Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Background: With the aging population and advancements in medical care worldwide, the number of older patients with end-stage kidney disease continues to rise. This study aimed to identify factors associated with osteoporosis and osteopenia in older patients undergoing incident hemodialysis and assess their impact on mortality. Methods: We analyzed a large multicenter retrospective cohort of patients aged ≥70 years undergoing incident hemodialysis to identify factors associated with osteoporosis using logistic regression analysis and to assess the association of death with osteoporosis and osteopenia using Cox multivariable analysis. Results: Among 710 patients, 39.0% and 19.6% had osteoporosis and osteopenia, respectively. Osteoporosis was significantly associated with female sex, a history of fractures, and the absence of phosphate binder use. During a median follow-up of 36.8 months, 348 participants (58.8%) died. Mortality rates were the highest in the osteoporosis group (79.8%), followed by the osteopenia (77.2%) and normal bone mineral density (BMD) groups (35.2%). Cox regression analysis revealed that even after adjusting for covariates, the osteoporosis group was significantly associated with a higher mortality risk than the normal BMD group. Osteoporosis at the start of hemodialysis was significantly associated with higher mortality. Conclusion We should consider the importance of bone health in patients undergoing incident hemodialysis and pay attention to the use of phosphate binders and fracture prevention.

Background: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. Methods: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. Results: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13–1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84–1.11), 1.10 (0.96–1.27), 1.24 (1.06–1.45), 1.37 (1.12–1.66), and 1.99 (1.42–2.79), respectively (p for trend < 0.001). Conclusion In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

Early mortality following hemodialysis initiation hinders survival improvement in older patients. This study aimed to develop a clinical risk model for predicting 6-month mortality after dialysis initiation in older Korean hemodialysis patients. Methods: We analyzed data from incident hemodialysis patients aged >70 years from the Korean Society of Geriatric Nephrology (KSGN) database. A prediction model was developed using multivariate logistic regression analysis and externally validated with independent datasets. Results: Among 1,751 incident hemodialysis patients, the 6-month mortality rate was 15.5%. Using multivariate logistic analysis, we constructed the KSGN score as an independent risk factor for 6-month mortality, and its components and score are as follows: old age at dialysis initiation (≥85 years, score 2); hypertension and renovascular disease as a primary etiology of end-stage kidney disease (ESKD) (score 1); malignancy history (yes, score 1); low serum albumin (<3.5 g/dL, score 1); hypertension treatment (yes, score –1); prepared vascular access on maintenance dialysis (arteriovenous fistula/arteriovenous graft, score –3). In the development cohort, the area under the curve (AUC) for the KSGN score was significantly higher than the Alberta Wick’s score (0.707 vs. 0.683, p = 0.001). In the validation cohort, the KSGN score’s performance was comparable to existing models. Conclusion: The KSGN score may be a valuable tool for predicting early mortality after dialysis initiation in older patients with ESKD, aiding in decision-making and management regarding dialysis initiation.

The prevalence of dementia is 2- to 7-fold higher among patients with end-stage kidney disease (ESKD) than among the general population; however, its clinical implications in this population remain unclear. Therefore, this study aimed to determine whether comorbid dementia increases mortality among older patients with ESKD undergoing newly initiated hemodialysis. Methods: We analyzed data from the Korean Society of Geriatric Nephrology retrospective cohort, which included 2,736 older ESKD patients (≥70 years old) who started hemodialysis between 2010 and 2017. Kaplan-Meier survival and Cox regression analyses were used to examine all-cause mortality between the patients with and without dementia in this cohort. Results: Of the 2,406 included patients, 8.3% had dementia at the initiation of dialysis; these patients were older (79.6 ± 6.0 years) than patients without dementia (77.7 ± 5.5 years) and included more women (male:female, 89:111). Pre-ESKD diagnosis of dementia was associated with an increased risk of overall mortality (hazard ratio, 1.503; p < 0.001), and this association remained consistent after multivariate adjustment (hazard ratio, 1.268; p = 0.009). In subgroup analysis, prevalent dementia was associated with mortality following dialysis initiation in female patients, those aged <85 years, those with no history of cerebrovascular accidents or severe behavioral disorders, those not residing in nursing facilities, and those with no or short-term hospitalization. Conclusion: A pre-ESKD diagnosis of dementia is associated with mortality following dialysis initiation in older Korean population. In older patients with ESKD, cognitive assessment at dialysis initiation is necessary.

Objective: Previous research on autism spectrum disorder (ASD) in Koreans has primarily focused on genetic diversity because of its high heritability. However, the emerging recognition of transgenerational epigenetic changes has recently shifted research attention towards epigenetic perspectives. Methods: This study investigated the DNA methylation patterns of the promoter regions of candidate genes such asNR3C1, ASCL1, and FOXO3 in blood samples from ASD probands and their unaffected siblings. The analysis included 54 families (ASD proband group: 54; unaffected biological sibling group: 63). The diagnostic process involved screening the probands and their siblings for ASD based on the Diagnostic and Statistical Manual of Mental Disorders 5th edition.Intelligence, social ability, and medical history were thoroughly assessed using various scales and questionnaires.Genomic DNA from blood samples was analyzed using a methylation-sensitive quantitative polymerase chain reaction to examine the DNA methylation status of candidate genes. Results: Methylation levels in candidate gene promoter regions differed significantly between the proband and sibling groups for all candidate genes. Correlation analysis between the proband and sibling groups revealed strong and significant correlations in NR3C1 and ASCL1 methylation. Additionally, in the analysis of the relationship between DNA and ASD phenotypes, FOXO3 methylation correlated with social quotient in probands, and ASCL1 methylation was associated with nonverbal communication, and daily living skills as measured by the Korean Vineland Adaptive Behavior Scale. Notably, ASCL1 methylation was significantly associated with parental age at pregnancy. Conclusion This study proposes DNA methylation of NR3C1, ASCL1, and FOXO3 in peripheral blood samples is a potential epigenetic biomarker of ASD.

Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.

Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.

Objective: Previous research on autism spectrum disorder (ASD) in Koreans has primarily focused on genetic diversity because of its high heritability. However, the emerging recognition of transgenerational epigenetic changes has recently shifted research attention towards epigenetic perspectives. Methods: This study investigated the DNA methylation patterns of the promoter regions of candidate genes such asNR3C1, ASCL1, and FOXO3 in blood samples from ASD probands and their unaffected siblings. The analysis included 54 families (ASD proband group: 54; unaffected biological sibling group: 63). The diagnostic process involved screening the probands and their siblings for ASD based on the Diagnostic and Statistical Manual of Mental Disorders 5th edition.Intelligence, social ability, and medical history were thoroughly assessed using various scales and questionnaires.Genomic DNA from blood samples was analyzed using a methylation-sensitive quantitative polymerase chain reaction to examine the DNA methylation status of candidate genes. Results: Methylation levels in candidate gene promoter regions differed significantly between the proband and sibling groups for all candidate genes. Correlation analysis between the proband and sibling groups revealed strong and significant correlations in NR3C1 and ASCL1 methylation. Additionally, in the analysis of the relationship between DNA and ASD phenotypes, FOXO3 methylation correlated with social quotient in probands, and ASCL1 methylation was associated with nonverbal communication, and daily living skills as measured by the Korean Vineland Adaptive Behavior Scale. Notably, ASCL1 methylation was significantly associated with parental age at pregnancy. Conclusion This study proposes DNA methylation of NR3C1, ASCL1, and FOXO3 in peripheral blood samples is a potential epigenetic biomarker of ASD.

Allergen immunotherapy (AIT) has been used for over a century and has been demonstrated to be effective in treating patients with various allergic diseases. AIT allergens can be administered through various routes, including subcutaneous, sublingual, intralymphatic, oral, or epicutaneous routes. Sublingual immunotherapy (SLIT) has recently gained clinical interest, and it is considered an alternative treatment for allergic rhinitis (AR) and asthma. This review provides an overview of the current evidence-based studies that address the use of SLIT for treating AR, including (1) mechanisms of action, (2) appropriate patient selection for SLIT, (3) the current available SLIT products in Korea, and (4) updated information on its efficacy and safety. Finally, this guideline aims to provide the clinician with practical considerations for SLIT.