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Huntington's disease (HD) is a neurodegenerative disorder with a significant impact on patients' quality of life, characterized by motor, behavioral, and cognitive impairments. This evidence-based review, conducted by the Korean Huntington Disease Society (KHDS) task force, systematically examines current pharmacological and non-pharmacological interventions for symptomatic management of HD. Following PRISMA guidelines, databases were searched for studies up to August 2022, focusing on 23 symptoms across four domains: motor, neuropsychological, cognition, and others. This review provides a comprehensive and systematic approach to the management of HD, highlighting the need for more high-quality clinical trials to develop robust evidence-based guidelines.

Background: We determined whether the severity of sleep apnea increases the risk of mortality in patients with multiple system atrophy (MSA) with and without stridor. MethodsThis retrospective study included patients who underwent polysomnography within one year after diagnosis of probable MSA. Stridor, sleep apnea, and arousal from sleep were determined using full-night polysomnography. Disease severity was measured using the Unified MSA Rating Scale (UMSARS). Survival data were collected and analyzed using Cox regression analysis., Results: Sixty-four patients with MSA were included. During a median follow-up of 34.5 months, 49 (76.6 %) patients died. Stridor was present in 56.3 % of patients. Patients with stridor had more severe sleep apnea and shorter sleep time than those without, but the hazard ratio (HR) for death did not differ between patients with and without stridor. Among patients without stridor, apnea-hypopnea index ≥30/h (HR, 6.850; 95 % confidence interval [CI], 1.983-23.664; p = 0.002) and a score of UMSARS I + II (HR, 1.080; 95 % CI, 1.040-1.121; p < 0.001) were independently associated with death. In contrast, among patients with stridor, frequent arousals from sleep (HR, 0.254; 95 % CI, 0.089-0.729; p = 0.011) were a significant factor associated with longer survival, while MSA-cerebellar type tended to be associated with poor survival (HR, 2.195; 95 % CI, 0.941-5.120; p = 0.069)., Conclusion: The severity of sleep apnea might be a significant predictor of shorter survival in MSA patients without stridor, whereas frequent arousals from sleep might be a significant predictor for longer survival in MSA patients with stridor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The prevalence of Parkinson's disease (PD) has increased steadily with the increase of the elderly population. PD may influence dietary intake and quality, and the gut microbiome composition. The present study examined differences in dietary intake and quality between PD patients and controls according to sex. In addition, we assessed the gut microbiome composition., Methods: This cross-sectional study was conducted at A Medical Center, Seoul, South Korea. PD severity, swallowing function, olfactory function, and constipation status were examined by a skilled nurse. Dietary data were collected through a semi-quantitative food frequency questionnaire. Stool samples were subjected to microbiome analysis. To examine dietary quality, the Dietary Quality Index-International (DQI-I), Healthy Eating Index (HEI), Index of Nutritional Quality (INQ), Dietary Diversity Score (DDS), and Mediterranean Diet Score (MDS) were used. An independent t-test was used to determine differences between patients and controls. A chi-square test was used to examine frequency differences., Results: Dietary intake did not differ between the PD patient and control groups. Regarding dietary quality, the patients consumed more saturated fat compared to controls. Overall, the dietary differences between the groups were minor. The composition of the gut microbiome differed between PD patients and controls. Lactobacillus and Bifidobacterium genus were most abundant in PD patients. Prevotella VZCB and other Faecalibacterium were most abundant in controls., Conclusions: Our results indicated that PD patients may experience gut microbiome change even in the early stage, while nutritional needs can be met when a balanced diet including various food groups are consumed.

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., Competing Interests: Sun Ju Chung, a contributing editor of the Journal of Clinical Neurology, was not involved in the editorial evaluation or decision to publish this article. All remaining authors have declared no conflicts of interest., (Copyright © 2024 Korean Neurological Association.)

Background: Brain-derived exosomes circulate in the bloodstream and other bodily fluids, serving as potential indicators of neurological disease progression. These exosomes present a promising avenue for the early and precise diagnosis of neurodegenerative conditions. Notably, miRNAs found in plasma extracellular vesicles (EVs) offer distinct diagnostic benefits due to their stability, abundance, and resistance to breakdown., Results: In this study, we introduce a method using transferrin conjugated magnetic nanoparticles (TMNs) to isolate these exosomes from the plasma of patients with neurological disorders. This TMNs technique is both quick (<35 min) and cost-effective, requiring no high-priced ingredients or elaborate equipment for EV extraction. Our method successfully isolated EVs from 33 human plasma samples, including those from patients with Parkinson's disease (PD), Multiple Sclerosis (MS), and Dementia. Using quantitative polymerase chain reaction (PCR) analysis, we evaluated the potential of 8 exosomal miRNA profiles as biomarker candidates. Six exosomal miRNA biomarkers (miR-195-5p, miR-495-3p, miR-23b-3P, miR-30c-2-3p, miR-323a-3p, and miR-27a-3p) were consistently linked with all stages of PD., Significance: The TMNs method provides a practical, cost-efficient way to isolate EVs from biological samples, paving the way for non-invasive neurological diagnoses. Furthermore, the identified miRNA biomarkers in these exosomes may emerge as innovative tools for precise diagnosis in neurological disorders including PD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: This study aimed to identify predictors for the recurrence of spontaneous intracranial hypotension (SIH) after epidural blood patch (EBP)., Background: Epidural blood patch is the main treatment option for SIH; however, the characteristics of patients who experience relapse after successful EBP treatment for SIH remain understudied., Methods: In this exploratory, retrospective, case-control study, we included 19 patients with SIH recurrence after EBP and 36 age- and sex-matched patients without recurrence from a single tertiary medical institution. We analyzed clinical characteristics, neuroimaging findings, and volume changes in intracranial structures after EBP treatment. Machine learning methods were utilized to predict the recurrence of SIH after EBP treatment., Results: There were no significant differences in clinical features between the recurrence and no-recurrence groups. Among brain magnetic resonance imaging signs, diffuse pachymeningeal enhancement and cerebral venous dilatation were more prominent in the recurrence group than no-recurrence group after EBP (14/19 [73%] vs. eight of 36 [22%] patients, p = 0.001; 11/19 [57%] vs. seven of 36 [19%] patients, p = 0.010, respectively). The midbrain-pons angle decreased in the recurrence group compared to the no-recurrence group after EBP, at a mean (standard deviation [SD]) of -12.0 [16.7] vs. +1.8[18.3]° (p = 0.048). In volumetric analysis, volume changes after EBP were smaller in the recurrence group than in the no-recurrence group in intracranial cerebrospinal fluid (mean [SD] -11.6 [15.3] vs. +4.8 [17.1] mL, p = 0.001) and ventricles (mean [SD] +1.0 [2.0] vs. +2.0 [2.5] mL, p = 0.003). Notably, the random forest classifier indicated that the model constructed with brain volumetry was more accurate in discriminating SIH recurrence (area under the curve = 0.80 vs. 0.52)., Conclusion: Our study suggests that volumetric analysis of intracranial structures may aid in predicting recurrence after EBP treatment in patients with SIH., (© 2024 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Objective: To evaluate the diagnostic performance of susceptibility map-weighted imaging (SMwI) taken in different acquisition planes for discriminating patients with neurodegenerative parkinsonism from those without., Materials and Methods: This retrospective, observational, single-institution study enrolled consecutive patients who visited movement disorder clinics and underwent brain MRI and 18 F-FP-CIT PET between September 2021 and December 2021. SMwI images were acquired in both the oblique (perpendicular to the midbrain) and the anterior commissure-posterior commissure (AC-PC) planes. Hyperintensity in the substantia nigra was determined by two neuroradiologists. 18 F-FP-CIT PET was used as the reference standard. Inter-rater agreement was assessed using Cohen's kappa coefficient. The diagnostic performance of SMwI in the two planes was analyzed separately for the right and left substantia nigra. Multivariable logistic regression analysis with generalized estimating equations was applied to compare the diagnostic performance of the two planes., Results: In total, 194 patients were included, of whom 105 and 103 had positive results on 18 F-FP-CIT PET in the left and right substantia nigra, respectively. Good inter-rater agreement in the oblique (κ = 0.772/0.658 for left/right) and AC-PC planes (0.730/0.741 for left/right) was confirmed. The pooled sensitivities for two readers were 86.4% (178/206, left) and 83.3% (175/210, right) in the oblique plane and 87.4% (180/206, left) and 87.6% (184/210, right) in the AC-PC plane. The pooled specificities for two readers were 83.5% (152/182, left) and 82.0% (146/178, right) in the oblique plane, and 83.5% (152/182, left) and 86.0% (153/178, right) in the AC-PC plane. There were no significant differences in the diagnostic performance between the two planes ( P > 0.05)., Conclusion: There are no significant difference in the diagnostic performance of SMwI performed in the oblique and AC-PC plane in discriminating patients with parkinsonism from those without. This finding affirms that each institution may choose the imaging plane for SMwI according to their clinical settings., Competing Interests: Chong Hyun Suh and Ho Sung Kim, who hold respective positions on the Assistants to the Editor and Section Editor of the Korean Journal of Radiology, were not involved in the editorial evaluation or decision to publish this article. The remaining author has declared no conflicts of interest., (Copyright © 2024 The Korean Society of Radiology.)

Normal pressure hydrocephalus (NPH) patients had altered white matter tract integrities on diffusion tensor imaging (DTI). Previous studies suggested disproportionately enlarged subarachnoid space hydrocephalus (DESH) as a prognostic sign of NPH. We examined DTI indices in NPH subgroups by DESH severity and clinical symptoms. This retrospective case-control study included 33 NPH patients and 33 age-, sex-, and education-matched controls. The NPH grading scales (0-12) were used to rate neurological symptoms. Patients with NPH were categorized into two subgroups, high-DESH and low-DESH groups, by the average value of the DESH scale. DTI indices, including fractional anisotropy, were compared across 14 regions of interest (ROIs). The high-DESH group had increased axial diffusivity in the lateral side of corona radiata (1.43 ± 0.25 vs. 1.72 ± 0.25, p = 0.04), and showed decreased fractional anisotropy and increased mean, and radial diffusivity in the anterior and lateral sides of corona radiata and the periventricular white matter surrounding the anterior horn of lateral ventricle. In patients with a high NPH grading scale, fractional anisotropy in the white matter surrounding the anterior horn of the lateral ventricle was significantly reduced (0.36 ± 0.08 vs. 0.26 ± 0.06, p = 0.03). These data show that DESH may be a biomarker for DTI-detected microstructural alterations and clinical symptom severity., (© 2023. The Author(s).)

Objectives: To develop and validate a nomogram based on MRI features for predicting iNPH., Methods: Patients aged  ≥ 60 years (clinically diagnosed with iNPH, Parkinson's disease, or Alzheimer's disease or healthy controls) who underwent MRI including three-dimensional T1-weighted volumetric MRI were retrospectively identified from two tertiary referral hospitals (one hospital for derivation set and the other for validation set). Clinical and imaging features for iNPH were assessed. Deep learning-based brain segmentation software was used for 3D volumetry. A prediction model was developed using logistic regression and transformed into a nomogram. The performance of the nomogram was assessed with respect to discrimination and calibration abilities. The nomogram was internally and externally validated., Results: A total of 452 patients (mean age ± SD, 73.2 ± 6.5 years; 200 men) were evaluated as the derivation set. One hundred eleven and 341 patients were categorized into the iNPH and non-iNPH groups, respectively. In multivariable analysis, high-convexity tightness (odds ratio [OR], 35.1; 95% CI: 4.5, 275.5), callosal angle  < 90° (OR, 12.5; 95% CI: 3.1, 50.0), and normalized lateral ventricle volume (OR, 4.2; 95% CI: 2.7, 6.7) were associated with iNPH. The nomogram combining these three variables showed an area under the curve of 0.995 (95% CI: 0.991, 0.999) in the study sample, 0.994 (95% CI: 0.990, 0.998) in the internal validation sample, and 0.969 (95% CI: 0.940, 0.997) in the external validation sample., Conclusion: A brain morphometry-based nomogram including high-convexity tightness, callosal angle  < 90°, and normalized lateral ventricle volume can help accurately estimate the probability of iNPH., Key Points: • The nomogram with MRI findings (high-convexity tightness, callosal angle, and normalized lateral ventricle volume) helped in predicting the probability of idiopathic normal-pressure hydrocephalus. • The nomogram may facilitate the prediction of idiopathic normal-pressure hydrocephalus and consequently avoid unnecessary invasive procedures such as the cerebrospinal fluid tap test, drainage test, and cerebrospinal fluid shunt surgery., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

The aim of the present study was to predict amyloid-beta positivity using a conventional T1-weighted image, radiomics, and a diffusion-tensor image obtained by magnetic resonance imaging (MRI). We included 186 patients with mild cognitive impairment (MCI) who underwent Florbetaben positron emission tomography (PET), MRI (three-dimensional T1-weighted and diffusion-tensor images), and neuropsychological tests at the Asan Medical Center. We developed a stepwise machine learning algorithm using demographics, T1 MRI features (volume, cortical thickness and radiomics), and diffusion-tensor image to distinguish amyloid-beta positivity on Florbetaben PET. We compared the performance of each algorithm based on the MRI features used. The study population included 72 patients with MCI in the amyloid-beta-negative group and 114 patients with MCI in the amyloid-beta-positive group. The machine learning algorithm using T1 volume performed better than that using only clinical information (mean area under the curve [AUC]: 0.73 vs. 0.69, p < 0.001). The machine learning algorithm using T1 volume showed better performance than that using cortical thickness (mean AUC: 0.73 vs. 0.68, p < 0.001) or texture (mean AUC: 0.73 vs. 0.71, p = 0.002). The performance of the machine learning algorithm using fractional anisotropy in addition to T1 volume was not better than that using T1 volume alone (mean AUC: 0.73 vs. 0.73, p = 0.60). Among MRI features, T1 volume was the best predictor of amyloid PET positivity. Radiomics or diffusion-tensor images did not provide additional benefits., (© 2023. The Author(s).)

Purpose: This study aimed to evaluate the effect of a home-based self-management intervention in community-dwelling patients with early Parkinson's diseases (PD)., Design: A randomized-controlled design., Methods: Thirty-two patients participated (15=intervention, 17=control), and the intervention group received 16 weeks of the intervention., Findings: Physical activity and non-motor symptoms improved more in the intervention group than in the control group., Conclusion: Home-based self-management intervention was effective in improving physical activity and non-motor symptoms for them., Clinical Evidence: Home-based intervention - comprising education, telephone counseling, smartphone-based message and information, and smart wearable devices - was feasible for patients with early PD.

Single-nucleotide variants (SNVs) associated with Parkinson's disease (PD) have been investigated mainly through genome-wide association studies. However, other genomic alterations, including copy number variations, remain less explored. In this study, we conducted whole-genome sequencing of primary (310 PD patients and 100 healthy individuals) and independent (100 PD patients and 100 healthy individuals) cohorts from the Korean population to identify high-resolution small genomic deletions, gains, and SNVs. Global small genomic deletions and gains were found to be associated with an increased and decreased risk of PD development, respectively. Thirty significant locus deletions were identified in PD, with most being associated with an increased PD risk in both cohorts. Small genomic deletions in clustered loci located in the GPR27 region had high enhancer signals and showed the closest association with PD. GPR27 was found to be expressed specifically in brain tissue, and GPR27 copy number loss was associated with upregulated SNCA expression and downregulated dopamine neurotransmitter pathways. Clustering of small genomic deletions on chr20 in exon 1 of the GNAS isoform was detected. In addition, we found several PD-associated SNVs, including one in the enhancer region of the TCF7L2 intron, which exhibited a cis-acting regulatory mode and an association with the beta-catenin signaling pathway. These findings provide a global, whole-genome view of PD and suggest that small genomic deletions in regulatory domains contribute to the risk of PD development., (© 2023. The Author(s).)

Background: Deep brain stimulation (DBS) of globus pallidus interna (GPi) is an established treatment for advanced Parkinson's disease (PD). However, in contrast to subthalamic nucleus (STN)-DBS, long-term outcomes of GPi-DBS have rarely been studied., Objective: We investigated the long-term motor outcomes in PD patients at 5 years after GPi-DBS., Methods: We retrospectively analyzed the clinical data for PD patients who underwent GPi-DBS. Longitudinal changes of UPDRS scores from baseline to 5 years after surgery were assessed., Results: Forty PD patients with a mean age of 59.5 ± 7.9 years at DBS surgery (mean duration of PD: 11.4 ± 3.4 years) were included at baseline and 25 patients were included in 5-year evaluation after DBS. Compared to baseline, sub-scores for tremor, levodopa-induced dyskinesia (LID), and motor fluctuation indicated improved states up to 5 years after surgery (p < 0.001). However, UPDRS Part 3 total score and sub-score for postural instability and gait disturbance (PIGD) gradually worsened over time until 5 years after surgery (p > 0.017 after Bonferroni correction). In a logistic regression model, only preoperative levodopa response was associated with the long-term benefits on UPDRS Part 3 total score and PIGD sub-score (OR = 1.20; 95% CI = 1.04-1.39; p = 0.015 and OR = 4.99; 95% CI = 1.39-17.89; p = 0.014, respectively)., Conclusions: GPi-DBS provides long-term beneficial effects against tremor, motor fluctuation and LID, but PIGD symptoms gradually worsen. This selective long-term benefit has implications for the optimal application of DBS in PD patients., (Copyright © 2022. Published by Elsevier B.V.)

Objective: Depression in Parkinson's disease (PD) affects the quality of life of patients. Postural instability and gait disturbance are associated with the severity and prognosis of PD. We investigated the association of depression with axial involvement in early-stage PD patients., Methods: This study involved 95 PD patients unexposed to antiparkinsonian drugs. After a baseline assessment for depression, the subjects were divided into a depressed PD group and a nondepressed PD group. Analyses were conducted to identify an association of depression at baseline with the following outcome variables: the progression to Hoehn and Yahr scale (H-Y) stage 3, the occurrence of freezing of gait (FOG), levodopa-induced dyskinesia, and wearing-off. The follow-up period was 53.40 ± 16.79 months from baseline., Results: Kaplan-Meier survival curves for H-Y stage 3 and FOG showed more prominent progression to H-Y stage 3 and occurrences of FOG in the depressed PD group than in the nondepressed PD group (log-rank p = 0.025 and 0.003, respectively). Depression in drug-naïve, early-stage PD patients showed a significant association with the progression to H-Y stage 3 (hazard ratio = 2.55; 95% confidence interval = 1.32-4.93; p = 0.005), as analyzed by Cox regression analyses. In contrast, the occurrence of levodopa-induced dyskinesia and wearing-off did not differ between the two groups (log-rank p = 0.903 and 0.351, respectively)., Conclusion: Depression in drug-naïve, early-stage PD patients is associated with an earlier occurrence of postural instability. This suggests shared nondopaminergic pathogenic mechanisms and potentially enables the prediction of early development of postural instability.

Objective: Associations between various metabolic conditions and Parkinson's disease (PD) have been previously identified in epidemiological studies. We aimed to investigate the causal effect of lipid levels, type 2 diabetes mellitus (T2DM), and body mass index (BMI) on PD in a Korean population via Mendelian randomization (MR)., Methods: Two-sample MR analyses were performed with inverse-variance weighted (IVW), weighted median, and MR-Egger regression approaches. We identified genetic variants associated with lipid concentrations, T2DM, and BMI in publicly available summary statistics, which were either collected from genome-wide association studies (GWASs) or from meta-analyses of GWAS that targeted only Korean individuals or East Asian individuals, including Korean individuals. The outcome dataset was a GWAS on PD performed in a Korean population., Results: From previous GWASs and meta-analyses, we selected single nucleotide polymorphisms as the instrumental variables. Variants associated with serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides, as well as with T2DM and BMI, were selected (n = 11, 19, 17, 89, and 9, respectively). There were no statistically significant causal associations observed between the five exposures and PD using either the IVW, weighted median, or MR-Egger methods (p-values of the IVW method: 0.332, 0.610, 0.634, 0.275, and 0.860, respectively)., Conclusion: This study does not support a clinically relevant causal effect of lipid levels, T2DM, and BMI on PD risk in a Korean population.

We aimed to investigate the predictive value of preoperative clinical factors and dopamine transporter imaging for outcomes after globus pallidus interna (GPi) deep brain stimulation (DBS) in patients with advanced Parkinson's disease (PD). Thirty-one patients with PD who received bilateral GPi DBS were included. The patients underwent preoperative [ 18 F] FP-CIT positron emission tomography before DBS surgery. The Unified Parkinson's Disease Rating Scale (UPDRS) were used to assess outcomes 12 months after DBS. Univariate and multivariate linear regression analysis were performed to investigate the association between clinical variables including sex, age at onset of PD, disease duration, cognitive status, preoperative motor severity, levodopa responsiveness, daily dose of dopaminergic medication, and dopamine transporter availability in the striatum and outcomes after GPi DBS. Younger age at onset of PD was associated with greater DBS motor responsiveness and lower postoperative UPDRS III score. Greater levodopa responsiveness, lower preoperative UPDRS III score and lower striatal dopamine transporter availability were associated with lower postoperative UPDRS III score. Younger age at onset was also associated with greater decrease in UPDRS IV score and dyskinesia score after GPi DBS. Our results provide useful information to select DBS candidates and predict therapeutic outcomes after GPi DBS in advanced PD., (© 2022. The Author(s).)

Background: About 40-50% of patients with amnestic mild cognitive impairment (MCI) are found to have no significant Alzheimer's pathology based on amyloid PET positivity. Notably, conversion to dementia in this population is known to occur much less often than in amyloid-positive MCI. However, the relationship between MCI and brain amyloid deposition remains largely unknown. Therefore, we investigated the influence of subthreshold levels of amyloid deposition on conversion to dementia in amnestic MCI patients with negative amyloid PET scans., Methods: This study was a retrospective cohort study of patients with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center. All participants underwent detailed neuropsychological testing, brain magnetic resonance imaging, and [ 18 F]-florbetaben (FBB) positron emission tomography scan (PET). Conversion to dementia was determined by a neurologist based on a clinical interview with a detailed neuropsychological test or a decline in the Korean version of the Mini-Mental State Examination score of more than 4 points per year combined with impaired activities of daily living. Regional cortical amyloid levels were calculated, and a receiver operating characteristic (ROC) curve for conversion to dementia was obtained. To increase the reliability of the results of the study, we analyzed the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset together., Results: During the follow-up period, 36% (39/107) of patients converted to dementia from amnestic MCI. The dementia converter group displayed increased standardized uptake value ratio (SUVR) values of FBB on PET in the bilateral temporal, parietal, posterior cingulate, occipital, and left precuneus cortices as well as increased global SUVR. Among volume of interests, the left parietal SUVR predicted conversion to dementia with the highest accuracy in the ROC analysis (area under the curve [AUC] = 0.762, P < 0.001). The combination of precuneus, parietal cortex, and FBB composite SUVRs also showed a higher accuracy in predicting conversion to dementia than other models (AUC = 0.763). Of the results of ADNI data, the SUVR of the left precuneus SUVR showed the highest AUC (AUC = 0.596, P = 0.006)., Conclusion: Our findings suggest that subthreshold amyloid levels may contribute to conversion to dementia in patients with amyloid-negative amnestic MCI., (© 2022. The Author(s).)

Although several studies have identified a distinct gut microbial composition in Parkinson's disease (PD), few studies have investigated the oral microbiome or functional alteration of the microbiome in PD. We aimed to investigate the connection between the oral and gut microbiome and the functional changes in the PD-specific gut microbiome using shotgun metagenomic sequencing. The taxonomic composition of the oral and gut microbiome was significantly different between PD patients and healthy controls (P = 0.003 and 0.001, respectively). Oral Lactobacillus was more abundant in PD patients and was associated with opportunistic pathogens in the gut (FDR-adjusted P < 0.038). Functional analysis revealed that microbial gene markers for glutamate and arginine biosynthesis were downregulated, while antimicrobial resistance gene markers were upregulated in PD patients than healthy controls (all P < 0.001). We identified a connection between the oral and gut microbiota in PD, which might lead to functional alteration of the microbiome in PD., (© 2022. The Author(s).)

Amyloid (Aβ) and tau proteins are pathologic hallmarks of Alzheimer disease (AD). It is well known that there is spatial disparity between Aβ and tau protein deposition but, crossed hemispheric accumulation of these 2 proteins has not been reported. Here we report the case of a 76-year-old woman with typical AD who underwent amyloid positron emission tomography (PET) ([ 18 F]-florbetaben) and tau PET scans ([ 18 F]PI-2620), revealing crossed accumulation of Aβ and tau in the cerebral hemisphere. A neuropsychological assessment showed impairment in memory with spared activities of daily living. In the PET analysis, amyloid deposition was observed only in the left side of the cerebral hemisphere and tau only in the right side. Neuroimaging follow-up indicated that the spatial pattern of these protein accumulations had not changed. This case suggests the possibility of independent Aβ and tau pathogenic pathways in AD., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To evaluate the effects of a mobile health intervention for self-management on self-efficacy, motor and non-motor symptoms, self-management, and quality of life in people with Parkinson's disease., Methods: A randomized controlled design was used. The participants were randomly assigned to an intervention or a control group. The intervention group (n = 20) received mobile health intervention comprising mobile applications, smartwatches, smartphone-based short text messages and information, and telephone counselling; whereas the control group (n = 23) received short text messages and telephone counselling for 16 weeks., Results: After 16 weeks, self-efficacy and non-motor symptom scores in the intervention group significantly improved compared to those in the control group. However, no significant differences were observed in the motor symptoms, self-management, and quality of life between the groups., Conclusions: The mobile health intervention for self-management is effective for self-efficacy and non-motor symptoms in people with Parkinson's disease., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Accumulation of aggregated amyloid-β (Aβ) in the brain is considered the first pathological event within the pathogenesis of Alzheimer's disease (AD). It is difficult to accurately identify the initial brain regions of Aβ accumulation due to the time-lag between the start of the pathophysiology and symptom onset. However, focal regional amyloid uptake on amyloid PET scans may provide insights into this. Hence, we aimed to evaluate the topographic distribution of amyloid deposition in patients with cognitive impairment and to identify the starting order of amyloid accumulation in the brain using conditional probability. We enrolled 58 patients composed of 9 normal cognition (NC), 32 mild cognitive impairment (MCI), and 17 dementia showing focal regional amyloid deposition corresponding to a brain amyloid plaque load (BAPL) score of 2 among those who visited the Memory Clinic of Asan Medical Center and underwent an 18 F-florbetaben PET scan (March 2013 to April 2019). Regions of interest (ROI) included the frontal, parietal, lateral temporal, and occipital cortices, the posterior cingulate/precuneus, and the striatum. The most frequent occurrence of Aβ deposition was in the posterior cingulate/precuneus (n = 41, 68.3%). The second most frequent site was the lateral temporal cortex (n = 24, 40.0%), followed by the lateral parietal cortex (n = 21, 35.6%) and other lesions, such as the frontal and occipital cortices. The striatum was the least frequently affected. Our study found that the posterior cingulate/precuneus and the lateral temporal and parietal cortices may be the earliest areas to be affected by Aβ accumulation. Longitudinal follow-up of focal brain amyloid deposition may help elucidate the evolutionary pattern of Aβ accumulation in the brain of people with AD continuum.

Objectives: This study aimed to compare susceptibility map-weighted imaging (SMwI) using various MRI machines (three vendors) with N-3-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophe nyl)nortropane ( 18 F-FP-CIT) PET in the diagnosis of neurodegenerative parkinsonism in a multi-centre setting., Methods: We prospectively recruited 257 subjects, including 157 patients with neurodegenerative parkinsonism, 54 patients with non-neurodegenerative parkinsonism, and 46 healthy subjects from 10 hospitals between November 2019 and October 2020. All participants underwent both SMwI and 18 F-FP-CIT PET. SMwI was interpreted by two independent reviewers for the presence or absence of abnormalities in nigrosome 1, and discrepancies were resolved by consensus. 18 F-FP-CIT PET was used as the reference standard. Inter-observer agreement was tested using Cohen's kappa coefficient. McNemar's test was used to test the agreement between the interpretations of SMwI and 18 F-FP-CIT PET per participant and substantia nigra (SN)., Results: The inter-observer agreement was 0.924 and 0.942 per SN and participant, respectively. The diagnostic sensitivity of SMwI was 97.9% and 99.4% per SN and participant, respectively; its specificity was 95.9% and 95.2%, respectively, and its accuracy was 97.1% and 97.7%, respectively. There was no significant difference between the results of SMwI and 18 F-FP-CIT PET (p > 0.05, for both SN and participant)., Conclusions: This study demonstrated that the high diagnostic performance of SMwI was maintained in a multi-centre setting with various MRI scanners, suggesting the generalisability of SMwI for determining nigrostriatal degeneration in patients with parkinsonism., Key Points: • Susceptibility map-weighted imaging helps clinicians to predict nigrostriatal degeneration. • The protocol for susceptibility map-weighted imaging can be standardised across MRI vendors. • Susceptibility map-weighted imaging showed diagnostic performance comparable to that of dopamine transporter PET in a multi-centre setting with various MRI scanners., (© 2021. The Author(s), under exclusive licence to European Society of Radiology.)

Introduction: Deep brain stimulation (DBS) has showed variable therapeutic effect on freezing of gait (FOG) in Parkinson's disease (PD). It is unclear which factors associated with the effect of DBS on FOG in patients with advanced PD. In this study, we investigated the correlation of pre and postoperative factors with the therapeutic effect of globus pallidus interna (GPi) DBS on FOG in PD patients., Methods: We retrospectively analyzed PD patients with FOG (N = 20) who underwent GPi DBS surgery. Postoperatively, video-based analysis for FOG severity was performed at the first DBS programming and patients were categorized into two groups according to DBS effect on FOG (11 FOG responders and 9 FOG non-responders) at medication-off state. We analyzed preoperative clinical characteristics, cognitive function, striatal dopamine transporter availability, postoperative DBS programming parameters, lead locations, and volume of tissue activated in functional subregions of GPi. Bootstrap enhanced Elastic-Net logistic regression was used to select pre and postoperative factors associated with the effect of GPi DBS., Results: Therapeutic effect of GPi DBS on FOG were correlated with the disease duration of PD before DBS surgery, preoperative improvement in FOG severity by levodopa medication, and the distance from active contact of DBS electrode to the prefrontal region of GPi anatomical site., Conclusions: Our study results suggest that the effect of GPi DBS on FOG is correlated with disease duration, levodopa responsiveness on FOG before DBS surgery and DBS electrode location, providing useful information to predict FOG outcome after GPi DBS in PD patients., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Cerebral amyloid angiopathy (CAA) often presents as cognitive impairment, but the mechanism of cognitive decline is unclear. Recent studies showed that number of microbleeds were associated with cognitive decline., Objective: We aimed to investigate how microbleeds contribute to cognitive impairment in association with white matter tract abnormalities or cortical thickness in CAA., Methods: This retrospective comparative study involved patients with probable CAA according to the Boston criteria (Aβ+ CAA) and patients with Alzheimer's disease (Aβ+ AD), all of whom showed severe amyloid deposition on amyloid PET. Using mediation analysis, we investigated how FA or cortical thickness mediates the correlation between the number of lobar microbleeds and cognition., Results: We analyzed 30 patients with Aβ+ CAA (age 72.2±7.6, female 53.3%) and 30 patients with Aβ+ AD (age 71.5±7.6, female 53.3%). The two groups showed similar degrees of cortical amyloid deposition in AD-related regions. The Aβ+ CAA group had significantly lower FA values in the clusters of the posterior area than did the Aβ+ AD group(family-wise error-corrected p < 0.05). The correlation between the number of lobar microbleeds and visuospatial function was indirectly mediated by white matter tract abnormality of right posterior thalamic radiation (PTR) and tapetum, while lobar microbleeds and language function was indirectly mediated by the abnormality of left PTR and sagittal stratum. Cortical thickness did not mediate the association between lobar microbleeds and cognition., Conclusion: This result supports the hypothesis that microbleeds burden leads to white matter tract damage and subsequent cognitive decline in CAA.

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.

Background: Around 15% to 20% of patients with clinically probable Alzheimer disease have been found to have no significant Alzheimer pathology on amyloid positron emission tomography. A previous study showed that conversion to dementia from amyloid-negative mild cognitive impairment (MCI) was observed in up to 11% of patients, drawing attention to this condition., Object: We gathered the detailed neuropsychological and neuroimaging data of this population to elucidate factors for conversion to dementia from amyloid-negative amnestic MCI., Methods: This study was a single-institutional, retrospective cohort study of amyloid-negative MCI patients over age 50 with at least 36 months of follow-up. All subjects underwent detailed neuropsychological testing, 3 tesla brain magnetic resonance imaging), and fluorine-18(18F)-florbetaben amyloid positron emission tomography scans., Results: During the follow-up period, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairment in all visual memory tasks. The volumetric analysis revealed that the converter group had significantly reduced total hippocampal volume on the right side, gray matter volume in the right lateral temporal, lingual gyri, and occipital pole., Conclusion: Our study showed that reduced gray matter volume related to visual memory processing may predict clinical progression in this amyloid-negative MCI population., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: The development of Parkinson disease (PD) may be promoted by exposure to air pollution., Objective: To investigate the potential association between exposure to particulate matters (PM2.5 and PM10), nitrogen dioxide (NO2), ozone (O3), sulfur dioxide (SO2), and carbon monoxide (CO) and the risk of incident PD., Design, Setting, and Participants: This retrospective cohort study used data from the Korean National Health Insurance Service. Among the 1 021 208 Korean individuals in the database, those who had lived in Seoul from January 2002 to December 2006 (n = 176 875) were screened for eligibility. A total of 78 830 adults older than 40 years without PD and who lived in Seoul between January 2002 and December 2006 were included in this study. Individuals diagnosed with PD before 2006 (n = 159) and individuals 40 years or younger (n = 97 886) were excluded. Each participant was followed up with annually from January 2007 to December 2015, thereby adding up to 757 704 total person-years of follow-up. Data were analyzed from January to September 2020., Exposures: Individual exposure levels to PM2.5, PM10, NO2, O3, SO2, and CO were estimated based on the participants' residential address at the district level. To evaluate long-term exposure to air pollution, time-varying 5-year mean air pollutant exposure was calculated for each participant., Main Outcomes and Measures: The outcome measure was the association between air pollution and the risk of incident PD measured as hazard ratios after adjusting for demographic factors, socioeconomic factors, and medical comorbidities., Results: At baseline, the mean (SD) age of the 78 830 participants was 54.4 (10.7) years, and 41 070 (52.1%) were female. A total of 338 individuals with newly diagnosed PD were identified during the study period. Exposure to NO2 was associated with an increase in risk of PD (hazard ratio for highest vs lowest quartile, 1.41; 95% CI, 1.02-1.95; P for trend = .045). No statistically significant associations between exposure to PM2.5, PM10, O3, SO2, or CO and PD incidence were found., Conclusions and Relevance: In this large cohort study, a statistically significant association between NO2 exposure and PD risk was identified. This finding suggests the role of air pollutants in PD development, advocating for the need to implement a targeted public health policy.

Introduction: Apraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia., Methods: We compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS., Results: In patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia., Conclusion: Group comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Microglial activation is a central player in the pathophysiology of Alzheimer's disease (AD). The soluble fragment of triggering receptor expressed on myeloid cells 2 (sTREM2) can serve as a marker for microglial activation and has been shown to be overexpressed in AD. However, the relationship of sTREM2 with other AD biomarkers has not been extensively studied. We investigated the relationship between cerebrospinal fluid (CSF) sTREM2 and other AD biomarkers and examined the correlation of plasma sTREM2 with CSF sTREM2 in a cohort of individuals with AD and without AD. Participants were consecutively recruited from Asan Medical Center from 2018 to 2020. Subjects were stratified by their amyloid positivity and clinical status. Along with other AD biomarkers, sTREM2 level was measured in the plasma as well as CSF. In 101 patients with either amyloid-positive or negative status, CSF sTREM2 was closely associated with CSF T-tau and P-tau and not with Abeta42. CSF sTREM2 levels were found to be strongly correlated with CSF neurofilament light chain. The comparison of CSF and plasma sTREM2 levels tended to have an inverse correlation. Plasma sTREM2 and P-tau levels were oppositely influenced by age. Our results suggest that neuroinflammation may be closely associated with tau-induced neurodegeneration.

Introduction: False memory, observed as intrusion errors or false positives (FPs), is prevalent in patients with Alzheimer's disease, but has yet to be thoroughly investigated in patients with amnestic mild cognitive impairment (a-MCI) with Alzheimer's disease pathology (ADP). We analyzed false versus veridical memory in individuals with a-MCI and measured the utility of false memory for ADP discrimination., Methods: Patients with a-MCI who received neuropsychological testing and amyloid PET were included. Patients were categorized into "with" and "without ADP" groups according to PET results. Memory tests assessed veridical and false memory, and the verity of patient responses was analyzed. A logistic regression model was used to evaluate false memory efficiency in discriminating ADP, and the sensitivity and specificity at the optimal level were estimated using the receiver-operating characteristic curve., Results: Thirty-seven ADP and 46 non-ADP patients were enrolled. The ADP group made more FPs in the recognition tests, and their response verity was significantly lower in every delayed memory test. No group difference, however, was observed in the veridical memory. The logistic regression analysis demonstrated that as the FPs increased, the risk of ADP increased 1.31 and 1.36 times in the verbal and visual recognition tests, respectively. The discriminatory accuracy of the FPs was estimated "low" to "moderate" in the visual and verbal recognition, respectively, with an optimal cutoff above 2.5., Conclusion: Increased false memory was the only feature to discriminate ADP from non-ADP in individuals with a-MCI. Further studies regarding false memory and its mechanism are warranted., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 by S. Karger AG, Basel.)

Background and Purpose: As part of network-specific neurodegeneration, changes in cerebellar gray matter (GM) volume and impaired cerebello-cerebral functional networks have been reported in Alzheimer disease (AD). Compared with healthy controls, a volume loss in the cerebellum has been observed in patients with continuum of AD. However, little is known about the anatomical or functional changes in patients with clinical AD but no brain amyloidosis. We aimed to identify the relationship between cerebellar volume and dementia conversion of amyloid-negative mild cognitive impairment (MCI)., Methods: This study was a retrospective cohort study of patients over the age 50 years with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center with no less than a 36-month follow-up period. All subjects underwent detailed neuropsychological tests, 3 T brain magnetic resonance imaging scans including three-dimensional T1 imaging, and fluorine-18[F 18 ]-florbetaben amyloid positron emission tomography scans. A spatially unbiased atlas template of the cerebellum and brainstem was used for analyzing cerebellar GM volume., Results: During the 36 months of follow-up, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairments in all visual memory tasks. In terms of volumetric analysis, reduced crus I/II volume adjusted with total intracranial volume, and age was observed in the converter group., Conclusions: Significant cerebellar GM atrophy involving the bilateral crus I/II may be a novel imaging biomarker for predicting dementia progression in amyloid-negative amnestic MCI patients., (© 2021 European Academy of Neurology.)

We aimed to investigate the role of the APOE genotype in cognitive and motor trajectories in Parkinson's disease (PD). Using PD registry data, we retrospectively investigated a total of 253 patients with PD who underwent the Mini-Mental State Exam (MMSE) two or more times at least 5 years apart, were aged over 40 years, and free of dementia at the time of enrollment. We performed group-based trajectory modeling to identify patterns of cognitive change using the MMSE. Kaplan-Meier survival analysis was used to investigate the role of the APOE genotype in cognitive and motor progression. Trajectory analysis divided patients into four groups: early fast decline, fast decline, gradual decline, and stable groups with annual MMSE scores decline of - 2.8, - 1.8, - 0.6, and - 0.1 points per year, respectively. The frequency of APOE ε4 was higher in patients in the early fast decline and fast decline groups (50.0%) than those in the stable group (20.1%) (p = 0.007). APOE ε4, in addition to older age at onset, depressive mood, and higher H&Y stage, was associated with the cognitive decline rate, but no APOE genotype was associated with motor progression. APOE genotype could be used to predict the cognitive trajectory in PD.

Objective: We developed and investigated the feasibility of a machine learning-based automated rating for the 2 cardinal symptoms of Parkinson disease (PD): resting tremor and bradykinesia., Methods: Using OpenPose, a deep learning-based human pose estimation program, we analyzed video clips for resting tremor and finger tapping of the bilateral upper limbs of 55 patients with PD (110 arms). Key motion parameters, including resting tremor amplitude and finger tapping speed, amplitude, and fatigue, were extracted to develop a machine learning-based automatic Unified Parkinson's Disease Rating Scale (UPDRS) rating using support vector machine (SVM) method. To evaluate the performance of this model, we calculated weighted κ and intraclass correlation coefficients (ICCs) between the model and the gold standard rating by a movement disorder specialist who is trained and certified by the Movement Disorder Society for UPDRS rating. These values were compared to weighted κ and ICC between a nontrained human rater and the gold standard rating., Results: For resting tremors, the SVM model showed a very good to excellent reliability range with the gold standard rating (κ 0.791; ICC 0.927), with both values higher than that of nontrained human rater (κ 0.662; ICC 0.861). For finger tapping, the SVM model showed a very good reliability range with the gold standard rating (κ 0.700 and ICC 0.793), which was comparable to that for nontrained human raters (κ 0.627; ICC 0.797)., Conclusion: Machine learning-based algorithms that automatically rate PD cardinal symptoms are feasible, with more accurate results than nontrained human ratings., Classification of Evidence: This study provides Class II evidence that machine learning-based automated rating of resting tremor and bradykinesia in people with PD has very good reliability compared to a rating by a movement disorder specialist., (© 2021 American Academy of Neurology.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Park, Jo, Kim, Jeon, Ryu, Kim, Park, Koh, Lee and Chung.)

Introduction: Cognitive impairment is not uncommon in patients with multiple system atrophy (MSA). This study investigated the cortical metabolic changes of MSA and the cortical structure associated with cognitive impairment., Methods: The study included probable/definite MSA patients who underwent fluorodeoxyglucose positron emission tomography and cognitive evaluation based on mini-mental status examination (MMSE). Cerebral metabolism of the entire MSA patients (n = 88) was compared with healthy controls (n = 19) by voxel-wise statistical parametric mapping. Eight brain regions of interest (ROIs) were selected accordingly: the dorsolateral prefrontal, medial superior frontal, insular, posterior parietal, precuneus, lateral temporal, medial temporal, and posterior cingulate regions. Using validated population-based norms, MSA patients were divided by MMSE z-scores into MSA with cognitive dysfunction (MSA-D, n = 30) and without cognitive dysfunction (MSA-ND, n = 58). Regional metabolism of the selected ROIs was compared between the MSA-D and MSA-ND groups by logistic regression models. Correlations between the regional metabolism of the selected ROIs and MMSE z-scores were analyzed with a linear regression model., Results: Voxel-wise analysis showed hypometabolism in the frontal, temporal, parietal, and limbic areas in MSA patients than in controls. ROI-based comparisons showed that metabolism in the posterior cingulate (P = 0.006) and medial temporal (P = 0.039) regions was significantly lower in the MSA-D than in the MSA-ND group. The degree of posterior cingulate metabolism correlated significantly with MMSE z-score (P = 0.023)., Conclusions: MSA shows fronto-temporo-parietal cortical involvement. Hypometabolism of the limbic regions is associated with cognitive impairment in MSA., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: The potential benefit of perampanel for sleep disturbances is unknown. This study determined whether insomnia is less prevalent and less severe in patients with epilepsy (PWE) who take perampanel as an adjuvant., Methods: This cross-sectional study was conducted in adults with epilepsy. Insomnia in patients treated or not treated with perampanel was diagnosed according to the criteria of the International Classification of Sleep Disorders, the third edition (ICSD-3) and the Insomnia Severity Index (ISI). Patients were also scored on the Epworth Sleepiness Scale (ESS), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7), and the groups were compared by stepwise linear or logistic regression analyses., Results: One hundred and twenty-six PWE were included in the study: 31 patients (24.6%) were taking perampanel. Insomnia was diagnosed in 15.9% and 20.6% of all patients according to the ICSD-3 and an ISI score of ≥15, respectively. Agreement between the two diagnostic methods was moderate (Cohen's kappa, 0.470). In a stepwise logistic regression model, insomnia diagnosed by either method was negatively associated with perampanel use (P<0.05) but positively correlated with depressive symptoms, anxiety, and duration of epilepsy. In a stepwise linear regression model, ISI scores correlated negatively with perampanel use (P=0.004) but positively with depressive symptoms (P<0.001) and anxiety (P=0.001)., Conclusions: Insomnia is less prevalent and less severe in PWE treated with perampanel independent of depressive symptoms, which will be helpful for treating PWE and comorbid sleep disturbances., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest in relation to this study., (Copyright © 2020. Published by Elsevier Inc.)

Background: Although dementia is a contraindication for deep brain stimulation (DBS) in patients with Parkinson's disease (PD), the concept is supported by little scientific evidence. Moreover, it is unclear whether PD with mild cognitive impairment (PD-MCI) or domain-specific cognitive impairments affect the outcome of DBS in non-demented PD patients., Objective: To investigate the influence of baseline cognitive profiles of PD on the outcome of DBS., Methods: Baseline cognitive levels of patients with PD who underwent DBS were classified into PD with dementia (PDD) (n = 15), PD-MCI (n = 210), and normal cognition (PD-NC) (n = 79). The impact of the cognitive level on key DBS outcome measures [mortality, nursing home admission, progression to Hoehn&Yahr (HY) stage 5 and progression to PDD] were analyzed using Cox regression models. We also investigated whether impairment of a specific cognitive domain could predict these outcomes in non-demented patients., Results: Patients with PDD showed a substantially higher risk of nursing home admission and progression to HY stage 5 compared with patients with PD-MCI [hazard ratio (HR) 4.20, P = .002; HR = 5.29, P < .001] and PD-NC (HR 7.50, P < .001; HR = 7.93, P < .001). MCI did not alter the prognosis in patients without dementia, but those with visuospatial impairment showed poorer outcomes for nursing home admission (P = .015), progression to HY stage 5 (P = .027) and PDD (P = .006)., Conclusions: Cognitive profiles may stratify the pre-operative risk and predict long-term outcomes of DBS in PD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Little is known about newly developed stroke in patients admitted to the intensive care unit (ICU)., Objective: This study aimed to investigate characteristics and outcomes of newly developed stroke in patients admitted to the non-neurological intensive care units (ICU-onset stroke, IOS)., Methods: A consecutive series of adult patients who were admitted to the non-neurological ICU were included in this study. We compared neurological profiles, risk factors, and mortality rates between patients with IOS and those without IOS., Results: Of 18,604 patients admitted to the ICU for non-neurological illness, 218 (1.2%) developed stroke (ischemic, n = 182; hemorrhagic, n = 36). The most common neurological presentation was altered mental status (n = 149), followed by hemiparesis (n = 55), and seizures (n = 28). The most common etiology of IOS was cardioembolism (50% [91/182]) for ischemic IOS and coagulopathy (67% [24/36]) for hemorrhagic IOS. In multivariable analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (adjusted odds ratio [AOR] = 1.04, 95% CI = 1.03-1.06, P < 0.001), prothrombin time (AOR = 0.99, 95% CI = 0.98-0.99, P = 0.013), cardiovascular surgery (AOR = 1.84, 95% CI = 1.34-2.50, P < 0.001), mechanical ventilation (AOR = 6.75, 95% CI = 4.87-9.45, P < 0.001), and extracorporeal membrane oxygenation (AOR = 2.77, 95% CI = 1.62-4.55, P < 0.001) were related to the development of IOS. Stroke was associated with increased 3-month mortality after hospital discharge (AOR, 2.20; 95% CI, 1.58-3.05; P < 0.001), after adjustment for APACHE II and comorbidities., Conclusions: Patients who developed IOS had characteristics of initial critical illness and managements performed in the ICU as well as neurological presentations. The occurrence of IOS was related to high morbidity and mortality.

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.

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., (Copyright © 2020 Ryu, Park, Choi, Kim, Park, Jo, Kim, Kim, Kim, Kim, Koh and Chung.)

Clinical factors associated with daytime sleepiness and insomnia in persons with epilepsy (PWE) were examined in this cross-sectional study of 126 participants (men, 50.8%). Excessive daytime sleepiness (EDS; score of ≥11 on the Epworth Sleepiness Scale (ESS)) was noted in 17.5% of participants (mean score, 6.1 ± 4.2), and moderate-to-severe insomnia (Insomnia Severity Index (ISI) scores of ≥15) was noted in 20.6% (mean score, 7.8 ± 6.4). Linear regression analyses revealed that ESS scores were independently associated with obstructive sleep apnea (OSA; snoring, tiredness, observed apnea, high blood pressure, body mass index, age, neck circumference, and gender (STOP-Bang) score of ≥3), an antiepileptic drug (AED) load of >3, depression (Patient Health Questionnaire-9 (PHQ-9) score of ≥10), female sex, and nocturnal seizures. Insomnia Severity Indices were independently associated with depression and anxiety (Generalized Anxiety Disorder-7 (GAD-7) score of ≥7). Notably, significant sex differences were found. Epworth Sleepiness Scale scores were associated with OSA in men but were associated with depression in women. In addition, anxiety was associated with insomnia in women only. Overall, OSA and depression were the most important significant clinical factors associated with daytime sleepiness and insomnia, respectively. However, there were sex differences for the associations between individual factors and sleep disturbances., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Amyloid PET allows for the assessment of amyloid β status in the brain, distinguishing true Alzheimer's disease from Alzheimer's disease-mimicking conditions. Around 15-20% of patients with clinically probable Alzheimer's disease have been found to have no significant Alzheimer's pathology on amyloid PET. However, a limited number of studies had been conducted on this subpopulation in terms of clinical progression., Objective: We investigated the risk factors that could affect the progression to dementia in patients with amyloid-negative amnestic mild cognitive impairment (MCI)., Methods: This study was a single-institutional, retrospective cohort study of patients over the age of 50 with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center with a follow-up period of more than 36 months. All participants underwent brain magnetic resonance imaging (MRI), detailed neuropsychological testing, and fluorine-18[F18]-florbetaben amyloid PET., Results: During the follow-up period, 39 of 107 patients progressed to dementia from amnestic MCI. In comparison with the stationary group, the progressed group had a more severe impairment in verbal and visual episodic memory function and hippocampal atrophy, which showed an Alzheimer's diseaselike pattern despite the lack of evidence for significant Alzheimer's disease pathology. Voxel-based morphometric MRI analysis revealed that the progressed group had a reduced gray matter volume in the bilateral cerebellar cortices, right temporal cortex, and bilateral insular cortices., Conclusion: Considering the lack of evidence of amyloid pathology, clinical progression of these subpopulation may be caused by other neuropathologies such as TDP-43, abnormal tau or alpha synuclein that lead to neurodegeneration independent of amyloid-driven pathway. Further prospective studies incorporating biomarkers of Alzheimer's disease-mimicking dementia are warranted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: This study investigated the protective effect of rapid eye movement (REM) sleep without atonia against obstructive sleep apnea (OSA) in patients with idiopathic REM sleep behavior disorder (RBD)., Methods: In this case-control study, patients with idiopathic RBD and OSA (RBD-OSA) were consecutively enrolled and OSA controls without RBD were matched for age, sex, and apnea-hypopnea index (AHI). Clinical and polysomnographic characteristics were compared between RBD-OSA patients and OSA controls. Additionally, differences in AHIs depending on sleep state and posture were analyzed., Results: In total, 109 OSA patients (81 males and 28 females) with idiopathic RBD were included in the study. In OSA controls without RBD, AHI and respiratory distress index (RDI) were significantly higher during REM sleep than during non-rapid eye movement (NREM) sleep (p < 0.01). In RBD-OSA patients, however, AHI and RDI were slightly lower during REM sleep than during NREM sleep (p < 0.05). During REM sleep, AHI and RDI were significantly lower in RBD-OSA patients than in OSA controls (p < 0.001). Differences in apnea severity between RBD-OSA patients and OSA controls increased in supine REM sleep but disappeared or lessened in non-supine REM sleep. The prevalence of REM-related OSA was lower in RBD-OSA patients (9.2%) than in OSA controls (33.0%)., Conclusions: REM sleep without atonia has protective effects against OSA in patients with idiopathic RBD. These protective effects are much more potent in supine sleep than in non-supine sleep., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Purpose: Decreasing the time delay for thrombolysis, including intravenous thrombolysis (IVT) with tissue plasminogen activator and intra-arterial thrombectomy (IAT), is critical for decreasing the morbidity and mortality of patients experiencing acute stroke. We aimed to decrease the in-hospital delay for both IVT and IAT through a multidisciplinary approach that is feasible 24 h/day., Methods: We implemented the Stroke Alert Team (SAT) on May 2, 2016, which introduced hospital-initiated ambulance prenotification and reorganized in-hospital processes. We compared the patient characteristics, time for each step of the evaluation and thrombolysis, thrombolysis rate, and post-thrombolysis intracranial hemorrhage from January 2014 to August 2016., Results: A total of 245 patients received thrombolysis (198 before SAT; 47 after SAT). The median door-to-CT, door-to-MRI, and door-to-laboratory times decreased to 13 min, 37.5 min, and 8 min, respectively, after SAT implementation ( P <0.001). The median door-to-IVT time decreased from 46 min (interquartile range [IQR] 36-57 min) to 20.5 min (IQR 15.8-32.5 min; P <0.001). The median door-to-IAT time decreased from 156 min (IQR 124.5-212.5 min) to 86.5 min (IQR 67.5-102.3 min; P <0.001). The thrombolysis rate increased from 9.8% (198/2,012) to 15.8% (47/297; P =0.002), and the post-thrombolysis radiological intracranial hemorrhage rate decreased from 12.6% (25/198) to 2.1% (1/47; P =0.035)., Conclusions: SAT significantly decreased the in-hospital delay for thrombolysis, increased thrombolysis rate, and decreased post-thrombolysis intracranial hemorrhage. Time benefits of SAT were observed for both IVT and IAT and during office hours and after-hours.