Purpose: Currently, trastuzumab plus chemotherapy is the standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic gastric cancer (mGC) or esophagogastric junction cancer. However, it is not clear whether the prognosis of HER2-positive mGC treated with trastuzumab plus chemotherapy is better than that of HER2-negative mGC treated with chemotherapy as the first-line therapy. Methods: We performed a retrospective study comparing the prognosis of mGC according to first-line treatment with trastuzumab plus chemotherapy or chemotherapy only, at the Korea Cancer Center Hospital from 2011 to 2018. The Kaplan-Meier method and Cox proportional hazards model were used for univariate and multivariate survival analyses. Results: The median overall survival of trastuzumab group was 26.1 months and that of chemotherapy group was 14.8 months (P=0.047). Trastuzumab group had a longer median progression-free survival than chemotherapy group (23.4 vs. 9.2 months, P=0.026). By univariate analysis, sex, age, World Health Organization (WHO) histology, HER2 status, primary tumor site, extent of disease, number of lesions, number of metastatic, measurability of disease, prior gastrectomy, and chemotherapy group are statistically significant. Using multivariate analysis, number of lesions, number of metastatic, prior gastrectomy, and trastuzumab group (hazard ratio, 0.594; 95% confidence interval, 0.384–0.921; P=0.020) were found to be independent prognostic factors of overall survival. Conclusion The result suggests prognosis of HER2-positive mGC treated by trastuzumab plus chemotherapy could be better than that of HER2-negative mGC treated by chemotherapy only. Well-designed prospective cohort studies are needed to confirm the results of this study. HER2 testing should be performed routinely in all patients newly diagnosed with mGC.

Purpose: Currently, trastuzumab plus chemotherapy is the standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic gastric cancer (mGC) or esophagogastric junction cancer. However, it is not clear whether the prognosis of HER2-positive mGC treated with trastuzumab plus chemotherapy is better than that of HER2-negative mGC treated with chemotherapy as the first-line therapy. Methods: We performed a retrospective study comparing the prognosis of mGC according to first-line treatment with trastuzumab plus chemotherapy or chemotherapy only, at the Korea Cancer Center Hospital from 2011 to 2018. The Kaplan-Meier method and Cox proportional hazards model were used for univariate and multivariate survival analyses. Results: The median overall survival of trastuzumab group was 26.1 months and that of chemotherapy group was 14.8 months (P=0.047). Trastuzumab group had a longer median progression-free survival than chemotherapy group (23.4 vs. 9.2 months, P=0.026). By univariate analysis, sex, age, World Health Organization (WHO) histology, HER2 status, primary tumor site, extent of disease, number of lesions, number of metastatic, measurability of disease, prior gastrectomy, and chemotherapy group are statistically significant. Using multivariate analysis, number of lesions, number of metastatic, prior gastrectomy, and trastuzumab group (hazard ratio, 0.594; 95% confidence interval, 0.384–0.921; P=0.020) were found to be independent prognostic factors of overall survival. Conclusion The result suggests prognosis of HER2-positive mGC treated by trastuzumab plus chemotherapy could be better than that of HER2-negative mGC treated by chemotherapy only. Well-designed prospective cohort studies are needed to confirm the results of this study. HER2 testing should be performed routinely in all patients newly diagnosed with mGC.

Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer’s disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3′,4′-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells, 3′,4′-dihydroxyflavone successfully inhibited production of chemokines such as nitric oxide and prostaglandin E2 and proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation. This indicates that the anti-inflammatory activities of 3′,4′-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and NF-κB signaling pathways. Similar anti-neuroinflammatory activities of the compound were observed in the mouse model. These findings suggest that 3′,4′-dihydroxyflavone is a potential drug candidate for the treatment of microglia-related neuroinflammatory diseases.
Animals ; Central Nervous System ; Chemokines ; Cytokines ; Dinoprostone ; Huntington Disease ; Interleukin-1beta ; Interleukin-6 ; Mice* ; Microglia* ; Neurodegenerative Diseases ; Nitric Oxide ; Parkinson Disease ; Phosphorylation ; Protein Kinases ; Tumor Necrosis Factor-alpha

OBJECTIVE: This study aimed to examine the usefulness of each subscale score of the Clinical Dementia Rating (CDR) for predicting Alzheimer's disease (AD) dementia progression in amnestic mild cognitive impairment (MCI) elderly subjects. METHODS: Fifty-nine elderly MCI individuals were recruited from a university dementia and memory disorder clinic. Standardized clinical and neuropsychological tests were performed both at baseline and at the time of 2 years follow-up. Logistic regression analyses were conducted to examine the ability of various clinical measures or their combinations to predict progression to AD dementia in MCI individuals. RESULTS: MCIp individuals showed significantly higher CDR Orientation subscale and CDR sum-of-boxes (SOB) score than MCInp ones, while there were no significant differences in other CDR subscale scores between the two. MCIp individuals also showed marginally higher MMSE scores than MCInp ones. A series of logistic regression analyses demonstrated that the model including CDR Orientation subscale had better AD dementia prediction accuracy than either the model with either MMSE or CDR-SOB. CONCLUSION: Our findings suggest that CDR Orientation subscale score, a simple and easily available clinical measure, could provide very useful information to predict AD dementia progression in amnestic MCI individuals in real clinical settings.
Aged ; Alzheimer Disease* ; Dementia* ; Follow-Up Studies ; Humans ; Logistic Models ; Memory Disorders ; Mild Cognitive Impairment* ; Neuropsychological Tests

OBJECTIVE: The Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's disease (KBASE) aimed to recruit 650 individuals, aged from 20 to 90 years, to search for new biomarkers of Alzheimer's disease (AD) and to investigate how multi-faceted lifetime experiences and bodily changes contribute to the brain changes or brain pathologies related to the AD process. METHODS: All participants received comprehensive clinical and neuropsychological evaluations, multi-modal brain imaging, including magnetic resonance imaging, magnetic resonance angiography, [11C]Pittsburgh compound B-positron emission tomography (PET), and [18F]fluorodeoxyglucose-PET, blood and genetic marker analyses at baseline, and a subset of participants underwent actigraph monitoring and completed a sleep diary. Participants are to be followed annually with clinical and neuropsychological assessments, and biannually with the full KBASE assessment, including neuroimaging and laboratory tests. RESULTS: As of March 2017, in total, 758 individuals had volunteered for this study. Among them, in total, 591 participants–291 cognitively normal (CN) old-aged individuals, 74 CN young- and middle-aged individuals, 139 individuals with mild cognitive impairment (MCI), and 87 individuals with AD dementia (ADD)–were enrolled at baseline, after excluding 162 individuals. A subset of participants (n=275) underwent actigraph monitoring. CONCLUSION: The KBASE cohort is a prospective, longitudinal cohort study that recruited participants with a wide age range and a wide distribution of cognitive status (CN, MCI, and ADD) and it has several strengths in its design and methodologies. Details of the recruitment, study methodology, and baseline sample characteristics are described in this paper.
Aging* ; Alzheimer Disease* ; Biomarkers ; Brain* ; Cohort Studies ; Dementia ; Early Diagnosis* ; Genetic Markers ; Magnetic Resonance Angiography ; Magnetic Resonance Imaging ; Mild Cognitive Impairment ; Neuroimaging ; Pathology ; Prospective Studies

OBJECTIVE: We examined the difference in responses to donepezil between carriers and non-carriers of the A allele at the +4 position of the choline acetyltransferase (ChAT) gene in Koreans. METHODS: Patients who met the criteria for probable Alzheimer's disease (AD) (n=199) were recruited. Among these, 145 completed the 12-week follow-up evaluation and 135 completed the 26-week scheduled course. Differences and changes in the Korean version of the mini-mental state examination (MMSE-KC) score, Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-K[N]) wordlist subtest score (WSS), CERAD-K(N) total score (TS), and the Korean version of geriatric depression scale (GDS-K) score between baseline and 12 weeks or 26 weeks were assessed by the Student's t-test. RESULTS: At 12 weeks, the changes in the MMSE-KC score, CERAD-K(N) WSS, and CERAD-K(N) TS from baseline were not significant between ChAT A allele carriers and non-carriers; however, at 26 weeks, these changes were significantly larger in ChAT A allele carriers than in non-carriers (p=0.02 for MMSE-KC and p=0.03 for CERAD-K(N) WSS respectively). CONCLUSION: Our findings in this study suggested that presence of the A allele at the +4 position of ChAT might positively influence the treatment effect of donepezil in the early stages of AD in Koreans.
Alleles ; Alzheimer Disease* ; Choline O-Acetyltransferase* ; Choline* ; Depression ; Follow-Up Studies ; Genotype* ; Humans ; Polymorphism, Single Nucleotide

PURPOSE: This study aimed to identify time-dependent prognostic factors and demonstrate the time-dependent effects of important prognostic factors in patients with advanced gastric cancer (AGC). MATERIALS AND METHODS: We retrospectively evaluated 3,653 patients with AGC who underwent curative standard gastrectomy between 1991 and 2005 at the Korea Cancer Center Hospital. Multivariate survival analysis with Cox proportional hazards regression was used in the analysis. A non-proportionality test based on the Schoenfeld residuals (also known as partial residuals) was performed, and scaled Schoenfeld residuals were plotted over time for each covariate. RESULTS: The multivariate analysis revealed that sex, depth of invasion, metastatic lymph node (LN) ratio, tumor size, and chemotherapy were time-dependent covariates violating the proportional hazards assumption. The prognostic effects (i.e., log of hazard ratio [LHR]) of the time-dependent covariates changed over time during follow-up, and the effects generally diminished with low slope (e.g., depth of invasion and tumor size), with gentle slope (e.g., metastatic LN ratio), or with steep slope (e.g., chemotherapy). Meanwhile, the LHR functions of some covariates (e.g., sex) crossed the zero reference line from positive (i.e., bad prognosis) to negative (i.e., good prognosis). CONCLUSIONS: The time-dependent effects of the prognostic factors of AGC are clearly demonstrated in this study. We can suggest that time-dependent effects are not an uncommon phenomenon among prognostic factors of AGC.
Follow-Up Studies ; Gastrectomy ; Humans ; Korea ; Lymphatic Metastasis ; Lymph Nodes ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Stomach Neoplasms*

We compared the predictive ability of the various neuroimaging tools and determined the most cost-effective, non-invasive Alzheimer's disease (AD) prediction model in mild cognitive impairment (MCI) individuals. Thirty-two MCI subjects were evaluated at baseline with [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET), MRI, diffusion tensor imaging (DTI), and neuropsychological tests, and then followed up for 2 yr. After a follow up period, 12 MCI subjects converted to AD (MCIc) and 20 did not (MCInc). Of the voxel-based statistical comparisons of baseline neuroimaging data, the MCIc showed reduced cerebral glucose metabolism (CMgl) in the temporo-parietal, posterior cingulate, precuneus, and frontal regions, and gray matter (GM) density in multiple cortical areas including the frontal, temporal and parietal regions compared to the MCInc, whereas regional fractional anisotropy derived from DTI were not significantly different between the two groups. The MCIc also had lower Mini-Mental State Examination (MMSE) score than the MCInc. Through a series of model selection steps, the MMSE combined with CMgl model was selected as a final model (classification accuracy 93.8%). In conclusion, the combination of MMSE with regional CMgl measurement based on FDG-PET is probably the most efficient, non-invasive method to predict AD in MCI individuals after a two-year follow-up period.
Aged ; Alzheimer Disease/complications/*diagnosis ; Atrophy/pathology ; Biomarkers/blood ; Brain/*pathology ; Diffusion Tensor Imaging/methods ; Female ; Glucose/*metabolism ; Gray Matter/*pathology ; Humans ; Male ; Mild Cognitive Impairment/*diagnosis/etiology ; Neuroimaging/methods ; Positron-Emission Tomography/methods ; Reproducibility of Results ; Sensitivity and Specificity ; Severity of Illness Index ; White Matter/*pathology

OBJECTIVE: This study aimed to investigate whether the supplementation of Verbal Fluency: Animal category test (VF) performance can improve the screening ability of Mini-Mental State Examination (MMSE) for mild cognitive impairment (MCI), dementia and their major subtypes. METHODS: Six hundred fifty-five cognitively normal (CN), 366 MCI [282 amnestic MCI (aMCI); 84 non-amnestic MCI (naMCI)] and 494 dementia [346 Alzheimer's disease (AD); and 148 non-Alzheimer's disease dementia (NAD)] individuals living in the community were included (all aged 50 years and older) in the study. RESULTS: The VF-supplemented MMSE (MMSE+VF) score had a significantly better screening ability for MCI, dementia and overall cognitive impairment (MCI plus dementia) than the MMSE raw score alone. MMSE+VF showed a significantly better ability than MMSE for both MCI subtypes, i.e., aMCI and naMCI. In the case of dementia subtypes, MMSE+VF was better than the MMSE alone for NAD screening, but not for AD screening. CONCLUSION: The results support the usefulness of VF-supplementation to improve the screening performance of MMSE for MCI and NAD.
Alzheimer Disease ; Animals ; Dementia* ; Mass Screening* ; Mild Cognitive Impairment* ; NAD

OBJECTIVE: The purpose of this study was to explore the effect of demographic variables on Digit Span test (DS) performance in an educationally diverse elderly population and to provide normative information. METHODS: The DS was administered to 784 community-dwelling volunteers aged 60-90 years with an educational history of from zero to 25 years of full-time education. People with serious neurological, medical and psychiatric disorders (including dementia) were excluded. RESULTS: Age, education and gender were found to be significantly associated with performance on the DS. Based on the results obtained, DS norms were stratified by age (2 strata), education (3 strata), and gender (2 strata). CONCLUSION: Our results on DS performance suggest that both attention and working memory are influenced by age, education and gender. The present study provides reasonably comprehensive normative information on the DS for an educationally diverse elderly population.
Age Factors ; Aged* ; Asian Continental Ancestry Group ; Education* ; Humans ; Memory, Short-Term ; Neuropsychological Tests ; Volunteers