• Proceeding of EDISON Challenge
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• 제6회(2017년)
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• pp.46-53
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• 2017

알츠하이머병은 치매를 유발하는 가장 주된 원인 질환으로 환자들은 인지장애를 겪게 된다. 현재 치료약으로 사용되는 약으로는 acetylcholinesterase 저해재가 있지만 이 약들의 효과는 미비하다. 그래서 인지기능에 영향을 미친다고 알려진 신경전달물질인 GABA, Glutamate, acetylcholine의 수치를 조절 할 수 있는 $5-HT_6$ receptor antagonist가 현재 개발되고 있다. 현재 여러 antagonist들이 임상실험 되었고, 인지 능력향상에 효과를 보이고 있다. 그러나, $5-HT_6$ receptor의 구조가 밝혀지지 않아 아직 원자적 수준의 결합 분석이 이루어지지 않았으므로 이 부분에 대한 연구가 필요하다. 따라서 본 연구에서는 Homology modeling을 통해 receptor의 구조를 예측하고, 현재 임상실험 중인 antagonist들 중 7개를 docking을 통해 단백질과 리간드의 결합을 예측하였다. Edison에서 Galaxy TBM과 Galaxy Refine을 사용하여 Homology modeling 한 결과 GPCR의 전형적인 모델에 특징적으로 긴 cterminal을 가졌다는 것을 확인 할 수 있었다. 생성된 구조를 가지고 Edison의 Dock 프로그램으로 7개의 antagonist가 어떠한 결합을 하는지 분석하였다. 그 결과, binding pose에 공통적으로 Trp102, Asp106, Val107, Pro177, Phe188, Val189, Ala192, Phe284, Phe285, Asn288, Thr306, Tyr310이 관여하는 것을 docking을 통해 알 수 있었다. 특히, Phe285는 7개의 antagonist 중에 4개와의 interaction을 하고 있는 것을 관찰하였다. 이 연구를 통하여 $5-HT_6$에 효과적으로 결합하여 치료효과를 낼 수 있는 신약을 개발할 수 있다.

• Korean Journal of Biological Psychiatry
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• 제21권4호
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• pp.115-117
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• 2014

Variety of biomarkers that are related to the Alzheimer's disease and its diagnosis and progress have been found. However, research lacks in predicting the reaction of the treatment. In addition, there is no definite treatment reaction to the disease but rather it is varied. The purpose of this review article is to study the research of the biomarkers that are able to predict the treatment reaction. There was a research that illustrated a relationship between plasma amyloid ${\beta}$ peptide, cerebrospinal fluid tau, neuroanatomical biomarkers and acetylcholinesterase inhibitors. Polymorphisms in genes of the cholinergic markers AChE, BuChE, ChAT and PON-1 were found to be associated with better clinical response to acetylcholinesterase inhibitors. Many pharmacogenetic studies have been conducted to evaluate the impact of the lipoprotein apolipoprotein E (APOE) genotype on treatment response to acetylcholinesterase inhibitor. However, there is no significant influence of the APOE genotypes on treatment response. Further research is needed to find other predictors of treatment with acetylcholinesterase inhibitors in patients with Alzheimer's disease.

• Journal of the Korean Society of Radiology
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• 제83권3호
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• pp.453-472
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• 2022

Over the past decades, the immense clinical need for early detection methods and treatments for dementia has become a priority worldwide. The advances in PET biomarkers play increasingly important roles in understanding disease mechanisms by demonstrating the protein pathology underlying dementia in the brain. Amyloid-β and tau deposition in PET images are now key diagnostic biomarkers for the Alzheimer's disease continuum. The inclusion of biomarkers in the diagnostic criteria has achieved a paradigm shift in facilitating early differential diagnosis, predicting disease prognosis, and influencing clinical management. Furthermore, in vivo images showing pathology could become prognostic as well as surrogate biomarkers in therapeutic trials. In this review, we focus on recent developments in radiotracers for amyloid-β and tau PET imaging in Alzheimer's disease and other neurodegenerative diseases. Further, we introduce their potential application as future perspectives.

• Korean Journal of Psychosomatic Medicine
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• 제29권1호
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• pp.67-76
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• 2021

Objectives : The aim of this study was to compare activities of daily living (ADLs) according to degenerative changes in brain [i.e., medial temporal lobe atrophy (MTA), white matter hyperintensities] and to examine the association between neurocognitive functions and ADLs in Korean patients with dementia due to Alzheimer's disease (AD) and mild cognitive impairment (MCI). Methods : Participants were 111 elderly subjects diagnosed with AD or MCI in this cross-sectional study. MTA in brain MRI was rated with standardized visual rating scales (Scheltens scale) and the subjects were divided into two groups according to Scheltens scale. ADLs was evaluated with the Korean version of Blessed Dementia Scale-Activity of daily living (BDS-ADL). Neurocognitive function was evaluated with the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease assessment packet (CERAD-K). Independent t-test was performed to compare ADLs with the degree of MTA. Pearson correlation and hierarchical multiple regression analyses were performed to analyze the relationship between ADLs and neurocognitive functions. Results : The group with high severity of the MTA showed significantly higher BDS-ADL scores (p<0.05). The BDS-ADL score showed the strongest correlation with the word list recognition test among sub-items of the CERAD-K test (r=-0.568). Findings from the hierarchical multiple regression analysis revealed that the scores of MMSE-K and word list recognition test were factors that predict ADLs (F=44.611, p<0.001). Conclusions : ADLs of AD and MCI patients had significant association with MTA. Our study, which identifies factors correlated with ADLs can provide useful information in clinical settings. Further evaluation is needed to confirm the association between certain brain structures and ADLs.

• Proceedings of the Korean Society of Computer Information Conference
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• 한국컴퓨터정보학회 2015년도 제52차 하계학술대회논문집 23권2호
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• pp.337-338
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• 2015

본 연구는 알츠하이머 관련 의료웹포럼을 장기적으로 사용한 사람의 사회연결망 영향력 사이의 관계를 살펴보았다. 빈도분석결과 알츠하이머 병의 의료웹포럼을 2개월 이하로 사용한 유저가 전체의 76%에 해당함을 발견하였다. 사회연결망분석을 통해 장기적으로 사용한 고객들이 연결중심성이 높은 그룹임을 확인하였고, 상관성분석 결과 연결중심성과 이용기간과의 유의한 상관성을 발견하였다. 이와 같은 결과를 통해 향후 의료 웹포럼을 활성화 시키기 위한 전략수립을 위한 기초자료를 제공하고자 하였다.

• Journal of the Korea Convergence Society
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• 제11권12호
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• pp.383-390
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• 2020

The present study was conducted to examine the differences and correlations between verbal fluency and story comprehension according to the working memory(WM) capacity, and to find out what WM factors influence the linguistic competence in Alzheimer's disease(AD) and vascular dementia(VaD) groups each consisting of 15 patients. The results of their performance produced firstly significant differences in phonemic fluency, story comprehension, delayed recall and recognition task between the two groups. Further analysis shows that VaD group had significant correlations between the scores of story comprehension and the recognition test scores additionally. These findings suggest that it is possible to differentiate the two groups even by story comprehension tasks and WM. In conclusion, the clinical application of the results is likely to contribute to appropriate treatment plans and effective interventions for elderly with AD and VaD as well as to improve the classification criteria for both types of dementia.

• Investigative Magnetic Resonance Imaging
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• 제16권2호
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• pp.115-123
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• 2012

Purpose : To evaluate white matter abnormalities on diffusion tensor imaging (DTI) in patients with mild Alzheimer disease (AD) and mild cognitive impairment (MCI), using tract-based spatial statistics (TBSS) and voxel-based morphometry (VBM). Materials and Methods: DTI was performed in 21 patients with mild AD, in 13 with MCI and in 16 old healthy subjects. A fractional anisotropy (FA) map was generated for each participant and processed for voxel-based comparisons among the three groups using TBSS. For comparison, DTI data was processed using the VBM method, also. Results: TBSS showed that FA was significantly lower in the AD than in the old healthy group in the bilateral anterior and right posterior corona radiata, the posterior thalamic radiation, the right superior longitudinal fasciculus, the body of the corpus callosum, and the right precuneus gyrus. VBM identified additional areas of reduced FA, including both uncinates, the left parahippocampal white matter, and the right cingulum. There were no significant differences in FA between the AD and MCI groups, or between the MCI and old healthy groups. Conclusion: TBSS showed multifocal abnormalities in white matter integrity in patients with AD compared with old healthy group. VBM could detect more white matter lesions than TBSS, but with increased artifacts.

• Journal of Life Science
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• 제29권6호
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• pp.747-753
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• 2019

Cognitive decline is characterized by reduced long-/short-term memory and attention span, and increased depression and anxiety. Such decline is associated with various degenerative brain disorders, especially Alzheimer's disease (AD) and Parkinson's disease (PD). The increases in elderly populations suffering from cognitive decline create social problems and impose economic burdens, and also pose safety threats; all of these problems have been extensively researched over the past several decades. Possible causes of cognitive decline include metabolic and hormone imbalance, infection, medication abuse, and neuronal changes associated with aging. However, no treatment for cognitive decline is available. In neurodegenerative diseases, changes in the gut microbiota and gut metabolites can alter molecular expression and neurobehavioral symptoms. Changes in the gut microbiota affect memory loss in AD via the downregulation of NMDA receptor expression and increased glutamate levels. Furthermore, the use of probiotics resulted in neurological improvement in an AD model. PD and gut microbiota dysbiosis are linked directly. This interrelationship affected the development of constipation, a secondary symptom in PD. In a PD model, the administration of probiotics prevented neuron death by increasing butyrate levels. Dysfunction of the blood-brain barrier (BBB) has been identified in AD and PD. Increased BBB permeability is also associated with gut microbiota dysbiosis, which led to the destruction of microtubules via systemic inflammation. Notably, metabolites of the gut microbiota may trigger either the development or attenuation of neurodegenerative disease. Here, we discuss the correlation between cognitive decline and the gut microbiota.

• Proceedings of the Korea Information Processing Society Conference
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• 한국정보처리학회 2014년도 춘계학술발표대회
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• pp.753-756
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• 2014

파킨슨병은 도파민계 신경이 파괴되는 질병으로 알츠하이머병과 함께 대표적인 퇴행성 뇌 질환으로 병의 진행을 완화시킬 수 있는 치료법이 존재하기 때문에 병의 진단이 굉장히 중요하다. 파킨슨병을 진단하기 위한 과거의 연구는 대부분 단일 생체지표를 이용하는 것이었지만 이러한 방법에는 한계성이 존재한다. 따라서 본 연구에서는 생화학적 생체지표인 뇌척수액 내의 ${\alpha}-synuclein$ 단백질 수치와 영상학적 생체지표인 확산 텐서 영상의 여러 모수들을 결합한 융합 생체지표를 특징으로 사용하는 파킨슨병 진단 모델을 개발하고 성능을 평가하였다. 10-fold cross validation 에서 모든 성능지표에 대해 최고 100%를 보였으며, cross validation 의 과적합을 감안하더라도 파킨슨병의 조기진단에 유용하게 사용될 수 있는 가능성을 제시하였다.

• Korean Journal of Psychosomatic Medicine
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• 제21권1호
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• pp.55-61
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• 2013

Objectives : Alzheimer's disease(AD) and mild cognitive impairment(MCI) affect several nervous structures involved with the autonomic nervous system. Association between neuropsychiatric deficits and heart rate variability has been observed. But cardiac autonomic function in AD has been scarcely studied and the results reported are conflicting. We investigated autonomic function in normal control, MCI, AD using heart rate variability(HRV) technique. Methods : Time and frequency-domain variability of 5-min R-R interval series was comparatively evaluated in 26 normal control subjects, 22 MCI subjects and 34 AD subjects. Analysis of variance(ANOVA) was used to compare the differences across groups. Correlations between MMSE-KC and HRV components were performed using Pearson's correlation coefficient. Results : No significant difference was observed among the groups in time, frequency-domain analysis of HRV(p>0.05). HRV were not found to be significantly correlated with the degree of cognitive impairment. Conclusions : There were no differences in HRV with MCI, AD subjects when compared with normal controls. Further investigation is required to use HRV technique as noninvasive parameters of MCI and AD.