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Background Skeletal muscle atrophy is a severe condition that involves loss of muscle mass and quality. Drug intake can also cause muscle atrophy. Biguanide metformin is the first‐line and most widely prescribed anti‐diabetic drug for patients with type 2 diabetes. The molecular mechanism of metformin in muscle is unclear. Methods Myostatin expression was investigated at the protein and transcript levels after metformin administration. To investigate the pathways associated with myostatin signalling, we used real‐time polymerase chain reaction, immunoblotting, luciferase assay, chromatin immunoprecipitation assay, co‐immunoprecipitation, immunofluorescence, primary culture, and confocal microscopy. Serum analysis, physical performance, and immunohistochemistry were performed using our in vivo model. Results Metformin induced the expression of myostatin, a key molecule that regulates muscle volume and triggers the phosphorylation of AMPK. AMPK alpha2 knockdown in the background of metformin treatment reduced the myostatin expression of C2C12 myotubes (−49.86 ± 12.03%, P 3.12‐fold ± 0.13, P 3.3‐fold, P

Objectives: The purpose of this study is to provide basic data for the development of effective post-traumatic stress disorder (PTSD) intervention programs for firefighters.Methods: Four domestic and four abroad databases were used, and 7 domestic and 4 abroad studies that met the criteria of this study were selected for systematic review and meta-analysis.Results: The overall effect size of the PTSD intervention program was 0.40 (95% confidence interval, CI: 0.17-0.64, p

Amyloid-β (Aβ) is a key protein in Alzheimer's disease (AD) in that its accumulation induces complex pathological changes. Although there has been extensive research on the metabolism of Aβ in AD, new compelling results have recently emerged. Historically, the production and clearance of Aβ have been thought to originate in the central nervous system (CNS). However, recent evidence suggests that the production and clearance of Aβ can also occur in the peripheral system, and that the peripherally driven Aβ migrates to the CNS and induces amyloidopathy with subsequent AD pathologic changes in the brain. This concept implies that AD is not restricted to the CNS but is a systemic disease instead. As such, the development of blood-based biomarkers targeting Aβ is of great interest. Central and peripheral Aβ are both active contributors to the pathology of AD and interact bidirectionally. Measuring peripheral Aβ is not just observing the reflection of the residual Aβ removed from the CNS but also tracking the ongoing process of AD pathology. Additionally, blood-based biomarkers could be a more accessible tool in clinical and research settings. Through arduous research, several blood-based biomarker assays have demonstrated notable results. In this review, we describe the metabolism of Aβ and the amyloid-targeting blood-based biomarkers of AD.

Background Neuropsychological tests (NPTs) are important tools for informing diagnoses of cognitive impairment (CI). However, interpreting NPTs requires specialists and is thus time-consuming. To streamline the application of NPTs in clinical settings, we developed and evaluated the accuracy of a machine learning algorithm using multi-center NPT data. Methods Multi-center data were obtained from 14,926 formal neuropsychological assessments (Seoul Neuropsychological Screening Battery), which were classified into normal cognition (NC), mild cognitive impairment (MCI) and Alzheimer’s disease dementia (ADD). We trained a machine learning model with artificial neural network algorithm using TensorFlow (https://www.tensorflow.org) to distinguish cognitive state with the 46-variable data and measured prediction accuracies from 10 randomly selected datasets. The features of the NPT were listed in order of their contribution to the outcome using Recursive Feature Elimination. Results The ten times mean accuracies of identifying CI (MCI and ADD) achieved by 96.66 ± 0.52% of the balanced dataset and 97.23 ± 0.32% of the clinic-based dataset, and the accuracies for predicting cognitive states (NC, MCI or ADD) were 95.49 ± 0.53 and 96.34 ± 1.03%. The sensitivity to the detection CI and MCI in the balanced dataset were 96.0 and 96.0%, and the specificity were 96.8 and 97.4%, respectively. The ‘time orientation’ and ‘3-word recall’ score of MMSE were highly ranked features in predicting CI and cognitive state. The twelve features reduced from 46 variable of NPTs with age and education had contributed to more than 90% accuracy in predicting cognitive impairment. Conclusions The machine learning algorithm for NPTs has suggested potential use as a reference in differentiating cognitive impairment in the clinical setting.

BACKGROUND Although dementia with Lewy bodies (DLB) is a degenerative disease involving irreversible pathological changes and subsequent progressive cognitive decline, some patients have presented with improved cognitive function at follow-ups. Their clinical and neuropsychological characteristics and the factors influencing this improvement remain unclear. OBJECTIVE To investigate differences in clinical and neuropsychological characteristics between DLB patients with and without cognitive improvement at a one-year follow-up, and to identify predictive factors of cognitive improvement. METHODS This retrospective study included 60 DLB patients, 28 patients in the improved group, and 32 patients in the non-improved group. A multiple linear regression model was used to compare changes in cognitive function test scores between groups over the course of one year. Binary logistic regression analysis was performed to determine the odds ratios (ORs) of depressive symptoms as a predictor for cognitive improvement. RESULTS The improved group showed significant increases in immediate and delayed verbal memory function in one year over the non-improved group. We also found that baseline depressive symptoms were associated with an increased probability of cognitive improvement (OR 1.234, CI 1.043- 1.460). CONCLUSION Depressive symptoms at baseline were related to a higher probability of a cognitive improvement at one-year follow-up. In addition, immediate and delayed verbal memory function showed significant improvement during one year in improved patients compared to non-improved patients.

Background: In this study, a known PRNP mutation, Val180Ile (c.G538A), was reported in a 58 years old female patient, clinically diagnosed with Alzheimer’s disease (AD). Case report: The patient presented slowly progressive cognitive decline in memory and visuospatial domain. Neuroimaging showed hippocampal atrophy in MRI and mild amyloid positivity in PET scan. Even though her cerebrospinal fluid (CSF) was positive for 14–3-3 protein, no sign of Creutzfeldt-Jakob diseases symptoms was observed. In addition, reduced Aβ42 and elevated total-Tau and phospho-Tau in CSF also proved the AD diagnosis. The mutation may disturb the hydrophobic core of prion protein, and result in abnormal intramolecular interactions. Due to 23andMe, PRNP Val180Ile could not be categorized either as a mutation with complete penetrance, or as neutral variant, and could have a possible role in neurodegeneration. Pathological overlap was observed between prion diseases and other neurodegenerative diseases, including AD or frontotemporal dementia. Conclusion: Whole exome sequencing and pathway analysis of patient revealed rare or possible risk variants in AD associated genes, such as SORL1 or ABCA7. Along with PRNP, AD risk genes may play a role in negative regulation of amyloid formation. Dysfunctions in these genes could possibly be associated in reduced neuroprotection and amyloid clearance.

Exosomes, which are small extracellular vesicles produced from various cell types, contain a variety of molecular constituents, such as proteins, lipids, and RNA. Recently, exosomal biomarkers have been investigated to probe the understanding and diagnosis of neurodegenerative disorders. Previous reports have demonstrated increased exosomal α-synuclein (α-syn) in patients with Parkinson’s disease (PD) in comparison to healthy controls (HC). Interestingly, the cholinergic loss was revealed in the central and peripheral nervous systems in histopathology and molecular neuroimaging. Thereby, we simultaneously examined acetylcholinesterase (AChE) with α-syn as exosomal markers. Exosomes were isolated from the plasma of 34 FP-CIT PET proven patients with PD and 29 HC. Exosomal α-syn and AChE activity were quantified andthe relationship with clinical parameters was analyzed. Remarkably, exosomal AChE activity was significantly decreased in PD compared to HC (P = 0.002). Moreover, exosomal AChE activity in PD revealed a strong negative correlation with disease severity, including H&Y (P = 0.007) and UPDRS part III (P = 0.047) scores. By contrast, no significant difference in exosomal α-syn concentration was observed between groups. These results support the occurrence of cholinergic dysfunction in PD, and they could be implicated with disease progression, especially motor deficits. Exosomal AChE activity with advanced exosome isolation techniques may be a reliable biomarker for the early diagnosis and prognosis of PD.

Unruptured intracranial aneurysms have a risk of rupture, so coil embolization is widely practiced as it preserves a patent artery. There are complications of coil procedures, such as patent artery occlusion and thromboembolism, which can result in retinal artery occlusion. We report onretinal artery occlusion following coil embolization of anterior communicating artery aneurysm. This is a rare case of a combination of cilioretinal and branch retinal artery occlusion, and is unusual in showing a functional recovery.

The objective of this study is to investigate the clinical significance of a specific behavior of misplacing items in a refrigerator (i.e., placing extremely unusual things such as remote control and/or cellular phone in a refrigerator) as a symptom of cognitive dysfunction. Patients with memory complaints were asked whether they ever experienced misplacing items in a refrigerator, such as placing a remote control, a cellular phone, or other extremely unusual things inside a refrigerator (referred to as the ‘fridge sign’). Among the 2172 individuals with memory complaints, 55 (2.5%) experienced symptoms of the ‘fridge sign’. We investigated the cognitive profiles of ‘fridge sign’-positive patients and performed follow-up evaluations with neuropsychological tests or telephone interviews. The ‘fridge sign’ was mostly found in individuals diagnosed as subjective cognitive decline (n = 33, 60%) or mild cognitive impairment (MCI, n = 20, 36.4%) with depressive mood and was relatively rare in dementia states (n = 2, 3.5%). Moreover, none of the ‘fridge sign’-positive patients showed significant cognitive decline over the follow-up period. We compared the cognitive profiles and the clinical progression of 20 ‘fridge sign’-positive MCI patients and 40 ‘fridge sign’-negative MCI patients. ‘Fridge sign’-positive MCI patients had worse scores on the Stroop test color reading and had higher scores on the geriatric depression scale than ‘fridge sign’-negative MCI patients, which indicates that the ‘fridge sign’ could be indicative of selective attention deficit in patients with depression rather than indicative of cognitive decline related to dementia.

Background Recently, several studies suggested potential involvements of α-synuclein in Alzheimer’s disease (AD) pathophysiology. Higher concentrations of α-synuclein were reported in cerebrospinal fluid (CSF) of AD patients with a positive correlation towards CSF tau, indicating its possible role in AD. We analyzed the CSF biomarkers to verify whether α-synuclein could be an additional supported biomarker in AD diagnosis. Methods In this cross-sectional study, CSF samples of 71 early-onset AD, 34 late-onset AD, 11 mild cognitive impairment, 17 subjective cognitive decline, 45 Parkinson’s disease, and 32 healthy control (HC) were collected. CSF amyloid-β1-42 (A), total tau (N), and phosphorylated tau181 (T) were measured by commercial ELISA kits, and in-house ELISA kit was developed to quantify α-synuclein. The cognitive assessments and amyloid-PET imaging were also performed. Results CSF α-synuclein manifested a tendency to increase in AD and to decreased in Parkinson’s disease compared to HC. The equilibrium states of total tau and α-synuclein concentrations were changed significantly in AD, and the ratio of total tau/α-synuclein (N/αS) was dramatically increased in AD than HC. Remarkably, N/αS revealed a strong positive correlation with tau phosphorylation rate. Also, the combination of N/αS with amyloid-β1-42/phosphorylated tau181 ratio had the best diagnosis performance (AUC = 0.956, sensitivity = 96%, specificity = 87%). In concordance analysis, N/αS showed the higher diagnostic agreement with amyloid-β1-42 and amyloid-PET. Analysis of biomarker profiling with N/αS had distinctive characteristics and clustering of each group. Especially, among the group of suspected non-Alzheimer’s disease pathophysiology, all A−T+N+ patients with N/αS+ were reintegrated into AD. Conclusions The high correlation of α-synuclein with tau and the elevated N/αS in AD supported the involvement of α-synuclein in AD pathophysiology. Importantly, N/αS improved the diagnostic performance, confirming the needs of incorporating α-synuclein as a biomarker for neurodegenerative disorders. The incorporation of a biomarker group [N/αS] could contribute to provide better understanding and diagnosis of neurodegenerative disorders.

Background Normal pressure hydrocephalus (NPH) is an etiology of dementia that is reversible following cerebrospinal fluid shunt placement, however, surgical intervention not always clinically effective and the respons to shunt therapy is poorly understood. Furthermore, NPH is a source of comorbidity in diseases with neurodegenerative pathology, such as Alzheimer's disease (AD). Case report A 61-year-old woman presented to the neurology clinic with progressive gait difficulties and cognitive impairment over five years. Nine years after ventriculoperitoneal (VP) shunt treatment, the patient began to experience frequent falls. There was no improvement in clinical symptoms after the alteration of valve pressure on the VP shunt. An 18F-florbetaben amyloid positron emission tomography scan showed increased diffusion uptake over the bilateral cortices, precuneus, and posterior cingulate cortex. Conclusions The patient of NPH was unresponsive to shunt therapy due to the development of AD.

Background and purpose Although progression of small deep subcortical infarct (PSDI) comprises 12% to 36% of all small deep subcortical infarcts, the therapy for progression is not clear. This study investigated whether induced-hypertension therapy using phenylephrine is a useful therapy for PSDI. Methods A group of 2427 consecutive patients, diagnosed with stroke at a tertiary hospital over a period of 4 years was reviewed retrospectively. We analyzed patients with small deep subcortical infarct using clinical, laboratory, and pulse wave velocity (PWV). PSDI is defined as one or more increase in the motor score according to the NIHSS. Good outcome was designated as a modified Rankin scale of 0 to 2 at discharge. Results Among all 662 patients who had a small deep subcortical infarct, 66 patients experienced motor progression (9.97%). The induced-hypertension therapy group (n = 25) received phenylephrine, and the conventional group (n = 41) received anticoagulation therapy such as heparin, volume expansion, or both. Although there were no significant differences in baseline clinical and laboratory findings, the PSDI group showed a significantly more frequent decrease in blood pressure at progression ( P P = 0.001). The phenylephrine group ( vs the conventional group) had a lower NIHSS score ( P = 0.036) and good outcome at discharge ( P = 0.004). In multiple regression analysis, PWV (OR, 1.004 per 1-cm/s increase; 95% CI, 1.001–1.008; P = 0.018) was an independent predictor of good outcome in the phenylephrine group. A side effect of phenylephrine treatment was dysuria (n = 1). Conclusions The present study suggests that vascular stiffness can be not only a predictor for PSDI but also a predictor of motor improvement after induced-hypertension therapy using phenylephrine in lacunar stroke.

Gerstmann-Straussler-Scheinker disease (GSS) is a rare prion disease characterized by cerebellar ataxia with progressive cognitive decline.

INTRODUCTION: Oligomeric amyloid ß (Aß) is one of the major contributors to the pathomechanism of AD; Aß oligomerization in plasma can be measured using a Multimer Detection System-Oligomeric Aß (MDS-OAß) after incubation with spiked synthetic Aß. METHODS: We evaluated the clinical sensitivity and specificity of the MDS-OAß values by inBlood TM OAß test using heparin-treated plasma samples from 52 AD patients in comparison with 52 community-based subjects with normal cognition (NC). The inclusion criterion was proposed by the NINCDS-ADRDA and additionally required for the least 6 months of follow-up from the initial clinical diagnosis in the course of AD. RESULTS: The MDS-OAβ values were 1.43 ± 0.30 ng/ml in AD and 0.45 ± 0.19 ( p

Multiple neurological complications have been associated with the coronavirus disease-19 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2. This is a narrative review to gather information on all aspects of COVID-19 in elderly patients with cognitive impairment. First, the following three mechanisms have been proposed to underlie the neurological complications associated with COVID-19: 1) direct invasion, 2) immune and inflammatory reaction, and 3) hypoxic brain damage by COVID-19. Next, because the elderly dementia patient population is particularly vulnerable to COVID-19, we discussed risk factors and difficulties associated with cognitive disorders in this vulnerable population. We also reviewed the effects of the patient living environment in COVID-19 cases that required intensive care unit (ICU) care. Furthermore, we analyzed the impact of stringent social restrictions and COVID-19 pandemic-mediated policies on dementia patients and care providers. Finally, we provided the following strategies for working with elderly dementia patients: general preventive methods; dementia care at home and nursing facilities according to the activities of daily living and dementia characteristics; ICU care after COVID-19 infection; and public health care system and government response. We propose that longitudinal follow-up studies are needed to fully examine COVID-19 associated neurological complications, such as dementia, and the efficacy of telemedicine/telehealth care programs., Graphical Abstract

Background Chemotherapy is a standard therapeutic regimen to treat triple-negative breast cancer (TNBC); however, chemotherapy alone does not result in significant improvement and often leads to drug resistance in patients. In contrast, combination therapy has proven to be an effective strategy for TNBC treatment. Whether metformin enhances the anticancer effects of cisplatin and prevents cisplatin resistance in TNBC cells has not been reported. Methods Cell viability, wounding healing, and invasion assays were performed on Hs 578T and MDA-MB-231 human TNBC cell lines to demonstrate the anticancer effects of combined cisplatin and metformin treatment compared to treatment with cisplatin alone. Western blotting and immunofluorescence were used to determine the expression of RAD51 and gamma-H2AX. In an in vivo 4T1 murine breast cancer model, a synergistic anticancer effect of metformin and cisplatin was observed. Results Cisplatin combined with metformin decreased cell viability and metastatic effect more than cisplatin alone. Metformin suppressed cisplatin-mediated RAD51 upregulation by decreasing RAD51 protein stability and increasing its ubiquitination. In contrast, cisplatin increased RAD51 expression in an ERK-dependent manner. In addition, metformin also increased cisplatin-induced phosphorylation of γ-H2AX. Overexpression of RAD51 blocked the metformin-induced inhibition of cell migration and invasion, while RAD51 knockdown enhanced cisplatin activity. Moreover, the combination of metformin and cisplatin exhibited a synergistic anticancer effect in an orthotopic murine model of 4T1 breast cancer in vivo. Conclusions Metformin enhances anticancer effect of cisplatin by downregulating RAD51 expression, which represents a novel therapeutic target in TNBC management.

Background Sundown syndrome (SS) in patients with Alzheimer's disease (AD) is characterized by aggravation of behavioral problems at sunset. Disturbance of the circadian rhythm, a possible cause of SS, also facilitates amyloidopathy and reduces sleep quality. However, the associations of SS with amyloidopathy and sleep quality remain unclear. Objective To investigate the prevalence of SS in patients with AD, the association between SS and APOEɛ4 carrier, representing an enhanced amyloid pathology, and the relationship between SS and sleep quality in AD. Methods We included 104 patients with late-onset AD and known APOE genotype. All participants underwent a structured interview via informant-based questionnaires to assess sleep quality and the presence of SS. Binary logistic regression analysis was performed to determine odds ratios (ORs) of APOEɛ4 carrier and parameters of sleep quality for SS. Results The prevalence of SS in AD was 27.8% (n = 29). Patients with SS were significantly more likely to be APOEɛ4 carriers and to have rapid eye movement sleep behavior disorder (RBD) and a higher Clinical Dementia Rating (CDR) score compared to those without SS. In the multivariate regression analysis, APOEɛ4 carrier (OR 3.158, CI 1.022-9.758), RBD (OR 2.166, CI 1.073-4.371), and higher CDR score (OR 2.453, CI 1.084-5.550) were associated with an increased risk of SS. Conclusion The prevalence of SS in patients with AD was 27.8%. The presence of the APOEɛ4 allele, RBD, and more severe dementia are associated with an increased risk of SS in AD.

Background: An accurate measurement of patient weight is important in determining the dosage for intravenous alteplase thrombolysis. In most emergency rooms, however, weight is not measured. We investigated the difference between stated and measured weight and its effect on hemorrhagic transformation and clinical outcomes. Methods: We enrolled 128 consecutive patients who had hyperacute stroke and were treated by alteplase. Alteplase dose was calculated using the weight provided by patient or guardian/caregiver, and the actual weight was measured after administration. Patients were classified into 2 groups: overused group (stated weight >measured weight) and underused group (measured weight ≥stated weight). The prevalence of hemorrhagic transformation on follow-up, determined by gradient-recalled echo MRI or non-enhanced CT, was compared between the 2 groups. The predictors for hemorrhage with progression, defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) by a value of 4 or more accompanied by hemorrhage, were determined using multivariable logistic regression analysis and included the overused or underused alteplase and baseline clinical and laboratory findings. Results: Sixty-six (51.6%) of 128 patients were in the underused group and 62 patients (48.4%) in the overused group. The median difference between the stated and measured weights was 1.5 (interquartile range 0.56-3.81) kg, with the largest difference being 25.6 kg. Although there were no significant difference in baseline clinical and laboratory findings between the 2 groups, the overused group showed a significantly higher prevalence of hemorrhagic transformation (p = 0.012) and hemorrhage with progression (p = 0.025). The multivariable logistic regression analysis demonstrated that overused alteplase (OR 7.26; 95% CI 1.24-42.45; p = 0.028), baseline glucose (>144 mg/dL; OR 5.03; 95% CI 1.00-25.26; p = 0.050), and initial NIHSS (OR 1.13 per 1-point NIHSS increase; 95% CI 1.00-1.27; p = 0.047) in model 1 that use alteplase overdose as a categorical variable and overused alteplase (OR 1.67 1-mg increase; 95% CI 1.05-2.66; p = 0.027) in model 2 that use an overused alteplase dose as numerical variable were significant predictors for hemorrhage with progression. Conclusion: More alteplase usage than actual weight led to higher hemorrhagic transformation. As one of the predictors for clinical deterioration, it is important to administrate alteplase based on an accurately measured weight.

This paper introduces some of the core ideas of an Open Source Educational Processes approach. Based in part on the practices of the Open Source communities of the late 20th and early 21st centuries such as the Linux community, along with the idea that human activity should be held as primary in human-Internet interactions, open source educational processes suggest that individuals will require new types of skills and self-efficacies in order to realize the potential of their Internet activities. Education for these skills is at least in part dependent on development of curricula that recognizes the dialectical relationship between individual agency and goal driven, online communities. It is the communities which drive individual motivations to search for new problem solving possibilities, create well-functioning communities that are capable of organizing and differentiating distributed sources of information, and act as inflection points in the flow of information, recognizing that knowledge is not an object but an ongoing activity. These types of communities are currently relatively rare, especially for distributed populations who do share an initial stake in its goals. One of the few places many students might be able to experience these types of communities and build their Internet skills and self-efficacies are in consciously designed communities provided in traditional education contexts. 21st century education should move (quickly) towards embracing the new types of thinking and intelligence made possible by the Internet through open source educative processes influenced curricula.

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by the loss of muscle atonia during REM sleep and dream enactment, which often leads to injury of the patient or the bed partner [1]. Although its precise pathophysiology is unclear, RBD occurs more frequently in patients with neurodegenerative disease than in the general population, and especially in patients with α-synucleinopathy such as Parkinson’s disease (PD), multiple systemic atrophy (MSA), and dementia with Lewy bodies (DLB) compared to non-synucleinopathy. A number of studies have attempted to reveal the association between RBD and α-synucleinopathies [2-4]. Up to 81% of the patients initially diagnosed with idiopathic RBD eventually developed neurodegenerative diseases in long-term follow-up studies [5,6]. Therefore, RBD is becoming recognized as a clinical predictive factor for neurodegenerative diseases [7,8]. RBD has been reported to be present in 15–72% of PD patients and is associated with poor parkinsonian symptoms, higher daily levodopa dosage, poor autonomic symptoms and cognitive impairment in PD patients [2,9-13]. In this study, we aimed to assess the differences in the clinical characteristics between PD patients with and without RBD in a Korean population. Although a definite diagnosis of RBD requires polysomnography (PSG), this technique is unsuitable for studies dealing with large populations or clinical settings because the exam is expensive and requires a skilled examiner. For this reason, various RBD screening tools, including the RBD screening questionnaire (RBDSQ), RBD questionnaire-Hong Kong, Mayo sleep questionnaire, and RBD Severity Scale have been developed and utilized in RBD studies [14]. In 2007, Stiasny-Kolster et al. [15] proposed the RBDSQ, a 10-item, patient self-rating tool that has demonstrated a high sensitivity and reasonable specificity for RBD diagnosis as confirmed by PSG. For this study, the Korean version of the RBDSQ (RBDSQ-K) has been developed and utilized for assessment of RBD in PD patients. Although the importance of RBD as predicting factor for PD is becoming more recognized and the number of studies examining the clinical characteristics of RBD patients continues to increase, there are only a few RBD studies in the Korean PD population. In this study, we aimed to analyze the differences in the clinical characteristics of PD patients with and without RBD.

Introduction Oligomeric amyloid-ß is a major toxic species associated with Alzheimer’s disease pathogenesis. Methods used to measure oligomeric amyloid-β in the blood have increased in number in recent years. The Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ) is a specific method to measure oligomerization tendencies in the blood. The objective of this study was to determine the association between amyloid-ß oligomerization in the plasma and structural changes of the brain. Methods We studied 162 subjects composed of 92 community-based normal healthy subjects, 17 with subjective cognitive decline, 14 with mild cognitive impairment and 39 with Alzheimer’s disease dementia. All subjects underwent MDS-OAβ and three-dimensional T1 magnetic resonance imaging. To determine the structural changes of the brain that are statistically correlated with MDS-OAβ level, we used voxel-based morphometry with corrections for age and total intracranial volume covariates. Results We found brain volume reduction in the bilateral temporal, amygdala, parahippocampal and lower parietal lobe and left cingulate and precuneus regions (family-wise error, p

Although driving by adults with cognitive impairment is an important public health concern, little is known about the indicators of driving cessation in patients with mild cognitive impairment (MCI). We aimed to investigate the prevalence of driving cessation in patients with MCI and the predictive value of cognitive performances for driving cessation. Patients with MCI were recruited in the Seoul National University Bundang Hospital; they met following inclusion criteria. Age range of 51–80 years, Clinical Dementia Rating scale score of 0.5, and ever car drivers including former and current drivers. All participants underwent comprehensive standardized cognitive assessments and information on driving status was obtained via an interview using a systematic questionnaire. The median age of the 135 participants was 72 years, and 54 participants (40%) were women; 93 patients (68.9%) were current drivers and 42 (31.1%) were former drivers. In univariate analysis, former drivers showed poorer performances in digit span backward and categorical fluency tests than current drivers. In multivariate logistic regression analysis, a poor digit span backward test score was significantly related with driving cessation (odds ratio: 0.493, 95% confidence interval: 0.258–0.939). In patients with MCI, poor performance in the digit span backward test, which represents impaired working memory capacity, was associated with a higher probability of driving cessation.

This study was conducted to assess the anthropogenic impact on the metal concentration in agricultural soils in the vicinity of a Zn smelter. We determined Pb isotope ratios to trace source of metals and calculate source apportionment. 19.7% of the agricultural soil samples had Zn concentrations exceeding the Korean worrisome level (WL). The isotopic variation in the contaminated agricultural soils reflected the input of contaminants derived from the Zn smelter. The spatial distribution of Zn concentrations and Pb isotopes suggested that the Zn smelter dust fallout was the major source of heavy metal pollution in the agricultural soils. Lead isotope compositions of soil horizon I was comparable to those of soil horizon II, indicating that smelter-origin Zn had migrated vertically. Binary mixing between Zn concentrates and background soils could explain the variations in Pb isotope ratios in the contaminated agricultural soils. Source apportionment calculations showed that for agricultural soils that were found to exceed the Korean countermeasure standard (CS), the average proportion of smelter-origin Zn was 45.8%-83.3% while for agricultural soils that exceeded the WL but were below the CS, the average proportion of smelter-origin Zn was 36.3%-68.1%. The remainder was derived from a geogenic source.

Background Approximately 10% to 30% of Alzheimer disease (AD) patients progress rapidly in severity and become more dependent on caregivers. Although several studies have investigated whether imaging biomarkers such as medial temporal atrophy (MTA) and posterior atrophy (PA) are useful for predicting the rapid progression of AD, their results have been inconsistent. Objective The study aims to investigate the association of visually rated MTA and PA with rapid disease progression in AD. Methods This was a retrospective cohort study of 159 AD patients who were initially diagnosed with mild AD and were followed for 1 year to determine whether they progressed rapidly (a decrease of three points or more on the Mini-Mental State Examination over 1 year). We used 5-point and 4-point visual rating scales to assess MTA and PA, respectively. MTA and PA scores for each patient were dichotomized as normal (without atrophy) or abnormal (atrophy). We performed a logistic regression analysis to determine the odds ratios (ORs) of MTA and PA for rapid disease progression with adjustment for covariates. Results Within the study population, 47 (29.6%) patients progressed rapidly. Visual assessment of the magnetic resonance imaging (MRI) scans revealed that 112 patients (70.4%) showed MTA, whereas 80 patients (50.3%) showed PA. The ORs with 95% confidence intervals for MTA and PA were 1.825 (0.819-4.070) and 2.844 (1.378-5.835), respectively. The association of visually assessed PA, but not MTA, with rapid progression was significant after adjustment for covariates. Conclusion In patients with mild AD, visual assessment of PA exhibits independent predictive value for rapid disease progression.

Trace element contamination (As, Cd, Cr, Co, Cu, Mo, Ni, Pb, S, Zn, and Zr) in both Asian dust (AD) and non-Asian dust (NAD) periods taken from Daejeon, Korea, in 2008 was examined, and the pollution sources were evaluated based on the Pb stable isotope. Additionally, temporal variation in the trace element concentrations of total suspended particulate matter, PM10 and PM2.5, was evaluated in 14 samples for AD and 46 samples for NAD collected from March 2007 to November 2008. Patterns showed that the monthly mean concentrations of trace elements in winter were 2–13 times higher than those in other seasons. In contrast, the monthly mean concentrations of sulfur were the highest in the summer monsoon season. Distinct temporal patterns were observed in the monthly mean concentrations of trace elements, due mainly to high coal combustion in China. These results were supported by the 206Pb/207Pb ratios of AD and NAD, which were identical or similar to those of the airborne particles in certain heavily industrialized Chinese cities and coal and coal combustion dust of China. The Pb isotopic composition in the particulate matter of NAD showed lower 206Pb/207Pb, 207Pb/204Pb, and 206Pb/204Pb ratios in the autumn, winter, and spring seasons, showing the influence of Pb from the heavily industrial cities of China, and higher values in the summer, indicating the dilution and/or mixing effect of the marine air mass from the south.

Background In patients with amyloid-positive mild cognitive impairment (MCI), neurodegenerative biomarkers such as medial temporal lobe atrophy (MTA) are useful to predict disease progression to dementia. Although posterior atrophy (PA) is a well-known neurodegenerative biomarker of Alzheimer’s disease, little is known about PA as a predictor in patients with amyloid-positive MCI. Methods We included 258 patients with amyloid-positive MCI with at least one follow-up visit, and who had low cerebrospinal fluid (CSF) β-amyloid1–42 concentration. Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative study. We assessed PA and MTA on magnetic resonance imaging (MRI) using visual rating scales and retrospectively determined progression to dementia during the follow-up period of up to 3 years (median 24 months). The Cox proportional hazards model was used to analyze hazard ratios (HRs) of PA and MTA for disease progression. Additionally, subjects were divided into four groups according to brain atrophy pattern (no atrophy, MTA only, PA only, both MTA and PA), and HRs for disease progression were compared with the no atrophy reference group. Analyses were conducted with and without adjustment for CSF phosphorylated tau181p (p-tau) and baseline demographics. Results A total of 123 patients (47.7%) showed MTA and 174 patients (67.4%) showed PA. Of the total cohort, 139 cases (53.9%) progressed to dementia. PA and MTA were associated with an increased risk for progression to dementia (HR 2.244, 95% confidence interval (CI) 1.497–3.364, and HR 1.682, 95% CI 1.203–2.352, respectively). In the analysis according to atrophy pattern, HR (95% CI) for progression was 2.998 (1.443–6.227) in the MTA only group, 3.126 (1.666–5.864) in the PA only group, and 3.814 (2.045–7.110) in both MTA and PA group. These results remained significant after adjustment. Conclusions In patients with amyloid-positive MCI, PA could predict progression to dementia independently of MTA. Electronic supplementary material The online version of this article (doi:10.1186/s13195-017-0326-y) contains supplementary material, which is available to authorized users.

In this study, a novel mutation in APP gene, Val669Leu (“Seoul APP”), was reported in a Korean female patient with Alzheimer's disease. She developed cognitive decline at 56 years of age, and her memory declined rapidly over one-year period from her 1st visit to the hospital. Her Mini-Mental State Examination scores dropped from 25/30 to 13/30. Two years later, she developed parkinsonian features, myoclonic jerk, and generalized seizure. As the disease progressed, aggravated diffuse brain atrophy and small-vessel ischemic lesion was also observed, and she became mute and vegetative in 4 years from the symptom onset. Magnetic resonance imaging showed mild medial temporal lobe and hippocampal atrophy, and 18F-fluoro-deoxyglucose positron emission tomography showed bilateral temporoparietal hypometabolism. Plasma amyloid oligomer analysis revealed highly elevated Aβ oligomers levels in the proband patient. Family history revealed positive without biochemical confirmation because family members testified similar type of cognitive decline from the proband's mother and one of her aunt/uncle. Her half-siblings did not present any signs of memory impairment. Sanger sequencing of the proband patient revealed a novel mutation in APP gene, Val669Leu, but mutation was not found in her unaffected half-sisters. A designed algorithm by Guerreiro et al. on early-onset Alzheimer's disease–associated mutations suggested the mutation as possibly pathogenic mutation. On the other hand, PolyPhen2 and SIFT tools suggested as otherwise. Since the mutation was located nearby the β-secretase cleavage site of APP, right next to the Swedish APP (Lys,Met670/671Asn,Leu) mutation, it was named as “Seoul APP” mutation. 3D modeling revealed that this mutation could result in significant changes in loop orientation of APP and also its intramolecular interactions. Hence, a novel APP Val669Leu mutation could alter the binding interactions between APP and β-secretase, which may influence the Aβ40 and Aβ42 generations.

A focal atonic seizure is a partial seizure in which the ictal manifestation consists of paresis of the extremities or muscles on one side of the body, and this phenomenon can easily be misdiagnosed as a transient ischemic attack. An 86-year-old woman visited our hospital complaining of transient right upper extremity weakness lasting for 10min following an unusual sensation in her chest accompanied by palpitations. On the third hospital day, she again complained of right arm weakness, which progressed to jerky movements of her right extremity accompanied by facial twitching and then generalized into a tonic–clonic seizure. The EEG displayed several interictal spikes in the contralateral temporal area, and the ictal SPECT, analyzed using the SISCOM system, showed an increased signal in both the contralateral superior parietal area and the mesial frontal area. In this case, the patient was diagnosed with focal atonic seizures as the cause of the monolimb weakness, which had been initially misdiagnosed aas transient ischemic attacks. In cases in which a patient presents with monolimb paresis, physicians should consider the possibility of an atonic seizure as the cause.

In this paper, we propose a novel intrusion detection technique using a deep neural network (DNN). In the proposed technique, in-vehicle network packets exchanged between electronic control units (ECU) are trained to extract low- dimensional features and used for discriminating normal and hacking packets. The features perform in high efficient and low complexity because they are generated directly from a bitstream over the network. The proposed technique monitors an exchanging packet in the vehicular network while the feature are trained off-line, and provides a real-time response to the attack with a significantly high detection ratio in our experiments.