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Introduction: Pathogenic variants of annexin A11 (ANXA11) have been identified in patients with amyotrophic lateral sclerosis (ALS) with or without frontotemporal dementia (FTD). We explored ANXA11 pathogenic variants in a Korean FTD cohort to investigate the prevalence and the role of ANXA11 variation in FTD., Methods: We used next-generation sequencing (NGS) to search for pathogenic variants in ANXA11 in two nationwide FTD cohorts in Korea., Results: We identified a pathogenic variant in ANXA11, c.119A > G (p.D40G), in six patients with semantic variant primary progressive aphasia (svPPA), representing 5.5% of the svPPA cohort (6/109), and representing 2.3% of the FTD cohort overall (6/259). Only one patient later developed features suggestive of ALS., Discussion: This study links a rare variant in ANXA11 to a sporadic clinical syndrome in which specific TAR DNA-binding protein-43 (TDP-43) forms an obligate co-fibril with annexin A11. The variant, p.D40G, lies within the N-terminal portion of annexin A11's TDP-43 type C interacting domain, suggesting that genetic variation in that region may promote co-fibrillization., Highlights: The pathogenic variant of annexin A11 (ANXA11I) is linked to frontotemporal dementia (FTD) syndrome. ANXA11 (p.D40G) may be one of the possible genetic causes of semantic variant primary progressive aphasia (svPPA). ANXA11 (p.D40G) may enhance heteromeric amyloid filaments of annexin A11 and TDP-43, promoting frontotemporal lobar degeneration with TAR DNA-binding protein-43 (TDP-43) inclusions (FTLD-TDP) type C., (© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Purpose: The current study aimed to examine the linguistic characteristics of Korean-speaking individuals diagnosed with primary progressive aphasia(PPA)., Methods: Two individuals with agrammatic/non-fluent variants of nfvPPA and two with semantic variants of svPPA participated in this study. Picture description tasks were used to collect connected speech samples. Analysis focused on linguistic variables, including quantitative(number of utterances, words, nouns, and verbs), syntactic(mean length of utterance in morphemes, case markers per utterance, predicates per utterance), and semantic variables(correct information units, verb types). Additionally, participants completed two types of confrontation naming tasks., Results: The nfvPPA group exhibited fewer linguistic units overall compared to the svPPA group, with noun-verb dissociation apparent only in the nfvPPA group. The svPPA group showed poorer performance in content-related linguistic variables. A notable clinical symptom specific to Korean, case marker deficits, was observed in the nfvPPA group., Discussion: The study identified distinct linguistic patterns associated with the subtype of PPA in Korean speakers. The evaluation and interpretation of Korean-specific linguistic variables are crucial for classifying Korean-speaking individuals with PPA. Understanding these variables can enhance our comprehension of the unique linguistic deficits present in Korean PPA, particularly in relation to confrontation naming tasks and their implications for diagnosis and classification.

Introduction: We investigated the efficacy of a multidomain intervention (MI) via face-to-face and video communication platforms using a tablet personal computer application in patients with mild cognitive impairment (MCI)., Methods: Three hundred participants with MCI and ≥ 1 modifiable dementia risk factor, aged 60-85 years, were randomly assigned to either the MI group, who underwent a 24-week intervention, or the control group, who received usual care., Results: The overall adherence rate to MI was 84.7%. The adjusted mean change from baseline at 24 weeks in the total scale index score of the repeatable battery for the assessment of neuropsychological status was 8.43 in the MI group and 4.26 in the control group (difference, 4.17; 95% confidence interval, 1.92-6.43; p < 0.001). MI showed significant beneficial effects on cognition in both apolipoprotein E (APOE) ε4 carriers and noncarriers., Discussion: MI can exert beneficial effects on the cognition of patients with MCI., Trial Registration: ClinicalTrials.gov identifier: NCT05023057 HIGHLIGHTS: Although the controls also demonstrated improved performance in cognition, multidomain interventions showed significantly greater benefits for cognition in MCI compared to the controls in a randomized controlled trial. Multidomain interventions improved depression and quality of life. Multidomain interventions significantly positively impacted cognition in both APOE ε4 carriers and noncarriers. Multidomain interventions may be more effective for amnestic than nonamnestic MCI., (© 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare white matter disease characterized by axonal and glial injury. Although its clinical characteristics have been described in case reports, the prevalence of CSF1R mutations in clinically suspected ALSP cases remains unclear. Herein, we analysed the frequency of CSF1R mutations in patients with probable or possible ALSP and describe the genetic, clinical, radiological, and pathological findings of ALSP cases in individuals of Korean ancestry. Twenty-eight patients with probable or possible ALSP diagnosed at Samsung Medical Center, Seoul, between January 2014 and August 2020, were retrospectively reviewed. All participants underwent brain magnetic resonance imaging (MRI) and CSF1R genetic testing. Overall, 9 of the 28 patients (32.1%) [5/6 (83.3%) of probable ALSP and 4/22 (18.2%) of possible ALSP] were confirmed to have pathogenic or likely pathogenic variants in CSF1R gene. Additionally, one patient without CSF1R mutation exhibited histopathological findings consistent with ALSP on brain biopsy. All patients with CSF1R mutation presented with cognitive impairment and/or psychiatric symptoms. Brain MRI revealed bilateral white matter hyperintensities in all patients, and 5/8 (62.5%) showed diffusion-restricted lesions. Notably, patients with CSF1R mutation had younger age at onset, rapidly progressive course, and diffuse hyperintensity in the splenium compared to patients without CSF1R mutation. Our findings suggest that for definite diagnosis, CSF1R genetic testing is recommended in patients who meet the diagnostic criteria for possible or probable ALSP. Our findings provide insights into the genetic, clinical, radiological, and pathological dimensions of ALSP in individuals of Korean ancestry., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

A shorter leukocyte telomere length (LTL) is reported to be associated with age-related diseases, including osteoporosis. Many studies have tried identifying the association between LTL and osteoporosis, although it remains controversial. This study aimed to determine whether osteoporosis is independently associated with LTL shortening in a prospective longitudinal cohort. The KBASE study is an independent multicenter prospective cohort in South Korea, which began in 2014. We compared the LTL values for each participant at baseline and over a 2-year follow-up period. Boxplots were used to demonstrate the differences in the change in LTL over a 2-year follow-up according to osteoporosis. Multivariable linear regression was conducted to identify whether osteoporosis is independently associated with the rate of telomere shortening. A total of 233 subjects (from 55 to 88 years) from the KBASE cohort were finally enrolled in the study. We observed that the LTL decreased by approximately 1.2 kbp over 2 years. While the LTL decreased as age increased, the rate of LTL shortening did not increase with age. Multivariable linear regression analysis indicated that only osteoporosis was independently associated with rapid LTL shortening over 2 years (B, -8.08; p = 0.038). We sought to identify an association between osteoporosis and LTL shortening in an independent prospective cohort. We found that participants with osteoporosis had significantly faster LTL shortening over 2 years than those without osteoporosis. We hope this study will help elucidate the underlying mechanisms in the relationship between LTL and osteoporosis in the future.

We examined whether there were differences in the presence of centrum semiovale-enlarged perivascular spaces (CSO-ePVS) and basal ganglia-ePVS (BG-ePVS) among patients with Alzheimer disease-related cognitive impairment (ADCI) based on their age of onset. Out of a total of 239 patients with cognitive impairment, 155 with positive amyloid-PET results were included. Among these, 43 had early-onset ADCI (EOADCI) and 112 had late-onset ADCI (LOADCI). Patients with LOADCI exhibited a higher prevalence of hypertension, lacunes, white matter hyperintensities, and BG-ePVS than those with EOADCI. BG-ePVS showed a significant correlation with age at the onset and the number of lacunes, whereas CSO-ePVS did not exhibit any association. The higher prevalence of BG-ePVS in patients with LOADCI might be attributable to vascular risk factors (hypertension) and cerebral small vessel disease (CSVD). These findings support the hypothesis that BG-ePVS is associated with CSVD and vascular risk factors, whereas CSO-ePVS is associated with cerebral amyloid angiopathy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

We employed a detection method to quantify Alexandrium catenella (Group I), one of the causative species for paralytic shellfish poisoning (PSP) in Jinhae-Masan Bay, Korea, targets sxtA4, via chip-based digital PCR. Additionally, we explored the dynamics of Alexandrium during the spring of 2022 using an rDNA-based quantitative PCR (qPCR) assay to enhance the performance of the dPCR assay. In matching dPCR results with PSP monitoring reports, we optimized a cell regulatory threshold of 102 cells L -1 , the maximum cell density when shellfish harvesting was permitted, for the dPCR assay. This threshold functioned similar to the PST threshold used in mouse bioassays (MBAs). Furthermore, we validated a total concordance rate of 83.8 % between the two assays for 2020-2022, reaching a maximum of 96.2 % in 2020. Thus, the result of dPCR could complement MBAs, facilitating the early detection of PSP outbreaks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Mutations in ITM2B have been reported to be associated with several familial dementias, such as Familial British dementia and familial Danish dementia. These are autosomal dominant disorders characterized by progressive dementia with an onset at around the fifth decade of life. We describe a family with cognitive impairment caused by a novel ITM2B p.*267Serext*11 mutation. The probands presented with cognitive impairment and cerebral infarction. MRI revealed diffuse white matter hyperintensity and microbleeds. Amyloid deposition was not observed on amyloid positron emission tomography. Our case suggests that the BRI2 mutation impacts cognition regardless of amyloid-β accumulation.

Low serum progranulin (PGRN) is known to be associated with granulin (GRN) gene mutation and T alleles of GRN rs5848 polymorphism. However, there have been only a few Asian studies exploring these. We investigated the serum PGRN levels, rs5848 genotypes, and their relations with cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers in the Korean population. Serum PGRN levels, GRN rs5848 polymorphism, and GRN mutations were evaluated in 239 participants (22 cognitively unimpaired participants and 217 patients with neurodegenerative diseases). CSF AD biomarkers were also evaluated in 214 participants. There was no significant difference in the serum PGRN levels among the diagnostic groups. We could not find any GRN mutation carrier in our sample. The differences in the frequencies of the rs5848 genotypes among the clinical groups or the effects of the rs5848 genotypes on serum PGRN were not observed. There was no correlation between the serum PGRN level or rs5848 genotype and CSF AD biomarkers. Neither the T allele nor the TT genotype had an effect on the development of AD. Our results showed that serum PGRN levels were not associated with rs5848 genotypes, indicating that multiple single nucleotide polymorphisms might affect PGRN concentrations in an ethnicity-specific manner., Competing Interests: The authors have declared that no competing interests exist.

The purpose of this study was to demonstrate the reliability and validity of the Korean version of the Caregiver Burden Inventory (CBI). The study was conducted as a multicenter cross-sectional survey for caregivers caring for patients with disabilities in outpatient or inpatient rehabilitation clinics. Sociodemographic characteristics and health-related quality of life were collected via questionnaires. The CBI and Burden Interview (BI) were administered, after which internal consistency and factor analysis of the CBI and correlation between the CBI and BI were explored. A total of 151 caregivers participated. The mean age of caregivers was 53.7 ± 12.4 years, and 80.8 % were women. The majority of caregivers were the main caregivers of stroke, spinal cord injury or traumatic brain injury. The factor analysis confirmed its five factorial structure. The time-dependence and physical burden scores of CBI were higher than those of other factors. All five-dimensional and total scores of CBI showed high internal consistency and were well correlated with BI. In conclusion, the CBI has proven its reliability, construct validity and concurrent validity for caregivers of disabled people and has shown its advantage as a multidimensional measure., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Genome-wide association studies (GWAS) have identified a number of genetic variants for Alzheimer's disease (AD). However, most GWAS were conducted in individuals of European ancestry, and non-European populations are still underrepresented in genetic discovery efforts. Here, we performed GWAS to identify single nucleotide polymorphisms (SNPs) associated with amyloid β (Aβ) positivity using a large sample of Korean population., Methods: One thousand four hundred seventy-four participants of Korean ancestry were recruited from multicenters in South Korea. Discovery dataset consisted of 1190 participants (383 with cognitively unimpaired [CU], 330 with amnestic mild cognitive impairment [aMCI], and 477 with AD dementia [ADD]) and replication dataset consisted of 284 participants (46 with CU, 167 with aMCI, and 71 with ADD). GWAS was conducted to identify SNPs associated with Aβ positivity (measured by amyloid positron emission tomography). Aβ prediction models were developed using the identified SNPs. Furthermore, bioinformatics analysis was conducted for the identified SNPs., Results: In addition to APOE, we identified nine SNPs on chromosome 7, which were associated with a decreased risk of Aβ positivity at a genome-wide suggestive level. Of these nine SNPs, four novel SNPs (rs73375428, rs2903923, rs3828947, and rs11983537) were associated with a decreased risk of Aβ positivity (p < 0.05) in the replication dataset. In a meta-analysis, two SNPs (rs7337542 and rs2903923) reached a genome-wide significant level (p < 5.0 × 10 -8 ). Prediction performance for Aβ positivity increased when rs73375428 were incorporated (area under curve = 0.75; 95% CI = 0.74-0.76) in addition to clinical factors and APOE genotype. Cis-eQTL analysis demonstrated that the rs73375428 was associated with decreased expression levels of FGL2 in the brain., Conclusion: The novel genetic variants associated with FGL2 decreased risk of Aβ positivity in the Korean population. This finding may provide a candidate therapeutic target for AD, highlighting the importance of genetic studies in diverse populations.

Background: The presence of ß-amyloid (Aß) in the brain can be identified using amyloid PET. In clinical practice, the amyloid PET is interpreted based on dichotomous visual rating, which renders focal Aß accumulation be read as positive for Aß. However, the prognosis of patients with focal Aß deposition is not well established. Thus, we investigated cognitive trajectories of patients with focal Aß deposition., Methods: We followed up 240 participants (112 cognitively unimpaired [CU], 78 amnestic mild cognitive impairment [aMCI], and 50 Alzheimer's disease (AD) dementia [ADD]) for 2 years from 9 referral centers in South Korea. Participants were assessed with neuropsychological tests and 18 F-flutemetamol (FMM) positron emission tomography (PET). Ten regions (frontal, precuneus/posterior cingulate (PPC), lateral temporal, parietal, and striatum of each hemisphere) were visually examined in the FMM scan, and participants were divided into three groups: No-FMM, Focal-FMM (FMM uptake in 1-9 regions), and Diffuse-FMM. We used mixed-effects model to investigate the speed of cognitive decline in the Focal-FMM group according to the cognitive level, extent, and location of Aß involvement, in comparison with the No- or Diffuse-FMM group., Results: Forty-five of 240 (18.8%) individuals were categorized as Focal-FMM. The rate of cognitive decline in the Focal-FMM group was faster than the No-FMM group (especially in the CU and aMCI stage) and slower than the Diffuse-FMM group (in particular in the CU stage). Within the Focal-FMM group, participants with FMM uptake to a larger extent (7-9 regions) showed faster cognitive decline compared to those with uptake to a smaller extent (1-3 or 4-6 regions). The Focal-FMM group was found to have faster cognitive decline in comparison with the No-FMM when there was uptake in the PPC, striatum, and frontal cortex., Conclusions: When predicting cognitive decline of patients with focal Aß deposition, the patients' cognitive level, extent, and location of the focal involvement are important.

Background: Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker cutoffs from immunoassays with low interlaboratory variability in diverse ethnic groups are necessary for their use in clinics and clinical trials. With lack of cutoffs from fully automated immunoassay platforms in diverse races, the aim of this study is to evaluate the clinical utility of CSF AD biomarkers from the Lumipulse fully automated immunoassay based on β-amyloid (Aβ) positron emission tomography (PET) status comparing with these from two manual immunoassays, in Koreans., Methods: Among 331 Korean participants enrolled from a prospective, 3-year longitudinal observational study of the validation cohort of Korean Brain Aging Study for the Early Diagnosis and Prediction of AD, 139 (29 CN, 58 SCD, 29 MCI, and 23 AD) provided CSF and 271 underwent baseline amyloid PET (n = 128 with overlapping CSF and Aβ-PET, and 143 without CSFs). Three annual cognitive and neuropsychiatric function tests were conducted. Aβ42, Aβ40, total-tau, and phosphorylated-tau 181 were measured by Lumipulse fully automated immunoassay and two manual immunoassays (INNO-BIA AlzBio3, INNOTEST). Clinical utility of CSF biomarker cutoffs, based on 128 participants with Aβ-PET, was evaluated., Results: Cognitive and neuropsychological scores differed significantly among the groups, with descending performance among CN>SCD>MCI>AD. Biomarker levels among immunoassays were strongly intercorrelated. We determined the Aβ-PET status in a subgroup without CSF (n = 143), and then when we applied CSF biomarker cutoffs determined based on the Aβ-PET status, the CSF biomarkers (cutoffs of 642.1 pg/mL for Aβ42, 0.060 for Aβ42/Aβ40, 0.315 for t-tau/Aβ42, and 0.051 for p-tau/Aβ42, respectively) showed good agreement with Aβ-PET (overall AUC ranges of 0.840-0.898). Use of the Aβ-PET-based CSF cutoffs showed excellent diagnostic discrimination between AD and CN (Aβ42, Aβ42/Aβ40, t-tau/Aβ42, and p-tau/Aβ42) with overall AUC ranges of 0.876-0.952. During follow-up, participants with AD-like CSF signature determined by Aβ-PET-based cutoffs from Lumipulse showed rapid progression of cognitive decline in 139 subjects, after adjustment for potential confounders, compared with those with a normal CSF signature., Conclusion: CSF AD biomarkers measured by different immunoassay platforms show strong intercorrelated agreement with Aβ-PET in Koreans. The Korean-specific Aβ-PET-based CSF biomarker cutoffs measured by the Lumipulse assay strongly predicts progression of cognitive decline. The clinical utility of CSF biomarkers from fully-automated immunoassay platforms should be evaluated in larger, more diverse cohorts.

WHAT IS KNOWN ON THE SUBJECT?: People in their twenties, including college students, experience a high level of stress and prevalence of related mental health problems including depression, anxiety and alcohol addiction, but they are the least likely age group in Korea to utilize professional help for mental health issues. Mental health literacy (MHL) refers to the knowledge and abilities necessary for maintaining mental health and preventing mental health problems. MHL also plays an important role in help-seeking for mental health issues. Therefore, studying MHL and other variables related to help-seeking is likely to enhance our overall understanding of students' mental health. WHAT THIS STUDY ADDS TO EXISTING KNOWLEDGE?: Although there have been some studies of college students' MHL in Korea, this is the first study to identify the paths and relationships between MHL and help-seeking intentions in Korean college students. Additionally, this study examined the mediating role of stigma in the relationship between MHL and attitudes toward help-seeking. The findings of this study suggest that MHL promotion can have a positive impact on the mental health of Korean college students by improving their attitudes toward help-seeking and increasing their help-seeking intentions. This study supports the idea that increased social support among Korean college students may reduce stigma and facilitate their seeking of professional help. The paths and relationships found in the present study provide evidence that a nursing intervention on-campus that improves students' MHL and reduces stigma may facilitate more effective use of help-seeking services among college students. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: MHL plays a significant role in how college students manage their mental health and the likelihood that they will seek professional help for mental health issues. Increasing MHL reduces mental health-related stigma and promotes positive attitudes toward help-seeking. A mental health nursing intervention that includes MHL improvement strategies would likely enhance students' utilization of mental health services on campus. Although students' MHL is improved by existing campus programmes and educational efforts to raise awareness of mental health, interventions should also address campus culture and stigma to facilitate mental health help-seeking. Ultimately, enhancing MHL will contribute to the prevention of mental health problems and protect the deterioration of mental health among college students. ABSTRACT: Introduction There is a high prevalence of mental health problems among college students in Korea. Although the usage rate for mental health services among Korean college students was not reported, it is known that the usage rate for Koreans is low compared to that in the United States. Aim To explore the relationships linking mental health literacy (MHL) to intentions of help-seeking in a sample of Korean college students. Method Using a cross-sectional study, data from 200 participants were analysed using a structural equation modelling approach. Results Mental health literacy had both direct and indirect effects on attitudes toward help-seeking and an indirect effect on attitudes toward help-seeking through stigma. The direct effect of MHL on attitudes toward help-seeking was fully mediated by stigma. Discussion Mental health nursing professionals have a responsibility and a challenge to enhance MHL in college students through individual or group interventions. Implications for practice MHL plays a significant role in individuals' willingness to seek professional help when in need of mental health care. Thus, mental health nursing interventions that include MHL improvement strategies would favourably enhance students' use of adequate sources of care and contribute to the prevention of mental health problems in college students., (© 2020 John Wiley & Sons Ltd.)

Objective: The Korean patient with Perry syndrome (PS) was the first to come to autopsy. We report a pathologically confirmed patient with PS, and compare to pathological findings of previous literatures., Materials and Methods: The patient had a family history of parkinsonism and had a mutation in the DCTN1 gene. After death an autopsy was performed. We analyzed macroscopic and microscopic findings of the patient., Results: There was no prominent cortical atrophy, but microscopy showed severe neuronal loss, microvacuolation, and gliosis in the substantia nigra (SN). We identified transactive response DNA-binding protein 43 (TDP-43)-positive neuronal cytoplasmic inclusions, dystrophic neurites, and glial cytoplasmic inclusions in surviving SN neurons. In addition, some neurofibrillary tangles (NFTs) were also seen in the parahippocampal gyrus., Conclusion: The neuropathology, including TDP-43 proteinopathy, is comparable to that reported previously in Caucasian populations. In addition to the stereotypic features of PS, our patient had NFTs in the parahippocampal gyrus, the pathology similar to that is described as primary age-related tauopathy (PART). These observations suggest that comorbid age-related neuropathologic change may also contribute to cognitive impairment in PS.

This study estimated the economic burden of people with brain disability in Korea during 2008-2011 using nationally representative data and was conducted to use the results as an evidence for determining the resources allocation of people with brain disability. We used a prevalence-based approach to estimate the economic burden, classified by direct costs (medical costs and nonmedical costs) and indirect costs (productivity loss of morbidity and premature death). Data from the National Health Insurance Service, the National Disability Registry, the National survey on persons with disabilities, the Korea National Statistical Office's records of causes of death, and the Labor Statistics were used to calculate direct and indirect costs. The treated prevalence of brain disability increased from 0.26% (2008) to 0.35% (2011). Total economic burden of brain-related diseases was US$1.88 billion in 2008 and increased to US$2.90 billion in 2011, with a 54% rate of increase. The economic burden of all diseases, which was 1.2 to 1.4 times higher than that of brain-related diseases, accounted for US$2.61 billion in 2008 and US$3.62 billion in 2011, increasing by 39%. Owing to the growing occurrence of brain disability, the annual prevalence and related costs are increasing. Health management programs are necessary to reduce the economic burden of brain disability in Korea.

To identify pathogenic variants in 107 Korean patients with sporadic frontotemporal dementia (FTD), 46 genes related to FTD, amyotrophic lateral sclerosis, and other dementias were screened by next-generation sequencing. Hexanucleotide repeats in C9orf72 gene were also tested by repeat-primed polymerase chain reaction. Next-generation sequencing revealed one known pathogenic variant (c.708+1G>A) in the GRN gene in a patient with behavioral variant FTD (bvFTD). In addition, a novel in-frame deletion (c.2675&#95;2683del) in the CSF1R gene was identified in a patient with bvFTD who had severe bifrontal atrophy with frontal subcortical white matter changes. Novel compound heterozygous variants in the AARS2 gene, c.1040+1G>A and c.636G>A (p.Met212Ile), were found in a patient with bvFTD. Forty-six variants of uncertain significance were detected in other patients. None of the patients had expanded hexanucleotide repeats in C9orf72. These results show that pathogenic variants of known FTD genes are rare in Korean FTD patients but the CSF1R and AARS2 genes should be screened for a genetic diagnosis of FTD or other dementias., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Obtaining brain tissue is critical to definite diagnosis and to furthering understanding of neurodegenerative diseases. The present authors have maintained the National Neuropathology Reference and Diagnostic Laboratories for Dementia in South Korea since 2016. We have built a nationwide brain bank network and are collecting brain tissues from patients with neurodegenerative diseases. We are aiming to facilitate analyses of clinic-pathological and image-pathological correlations of neurodegenerative disease and to broaden understanding thereof., Materials and Methods: We recruited participants through two routes: from memory clinics and the community. As a baseline evaluation, clinical interviews, a neurological examination, laboratory tests, neuropsychological tests, and MRI were undertaken. Some patients also underwent amyloid PET., Results: We recruited 105 participants, 70 from clinics and 35 from the community. Among them, 11 died and were autopsied. The clinical diagnoses of the autopsied patients included four with Alzheimer's disease (AD), two with subcortical vascular dementia, two with non-fluent variant primary progressive aphasia, one with leukoencephalopathy, one with frontotemporal dementia (FTD), and one with Creutzfeldt-Jakob disease (CJD). Five patients underwent amyloid PET: two with AD, one with mixed dementia, one with FTD, and one with CJD., Conclusion: The clinical and neuropathological information to be obtained from this cohort in the future will provide a deeper understanding of the neuropathological mechanisms of cognitive impairment in Asia, especially Korea., Competing Interests: The authors have no financial conflicts of interest., (© Copyright: Yonsei University College of Medicine 2018.)

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.

Background: Personality may predispose family caregivers to experience caregiving differently in similar situations and influence the outcomes of caregiving. A limited body of research has examined the role of some personality traits for health-related quality of life (HRQoL) among family caregivers of persons with dementia (PWD) in relation to burden and depression., Methods: Data from a large clinic-based national study in South Korea, the Caregivers of Alzheimer's Disease Research (CARE), were analyzed (N = 476). Path analysis was performed to explore the association between family caregivers' personality traits and HRQoL. With depression and burden as mediating factors, direct and indirect associations between five personality traits and HRQoL of family caregivers were examined., Results: Results demonstrated the mediating role of caregiver burden and depression in linking two personality traits (neuroticism and extraversion) and HRQoL. Neuroticism and extraversion directly and indirectly influenced the mental HRQoL of caregivers. Neuroticism and extraversion only indirectly influenced their physical HRQoL. Neuroticism increased the caregiver's depression, whereas extraversion decreased it. Neuroticism only was mediated by burden to influence depression and mental and physical HRQoL., Conclusions: Personality traits can influence caregiving outcomes and be viewed as an individual resource of the caregiver. A family caregiver's personality characteristics need to be assessed for tailoring support programs to get the optimal benefits from caregiver interventions.

Early-onset Alzheimer's disease (EOAD) has distinct clinical characteristics in comparison to late-onset Alzheimer's disease (LOAD). The genetic contribution is suggested to be more potent in EOAD. However, the frequency of causative mutations in EOAD could be variable depending on studies. Moreover, no mutation screening study has been performed yet employing large population in Korea. Previously, we reported that the rate of family history of dementia in EOAD patients was 18.7% in a nationwide hospital-based cohort study, the Clinical Research Center for Dementia of South Korea (CREDOS) study. This rate is much lower than in other countries and is even comparable to the frequency of LOAD patients in our country. To understand the genetic characteristics of EOAD in Korea, we screened the common Alzheimer's disease (AD) mutations in the consecutive EOAD subjects from the CREDOS study from April 2012 to February 2014. We checked the sequence of APP (exons 16-17), PSEN1 (exons 3-12), and PSEN2 (exons 3-12) genes. We identified different causative or probable pathogenic AD mutations, PSEN1 T116I, PSEN1 L226F, and PSEN2 V214L, employing 24 EOAD subjects with a family history and 80 without a family history of dementia. PSEN1 T116I case demonstrated autosomal dominant trait of inheritance, with at least 11 affected individuals over 2 generations. However, there was no family history of dementia within first-degree relation in PSEN1 L226F and PSEN2 V214L cases. Approximately, 55.7% of the EOAD subjects had APOE ε4 allele, while none of the mutation-carrying subjects had the allele. The frequency of genetic mutation in this study is lower compared to the studies from other countries. The study design that was based on nationwide cohort, which minimizes selection bias, is thought to be one of the contributors to the lower frequency of genetic mutation. However, the possibility of the greater likeliness of earlier onset of sporadic AD in Korea cannot be excluded. We suggest early AD onset and not carrying APOE ε4 allele are more reliable factors for predicting an induced genetic mutation than the presence of the family history in Korean EOAD population., Competing Interests: The authors report no conflicts of interest in this work.

Objectives: The purpose of this study is to examine the relationship between 5-HTTLPR polymorphism (44-bp insertion/deletion polymorphism of serotonin transporter gene) and methylphenidate (MPH) treatment response, as well as the association between the adverse events of MPH treatment and 5-HTTLPR polymorphism in children with attention-deficit/hyperactivity disorder (ADHD)., Methods: A total of 114 children with ADHD (mean age 9.08 ± 1.94 years) were recruited from the child psychiatric clinic in a hospital in South Korea. We have extracted the genomic DNA of the subjects from their blood lymphocytes and analyzed 5-HTTLPR polymorphism of the SLC6A4 gene. All children were treated with MPH for 8 weeks, with clinicians monitoring both the improvement of ADHD symptoms and the side effects. We compared the response to MPH treatment and adverse events among those with the genotype of 5-HRRLPR polymorphism., Results: There was no significant association between the 5-HTTLPR genotype and the response to MPH treatment in children with ADHD. Subjects with the S/L+L/L genotype tended to have tics and nail biting (respectively, p < 0.001, p = 0.017)., Conclusions: The results of this study do not support the association between the 5-HTTLPR polymorphism and treatment response with MPH in ADHD. However, our findings suggest the association between 5-HTTLPR polymorphism and the occurrence of tics and nail-biting as an adverse event of methylphenidate. This may aid in our understanding of the genetic contribution and genetic susceptibility of a particular allele in those ADHD patients with tics or nail biting.

This study explored factors contributing to the quality of life of community-based home visiting care service users in Korea through a two-level multilevel model. The community health care center's organizational factors including the total number of visiting nurses and visiting nurses' rehire rate were treated as covariates. For participant's individual factors (Level 1), only subjective health status and the presence of cerebral vascular disease significantly explained the quality of life. Visiting nurses' demographic factors (Level 2) were not statistically significant. However, the total number of visiting nurses and visiting nurses' rehire rate were significant. Therefore, to increase an elderly adult's quality of life through community-based home visiting care services, a community health care center's organizational factors should be considered in addition to patient characteristics. This result may prove useful not only for Korea but also for other countries that intend to reform their community-based home visiting care services.

IgE-dependent activation of mast cells and basophils through the high-affinity IgE receptor (FcεRI) is involved in the pathogenesis of allergen-induced immune responsiveness in atopic diseases like atopic dermatitis (AD). We sought to determine FcεRI gene polymorphisms are associated with AD in Korean patients, and analyzed the relevance of FcεRI gene polymorphisms and serum IgE levels. We conducted a case-control association analysis (175 patients and 56 controls) of Korean subjects. Genotyping was performed using the TaqMan fluorogenic 5' nuclease assay, and serum levels of IgE were measured using a fluorescence enzyme immunoassay. We found that there were no significant relationships between FcεRI and AD, although there were trends towards an association between the 66T>C (rs2251746) polymorphism and total serum IgE levels in the Korean AD patients. In conclusion, while the 66T>C (rs2251746) of the FcεRIα polymorphism may be linked to AD and higher serum IgE levels, polymorphisms in the FcεRIβ gene did not confer susceptibility to AD in our patient sample.

Aims and Objectives: The purpose of this study was to assess the level of anxiety and uncertainty in Korean mothers of children with febrile convulsion and to identify factors associated with maternal anxiety., Background: In general, febrile convulsions are harmless to the child, but parents perceive the convulsion as frightening. Previous authors of a few studies suggested that providing information was helpful for parents' knowledge, attitude and fear about a febrile convulsion., Design: This was a descriptive, cross-sectional survey., Methods: The sample comprised 102 mothers whose children had been diagnosed with a febrile convulsion and admitted to paediatric wards in five general hospitals in South Korea. The researchers gave the questionnaires to nursing departments for distribution and collection by paediatric nurses. To test differences in anxiety and uncertainty by participants' characteristics, t-tests and anova were conducted. Linear regression was used to identify factors associated with maternal state anxiety. Statistical significance level was set at 0.05., Results: A multiple linear regression of maternal anxiety showed that four statistically significant predictors explained 56% of the total variations of maternal anxiety. The significant predictors were uncertainty, frequency of febrile convulsion, income and information about febrile convulsion. Among the significant variables, uncertainty was the dominant contributing factor (p < 0.001)., Conclusions: Anxiety in mothers of children with febrile convulsion was especially related to uncertainty, so health care providers can reduce anxiety through decreasing uncertainty., Relevance to Clinical Practice: For interventions to decrease maternal anxiety, provision of information and psychosocial support are needed for parents of hospitalised children with febrile convulsions., (© 2011 Blackwell Publishing Ltd.)

Frontotemporal lobar degeneration (FTLD) can be subdivided into frontotemporal dementia (FTD), FTD combined with motor neuron disease (FTD-MND), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). FTLD has been considered a rare disorder, and its' demographic and survival data have rarely been studied in Asian population. A survival analysis using the Kaplan-Meier method was performed for 121 consecutive patients with clinically diagnosed FTLD who attended the Memory Disorder Clinic at Samsung Medical Center in Seoul, Republic of Korea, between January 1995 and September 2006. The overall median survival from the onset of the first symptom was 9.6 years (95% CI=8.3-10.8 y). The survival was shortest in FTD-MND (3 y) and longest in SD (11.3 y). The median survival time of FTD (9.8 y) was shorter than that of SD and longer than that of FTD-MND and PNFA. The use of the Cox proportional-hazards model to examine the effect of demographics on survival revealed that only age at onset was associated with survival. In general, our data are comparable with those from the Western countries. However, the female proportion was greater across all subtypes of FTLD and the survival of patients with PNFA was shorter than those of other groups.

Creutzfeldt-Jakob disease (CJD) is an uncommon neurodegenerative disorder with an incidence of 1 per 1000,000 per year typically characterized by rapidly progressive dementia, ataxia, myoclonus and behavioral changes. Genetic prion diseases, which develop due to a mutations in the prion protein gene (PRNP), account for an estimated 10 to 15% of all CJD cases. We report a 75-yr-old woman with familial CJD carrying a V180I mutation which features late onset, slow progression, no periodic sharp wave complexes on electroencephalography, and extensive cortical ribboning with spared the cerebellum and the medial occipital lobes posterior to the parieto-occipital sulcus on MRI. To our knowledge, this is the first documented case of a point mutation at codon 180 in South Korea.