Sun Min Lee

Background and ObjectivesMild cognitive impairment (MCI) is a high-risk stage for progression to dementia. The SUPERBRAIN-MEET trial previously demonstrated cognitive benefits of a multidomain life...

Ha HJ, et al. Dement Neurocogn Disord. 2026 Oct;25(4):210-227. https://doi.org/10.12779/dnd.2026.25.4.210

Kim DA, et al. J Clin Neurol. 2026 ;22:e43. https://doi.org/10.3988/jcn.2025.0635

Background and Purpose: Given the irreversible nature of dementia, this study examined the effects of a 20-week exercise-based dementia prevention program in community-dwelling older adults, focusing on prior exercise experience and program adherence. Methods: In this exploratory, non-randomized trial, 55 older adults (65-79 years) were allocated to an intervention (n=26) or control (n=29) group, and blinding was not feasible. The intervention comprised supervised rhythmic aerobic exercise with cognitive-motor components performed three times per week. Cognition was the primary outcome, and secondary outcomes included physical fitness, blood pressure, and blood biomarkers. Subgroup analyses classified participants by prior exercise experience and intervention exposure: G1 and G2 comprised control subgroups with no intervention exposure, whereas G3 and G4 comprised intervention-exposed subgroups stratified by adherence. Results: No significant group-by-time interactions were observed for cognitive outcomes. Participants with prior exercise experience and low adherence (G2) showed significant improvement on the Korean Mini-Mental State Examination (β=1.66, p=0.024) despite declines in physical fitness, whereas higher adherence in G3-G4 was associated with stable or favorable physical performance, with G4 showing a positive trend in the 30-second sit-tostand test. Systolic blood pressure decreased significantly in G2-G4. Conclusions: Although overall cognitive gains were modest and not group specific, prior exercise experience and sustained adherence were associated with favorable changes in physical fitness and vascular outcomes, suggesting that tailored multicomponent exercise programs and long-term engagement may help promote cognitive health in older adults.

Background and Purpose: Tailored physical exercise interventions have the potential to promote cognitive health in older adults and offer significant advantages for those more vulnerable to decline. The specific relationship between physical fitness and cognition among the elderly has not been clearly established. The purpose of this investigation was to assess the relationship between physical fitness and cognitive function in older Korean adults. Methods: Eighty-four community-dwelling older adults (mean age: 70.7±5.3 years; 81.0% female) completed a standardized physical fitness battery assessing handgrip strength, sit-and-reach, 30-second sit-to-stand, 2-minute stationary march, 3-m sit-walk-and-return, figure-8-walk, and T-wall response time. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Descriptive statistics, partial correlation analyses, and stepwise multiple linear regression were conducted. Results: Slower T-wall response time was significantly correlated with lower RBANS total index, immediate memory, and delayed memory scores. In regression models, slower T-wall response time was independently associated with lower RBANS total index (β=-0.234, p=0.026) and delayed memory scores (β=-0.295, p=0.029). The regression model for immediate memory was not statistically significant overall; therefore, no predictive conclusion was drawn for this domain. Higher education showed a significant positive association with cognitive performance. Conclusions: Coordination, as measured by T-wall response time, emerged as the only physical fitness component consistently associated with cognitive performance in older

Young Joon Cho, Sunwoo Yoon, Yeojin Kim, Ho Min Song, You Jin Nam, Sang Hyuk Lee, Sehee Lee, Donghyuk Shin, Sun Min Lee, So Young Moon, Eun-Joo Kim, Soo Hyun Cho, Byeong C. Kim, Seong Hye Choi, Sang Won Seo, Jin Cheol Kim, Young Joon Park, Hee Young Kang, Sang-Rae Lee, Sunhwa Hong, Sang Joon Son, Chang Hyung Hong, Hyun Woong Roh. Clin Psychopharmacol Neurosci -0001;0:. https://doi.org/10.9758/cpn.25.1360

Objective Numerous studies have identified various risk factors associated with Alzheimer’s disease (AD). However, the experimental limitations of disease modeling make it challenging to directly interpret their effects. These limitations include constraints of postmortem samples, animal experiments, and challenges associated with brain tissue studies. Ex vivo experiments effectively address these issues by enabling patient-specific identification and highlighting potential biomarkers. This study aimed to characterize the transcriptional profile of fibroblasts derived from patients with AD in response to endoplasmic reticulum (ER) stress and propose potential biomarkers.Methods We utilized an ex vivo platform to identify genes differentially responsive to ER stress. The transcriptional feature of fibroblasts in both healthy controls (n=22) and patients with AD (n=20) was analyzed using bulk RNA sequencing. The cytotoxicity of the selected target gene was evaluated through knockdown experiments.Results A total of 468 differentially expressed genes (DEGs) were identified. Gene ontology and pathway enrichment analysis revealed that 210 DEGs, which were less responsive in AD, are involved in lipid-related terms and pathways. By narrowing down AD-related genes, we identified 49 highly reliable AD-associated genes. The most significant gene, DCTN2, exhibited a fold change that positively correlated with cognitive function and negatively correlated with blood-based biomarkers (pTau217, amyloid beta 42/40 ratio), aligning with the amyloid/Tau/neurodegeneration research criteria for AD. Additionally, the knockdown of DCTN2 in glial cell lines resulted in increased cell toxicity and apoptosis.Conclusion Identifying differentially responsive genes in ex vivo experiments not only provides insights into the pathology of AD but also offers potential biomarkers for disease diagnosis.

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.

Background: The adoption of Alzheimer's disease (AD) biomarkers in clinical practice is expected to increase following recent approval of disease-modifying therapies. Fully automated immunoassays, Elecsys platform, offer convenience and enhanced reliability. Objective: This study was performed to evaluate the performance of the Elecsys assay in a Korean clinical setting, comparing its effectiveness to ELISA for detecting amyloid-PET positivity. Methods: Cerebrospinal fluid (CSF) Aβ ₄₂ , pTau ₁₈₁ , tTau, pTau ₁₈₁ /Aβ ₄₂ , and tTau/Aβ ₄₂ were evaluated using Elecsys kits on a Cobas e 411 analyzer and manual Innotest ELISA with paired frozen samples ( n = 118) from subjects with cognitive status ranging from unimpaired to mild cognitive impairment and dementia. Results: Strong linear correlations were observed between Elecsys- and ELISA-measured Aβ ₄₂ , pTau ₁₈₁ , and tTau levels. Receiver operating characteristic-based cutoff points for pTau ₁₈₁ /Aβ ₄₂ (0.0252) and tTau/Aβ ₄₂ (0.258) in Elecsys demonstrated the highest areas under the curve (0.97 and 0.96) and predictive values (96.6% for both) for detecting amyloid-PET abnormalities. No cases of abnormal amyloid PET status were found without concurrent abnormal CSF biomarkers when considering Elecsys Aβ ₄₂ and the pTau ₁₈₁ /Aβ ₄₂ ratio simultaneously. In addition, previously established cutoffs for combined ratios effectively differentiated amyloid PET status in our samples. Conclusions: This study demonstrated the utility of Elecsys-measured CSF AD biomarkers in agreement with amyloid-PET classification in the Korean population. The pTau ₁₈₁ /Aβ ₄₂ and tTau/Aβ ₄₂ ratios were the most accurate in detecting amyloid-PET (+), with Elecsys showing higher accuracy than ELISA. The study also supported the applicability of common cutoffs from Western countries for these biomarkers in our samples.

Kim Y, et al. Dement Neurocogn Disord. 2025 Jan;24(1):1-23. https://doi.org/10.12779/dnd.2025.24.1.1