in Elderly Patients: A Multicenter Study.

The outbreak of the COVID-19 pandemic is a substantial threat to the health of all populations worldwide, and old age is a robust risk factor for poor prognosis of COVID-19 infection. To reduce the fatality rate of COVID-19 infection, further understanding of elderly patients with COVID-19 is necessary. We aimed to investigate the prognostic factors in elderly patients with COVID-19. This was a multicenter and retrospective study. Overall, 340 elderly patients with COVID-19 were enrolled in 3 hospitals in Daegu, South Korea. Death and severe pneumonia requiring oxygen treatment were defined as poor clinical outcomes. Of the patients studied, 15% died and 35.2% were classified as having severe pneumonia. In binary logistic regression analysis, activities of daily living (ADL) impairment, fever during hospitalization, initial infiltration on chest radiograph, and initial increased C-reactive protein (CRP) were significantly associated with severe pneumonia (OR = 5.33, p < 0.001; OR = 3.2, p = 0.002; OR = 2.32, p = 0.044; and OR = 1.33, p < 0.001, respectively). ADL impairment, comorbidity, fever during hospitalization, and initial increased CRP were significantly associated with death (OR = 7.13, p < 0.001; OR = 3.28, p = 0.005; OR = 3.15, p = 0.032, and OR = 1.18, p < 0.001, respectively). ADL impairment, fever, and initial CRP were poor prognostic factors in elderly patients with COVID-19. Understanding these poor prognostic factors is necessary to control the disease in elderly patients.

Post-Pump Chorea and Progressive Supranuclear Palsy-Like Syndrome Following Major Cardiac Surgery.

BACKGROUND: Post-pump chorea and progressive-supranuclear palsy (PSP)-like syndrome after aortic surgery are 2 distinct movement disorders following major cardiac surgeries. CASES: We herein report 3 patients with movement disorders that developed after major cardiac surgeries. Two patients developed post-pump chorea after pulmonary endarterectomy, and 1 further case developed PSP-like syndrome after aortic replacement surgery. The 2 conditions share several common aspects. Both are preceded by surgeries that undergo cardiopulmonary bypass and deep hypothermia circulatory arrest procedures. Most cases present with biphasic course. However, post-pump chorea occurs in all age populations after any surgeries that undergo deep hypothermia circulatory arrest, whereas PSP-like syndrome is reported exclusively in the adult population after aortic surgery. CONCLUSIONS: Post-pump chorea and PSP-like syndrome are neurologic complications of major cardiac surgeries that should not be underrecognized. Further reports to establish their common pathogenic mechanism should be encouraged.

Therapeutic Effect of Levodopa/Carbidopa/Entacapone on Sleep Disturbance in Patients with Parkinson's Disease.

OBJECTIVE: To investigate the efficacy of levodopa/carbidopa/entacapone (LCE) at bedtime for treating sleep disturbance in patients with Parkinson's disease (PD) with motor fluctuations. METHODS: Participants included 128 PD patients with motor fluctuations. All patients were assessed for motor, nonmotor, and sleep-specific symptoms using the United Parkinson's Disease Rating Scale (UPDRS), the Korean version of the Nonmotor Symptom Scale, the Parkinson's Disease Sleep Scale (PDSS), the Epworth Sleepiness Scale, and the Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ). We compared the baseline characteristics of patients with sleep disturbance (PDSS score < 120) and those without sleep disturbance (PDSS score ≥ 120). Thirty-nine patients with sleep disturbance who agreed to take LCE at bedtime completed 3-month follow-ups. We analyzed changes in the scores of motor, nonmotor, and sleep symptom scales over the 3 months. RESULTS: PD patients with sleep disturbance were at more advanced disease stages and had more severe motor, nonmotor, and sleep symptoms than those without sleep disturbance. Patients who took LCE at night showed improvements in motor (UPDRS part III, p = 0.007) and sleep symptoms (total PDSS, p < 0.001). Sleep features that benefitted from LCE included not only nocturnal motor components but also insomnia (PDSS items 2 and 3, p = 0.005 and p < 0.001) and rapid eye movement behavior disorder (PDSS item 6, p = 0.002; and RBDSQ, p < 0.001). CONCLUSION: The use of LCE at bedtime may be a useful treatment for sleep disturbance in advanced PD patients with motor fluctuations.

Genomic Analysis Identifies New Loci Associated With Motor Complications in Parkinson's Disease.

Background: Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by a clinical symptomatology involving both motor and non-motor symptoms. Motor complications associated with long-term dopaminergic treatment include motor fluctuations and levodopa-induced dyskinesia (LID), which may have a major impact on the quality of life. The clinical features and onset time of motor complications in the disease course are heterogeneous, and the etiology remains unknown. Objective: We aimed to identify genomic variants associated with the development of motor fluctuations and LID at 5 years after the onset of PD. Methods: Genomic data were obtained using Affymetrix Axiom KORV1.1 array, including an imputation genome-wide association study (GWAS) grid and other GWAS loci; functional variants of the non-synonymous exome; pharmacogenetic variants; variants in genes involved in absorption, distribution, metabolism, and excretion of drugs; and expression quantitative trait loci in 741 patients with PD. Results: FAM129B single-nucleotide polymorphism (SNP) rs10760490 was nominally associated with the occurrence of motor fluctuations at 5 years after the onset of PD [odds ratio (OR) = 2.9, 95% confidence interval (CI) = 1.8-4.8, P = 6.5 × 10-6]. GALNT14 SNP rs144125291 was significantly associated with the occurrence of LID (OR = 5.5, 95% CI = 2.9-10.3, P = 7.88 × 10-9) and was still significant after Bonferroni correction. Several other genetic variants were associated with the occurrence of motor fluctuations or LID, but the associations were not significant after Bonferroni correction. Conclusion: This study identified new loci associated with the occurrence of motor fluctuations and LID at 5 years after the onset of PD. However, further studies are needed to confirm our findings.

Genomic Association Study for Cognitive Impairment in Parkinson's Disease.

Background: Cognitive impairment is very common in Parkinson's disease (PD) and constitutes the most debilitating complication of this disease. However, to date, few studies have investigated a genome-wide association in the development of cognitive impairment of PD. We aimed to identify the genetic loci associated with cognitive impairment in patients with sporadic PD by ethnicity-specific genotyping. Materials and methods: We recruited 1,070 patients with PD and performed a genome-wide association study using the Korean Chip, a microarray chip containing 827,400 single-nucleotide polymorphisms (SNPs) optimized for the Korean population. Multiple logistic regression models adjusting for age, sex, years of education, and disease duration were used to compare between patients with and without cognitive impairment, which was defined using the Mini-Mental Status Examination (MMSE) score (MMSE score ≥ 26 vs. < 26) or the Montreal Cognitive Assessment (MoCA) score (MoCA score ≥24 vs. < 24). Results: RYR2 SNP rs10495397 was most significantly associated with cognitive impairment based on the MMSE scores (OR = 3.21; 95% CI = 1.96-5.25, P = 3.36 × 10-6) and CASC17 showed the strongest association with cognitive impairment based on the MoCA scores. However, none of the SNPs were statistically significant after Bonferroni correction. Conclusion: RYR2 may play a role in cognitive impairment in PD by the pathogenic mechanism of neuroinflammation. However, more studies are needed to replicate and validate the results of our functional study.

Age-dependent efficacy of subthalamic nucleus deep brain stimulation in young- and late-onset Parkinson's disease based on a 10 year follow-up.

INTRODUCTION: Long-term efficacy and safety of subthalamic nucleus deep brain stimulation (STN DBS) in patients with young-onset Parkinson's disease (YOPD) and late-onset PD (LOPD) (i.e. motor symptom initial appearance at ages ≤40 and > 40 years, respectively) was compared to identify relationships between PD onset age and the efficacy of DBS. METHODS: Statistical analyses compared specific motor and non-motor features among 13 patients with YOPD and 11 with LOPD. Medication reduction patterns and dyskinesia severity scores at baseline and after 1, 3, 5, and 10 years of follow-up were also analyzed using a repeated measures ANOVA tests. Lastly, a correlation analysis identified relationships between the impact of DBS settings (volume of activated tissue) and levodopa equivalent daily dose (LED), dyskinesia severity scores, Unified Parkinson's Disease Rating Scale (UPDRS) part III, and UPDRS part II (disability) scores. RESULTS: Ten years after DBS surgery, the reduction of LED from baseline (85.9 ± 592.6 mg versus 623.2 ± 464.9 mg; p = .023) and levodopa-induced dyskinesia (LID) scores (Unified Dyskinesia Rating Scale [UDysRS] parts III items 16-22; 1.6 ± 2.8 versus 5.5 ± 4.1; p = .013) were significantly lower in YOPD patients than LOPD patients. There were no significant differences between the two groups regarding UPDRS part III score improvement in response to levodopa, psychosis occurrence, or adverse effects. CONCLUSION: Ten years after STN DBS surgery, LOPD patients showed greater LED reduction, and YOPD patients showed greater LID improvement, although the general long-term outcomes were similar between YOPD and LOPD patients.

Pupillary dysfunction of multiple system atrophy: Dynamic pupillometric findings and clinical correlations.

INTRODUCTION: Although autonomic dysfunction is the prominent clinical feature in multiple system atrophy (MSA), little is known about the pupillary autonomic aspect of MSA. We aimed to evaluate pupillary autonomic function in MSA patients using dynamic pupillometry, which can quantify the pupillary light reflex. METHODS: Dynamic pupillometry parameters were compared in 21 MSA patients and 21 healthy controls. Pupillometric parameters were correlated with total Unified Multiple System Atrophy Rating Scale (UMSARS) scores and autonomic symptom severity. RESULTS: Average constriction (p = 0.034) and dilation (p = 0.003) velocities were significantly slowed in MSA patients compared with controls. Total UMSARS correlated with the average constriction (r = -0.527, p = 0.017) and maximum constriction (r = -0.658, p = 0.003) velocities. Autonomic symptom severity correlated with average constriction (r = -0.544, p = 0.013), maximum constriction (r = -0.607, p = 0.005) and average dilation (r = -0.499, p = 0.025) velocities. CONCLUSION: Dynamic pupillometry may provide useful information about pupillary autonomic dysfunction, which correlated with the clinical severity, in patients with MSA.