1.Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine
Yeshin KIM ; Dong Woo KANG ; Geon Ha KIM ; Ko Woon KIM ; Hee-Jin KIM ; Seunghee NA ; Kee Hyung PARK ; Young Ho PARK ; Gihwan BYEON ; Jeewon SUH ; Joon Hyun SHIN ; YongSoo SHIM ; YoungSoon YANG ; Yoo Hyun UM ; Seong-il OH ; Sheng-Min WANG ; Bora YOON ; Sun Min LEE ; Juyoun LEE ; Jin San LEE ; Jae-Sung LIM ; Young Hee JUNG ; Juhee CHIN ; Hyemin JANG ; Miyoung CHOI ; Yun Jeong HONG ; Hak Young RHEE ; Jae-Won JANG ;
Dementia and Neurocognitive Disorders 2025;24(1):1-23
Background:
and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia.
Methods:
Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.
Results:
Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects.
Conclusions
This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.
2.A Real-World, Prospective, Observational Study of Rivaroxaban on Prevention of Stroke and Non-Central Nervous Systemic Embolism in Renally Impaired Korean Patients With Non-Valvular Atrial Fibrillation:XARENAL
Il-Young OH ; Chang Hoon LEE ; Eue-Keun CHOI ; Hong Euy LIM ; Yong-Seog OH ; Jong-Il CHOI ; Min-Soo AHN ; Ju Youn KIM ; Nam-Ho KIM ; Namsik YOON ; Martin SANDMANN ; Kee-Joon CHOI
Korean Circulation Journal 2025;55(2):121-131
Background and Objectives:
Several real-world studies have been done in patients with nonvalvular atrial fibrillation (NVAF); however, information on its safety profile in patients with renal impairment is limited. XARENAL, a real-world study, aimed to prospectively investigate the safety profile of rivaroxaban in patients with NVAF with renal impairment (creatinine clearance [CrCl], 15–49 mL/min).
Methods:
XARENAL is an observational single-arm cohort study in renal impairment NVAF patients. Patients were followed up approximately every 3 months for 1 year or until 30 days following early discontinuation. The primary endpoint was major bleeding events. All adverse events, symptomatic thromboembolic events, treatment duration, and renal function change from baseline were the secondary endpoints.
Results:
XARENAL included 888 patients from 29 study sites. Overall, 713 (80.3%) had moderate renal impairment (CrCl, 30–49 mL/min), and 175 (19.7%) had severe renal impairment (CrCl, 15–29 mL/min) with a mean estimated glomerular filtration rate (eGFR) of 45.2±13.0 mL/min/1.73 m 2 . The mean risk scores were 3.3±1.4 and 1.7±0.9 for CHA 2 DS 2 -VASc score and HAS-BLED score, respectively. An incidence proportion of 5.6% (6.2 events per 100 patient-years) developed major bleeding; however, fatal bleeding occurred in 0.5% (0.5 events per 100 patient-years). The mean change in the eGFR was 2.22±26.47 mL/min/1.73 m 2 per year.
Conclusions
XARENAL observed no meaningful differences in major bleeding events from other previous findings as well as renal function changes in rivaroxaban-treated NVAF patients with renal impairment, which is considered to be acceptable in clinical practice.
3.YAK577 Attenuates Cardiac Remodeling and Fibrosis in Isoproterenol-Infused Heart Failure Mice by Downregulating MMP12
Hongyan ZHOU ; Hae Jin KEE ; Le WAN ; Yodita ASFAHA ; Fabian FISCHER ; Matthias U KASSACK ; Thomas KURZ ; Seong Hoon KIM ; Seung-Jung KEE ; Young Joon HONG ; Myung Ho JEONG
Korean Circulation Journal 2025;55(3):231-247
Background and Objectives:
Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism.
Methods:
New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12).
Results:
YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes.
Conclusions
YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.
4.A Real-World, Prospective, Observational Study of Rivaroxaban on Prevention of Stroke and Non-Central Nervous Systemic Embolism in Renally Impaired Korean Patients With Non-Valvular Atrial Fibrillation:XARENAL
Il-Young OH ; Chang Hoon LEE ; Eue-Keun CHOI ; Hong Euy LIM ; Yong-Seog OH ; Jong-Il CHOI ; Min-Soo AHN ; Ju Youn KIM ; Nam-Ho KIM ; Namsik YOON ; Martin SANDMANN ; Kee-Joon CHOI
Korean Circulation Journal 2025;55(2):121-131
Background and Objectives:
Several real-world studies have been done in patients with nonvalvular atrial fibrillation (NVAF); however, information on its safety profile in patients with renal impairment is limited. XARENAL, a real-world study, aimed to prospectively investigate the safety profile of rivaroxaban in patients with NVAF with renal impairment (creatinine clearance [CrCl], 15–49 mL/min).
Methods:
XARENAL is an observational single-arm cohort study in renal impairment NVAF patients. Patients were followed up approximately every 3 months for 1 year or until 30 days following early discontinuation. The primary endpoint was major bleeding events. All adverse events, symptomatic thromboembolic events, treatment duration, and renal function change from baseline were the secondary endpoints.
Results:
XARENAL included 888 patients from 29 study sites. Overall, 713 (80.3%) had moderate renal impairment (CrCl, 30–49 mL/min), and 175 (19.7%) had severe renal impairment (CrCl, 15–29 mL/min) with a mean estimated glomerular filtration rate (eGFR) of 45.2±13.0 mL/min/1.73 m 2 . The mean risk scores were 3.3±1.4 and 1.7±0.9 for CHA 2 DS 2 -VASc score and HAS-BLED score, respectively. An incidence proportion of 5.6% (6.2 events per 100 patient-years) developed major bleeding; however, fatal bleeding occurred in 0.5% (0.5 events per 100 patient-years). The mean change in the eGFR was 2.22±26.47 mL/min/1.73 m 2 per year.
Conclusions
XARENAL observed no meaningful differences in major bleeding events from other previous findings as well as renal function changes in rivaroxaban-treated NVAF patients with renal impairment, which is considered to be acceptable in clinical practice.
5.YAK577 Attenuates Cardiac Remodeling and Fibrosis in Isoproterenol-Infused Heart Failure Mice by Downregulating MMP12
Hongyan ZHOU ; Hae Jin KEE ; Le WAN ; Yodita ASFAHA ; Fabian FISCHER ; Matthias U KASSACK ; Thomas KURZ ; Seong Hoon KIM ; Seung-Jung KEE ; Young Joon HONG ; Myung Ho JEONG
Korean Circulation Journal 2025;55(3):231-247
Background and Objectives:
Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism.
Methods:
New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12).
Results:
YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes.
Conclusions
YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.
6.Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine
Yeshin KIM ; Dong Woo KANG ; Geon Ha KIM ; Ko Woon KIM ; Hee-Jin KIM ; Seunghee NA ; Kee Hyung PARK ; Young Ho PARK ; Gihwan BYEON ; Jeewon SUH ; Joon Hyun SHIN ; YongSoo SHIM ; YoungSoon YANG ; Yoo Hyun UM ; Seong-il OH ; Sheng-Min WANG ; Bora YOON ; Sun Min LEE ; Juyoun LEE ; Jin San LEE ; Jae-Sung LIM ; Young Hee JUNG ; Juhee CHIN ; Hyemin JANG ; Miyoung CHOI ; Yun Jeong HONG ; Hak Young RHEE ; Jae-Won JANG ;
Dementia and Neurocognitive Disorders 2025;24(1):1-23
Background:
and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia.
Methods:
Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.
Results:
Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects.
Conclusions
This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.
7.Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine
Yeshin KIM ; Dong Woo KANG ; Geon Ha KIM ; Ko Woon KIM ; Hee-Jin KIM ; Seunghee NA ; Kee Hyung PARK ; Young Ho PARK ; Gihwan BYEON ; Jeewon SUH ; Joon Hyun SHIN ; YongSoo SHIM ; YoungSoon YANG ; Yoo Hyun UM ; Seong-il OH ; Sheng-Min WANG ; Bora YOON ; Sun Min LEE ; Juyoun LEE ; Jin San LEE ; Jae-Sung LIM ; Young Hee JUNG ; Juhee CHIN ; Hyemin JANG ; Miyoung CHOI ; Yun Jeong HONG ; Hak Young RHEE ; Jae-Won JANG ;
Dementia and Neurocognitive Disorders 2025;24(1):1-23
Background:
and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia.
Methods:
Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.
Results:
Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects.
Conclusions
This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.
8.A Real-World, Prospective, Observational Study of Rivaroxaban on Prevention of Stroke and Non-Central Nervous Systemic Embolism in Renally Impaired Korean Patients With Non-Valvular Atrial Fibrillation:XARENAL
Il-Young OH ; Chang Hoon LEE ; Eue-Keun CHOI ; Hong Euy LIM ; Yong-Seog OH ; Jong-Il CHOI ; Min-Soo AHN ; Ju Youn KIM ; Nam-Ho KIM ; Namsik YOON ; Martin SANDMANN ; Kee-Joon CHOI
Korean Circulation Journal 2025;55(2):121-131
Background and Objectives:
Several real-world studies have been done in patients with nonvalvular atrial fibrillation (NVAF); however, information on its safety profile in patients with renal impairment is limited. XARENAL, a real-world study, aimed to prospectively investigate the safety profile of rivaroxaban in patients with NVAF with renal impairment (creatinine clearance [CrCl], 15–49 mL/min).
Methods:
XARENAL is an observational single-arm cohort study in renal impairment NVAF patients. Patients were followed up approximately every 3 months for 1 year or until 30 days following early discontinuation. The primary endpoint was major bleeding events. All adverse events, symptomatic thromboembolic events, treatment duration, and renal function change from baseline were the secondary endpoints.
Results:
XARENAL included 888 patients from 29 study sites. Overall, 713 (80.3%) had moderate renal impairment (CrCl, 30–49 mL/min), and 175 (19.7%) had severe renal impairment (CrCl, 15–29 mL/min) with a mean estimated glomerular filtration rate (eGFR) of 45.2±13.0 mL/min/1.73 m 2 . The mean risk scores were 3.3±1.4 and 1.7±0.9 for CHA 2 DS 2 -VASc score and HAS-BLED score, respectively. An incidence proportion of 5.6% (6.2 events per 100 patient-years) developed major bleeding; however, fatal bleeding occurred in 0.5% (0.5 events per 100 patient-years). The mean change in the eGFR was 2.22±26.47 mL/min/1.73 m 2 per year.
Conclusions
XARENAL observed no meaningful differences in major bleeding events from other previous findings as well as renal function changes in rivaroxaban-treated NVAF patients with renal impairment, which is considered to be acceptable in clinical practice.
9.YAK577 Attenuates Cardiac Remodeling and Fibrosis in Isoproterenol-Infused Heart Failure Mice by Downregulating MMP12
Hongyan ZHOU ; Hae Jin KEE ; Le WAN ; Yodita ASFAHA ; Fabian FISCHER ; Matthias U KASSACK ; Thomas KURZ ; Seong Hoon KIM ; Seung-Jung KEE ; Young Joon HONG ; Myung Ho JEONG
Korean Circulation Journal 2025;55(3):231-247
Background and Objectives:
Heart failure is a potentially fatal event caused by diverse cardiovascular diseases, leading to high morbidity and mortality. Histone deacetylase (HDAC) inhibitors positively influence cardiac hypertrophy, fibrosis, hypertension, myocardial infarction, and heart failure, causing some side effects. We aimed to investigate the effect of the novel HDAC inhibitor YAK577 on the heart failure mouse model and its underlying mechanism.
Methods:
New hydroxamic acid YAK577 was prepared via methyl-2,3-diphenylpropanoate synthesis using carboxylic acids. We used a micro-osmotic pump, including isoproterenol (ISO; 80 mg/kg/day), to induce a heart failure with reduced ejection fraction. Cardiac hypertrophy was assessed by heart weight to body weight ratio and cross-sectional area.The left ventricular (LV) function was assessed by echocardiography. Fibrosis was evaluated using picrosirius red staining. Overexpression and knockdown experiments were performed to investigate the association between HDAC8 and matrix metalloproteinase 12 (MMP12).
Results:
YAK577 treatment restored ISO-induced reduction in LV fractional shortening and ejection fraction (n=9–11). YAK577 significantly downregulated cardiac hypertrophy marker genes (natriuretic peptide B, NPPB, and myosin heavy chain 7, MYH7) and cardiomyocyte size in vitro but not in vivo. YAK577 ameliorated cardiac fibrosis and fibrosis-related genes in vivo and in vitro. Additionally, YAK577 reduced elevated HDAC8 and MMP12 mRNA and protein expressions in ISO-infused mice, H9c2 cells, and rat neonatal cardiomyocytes.HDAC8 overexpression stimulated MMP12 and NPPB mRNA levels, while HDAC8 knockdown downregulated these genes.
Conclusions
YAK577 acts as a novel heart failure drug through the HDAC8/MMP12 pathway.
10.Clinical Practice Guidelines for Dementia: Recommendations for Cholinesterase Inhibitors and Memantine
Yeshin KIM ; Dong Woo KANG ; Geon Ha KIM ; Ko Woon KIM ; Hee-Jin KIM ; Seunghee NA ; Kee Hyung PARK ; Young Ho PARK ; Gihwan BYEON ; Jeewon SUH ; Joon Hyun SHIN ; YongSoo SHIM ; YoungSoon YANG ; Yoo Hyun UM ; Seong-il OH ; Sheng-Min WANG ; Bora YOON ; Sun Min LEE ; Juyoun LEE ; Jin San LEE ; Jae-Sung LIM ; Young Hee JUNG ; Juhee CHIN ; Hyemin JANG ; Miyoung CHOI ; Yun Jeong HONG ; Hak Young RHEE ; Jae-Won JANG ;
Dementia and Neurocognitive Disorders 2025;24(1):1-23
Background:
and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia.
Methods:
Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.
Results:
Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects.
Conclusions
This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

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