• Dementia and Neurocognitive Disorders
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• v.22 no.3
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• pp.100-108
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• 2023

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-to-severe 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.

• Korean Journal of Adult Nursing
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• v.21 no.3
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• pp.339-348
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• 2009

Purpose: We aimed to describe and compare the cognitive function, anxiety, and quality of life for the demented elderly in day care centers or nursing homes. Methods: We selected 44 subjects from day care centers and 63 subjects from nursing homes by performing convenience sampling. The Korean version of Mini Mental Status Examination was used for measuring cognitive status; Rating Anxiety in Dementia, for assessing anxiety; Korean Version of Quality of Life-Alzheimer's Disease, for assessing the quality of life. The data were collected from May to June 2008 and analyzed by SPSS/WIN 14.0. Results: 1) The cognitive function of the subjects in the day care center was higher than that of the subjects in the nursing home. Anxiety in the subjects in the nursing home was higher than that in the subjects in the day care center. 2) The cognitive function and quality of life of the subjects in the day care center showed statistically significant correlation, 3) The anxiety and quality of life of the subjects in the nursing home showed statistically significant correlation. Conclusions: Nursing interventions that improve the quality of life of the demented elderly should be considered and applied according to the degree of cognitive function and anxiety.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.374-380
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• 2000

Propentofylline (PPF, 3-methyl-1-(5-oxohexyl)-7-propylxanthine) has been reported to be a compound for treatment of both vascular dementia and dementia of the Alzheimer type. The short half-life (about 15 min) of PPF at the terminal elimination phase and poor bioavailability after oral administration of PPF to rabbits (Kim et al., 1992) suggest in part that this drug takes the extensive first-pass metabolism in the liver. In addition, the metabolic pathway for PPF remains unclear. The objective of this experiment is to identify urinary metabolites of PPF in rats. For the identification of the metabolites, rat urine was collected after oral administration of 100${m}g/kg$ PPF. PPF metabolite, 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine, was synthesized and confirmed by gas chromatography/mass spectroscopy (GC/MS) and $^1H$ nuclear magnetic resonance spectroscopy. The urinary metabolites of PPF were extracted with diethyl ether and identified by electron impact and chemical ionization GC/MS. One urinary metabolite was confirmed to be 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine by synthesized authentic compound. Several metabolites of monohydroxy- and dihydroxy-PPF were identified based on mass fragmentation of both intact and trimethylsilylated derivatives of PPF metabolites and the novel structure of these metabolites is suggested based on mass spectra.

• Annals of Clinical Neurophysiology
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• v.22 no.2
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• pp.82-91
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• 2020

Electroencephalography (EEG) produces time-series data of neural oscillations in the brain, and is one of the most commonly used methods for investigating both normal brain functions and brain disorders. Quantitative EEG analysis enables identification of frequencies and brain activity that are activated or impaired. With studies on the structural and functional networks of the brain, the concept of the brain as a complex network has been fundamental to understand normal brain functions and the pathophysiology of various neurological disorders. Functional connectivity is a measure of neural synchrony in the brain network that refers to the statistical interdependency between neural oscillations over time. In this review, we first discuss the basic methods of EEG analysis, including preprocessing, spectral analysis, and functional-connectivity and graph-theory measures. We then review previous EEG studies of brain network characterization in several neurological disorders, including epilepsy, Alzheimer's disease, dementia with Lewy bodies, and idiopathic rapid eye movement sleep behavior disorder. Identifying the EEG-based network characteristics might improve the understanding of disease processes and aid the development of novel therapeutic approaches for various neurological disorders.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.303-310
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• 2002

Ancient Korean physicians have used several oriental herbs to cure dementia and these effects were described in the Korean herbal books. Some cognitive-enhancing oriental herbs have been widely used as a herbal medicine against dementia. However, few of studies have proved their efficacy in treatment for dementia. In the present study, we investigated the effects of herbal compounds, which are mainly consisted of Uncaria sinensis, Corydalis yanhusuo and Acorus gramineus on learning and memory in Mortis water maze task and the central cholinergic system of the rats with neurotoxic medial septum lesion. In water maze test, the animals were trained to find a platform in a fixed position during 6 days and then received a 60-s probe trial in which the platform was removed from the pool on the 7th day. Ibotanic and 192 saporin lesion of the medial septum (MS) impaired the performance of maze test and degenerated choline acetyltransferase (ChAT) in the brain, which is a marker of the central cholinergic system. Daily administrations of herbal medicine (100mg/kg, p.o.) for 21 consecutive days produced significant reversals of the neurotoxic-induced deficit in learning and memory. These treatments also reduced the loss of cholinergic immunoreactive neurons in the brain induced by neurotoxin. These results demonstrated that herbal compounds ameliorated learning and memory deficits through effects on the central nervous system, partly through effect on the acetylcholine system. Our studies suggest an evidence of these herbs as treatment of Alzheimer's disease.

• Journal of Korea Multimedia Society
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• v.21 no.2
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• pp.147-157
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• 2018

Alzheimer's disease has the significant factors for the both specific and characteristic features according to the disease progressing that are the volumetry and surface area by the brain hippocampus shrinking and thinning. However, we have suggested a shape analysis to calculate the variance by the roughness, coarseness or uneven surface on 3D MR images. For the reasons we have presented two methods: the first method is the distance calculation from major axis to edge points and the second method is the distance calculation from centroidal point to edge points on a coronal plane. Then we selected the shortest distance and the longest distance in each slice and analyzed the ANOVA and average distances. Consequently we obtained the available and great results by the longest distance of the axial and centroidal point. The results of average distances were 44.85(AD), 45.04(MCI) and 49.31(NC) from the axial points and 39.30(AD), 39.58(MCI) and 44.78(NC) from centroidal points respectively. Finally the distance variations for the easily recognized visualization were shown by the color mapping. This research could be provided an indicator of biomarkers that make diagnosis and prognosis the Alzheimer's diseases in the future.

• Journal of Korea Multimedia Society
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• v.23 no.8
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• pp.940-952
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• 2020

The Alzheimer's disease (AD) is a neurodegenerative disease commonly found in the elderly individuals. It is one of the most common forms of dementia; patients with AD suffer from a degradation of cognitive abilities over time. To correctly diagnose AD, compuated-aided system equipped with automatic classification algorithm is of great importance. In this paper, we propose a novel deep learning based classification algorithm that takes advantage of MRI biomarker images including brain areas of hippocampus and cerebrospinal fluid for the purpose of improving the AD classification performance. In particular, we develop a new approach that effectively applies MRI biomarker patch images as input to 3D Deep Convolution Neural Network. To integrate multiple classification results from multiple biomarker patch images, we proposed the effective confidence score fusion that combine classification scores generated from soft-max layer. Experimental results show that AD classification performance can be considerably enhanced by using our proposed approach. Compared to the conventional AD classification approach relying on entire MRI input, our proposed method can improve AD classification performance of up to 10.57% thanks to using biomarker patch images. Moreover, the proposed method can attain better or comparable AD classification performances, compared to state-of-the-art methods.

• Journal of Preventive Medicine and Public Health
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• v.49 no.2
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• pp.134-138
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• 2016

Objectives: Season of birth, an exogenous indicator of early life environment, has been related to higher risk of adverse psychiatric outcomes but the findings for Alzheimer's disease (AD) have been inconsistent. We investigated whether the month or season of birth are associated with AD. Methods: A nationwide nested case-control study including all community-dwellers with clinically verified AD diagnosed in 2005 to 2012 (n=70 719) and up to four age- sex- and region of residence-matched controls (n=282 862) residing in Finland. Associations between month and season of birth and AD were studied with conditional logistic regression. Results: Month of birth was not associated with AD (p=0.09). No strong associations were observed with season (p=0.13), although in comparison to winter births (December-February) summer births (June-August) were associated with higher odds of AD (odds ratio, 1.03; 95% confidence interval, 1.00 to 1.05). However, the absolute difference in prevalence in winter births was only 0.5% (prevalence of those born in winter were 31.7% and 32.2% for cases and controls, respectively). Conclusions: Although our findings do not support the hypothesis that season of birth is related to AD/dementia risk, they do not invalidate the developmental origins of health and disease hypothesis in late-life cognition. It is possible that season does not adequately capture the early life circumstances, or that other (postnatal) risk factors such as lifestyle or socioeconomic factors overrule the impact of prenatal and perinatal factors.

• Herbal Formula Science
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• v.13 no.1
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• pp.103-121
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• 2005

Alzheimer's disease(AD) is a geriatric dementia that is widespread in old age. In the near future AD will be the biggest problem in public health service. It has been widely believed that $A{\beta}$ peptide devided from APP causes apoptotic neurotoxicity in AD brain. However, recent evidence suggests that n99 may be an important factor causing neurotoxicity in AD. Mouse Neuro 2A cells expressed with CT99 exhibited remarkable apoptotic cell damage. We invesgated the protective effects of Ikgiansintang water extract(IGA). Findings from our experiment have shown that IGA inhibits the activities of CT99, which has neurotoxicities and apoptotic activities in cell line. In addition treatment of IGA($50{\mu}g/ml$ for 24 hours) partially prevented CT99-induced cytotoxicity in Neuro 2A cells. As the result of this study, In IGA group, the apoptosis in the nervous system is inhibited, the repair against the degerneration of Neuro 2A cells by n99 expression is promoted. Base on these findings, IGA may be beneficial for the treatment of AD.

• Proceeding of EDISON Challenge
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• 2015.03a
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• pp.14-23
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• 2015

Alzheimer's disease is one of the most common types of degenerative dementia. As a considerable cause of Alzheimer's disease, neurotoxic plaques composed of 39 to 42 residue-long amyloid beta($A{\beta}$) fibrils have been found in the patient's brain in large quantity. A previous study found that erythrosine B (ER), a red color food dye approved by FDA, inhibits the formation of amyloid beta fibril structures. Here, in an attempt to elucidate the inhibition mechanism, we performed molecular dynamics simulations to demonstrate the conformational change of $A{\beta}40$ induced by 2 ERs in atomistic detail. During the simulation, the ERs bound to the surfaces of both N-terminus and C-terminus regions of $A{\beta}40$ rapidly. The observed stacking of the ERs and the aromatic side chains near the N-terminus region suggests a possible inhibition mechanism in which disturbing the inter-chain stacking of PHEs destabilizes beta-sheet enriched in amyloid beta fibrils. The bound ERs block water molecules and thereby help stabilizing alpha helical structure at the main chain of C-terminus and interrupt the formation of the salt-bridge ASP23-LYS28 at the same time. Our findings can help better understanding of the current and upcoming treatment studies for Alzheimer's disease by suggesting inhibition mechanism of ER on the conformational transition of $A{\beta}40$ at the molecular level.