1.SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through Multidomain interventions via facE-to-facE and video communication plaTforms in mild cognitive impairment (SUPERBRAIN-MEET): Protocol for a Multicenter Randomized Controlled Trial
Soo Hyun CHO ; Hae Jin KANG ; Yoo Kyoung PARK ; So Young MOON ; Chang Hyung HONG ; Hae Ri NA ; Hong-Sun SONG ; Muncheong CHOI ; Sooin JEONG ; Kyung Won PARK ; Hyun Sook KIM ; Buong-O CHUN ; Jiwoo JUNG ; Jee Hyang JEONG ; Seong Hye CHOI
Dementia and Neurocognitive Disorders 2024;23(1):30-43
Background:
and Purpose: The SoUth Korea study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention (SUPERBRAIN) proved the feasibility of multidomain intervention for elderly people. One-quarter of the Korean population over 65 years of age has mild cognitive impairment (MCI). Digital health interventions may be costeffective and have fewer spatial constraints. We aim to examine the efficacy of a multidomain intervention through both face-to-face interactions and video communication platforms using a tablet personal computer (PC) application in MCI.
Methods:
Three hundred participants aged 60–85 years, with MCI and at least one modifiable dementia risk factor, will be recruited from 17 centers and randomly assigned in a 1:1 ratio to the multidomain intervention and the waiting-list control groups. Participants will receive the 24-week intervention through the tablet PC SUPERBRAIN application, which encompasses the following five elements: managing metabolic and vascular risk factors, cognitive training,physical exercise, nutritional guidance, and boosting motivation. Participants will attend the interventions at a facility every 1–2 weeks. They will also engage in one or two self-administered cognitive training sessions utilizing the tablet PC application at home each week. They will participate in twice or thrice weekly online exercise sessions at home via the ZOOM platform. The primary outcome will be the change in the total scale index score of the Repeatable Battery for the Assessment of Neuropsychological Status from baseline to study end.
Conclusions
This study will inform the effectiveness of a comprehensive multidomain intervention utilizing digital technologies in MCI.
2.Clinical Relevance of Enlarged Perivascular Spaces in Neurodegenerative Disease
Yu-Ri JE ; Hong-Gi HAM ; Yu-Hyun PARK ; Tae-Yun KIM ; Min-su GO ; Hye-In LEE ; Da Eun KIM ; Na-Yeon JUNG ; Myung Jun LEE ; Sang-Won SEO ; Eun-Joo KIM
Journal of the Korean Neurological Association 2023;41(4):281-292
Background:
Enlarged perivascular space (ePVS) is recently reported to be associated with cerebral small vessel disease (SVD) and Alzheimer’s disease (AD). The topographical location of ePVS may relate to the underlying pathology; basal ganglia (BG)-ePVS has been associated with cerebral vascular diseases and centrum semi-ovale (CSO)-ePVS associated with cerebral amyloid angiopathy (CAA). However, the effects of ePVS on various neurological conditions remain still controversial. To investigate the clinical relevance of ePVS in neurodegenerative diseases, we tested relationships between ePVS and cognition, markers of SVD, vascular risk factors, or amyloid pathology.
Methods:
We retrospectively reviewed 292 patients (133 AD dementia, 106 mild cognitive impairment, 39 other neurodegenerative diseases, 14 subjective cognitive decline) who underwent both amyloid positron emission tomography and brain magnetic resonance imaging. Vascular risk factors and cognitive tests results were collected. The ePVS in the BG and CSO, SVD markers and the volume of white matter hyperintensities were measured.
Results:
There were no significant differences in the severity and distribution of ePVS among clinical syndromes. Both BG- and CSO-ePVS were not related to cognitive function. Patients with lacunes were more likely to have high-degree BG-ePVS. High degree CSO-ePVS had an odds ratio (OR) for amyloid positive of 2.351, while BG-ePVS was a negative predictor for amyloid pathology (OR, 0.336).
Conclusions
Our findings support that ePVS has different underlying pathologies according to the cerebral topography. BG-ePVS would be attributed to hypertensive angiopathy considering the relation with SVD markers, whereas and CSO-ePVS would be attributed to CAA considering the association with amyloid pathology.
3.Development of a Guideline for Antipsychotic-induced Hyperprolactinemia in Korea Using the ADAPTE Process
Hye Ri KIM ; Sun Mi KIM ; Won Sub KANG ; Hong Jun JEON ; Seung-Ho JANG ; Duk-In JON ; Jeongwan HONG ; Jong-Hyun JEONG
Clinical Psychopharmacology and Neuroscience 2023;21(3):447-456
Objective:
To develop an evidence-based guideline for the diagnosis and treatment of antipsychotic-induced hyperprolactinemia by adapting existing high-quality clinical guidelines with a view to improve the clinical symptoms and long-term quality of life of patients by providing appropriate management.
Methods:
This guideline was developed according to the ADAPTE methodology. The adaptation process included determining key health questions, systematically searching and screening guidelines, evaluating the quality and contents of these guidelines, deriving recommendations for key questions, and performing a peer review. The selection criteria for the guideline search were (1) evidence-based guidelines, (2) published within the last 5 years, and (3) written in English or Korean.
Results:
After evaluating the quality and content, we finally selected three guidelines for adaptation. The final output of the development process was 25 recommendations for 10 key questions. We adopted the Agency for Health Research Quality methodology and presented the level of evidence from levels I to IV. In addition, we defined the recommendation grades from grade A (strongly recommended) to D (no recommendation) based on the level of evidence and clinical significance of the recommendation.
Conclusion
The development and dissemination of the adapted guideline is expected to increase the certainty of medical decision making and improve the quality of medical care. Further studies on the effectiveness and applicability of the developed guideline are necessary.
4.Risk factors associated with death due to severe fever with thrombocytopenia syndrome in hospitalized Korean patients (2018–2022)
Jia KIM ; Hyo-jeong HONG ; Ji-hye HWANG ; Na-Ri SHIN ; Kyungwon HWANG
Osong Public Health and Research Perspectives 2023;14(3):151-163
Objectives:
Severe fever with thrombocytopenia syndrome (SFTS) has no vaccine or treatment and an extremely high fatality rate. We aimed to analyze and evaluate the risk factors for death associated with SFTS.
Methods:
Among reports from 2018 to 2022, we compared and analyzed 1,034 inpatients aged 18 years or older with laboratory-confirmed SFTS who underwent complete epidemiological investigations.
Results:
Most of the inpatients with SFTS were aged 50 years or older (average age, 67.6 years). The median time from symptom onset to death was 9 days, and the average case fatality rate was 18.5%. Risk factors for death included age of 70 years or older (odds ratio [OR], 4.82); agriculture-related occupation (OR, 2.01); underlying disease (OR, 7.20); delayed diagnosis (OR, 1.28 per day); decreased level of consciousness (OR, 5.53); fever/chills (OR, 20.52); prolonged activated partial thromboplastin time (OR, 4.19); and elevated levels of aspartate aminotransferase (OR, 2.91), blood urea nitrogen (OR, 2.62), and creatine (OR, 3.21).
Conclusion
The risk factors for death in patients with SFTS were old age; agriculture-related occupation; underlying disease; delayed clinical suspicion; fever/chills; decreased level of consciousness; and elevated activated partial thromboplastin time, aspartate aminotransferase, blood urea nitrogen, and creatine levels.
5.Effects of GV1001 on Language Dysfunction in Patients With Moderate-to-Severe Alzheimer’s Disease: Post Hoc Analysis of Severe Impairment Battery Subscales
Hyuk Sung KWON ; Seong-Ho KOH ; Seong Hye CHOI ; Jee Hyang JEONG ; Hae Ri NA ; Chan Nyoung LEE ; YoungSoon YANG ; Ae Young LEE ; Jae-Hong LEE ; Kyung Won PARK ; Hyun Jeong HAN ; Byeong C. KIM ; Jinse PARK ; Jee-Young LEE ; Kyu-Yong LEE ; Sangjae KIM
Dementia and Neurocognitive Disorders 2023;22(3):100-108
Background:
and Purpose: The efficacy and safety of GV1001 have been demonstrated in patients with moderate-to-severe Alzheimer’s disease (AD). In this study, we aimed to further demonstrate the effectiveness of GV1001 using subscales of the Severe Impairment Battery (SIB), which is a validated measure to assess cognitive function in patients with moderate-tosevere AD.
Methods:
We performed a post hoc analysis of data from a 6 month, multicenter, phase 2, randomized, double-blind, placebo-controlled trial with GV1001 (ClinicalTrials.gov, NCT03184467). Patients were randomized to receive either GV1001 or a placebo for 24 weeks. In the current study, nine subscales of SIB—social interaction, memory, orientation, language, attention, praxis, visuospatial ability, construction, and orientation to name— were compared between the treatment (GV1001 1.12 mg) and placebo groups at weeks 12 and 24. The safety endpoints for these patients were also determined based on adverse events.
Results:
In addition to the considerable beneficial effect of GV1001 on the SIB total score, GV1001 1.12 mg showed the most significant effect on language function at 24 weeks compared to placebo in both the full analysis set (FAS) and per-protocol set (PPS) (p=0.017 and p=0.011, respectively). The rate of adverse events did not differ significantly between the 2 groups.
Conclusions
Patients with moderate-to-severe AD receiving GV1001 had greater language benefits than those receiving placebo, as measured using the SIB language subscale.
6.Development of a Next-generation Sequencing-based Gene Panel Test to Detect Measurable Residual Disease in Acute Myeloid Leukemia
Jin Ju KIM ; Ji Eun JANG ; Hyeon Ah LEE ; Mi Ri PARK ; Hye Won KOOK ; Seung-Tae LEE ; Jong Rak CHOI ; Yoo Hong MIN ; Saeam SHIN ; June-Won CHEONG
Annals of Laboratory Medicine 2023;43(4):328-336
Background:
AML is a heterogeneous disease, and despite intensive therapy, recurrence is still high in AML patients who achieve the criterion for cytomorphologic remission (residual tumor burden [measurable residual disease, MRD]<5%). This study aimed to develop a targeted next-generation sequencing (NGS) panel to detect MRD in AML patients and validate its performance.
Methods:
We designed an error-corrected, targeted MRD-NGS panel without using physical molecular barcodes, including 24 genes. Fifty-four bone marrow and peripheral blood samples from 23 AML patients were sequenced using the panel. The panel design was validated using reference material, and accuracy was assessed using droplet digital PCR.
Results:
Dilution tests showed excellent linearity and a strong correlation between expected and observed clonal frequencies (R>0.99). The test reproducibly detected MRD in three dilution series samples, with a sensitivity of 0.25% for single-nucleotide variants. More than half of samples from patients with morphologic remission after one month of chemotherapy had detectable mutations. NGS-MRD positivity for samples collected after one month of chemotherapy tended to be associated with poor overall survival and progression-free survival.
Conclusions
Our highly sensitive and accurate NGS-MRD panel can be readily used to monitor most AML patients in clinical practice, including patients without gene rearrangement. In addition, this NGS-MRD panel may allow the detection of newly emerging clones during clinical relapse, leading to more reliable prognoses of AML.
7.Predictive Factors of Event-Free Survival at 24 Months in Patients with Peripheral T-Cell Lymphoma: A Retrospective Study
Yu Ri KIM ; Soo-Jeong KIM ; Hye Sun LEE ; Soyoung JEON ; Hyunsoo CHO ; Haerim CHUNG ; Ji Eun JANG ; June-Won CHEONG ; Yoo Hong MIN ; Jin Seok KIM
Cancer Research and Treatment 2022;54(2):613-620
Purpose:
Event-free survival at 24 months (EFS24) is known to be a surrogate marker for overall survival (OS) for patients with peripheral T-cell lymphoma (PTCL). We examined the role of EFS24 in PTCL compared to diffuse large B-cell lymphoma (DLBCL), and then assessed the clinical predictive factors of achieving EFS24.
Materials and Methods:
Patients with newly diagnosed PTCL treated with anthracycline-based chemotherapy were included. Subsequent OS was defined as the time elapsed from 24 months after diagnosis until death from any cause in those who achieved EFS24.
Results:
Overall, 153 patients were evaluated, and 51 patients (33.3%) achieved EFS24. Patients who achieved EFS24 showed superior OS compared to patients who did not (p < 0.001). EFS24 could stratify the subsequent OS although it did not reach to that of the general population. After matching the PTCL group to the DLBCL group based on the international prognostic index, the subsequent OS in patients who achieved EFS24 was similar between the two groups (p=0.094). Advanced stage was a significant factor to predict the failing EFS24 by multivariable analysis (p < 0.001).
Conclusion
Patients with PTCL who achieve EFS24 could have a favorable subsequent OS. Since advanced disease stage is a predictor of EFS24 failure, future efforts should focus on developing novel therapeutic strategies for PTCL patients presenting with advanced disease.
8.The Effect of Dementia Prevention Nutrition Program Using MIND Diet on the Changes in Cognitive Function of the Elderly with High-Dementia Risks
Jaeeun SONG ; Seong Hye CHOI ; Chang Hyung HONG ; Jee Hyang JEONG ; So Young MOON ; Hae Ri NA ; Hee Kyung PARK ; Yoo Kyoung PARK
Journal of the Korean Dietetic Association 2021;27(4):248-262
This study examined the effect of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet of the Korean multi-domain dementia prevention program on the cognitive functions of the elderly with dementia risk factors. We developed the program including nutrition, exercise, cognitive training, vascular disease prevention, and motivation. One- hundred and fifty-three participants aged 60∼79 years with at least 1 dementia risk factor were randomly assigned in a 1:1:1 ratio to the facility-based intervention (FMI), home-based intervention (HMI), and the control group. The nutrition education program consisted of 10 classes over 24 weeks: the FMI received 7 group sessions and three 1:1 sessions, the HMI received 4 group sessions and three 1:1 sessions with 3 homework sessions. The Nutrition Quotient for Elderly (NQ-E) and the Mini Nutritional Assessment (MNA) were used to evaluate nutritional status. The Repeatable Battery for the Assessment Neuropsychological Status (RBANS), Korean Mini-Mental State Examination (K-MMSE), and the Cognitive Complaint Interview (CCI) were used to evaluate cognitive functions. A total of 136 people completed the program with an 11.1% dropout rate. The NQ-E (P=0.009) and RBANS (P=0.001) scores significantly increased in the FMI (N=45) and HMI (N=49) groups compared to the control group (N=42) after the study. The changes in the score of MNA and CCI did not differ significantly between groups. In conclusion, the nutritional intervention which focused on the MIND diet as a part of a multi-domain intervention program had a positive effect on the improvement of healthy eating habits and cognitive function scores in the high-risk dementia group.
9.Screening for Atrial Fibrillation Using a Smartphone-Based Electrocardiogram in Korean Elderly
Nu Ri KIM ; Chang Kyun CHOI ; Hyeong Suk KIM ; Su Hyun OH ; Jung Hwa YANG ; Ki Hong LEE ; Ju Han KIM ; Man Seok PARK ; Hye Yeon KIM ; Min Ho SHIN
Chonnam Medical Journal 2020;56(1):50-54
Atrial fibrillation (AF) is responsible for 10–20% of cerebral infarctions. Several mobile devices have been developed to screen for AF and studies of AF screening have been conducted in several countries to evaluate the applicability of these mobile devices. In this tradition, we conducted a community-based AF screening using an automated single-lead electrocardiogram (SL-ECG). This survey examined 2,422 participants in a community dementia screening program who were aged 60 years or older in the preliminary study, and 5,366 participants at 9 Senior Welfare Centers aged 60 years or older in the expanded study. AF screening was conducted using an automated SL-ECG (Kardia Mobile, AliveCor, Mountain View, CA, USA). AF was confirmed with a 12-lead electrocardiogram in subjects classified as having AF on the SL-ECG. In the preliminary study, of the 2,422 subjects, 124 had AF on the SL-ECG. The prevalence of AF was 3.0% (95% confidence interval [CI]: 2.4–3.8). The positive predictive value (PPV) of SL-ECG was 58.9% (95% CI: 50.1–67.1). Of the subjects diagnosed with AF, 65.8% (95% CI: 54.3–75.6) were newly diagnosed. In an expanded study, of the 5,366 subjects, 289 had AF on SL-ECG. The prevalence was 2.6% (95% CI: 2.2–3.1) and PPV of SL-ECG was 48.8% (95% CI: 43.1–54.5). In this community-based AF screening, we found that AF is underdiagnosed and undertreated. These results suggest that the early detection of AF using mobile devices is needed in Korea.
10.South Korean Study to Prevent Cognitive Impairment and Protect Brain Health Through Lifestyle Intervention in At-Risk Elderly People: Protocol of a Multicenter, Randomized Controlled Feasibility Trial
Hee Kyung PARK ; Jee Hyang JEONG ; So Young MOON ; Yoo Kyoung PARK ; Chang Hyung HONG ; Hae Ri NA ; Hong-Sun SONG ; Sun Min LEE ; Muncheong CHOI ; Kyung Won PARK ; Byeong C. KIM ; Soo Hyun CHO ; Buong-O CHUN ; Seong Hye CHOI
Journal of Clinical Neurology 2020;16(2):292-303
Background:
and PurposeThe prevalence of dementia is increasing in South Korea. Multidomain interventions may be useful for preventing dementia. Such programs need to be disseminated to elderly Koreans throughout the country. We have developed programs of the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), which consists of a facility-based multidomain intervention (FMI) program and a home-based multidomain intervention (HMI) program suitable for elderly Koreans. We aim to determine the feasibility of the SUPERBRAIN programs before a large-scale randomized controlled trial.
Methods:
We will recruit 150 participants among those without dementia aged 60–79 years with at least 1 modifiable dementia risk factor. They will be randomly assigned in a 1:1:1 ratio to the FMI, HMI, and the waiting-list control arm. The 6-month multidomain intervention consists of management of metabolic and vascular risk factors, cognitive training and social activity, physical exercise, nutritional guidance, and motivational enhancement programs. The primary outcomes are adherence and retention rates and changes in the total scale index score of the Repeatable Battery for the Assessment of Neuropsychological Status from baseline to the study end. The main secondary outcomes are disability, depressive symptoms, quality of life, vascular risk factors, physical performance, nutritional assessment, and motivation questionnaire. There will be an exploratory evaluation of neurotrophic, neurodegeneration, and neuroinflammation factors, microbiome, telomere length, electroencephalography, and neuroimaging measures.
Conclusions
The results obtained will provide information on the applicability of these multidomain intervention programs to at-risk elderly people.

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