• Title/Summary/Keyword: Alzheimer dementia

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Plant Phenolics as ${\beta}$-Secretase (BACE1) Inhibitors

  • Jun, Mi-Ra;Lee, Seung-Ho;Choi, Sun-Ha;Bae, Ki-Hwan;Seong, Yeon-Hee;Lee, Kyung-Bok;Song, Kyung-Sik
    • Food Science and Biotechnology
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    • v.15 no.4
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    • pp.617-624
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    • 2006
  • Various plant phenolics were assessed for (${\beta}$-secretase (BACE1) inhibitory activity in order to screen for anti-dementia agents. Among 39 phenolics, eight compounds, 1,2,3-trigalloyl glucopyranoside, acetonyl geraniin, euphorscopin, furosine, helioscopinin A, helioscopinin B, jolkinin, and rugosin E exhibited strong inhibition of BACE1 with $IC_{50}$ values of $5.87{\times}10^{-8}-54.93{\times}10^{-6}\;M$. Among them, rugosin E was the most potent ($IC_{50}$ $5.87{\times}10^{-8}\;M$). The active compounds were shown to be non-competitive inhibitors by Dixon plot. All the phenolic BACE1 inhibitors except furosin also suppressed prolyl endopeptidase (PEP) activity. However, these phenolic compounds caused less inhibition of ${\alpha}$-secretase (tumor necrosis factor a converting enzyme; TACE) and no significant inhibition of other serine proteases such as trypsin, chymotrypsin, and elastase was seen, demonstrating that they are relatively specific to both BACE1 and PEP. No significant structure-activity relationships were found.

Effect of Water and Ethanol Extracts Codonopsis lanceolata on Spatial Learning and Memory in Mice (더덕 물 추출물과 에탄올 추출물의 인지능 개선 활성 비교)

  • Weon, Jin Bae;Lee, Jiwoo;Eom, Min Rye;Jung, Youn Sik;Ko, Hyun-Jeong;Lee, Hyeon Yong;Park, Dong-Sik;Chung, Hee-Chul;Chung, Jae Youn;Ma, Choong Je
    • YAKHAK HOEJI
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    • v.58 no.5
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    • pp.287-293
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    • 2014
  • Alzheimer's disease (AD), most common form of dementia is characterized that memory deficit and loss of cognitive function. This study was evaluated cognitive enhancing effect of water and ethanol extracts of Codonopsis lanceolata and compared using Morris water maze and passive avoidance test. The water and 70% ethanol extracts (100, 300 and 500 mg/kg) were administered to mice. The neuroprotective effect on glutamate-induced cell death in HT22 cells was additionally investigated using MTT assay. Results showed 70% ethanol extract of Codonopsis lanceolata enhanced cognitive function than water extract, as shown by decrease in escape latency time in Morris water maze test. In passive avoidance test, 70% ethanol extract also increased the latency time compared to the water extract. Furthermore, 70% ethanol extract significantly protected neuronal cell against glutamate cytotoxicity and showed higher than neuroprotective effect of water extract. These results indicate that 70% ethanol extract more improve spatial cognitive ability and protected neuronal cells than water extract.

[ $\beta$ ]-Secretase (BACE1) Inhibitors from Pomegranate (Punica granatum) Husk

  • Kwak Hye-Min;Jeon So-Young;Sohng Bang-Ho;Kim Jong-Guk;Lee Jin-Man;Lee Kyung-Bok;Jeong Hyun­Hee;Hur Jong-Moon;Kang Young-Hwa;Song Kyung-Sik
    • Archives of Pharmacal Research
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    • v.28 no.12
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    • pp.1328-1332
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    • 2005
  • In the course of screening for anti-dementia agents from natural products, two $\beta$-secretase (BACE1) inhibitors were isolated from the husk of pomegranate (Punica granatum) by activity-guided purification. They were identified as ellagic acid and punicalagin with $IC_{50}$ values of 3.9 $\times$$10^{-6}$ and 4.1$\times$$10^{-7}$ M and Ki values of 2.4$\times$$10^{-5}$and 5.9$\times$$10^{-7}$ M, respectively. The compounds were non-competitive inhibitors with a substrate in the Dixon plot. Ellagic acid and punicalagin were less inhibitory to $\alpha$-secretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, thus indicating that they were relatively specific inhibitors of BACE1.

Analysis of EEG Signals for Attention Training Game Contents (주의력 훈련 게임 콘텐츠에 대한 EEG 신호 분석)

  • Kang, Sung-Ho;Park, Jung-Hyun;Shin, Sung-Wook;Chung, Sung-Taek
    • The Journal of the Institute of Internet, Broadcasting and Communication
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    • v.19 no.3
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    • pp.83-90
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    • 2019
  • Recently, the need to prevent or treat cognitive impairment in older adults has been arising. In particular, they tried to diagnose MCI as an early stage of Alzheimer's disease and to delay the progression to dementia through training cognitive function. Most of cognitive function training have been manufactured to game contents which related to several cognitive function, and it needs to be verified quantitatively whether subjects are paying attention to cognitive function training. Thus in this study, we measured and analyzed EEG signals while performing attention training game contents. As an analysis method, we utilized CI, which shows how much they are focusing on, and RI, which shows how stable they are. The result of this study can be seen that all the subjects' CI were increased, which means that the subjects performed game contents with concentration.

Cognitive-based Intervention for the Older Adults with Mild Cognitive Impairment: A Literature Review (경도인지장애 노인에게 적용된 인지기반 중재연구의 분석적 고찰)

  • Lim, Se-Hyun
    • Journal of the Korea Convergence Society
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    • v.12 no.2
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    • pp.327-336
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    • 2021
  • It is important to prevent progression of mild cognitive impairment (MCI) to Alzheimer's disease or other dementia. This study was conducted to investigate cognitive-based intervention and its effectiveness for the older patients with MCI through systematic review. Data search was conducted in September 2020, using the Korea Research Information Service (Riss) and KoreaMed. After selection of literatures according to the predefined inclusion criteria, a total of 12 articles were included. It is revealed that the cognitive-based intervention for the older adults with MCI was found to have a positive effect on the various factors including cognitive function, depression, physical health status, quality of life, and communication. However, it is difficult to draw a definite conclusion due to the various intervention strategies and instruments used. Thus, based on the results of this study, we suggest more studies to verify the effectiveness of such programs.

A Study on the Combination Effect of Herbal Medicine and Western Medicine on BPSD in Patients with Alzheimer's Disease: A Systematic Review (알츠하이머병 환자의 이상행동심리증상(BPSD)에 대한 한약과 양약의 병용 효과에 대한 연구: 체계적 문헌 고찰)

  • Kim, Man-Gi;Chang, Seok-Joo;Hong, Min-Ho;Kim, Geun-Woo;Koo, Byung-Soo
    • Journal of Oriental Neuropsychiatry
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    • v.31 no.4
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    • pp.301-314
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    • 2020
  • Objectives: The purpose of this study was to provide clinical evidence to support the use of herbal medicine combined with western medicine for BPSD. Methods: Studies were identified by searching CNKI, Pubmed, EMBASE, Cochrane Library, SCIENCEON, RISS, KMbase, KISS, OASIS. Literature searches of Chinese, English, and Korean databases were performed. Two authors independently extracted the data and evaluated the quality of each study. Results: The literature search identified 203 articles. Of these, 7 were selected for the analysis. The risk of bias in most studies was unclear. The most frequently used diagnostic tools were the NINCDS-ADRDA and DSM-IV. The most commonly used results indicator was NPI. In 6 of the 7 papers, combination treatment (herbal & Western medicine) was statistically significantly more effective than single treatment (Western medicine alone) for BPSD. No significant adverse events were reported. Conclusions: Herbal medicine in combination with Western medicine is more effective for treating BPSD than Western medicine alone. However, the quality of the studies used in this study was uncertain and the sample size was too small. Based on the findings of this study, more high-quality clinical trials are needed to confirm the efficacy of combination treatment.

Awareness on expiration date of repackaged prescription medications and pulverization of solid pills: A questionnaire study (소분조제된 처방약의 사용기한과 성인 산제조제에 대한 인식)

  • Kim, So Yeon;Choi, Yeo Jin;Sohn, Hyun Soon
    • Korean Journal of Clinical Pharmacy
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    • v.31 no.2
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    • pp.96-103
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    • 2021
  • Background: The number of elderly people with comorbidities who experience dysphagia associated with geriatric disorders, such as stroke, Parkinson's disease, and Alzheimer's dementia, is increasing. Consequently, the demand for long-term prescriptions of powdered medications is expected to rise. Most patients procure repackaged prescription medications from pharmacies; however, the guidelines regarding their expiration dates are unclear. Objectives: The aim of this study was to assess awareness among adults regarding the expiration dates and drug stability issues associated with repackaged prescription medications, including powdered medications. Methods: A questionnaire with 16 components was designed and distributed online (August 1-September 1, 2019) to adults aged 19 years or older. Statistical analyses, including descriptive analysis and chi-square test, were conducted on the obtained data. A p-value <0.05 was considered significant. Results: Data from 254 respondents were analyzed; 191 (75.20%) respondents worked in non-healthcare-related fields. A significant number of healthcare workers recognized the stability issues associated with powdered medications (p<0.001). However, a large proportion of healthcare workers were not aware of the expiration dates (p>0.05). Conclusions: More than half of the total respondents, including healthcare workers, were not familiar with the appropriate expiration dates of repackaged prescription medications. The establishment of evidence-based guidelines regarding drug expiration dates and the dissemination of awareness among patients are required. Furthermore, clinical practices including repackaging or pulverizing medications for long-term prescriptions should be avoided owing to the associated drug stability issues.

Recent clinical trials with ultrasound induced blood-brain barrier opening (초음파 기반 혈뇌장벽 개방에 관한 최신 임상시험 연구 현황)

  • Park, Juyoung
    • The Journal of the Acoustical Society of Korea
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    • v.41 no.5
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    • pp.564-569
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    • 2022
  • Blood-Brain Barrier (BBB) is the brain protecting system blocking the inflow of harmful substances into brain parenchyma from brain blood vessel. However, the BBB has a negative effect on the treatment of various brain diseases such as Alzheimer's dementia or brain tumors because it also prevents drug delivery into brain parenchyma. To overcome this problem, a brain drug delivery technique using Focused Ultrasound (FUS) which allows BBB to be temporarily opened by inducing the acoustic cavitation effect of microbubbles has been developed. Thus far, various studies using the FUS technique has been conducted to improve drug delivery efficiency, and therefore, this paper discusses recently developed drug delivery technologies using the FUS-induced BBB opening.

The Effect of Treadmill Exercise on Tau Hyperphosphorylayion in an Aged Transgenic Mouse Model of Taupathies

  • Wang, Seong-Hwan;Kang, Eun-Bum;Kwon, In-Su;Koo, Jung-Hoon;Shin, Kwang-O;Jang, Yong-Chul;Um, Hyun-Sub;Oh, Yoo-Sung;Kim, Chul-Hyun;Cho, In-Ho;Cho, Joon-Yong
    • Korean Journal of Exercise Nutrition
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    • v.16 no.2
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    • pp.93-100
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    • 2012
  • Alzheimer's disease (AD) is the most common cause of dementia in adults. Microtubule associated protein tau is abnormally phosphorylated in AD and aggregates as paired helical filaments (PHFs) in neurofibrillary tangles (NFTs). NFTs are the most common intraneuronal inclusion in the brains of patients with AD and have been implicated in mediating neuronal cell death and cognitive deficit. Aberrant phosphorylation of tau is an early pathological event in AD, but the underlying mechanisms are unclear. MAP kinases are a family of Serine/Threonine (Ser/Thr) kinases that involved hyper - phosphorylation of tau in AD. The purpose of this study was to investigate the effect of treadmill exercise on phosphorylation of tau level and activation of MAPKs including JNK, ERK, p38-MAPK. To address this, Tg mouse model of AD, Tg-NSE/hTau 23, which expresses human tau 23 in the brain, was chosen. Animals were subjected to treadmill exercise for 12 weeks from 24 months of age. Treadmill exercise in Tg group improved cognitive function compared with Tg-SED group in watermaze test. In addition, treadmill exercised Tg mice significantly reduced the activation of JNK54/46, p38-MAPK and tau (Ser404, Ser202, Thr231), and increased activation of ERK44/42 in cerebral cortex. These results suggest that treadmill exercise may provide a therapeutic potential to alleviate the tau pathology like AD.

Cortical Iron Accumulation as an Imaging Marker for Neurodegeneration in Clinical Cognitive Impairment Spectrum: A Quantitative Susceptibility Mapping Study

  • Hyeong Woo Kim;Subin Lee;Jin Ho Yang;Yeonsil Moon;Jongho Lee;Won-Jin Moon
    • Korean Journal of Radiology
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    • v.24 no.11
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    • pp.1131-1141
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    • 2023
  • Objective: Cortical iron deposition has recently been shown to occur in Alzheimer's disease (AD). In this study, we aimed to evaluate how cortical gray matter iron, measured using quantitative susceptibility mapping (QSM), differs in the clinical cognitive impairment spectrum. Materials and Methods: This retrospective study evaluated 73 participants (mean age ± standard deviation, 66.7 ± 7.6 years; 52 females and 21 males) with normal cognition (NC), 158 patients with mild cognitive impairment (MCI), and 48 patients with AD dementia. The participants underwent brain magnetic resonance imaging using a three-dimensional multi-dynamic multi-echo sequence on a 3-T scanner. We employed a deep neural network (QSMnet+) and used automatic segmentation software based on FreeSurfer v6.0 to extract anatomical labels and volumes of interest in the cortex. We used analysis of covariance to investigate the differences in susceptibility among the clinical diagnostic groups in each brain region. Multivariable linear regression analysis was performed to study the association between susceptibility values and cognitive scores including the Mini-Mental State Examination (MMSE). Results: Among the three groups, the frontal (P < 0.001), temporal (P = 0.004), parietal (P = 0.001), occipital (P < 0.001), and cingulate cortices (P < 0.001) showed a higher mean susceptibility in patients with MCI and AD than in NC subjects. In the combined MCI and AD group, the mean susceptibility in the cingulate cortex (β = -216.21, P = 0.019) and insular cortex (β = -276.65, P = 0.001) were significant independent predictors of MMSE scores after correcting for age, sex, education, regional volume, and APOE4 carrier status. Conclusion: Iron deposition in the cortex, as measured by QSMnet+, was higher in patients with AD and MCI than in NC participants. Iron deposition in the cingulate and insular cortices may be an early imaging marker of cognitive impairment related neurodegeneration.