Effect of Dietary Habits on Alzheimer's Disease Progression.

PURPOSE: Research on the relationship between diet and dementia among Koreans are lacking. This study investigated the association between dietary habits and dementia progression over 3 years in patients with Alzheimer's disease dementia (ADD). MATERIALS AND METHODS: This study included 705 patients with mild-to-moderate ADD. Dietary habits were assessed using the Mini Dietary Assessment Index, comprising 10 questions. Outcome measures included the Clinical Dementia Rating scale-Sum of Boxes (CDR-SB), Seoul-Instrumental Activities of Daily Living, Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI), and neuropsychological test battery (NTB) z-scores, which were evaluated annually over 3 years. RESULTS: In Q10 (eat all food evenly without being picky), the 3-year mean differences in CDR-SB (increases in scores represent worsening) compared to the "rarely" group were -1.86 [95% confidence interval (CI)=-3.64 - -0.09, p=0.039] for the "usually" group and -2.23 (95% CI=-4.40 - -0.06, p=0.044) for the "always" group. In Q7 (add salt or soy sauce to food when eating), the 3-year mean differences in CDR-SB compared to the "always" group were -2.47 (95% CI=-4.70 - -0.24, p=0.030) for the "usually" group and -3.16 (95% CI=-5.36 - -0.96, p=0.005) for the "rarely" group. The "rarely" and "usually" groups in Q7 showed significantly less decline in NTB z-score and CGA-NPI compared to the "always" group. CONCLUSION: Eating a balanced diet and reducing salt intake were associated with a slower decline in dementia severity, cognition, and behavioral alterations in patients with ADD.

Analysis of Mortality in Intracerebral Hemorrhage Patients with Hyperacute Ischemic Stroke Treated Using Thrombolytic Therapy: A Nationwide Population-based Cohort Study in South Korea.

This study investigated the impact of intracerebral hemorrhage (ICH) on the cumulative mortality of patients with hyperacute ischemic stroke. This population-based retrospective cohort study used claims data from the National Health Insurance Service customized database of South Korea. The recruitment period was 2005−2018. The study population included patients with hyperacute ischemic stroke who had received intravenous thrombolysis. The primary endpoint was 12-month cumulative mortality, which was analyzed in both the ICH and no-ICH groups. Of the 50,550 patients included, 2567 (5.1%) and 47,983 (94.9%) belonged to the ICH and no-ICH groups, respectively. In the univariable analysis for 12-month mortality, ICH patients were substantially more prevalent among dead patients than among patients who survived (11.6% versus 3.6%; p < 0.001). The overall 12-month cumulative mortality rate was 18.8%. Mortality in the ICH group was higher than that in the no-ICH group (42.8% versus 17.5%; p < 0.001). In the multivariable analysis, the risk of 12-month cumulative mortality was 2.97 times higher in the ICH group than in the no-ICH group (95% confidence interval, 2.79−3.16). The risk of 12-month cumulative mortality in hyperacute ischemic stroke can increase approximately threefold after the occurrence of spontaneous ICH following intravenous thrombolysis.

Content Analysis of Korean Videos Regarding Restless Legs Syndrome on YouTube.

OBJECTIVE: To evaluate the accuracy and quality of Korean videos associated with restless legs syndrome (RLS) on YouTube. METHODS: A YouTube search was performed on April 1, 2020 using the term "restless legs syndrome" in the Korean language. Two reviewers coded the source, content, and demographics of the included videos. Video quality was assessed using the modified DISCERN (mDISCERN) instrument. RESULTS: Among the 80 videos analyzed, 44 (55.0%) were reliable, and 36 (45.0%) were misleading. There was a trend toward a higher number of mean daily views in the misleading videos than in the reliable videos. Most of the misleading videos (72.2%) advocated complementary and alternative medicine as a primary treatment for RLS. Although the reliable videos had higher mDISCERN scores than the misleading videos, the overall quality of the reliable videos was low. CONCLUSION: Many Korean videos regarding RLS on YouTube involve a risk of exposure to misinformation and are of unsatisfactory quality.

Body Fat Mass and Risk of Cerebrovascular Lesions: The PRESENT (Prevention of Stroke and Dementia) Project.

Obesity is known to increase the risk of stroke. It is unclear whether high absolute fat mass (FM) increases the risk of stroke independently. We studied the correlation between FM and silent brain infarction/white matter change (SI/WMC) using brain computed tomography. We selected subjects from the local government health promotion project. We randomly selected a target population that had never been diagnosed with stroke or dementia. FM was measured by bioelectrical impedance analysis (BIA). We divided the subjects into three groups according to the FM (gender-specific tertiles [GTx]). Seven hundred and twenty-two subjects (321 men) between 50 and 75 years of age were recruited. The overall odds ratio (OR) of SI/WMC was 2.23 (95% confidence interval (CI), 1.34-3.71; p = 0.002) times higher in the 37th to 100th percentiles (GT3) than in the first to 32nd percentiles (GT1). When men and women were separated, the OR of GT3 was 1.35 (CI, 0.62-2.94; p = 0.45) in men and 3.2 (CI, 1.60-6.40; p = 0.001) in women. The findings were not found to be statistically significant after adjusting for the well-known stroke risk factors. When the subjects were divided into a high FM (HFMG, GT3) and low FM group (LFMG, GT1 + GT2), the HFMG showed an increased OR of SI/WMC in women. Similar results were seen after adjusted (overall: OR, 1.38; CI, 0.85-2.25, p = 0.198; men: OR, 0.93; CI, 0.422-2.051; p = 0.86; women: OR, 2.02; CI, 1.06-3.86; p = 0.03). The findings suggest that high FM may be an independent risk factor for ischemic stroke among adults free from stroke and dementia, especially in women.

Amyloid beta in nasal secretions may be a potential biomarker of Alzheimer's disease.

We investigated the level of amyloid beta (Aß) in nasal secretions of patients with Alzheimer's disease dementia (ADD) using interdigitated microelectrode (IME) biosensors and determined the predictive value of Aß in nasal secretions for ADD diagnosis. Nasal secretions were obtained from 35 patients with ADD, 18 with cognitive decline associated with other neurological disorders (OND), and 26 cognitively unimpaired (CU) participants. Capacitance changes in IMEs were measured by capturing total Aß (ΔCtAß). After 4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid (EPPS) was injected, additional capacitance changes due to the smaller molecular weight Aß oligomers disassembled from the higher molecular weight oligomeric Aß were determined (ΔCoAß). By dividing two values, the capacitance ratio (ΔCoAß/ΔCtAß) was determined and then normalized to the capacitance change index (CCI). The CCI was higher in the ADD group than in the OND (p = 0.040) and CU groups (p = 0.007). The accuracy of the CCI was fair in separating into the ADD and CU groups (area under the receiver operating characteristic curve = 0.718, 95% confidence interval = 0.591-0.845). These results demonstrate that the level of Aß in nasal secretions increases in ADD and the detection of Aß in nasal secretions using IME biosensors may be possible in predicting ADD.

Effect of Physical Activity on the Progression of Alzheimer's Disease: The Clinical Research Center for Dementia of South Korea Study.

BACKGROUND: There is a lack of research on the effects of physical activity (PA) on the progression of Alzheimer's disease (AD). OBJECTIVES: We investigated whether PA is associated with progression of dementia and mortality in AD. METHODS: In the present study, 934 patients with mild-to-moderate AD were included. PA was evaluated using a questionnaire written by the caregiver. The outcome measures were the Clinical Dementia Rating-Sum of Boxes (CDR-SB), Seoul-Instrumental Activities of Daily Living (S-IADL), Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI), a global composite score of neuropsychological subtests, and mortality. They were evaluated annually and received a maximum of three follow-up examinations. RESULTS: Between-group differences compared with the no PA group in the change of CDR-SB scores were -0.431 (95% CI = -0.824∼-0.039; p = 0.031) for the moderate PA group (150-750 minutes per week of moderate intensity PA), and -1.148 (-1.656∼-0.639; p < 0.001) for the high PA group (>750 minutes per week). As PA increased, there was a significant trend to slow the rate of increase in the CDR-SB, S-IADL, and CGA-NPI scores. The patients with ≥150 minutes per week for each of non-recreational and recreational PAs had a lower risk of mortality compared to those with <150 minutes per week for each of the PAs (hazard ratio 0.22, 95% CI = 0.05∼0.88; p = 0.033). CONCLUSION: More PA is associated with slower progression of dementia severity, functional decline, and abnormal behavior, and with a lower risk of mortality in AD.

The Effect of Mental Rotation on Surgical Pathological Diagnosis.

PURPOSE: Pathological diagnosis involves very delicate and complex consequent processing that is conducted by a pathologist. The recognition of false patterns might be an important cause of misdiagnosis in the field of surgical pathology. In this study, we evaluated the influence of visual and cognitive bias in surgical pathologic diagnosis, focusing on the influence of "mental rotation." MATERIALS AND METHODS: We designed three sets of the same images of uterine cervix biopsied specimens (original, left to right mirror images, and 180-degree rotated images), and recruited 32 pathologists to diagnose the 3 set items individually. RESULTS: First, the items found to be adequate for analysis by classical test theory, Generalizability theory, and item response theory. The results showed statistically no differences in difficulty, discrimination indices, and response duration time between the image sets. CONCLUSION: Mental rotation did not influence the pathologists' diagnosis in practice. Interestingly, outliers were more frequent in rotated image sets, suggesting that the mental rotation process may influence the pathological diagnoses of a few individual pathologists.

A multicenter prospective observational study on the safety and efficacy of tacrolimus in patients with myasthenia gravis.

INTRODUCTION: Several clinical studies using tacrolimus revealed reasonable therapeutic mechanisms and efficacy in patients with myasthenia gravis (MG). However, long-period studies in a large number of patients with MG are limited; therefore, the aim of this study was to investigate the therapeutic efficacies and safety of tacrolimus in patients with MG during a 12-month follow-up period. METHODS: Tacrolimus was administered to 150 patients with MG who were recruited based on the inclusion criteria. Fifteen medical centers in Korea participated in this study. The efficacy of tacrolimus was assessed using MG composite scales (MGCS) and the prednisolone-sparing effect. And the adverse drug reactions (ADRs) of tacrolimus were monitored in each patient from the beginning of tacrolimus treatment to the end of the follow-up period. RESULTS: After starting tacrolimus, the 32 patients were affected by ADRs, and consequentially 134 patients of the enrolled patients were followed up for 12months. They showed that the mean prednisolone dosage significantly decreased (6.1±7.6mg/day), compared to that in the baseline (11.3±9.5mg/day), and MGCS significantly improved after 12months of tacrolimus treatment, compared to that at the baseline. CONCLUSIONS: Our study showed that tacrolimus would be an effective immunosuppressant as an initial therapeutic agent in patients with MG; in addition, it showed tolerable safety profiles during the 12-month follow-up evaluation.

Higher skeletal muscle mass may protect against ischemic stroke in community-dwelling adults without stroke and dementia: The PRESENT project.

BACKGROUND: It is well known that a low skeletal muscle mass (SMM) is associated with stroke. However, it is unknown whether increasing muscle mass can prevent stroke. METHODS: This community-based cross-sectional study was supported by the regional government. SMM measurements and brain computed tomography was performed in 722 stroke-free and dementia-free subjects (aged 50-75 years). Subjects were divided into quartiles (Q) by SMM, checked using the bioelectrical impedance analysis method (InBody 770, InBody, Seoul, Korea). Odds ratios (ORs) of brain white matter changes/silent infarction (WMC/SI) were calculated. The subjects were then divided into two groups by sex and evaluated. RESULTS: In the analysis of the four groups, the unadjusted ORs of Q2-Q4 were 0.616 (95% confidence interval [CI], 0.372-1.022; P = 0.061), 0.290 (CI, 0.159-0.530; P < 0.001), and 0.209 (CI, 0.108-0.403; P < 0.001) for the risk of WMC/SI. Adjusted ORs for age, hypertension, diabetes mellitus, education, hypercholesterolemia, and smoking were 0.994 (CI, 0.513-1.740; P = 0.085), 0.669 (CI, 0.329-1.362; P = 0.268), and 0.464 (CI, 0.219-0.984; P = 0.045). In the two-group (dichotomized) analysis, the unadjusted OR for the higher muscle mass groups (Q3 + Q4) was 0.313 (CI, 0.200-0.491; P < 0.001). The adjusted OR was 0.577 (CI, 0.340-0.979; P = 0.042). Considering sex, the adjusted OR were 0.351 (CI, 0.141-0.869; P = 0.024) in men and 0.771 (CI, 0.391-1.519; P = 0.452) in women. CONCLUSIONS: Our findings suggest that increased SMM may protect against WMC/SI, especially in men.

Noggin Over-Expressing Mouse Embryonic Fibroblasts and MS5 Stromal Cells Enhance Directed Differentiation of Dopaminergic Neurons from Human Embryonic Stem Cells.

Directed methods for differentiating human embryonic stem cells (hESCs) into dopaminergic (DA) precursor cells using stromal cells co-culture systems are already well established. However, not all of the hESCs differentiate into DA precursors using these methods. HSF6, H1, H7, and H9 cells differentiate well into DA precursors, but CHA13 and CHA15 cells hardly differentiate. To overcome this problem, we modified the differentiation system to include a co-culturing step that exposes the cells to noggin early in the differentiation process. This was done using γ-irradiated noggin-overexpressing CF1-mouse embryonic fibroblasts (MEF-noggin) and MS5 stromal cells (MS5-noggin and MS5-sonic hedgehog). After directed differentiation, RT-PCR analyses revealed that engrailed-1 (En-1), Lmx1b, and Nurr1, which are midbrain DA markers, were expressed regardless of differentiation stage. Moreover, tyrosine hydroxylase (Th) and an A9 midbrain-specific DA marker (Girk2) were expressed during differentiation, whereas levels of Oct3/4, an undifferentiated marker, decreased. Immunocytochemical analyses revealed that protein levels of the neuronal markers TH and TuJ1 increased during the final differentiation stage. These results demonstrate that early noggin exposure may play a specific role in the directed differentiation of DA cells from human embryonic stem cells.

MicroRNA-200 family members and ZEB2 are associated with brain metastasis in gastric adenocarcinoma.

Although the incidence of brain metastasis in gastric cancer is relatively low, its prevalence may increase with improved therapy and longer survival tumors. The molecular mechanisms underlying brain metastases are not well understood. To gain insight into the mechanism of brain metastasis, we studied differences in microRNA (miRNA) expression levels in 8 cases of matched primary gastric adenocarcinoma and brain metastatic adenocarcinoma using the Illumina microRNA microarray chip. We identified 6 upregulated and 2 downregulated miRNAs in all 8 cases simultaneously. Interestingly, 2 out of 8 miRNAs (hsa-miR­141-3p and hsa-miR-200b-3p) belonged to the miR-200 family. Online microRNA database searching revealed that ZEB2 is the top-ranked target gene for hsa-miR141-3p and hsa-miR-200b-3p, prompting us to focus ZEB2 expression in brain metastatic adenocarcinoma. We confirmed that ZEB2 expression was markedly downregulated in some brain metastatic samples. In addition, decreased ZEB2 expression was noted by western blot analysis of 2 metastatic gastric adenocarcinoma cell types that were derived by in vivo selection following intracardiac injection of gastric cancer cell lines. In conclusion, we demonstrate that expression of miRNA-200 family members and ZEB2 are associated with brain metastases of gastric adenocarcinoma, not only in matched patient samples, but also in metastatic cell lines that were derived by in vivo selection.

Tooth loss is associated with brain white matter change and silent infarction among adults without dementia and stroke.

Periodontal disease is a predictor of stroke and cognitive impairment. The association between the number of lost teeth (an indicator of periodontal disease) and silent infarcts and cerebral white matter changes on brain CT was investigated in community-dwelling adults without dementia or stroke. Dental examination and CT were performed in 438 stroke- and dementia-free subjects older than 50 yr (mean age, 63 ± 7.9 yr), who were recruited for an early health check-up program as part of the Prevention of Stroke and Dementia (PRESENT) project between 2009 and 2010. In unadjusted analyses, the odds ratio (OR) for silent cerebral infarcts and cerebral white matter changes for subjects with 6-10 and > 10 lost teeth was 2.3 (95% CI, 1.38-4.39; P = 0.006) and 4.2 (95% CI, 1.57-5.64; P < 0.001), respectively, as compared to subjects with 0-5 lost teeth. After adjustment for age, education, hypertension, diabetes mellitus, hyperlipidemia, and smoking, the ORs were 1.7 (95% CI, 1.08-3.69; P = 0.12) and 3.9 (95% CI, 1.27-5.02; P < 0.001), respectively. These findings suggest that severe tooth loss may be a predictor of silent cerebral infarcts and cerebral white matter changes in community-dwelling, stroke- and dementia-free adults.

IDH1 mutation analysis in low cellularity specimen: a limitation of diagnostic accuracy and a proposal for the diagnostic procedure.

Recently, new techniques for detecting IDH1 mutations have been developed. Most studies assessed the mutation status in glioma tissue without consideration of the size of the samples. We assessed the mutation status of IDH1 in simulated small biopsied tissue from 5 low grade gliomas, prepared by grid cutting procedure with direct sequencing, IDH1 immunohistochemistry (IHC), multiplex PCR with single base extension (SBE) assay and PNA-clamping method, and then analyzed the agreement between the methods. Kappa values were 0.53 (direct sequencing), 0.59 (multiplex PCR with SBE assay), and 0.69 (PNA-clamping method). Discrepant results between the methods were observed in lower cellularity samples. Twelve out of 25 cases were classified as wild type by direct sequencing, even with IDH1 IHC-positive cells, whereas 6, 8, and 11 of IHC-negative cases were classified as mutant cases by other 3 methods. In conclusion, newly developed sensitive methods, such as the PNA-clamping method and multiplex PCR with SBE assay, are practically useful in addition to the conventional IDH1 IHC in small biopsied samples.

Sequential involvement of the nervous system in subacute combined degeneration.

PURPOSE: Subacute combined degeneration (SCD) involves progressive degeneration of the spinal cord, optic nerve, and peripheral nerves. Vitamin B12 (VB12) is a co-factor in myelin synthesis. Because each cell that constitutes the myelin component in the central nervous system and peripheral nervous system is different, it is improbable that these cells undergo simultaneous degeneration. However, the sequence of degeneration in SCD has not been established. MATERIALS AND METHODS: In this study, we analysed medical records and electrophysiological data of patients who showed neurological symptoms and whose serum VB12 levels were lower than 200 pg/mL. RESULTS: We enrolled 49 patients in this study. Their mean VB12 level was 68.3 pg/mL. Somatosensory evoked potential (SEP) study showed abnormal findings in 38 patients. Of the 40 patients who underwent visual evoked potential (VEP) study, 14 showed abnormal responses. Eighteen patients showed abnormal findings on a nerve conduction study (NCS). In this study, abnormal posterior tibial nerve SEPs only were seen in 16 patients, median nerve SEPs only were seen in 3 patients, abnormal VEPs only in two, and abnormal NCS responses in one patient. No patient complained of cognitive symptoms. CONCLUSION: In SCD, degeneration appears to progress in the following order: lower spinal cord, cervical spinal cord, peripheral nerve/optic nerve, and finally, the brain.

Long-term outcomes of acute ischemic stroke in patients aged 80 years and older.

PURPOSE: Short life expectancy influences decision-making when treating very old patients with acute ischemic stroke (AIS). We investigated mortality and survival duration in very old AIS patients (>or= 80 years) who received hospital care. PATIENTS AND METHODS: Mortality data were obtained from medical records, structured telephone inquiries, death certificates from the Korean National Statistical Office, and social security data 5+/-1.9 years after stroke onset. Age, gender, vascular risk factors, and functional outcomes from modified Rankin scales (MRS) at discharge were analyzed as predictors of mortality. RESULTS: Among 134 patients, 92 (68.7%) died. On Kaplan-Meier analysis, duration of survival of patients aged 80-84 years was longer than those aged 85-89 or 90-94 (24+/-6.4, 8+/-7.3, 7+/-2.0 months, respectively, p=0.002). Duration of survival of patients discharged in a state of MRS 0-1 was longer than the remaining groups at 47+/-4.8 months (p<0.001). In Cox proportional hazard analysis, age and MRS at discharge were independent predictors of mortality. CONCLUSION: Long-term outcomes of very old patients with AIS are not uniformly grave, therefore predictors of mortality and estimated duration of survival should be considered during decision-making for treatment.

Induction of apoptosis signal-regulating kinase 1 and oxidative stress mediate age-dependent vulnerability to 3-nitropropionic acid in the mouse striatum.

The mitochondrial toxin, 3-nitropropionic acid (3-NP), produces age-dependent oxidative stress and selective striatal damage, which may simulate Huntington's disease starting in middle age. Recent reports showed that apoptosis signal-regulating kinase 1 (Ask1) activated by oxidative stress triggers a cell death signaling pathway. 3-NP was injected to the striatum in C57BL/6J mice. We have confirmed that striatal lesion volume and DNA fragmentation were age-dependent after 3-NP treatment. In the non-injured striatum of the middle-aged group, the protein levels of Ask1 and its active form, phosphorylated Ask1 (pAsk1), were significantly higher than in the young group. Ask1 increased more in the 3-NP injured striatum of the middle-aged group than in the non-injured striatum, and subsequently the activity of pAsk1 was significantly higher than in the young group. However, middle-aged SOD1Tg mice showed significant reductions of Ask1 and pAsk1 in the injured and the non-injured striatum compared to the middle-aged group. In particular, apoptosis signal transduction and cell death were significantly inhibited by the reduction of Ask1 expression using siRNA. Present results suggest that age-related upregulation of Ask1 and oxidative stress may mediate age-dependent striatal vulnerability to 3-NP.

Stroke after burn.

BACKGROUND: Stroke is regarded as a possible complication of burn. Some author reported that stroke developed in 22% of burned patients. However, the true incidence and the clinical characteristics of stroke occurring after burn injury are unknown. METHODS: We reviewed the medical records of patients who had been admitted to the Burn Center at the Hangang Sacred Heart Hospital between January 1997 and May 2005. Patients with mild burns who did not require admission to the hospital were excluded from the study. Stroke patients were selected. RESULTS: A total of 13,468 patients were admitted due to burn injury during the above-mentioned period. Nine (0.07%) patients (5 men, 4 women; mean age, 55 years) developed stroke while being under treatment for their burn injuries. The median duration between the burn injury and stroke onset was 33 days (range, 2-307). The mean surface area of the burn wound was 21% (range, 3-50). Ischemic infarction was observed in 4 patients, intracerebral hemorrhage in 3 others, and multiple hemorrhagic infarction and subdural hematoma in 1 patient each. Seven out of the 9 patients revealed the presence of septic conditions that occurred subsequent to the burn. CONCLUSION: Stroke is a rare complication of a burn injury in the clinical setting. It develops in moderate burns (10-50% of the total body surface area) after some time. Prevention of infection/sepsis is important to alleviate the occurrence of a stroke in these patients.