• Journal of Veterinary Science
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• 제25권5호
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• pp.60.1-60.6
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• 2024

Importance: Alzheimer's disease (AD) is the most common cause of dementia in the elderly with the incidence rising exponentially after the age of 65 years. Unfortunately, effective treatments are extremely limited and definite diagnosis can only be made at autopsy. This is in part due to our limited understanding of the complex pathophysiology, including the various genetic, environmental, and metabolic contributing factors. In an effort to better understand this complex disease, researchers have employed nonhuman primates as translational models. Case Presentation: This report aims to describe the AD-like neuropathology in the brain of a 37-year-old female baboon (Papio hamadryas), which at the time of her death made her the oldest hamadryas baboon at any member institution of the Association of Zoos and Aquariums. A diagnostic necropsy was performed, and the brain was evaluated for neurodegenerative disease. Frequent amyloid-β deposits were identified, consistent with what has been described in other geriatric nonhuman primates. Phospho-tau pathology, including neurofibrillary tangles, a feature not well-described in other primate models, was also abundant. Conclusions and Relevance: Our results suggest that more detailed, prospective, longitudinal studies are warranted utilizing this particular species to see if they represent a viable model for human brain aging.

• 한국산학기술학회논문지
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• 제15권11호
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• pp.6728-6738
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• 2014

본 연구는 노인요양시설 입소 노인의 통증, 우울 및 일상생활활동의 관계를 확인하고 통증의 영향요인을 파악하기 위하여 수행되었다. S시의 노인요양시설 4개소에서 2013년 1월부터 2월까지 구조화된 설문지를 이용하여 자료를 수집하였다. 자가보고 통증평가 도구인 NRS(numeric rating scale)와 행동관찰 통증평가 도구인 DS-DAT(discomfort scale-dementia of the Alzheimer's type)를 사용하여 통증을 측정하였고, GDSSF-K(Geriatric Depression Scale Short Form-Korea Version), BADL(Barthel activities of daily living)로 우울과 일상생활활동 수준을 측정하였다. 수집된 자료는 SPSS PC 20.0 program을 이용하여 Pearson's correlation coefficient, 위계적 다중회귀분석을 실시하였다. 연구결과는 NRS와 DS-DAT 모두 일상생활활동과는 음의 상관관계를 보였으며, 우울과는 양의 상관관계를 보였다. 회귀분석을 통하여 성별, 관절염, 우울, 일상생활활동이 NRS를 28.1% 설명하는 영향요인이었고, DS-DAT에서는 우울과 일상생활활동이 21.5%를 설명하는 영향요인으로 확인되었다. 이상의 결과를 바탕으로 노인요양시설 입소노인의 통증관리에 있어서 우울을 완화하고 일상생활활동 능력을 향상시킬 수 있는 프로그램의 개발과 적용이 요구된다.

• 한국산학기술학회논문지
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• 제14권5호
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• pp.2393-2399
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• 2013

본 논문에서는 특이값 분해(SVD: singular value decomposition)에 의한 기저 스펙트럼의 합성을 통해 혈소판 라만 스펙트럼에서 알츠하이머병(AD: Alzheimer's disease)을 검출하는 방법을 제안하였다. AD가 유도된 형질 전환 실험용 쥐의 혈소판에서 측정한 라만 스펙트럼은 가산 잡음과 배경 잡음의 제거와 정규화로 구성된 전처리 과정을 수행한다. 각 데이터 행렬의 열벡터는 AD와 정상(NR: normal)의 라만 스펙트럼으로 구성한다. 이 데이터 행렬을 SVD로 분해한 다음 각 행렬의 열벡터 12개를 AD와 NR의 기저 스펙트럼으로 결정한다. 분류 과정은 각 클래스의 기저 스펙트럼을 선형 합성한 스펙트럼과 분류 스펙트럼의 평균제곱근오차(root mean square error)가 최소인 클래스를 선택하는 것으로 완료된다. 278개의 혈소판 라만 스펙트럼을 사용한 실험에 따르면 제안한 방법의 평균 분류율은 약 97.6%로 주성분 분석(principle components analysis)으로 추출한 특징에 MLP(multi-layer perceptron)를 이용한 경우보다 약 6.1% 정도의 우수한 성능을 보였다. 이 결과에서 SVD에 의한 기저 스펙트럼이 혈소판 라만 스펙트럼에서 AD의 검출에 적합하게 사용될 수 있음을 확인하였다.

• 대한한의학회지
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• 제28권2호통권70호
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• pp.213-223
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• 2007

Objective : Alzheimer's disease (AD) is a geriatric dementia that is widespread in old age. With an aging populace, AD is a looming problem in public health service. Alzheimer's disease is characterized by specific neuronal degeneration in certain areas of the brain. Mutations and abnormal expression of several genes are associated with ${\beta}-amyloid$ deposits and Alzheimer's disease; among them APP, PS1, and PS2, SOD, free radical, ROS. Methods:We studied herbal medicines that have a relationship to brain degeneration. From pre-modern times, although a variety of oriental prescriptions of Aster tataricus have been traditionally utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet been fully elucidated. Result : Based on morphological observations by phase-contrast microscope, TUNEL assay and MTT in the culture media, $H_20_2-induced$ cell death was significantly inhibited by Aticus. We examined by ROS formation, catalase activity and GSH activity. We studied the protective effect and inhibitory effects of neurotoxicity in $H_20_2-induced$ PC-12 cells by Aticus. Findings from our experiments show that Aticus inhibits apoptosis, which has neurotoxicities and cell damage in PC-12 cells. In addition, treatment with Aticus ($>25{\mu}g/ml$ for 6hrs) partially prevented $H_20_2-induced$ cytotoxicity in PC-12 cells, and induced a protective effect. Conclusion : As the result of this study, in the Aticus group, the apoptosis in the nervous system was inhibited, protected against the degeneration of PC-12 cells by $H_20_2$. Taken together, Aticus exhibited inhibition of $H_20_2-induced$ apoptotic cell death. Aticus was found to induce protective effect on GSH and catalase in PC-12 cells. Based on these findings, Aticus may be beneficial for the treatment of AD.

• Journal of Nutrition and Health
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• 제41권8호
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• pp.718-732
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• 2008

본 연구는 2007년 2월부터 5월까지 서울에 위치한 A 대학병원 치매클리닉에 내원한 65세 이상 노인 38명을 대상으로 영양섭취 상태와 인지기능에 관련이 있는 영양소 및 식품의 요인을 알아보고자 실시되었으며 연구결과는 다음과 같다. 알쯔하이머병 노인의 평균연령은 75.8 ${\pm}$ 5.8세로 남녀 성비에서 여자 노인의 비율이 더 높았으며, 체질량지수 과체중과 비만 범위의 분포가 가장 높게 나타났다. 섭취한 총 열량은 1,656.4 ${\pm}$ 528.1 kcal로 2005 국민 건강.영양조사와 비교하여 단백질, 지방, 철분, 칼륨, 비타민 Bl, 비타민 B2, 나이아신, 비타민 C는 더 많이 섭취하였고, 당질, 섬유소, 칼슘, 인, 나트륨, 비타민 A는 더 적게 섭취하는 것으로 나타났다. 식품군별 섭취량에서는 채소류를 309.0 ${\pm}$ 152.4 g로 가장 많이 섭취하였고, 설탕은 7.2 ${\pm}$ 9.3 g로 가장 적게 섭취한 것으로 나타났다. 알쯔하이머병 노인의 인지기능과 관련이 있는 식이요인은 주의집중력에서 식물성 칼슘이 부정적으로 관련이 있는 것으로 나타났고, 언어능력에서는 아연이, 기억력에서는 생선 및 어패류, 두류 및 종실류, 당류군의 섭취가 긍정적인 관련성을 가지는 것으로 나타났다. 간이정신상태검사의 시간지남력에서 계란은 인지기능과 부정적으로 관련성을 가지는 것으로 나타났으며 기억회상에는 지방, 시공간구성력에는 당류의 섭취가 인지기능에 긍정적으로 관련이 있는 요인으로 나타났다. 본 연구의 결과에서 알쯔하이머병 노인들의 인지기능과 식품 및 영양소의 섭취가 관련이 있다는 것을 알 수 있었다. 그러나 대조군이 없는 연구이므로 향후 알쯔하이머병이 없는 노인들을 포함한 비교연구와 시간경과에 따른 식이섭취 양상과 인지기능 상태에 대한 전향적인 연구가 필요할 것으로 사료된다. 더 나아가 알쯔하이머병 노인들에게 나타날 수 있는 식사와 관련한 이상행동을 고려하여 인지기능의 세분화 된 특정 영역과 밀접하게 관련된 식이요인에 대한 심층적인 연구를 통하여 알쯔하이머병 노인들의 식사의 질 향상과 더불어 이상행동의 예후 또한 좋게 하고 삶의 질을 높이는데 기여할 수 있을 것이다.

• 대한한방내과학회지
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• 제41권3호
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• pp.326-338
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• 2020

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease that causes disorientation, mood swings, problems with language, and difficulty remembering recent events. Acetylcholinesterase inhibitors (AchEIs) and memantine have been used to slow the course of the disease, but they can neither modify its progression nor prevent disease onset. Previous studies have suggested that Kami-guibi-tang (KGT) could be beneficial for supporting cognitive function in AD patients, but few clinical trials have been published. This pilot study aimed to evaluate the effect of KGT in improving cognitive function in AD patients. Methods: The study will be a randomized, placebo-controlled, double-blind, single-center trial conducted using subjects diagnosed with mild AD by neurologists. Study subjects will be randomly assigned to either a treatment or control group. The treatment group will receive KGT granules for 24 weeks, while the control group will receive placebo granules. AchEI administration will be maintained in both groups during the entirety of the study. Subjects will be assessed using the following exams: the Seoul Neuropsychologic Screening Battery (SNSB) for cognitive function; brain magnetic resonance imaging (MRI) for brain metabolite, neurotransmitter, and cerebral blood flow (CBF) measurements; the Korean version of Quality of Life-Alzheimer's Disease (KQol-AD) for quality of life; the Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI) for neurobehavioral symptoms; blood tests for amyloid and tau proteins and general blood parameters; and electrocardiography (ECG) before and after taking the medication. Discussion: Our findings will provide insight into the feasibility of large-scale trials to consolidate evidence for the efficacy of KGT for dementia treatment. Registration ID in CRIS: KCT0002904 (Clinical Research Information Service of the Republic of Korea).

• 동의생리병리학회지
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• 제38권1호
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• pp.1-9
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• 2024

Cognitive reserve (CR) is a concept that can explain the discrepancies between the pathologic burden of the disease and clinical manifestations. It refers to the individual susceptibility to age-related brain changes and pathologies related to Alzheimer's disease, thus recognized as a factor affecting the trajectories of the disease. The purpose of this study was to explore the current states of clinical studies on neural substrates of CR in Alzheimer's disease using functional magnetic resonance imaging. We searched for clinical studies on CR using fMRI in the Pubmed, Cochrane library, RISS, KISS and ScienceON on August 14, 2023. Once the online search was finished, studies were selected manually by the inclusion criteria. Finally, we analyzed the characteristics of selected articles and reviewed the neural substrates of CR. Total thirty-four studies were included in this study. As surrogate markers of CR, not only education and occupational complexity, but also composite score and questionnaire-based method, which cover various areas of life, were mainly used. The most utilized methods in resting-state fMRI were independent component analysis, seed-based analysis, and graph theory analysis. Through the analysis, we demonstrated that neuroimaging techniques could capture the neural substrates associated with cognitive reserve. Moreover, functional connectivity of brain regions centered on prefrontal and parietal cortex and network areas such as default mode network showed a significant correlation with CR, which indicated a significant association with cognitive performance. CR may induce differential effects according to the disease status. We hope that this perspective on cognitive reserve would be helpful when conducting clinical researches on the mechanisms of traditional Korean medicine for Alzheimer's disease in the future.

• 동의생리병리학회지
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• 제22권5호
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• pp.1215-1222
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• 2008

Recent studies indicate that the deposition of ${\beta}$-amyloid ($A{\beta}$) is associated with the pathogenesis of Alzheimer's disease (AD), but the underlying mechanism is not clear yet. To investigate the effects of Jangwonhwangagambang (JWHG) extract on AD pathogenicity, we have generated transgenic Drosophila model in which GMR-APP-GAL4/UAS-GRIM system was designed to overexpress amyloid precursor protein(APP), We examined fly's survival ratio, flight behavior, and morphological patterns of chest and eye. We found that JWHG treatment improved fly's survival ratio by inhibiting apoptosis and flight behavior. APP-GRIM transgenic flies treated with JWHG showed had significantly lower levels of APP deposition in the chest and eye compared to control animals. JWHG treatment further inhibited chest and eye degeneration. These results suggest that JWHG prevents APP-induced neurotoxicity, and thus may be applicable for the development of preventive or therapeutic agents for AD treatment.

• 생약학회지
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• 제49권2호
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• pp.182-187
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• 2018

Many plant derived phytochemicals have been considered as the main therapeutic strategy against Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder, and the most predominant cause of dementia in the elderly. Cholinergic deficit, senile plaque/${\beta}$-amyloid ($A{\beta}$) peptide deposition and oxidative stress have been identified as three main pathogenic pathways which contribute to the progression of AD. We screened many different plant species for their effective use in both modern and traditional system of medicines. In this study, we tested that MeOH extract of the stem bark of Hopea chinensis (Merr.) Hand.-Mazz. (HCM) affects on the processing of Amyloid precursor portein (APP) from the APPswe over-expressing Neuro2a cell line. We showed that HCM reduced the secretion level of $A{\beta}42$ and $A{\beta}40$ in a dose dependent manner. We found that HCM increased over 1.5 folds of the secretion level of $sAPP{\alpha}$, a metabolite of ${\alpha}$-secretase. Furthermore, we found that HCM inhibited acetylcholinesterase activity in vitro. We suggest that the stem bark of Hopea chinensis may be a useful source to develop a therapeutics for AD.

• 대한치매학회지
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• 제23권1호
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• pp.22-29
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• 2024

Background and Purpose: Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive decline in cognition and performance of daily activities. Recent studies have attempted to establish the relationship between AD and sleep. It is believed that patients with AD pathology show altered sleep characteristics years before clinical symptoms appear. This study evaluated the differences in sleep characteristics between cognitively asymptomatic patients with and without some amyloid burden. Methods: Sleep characteristics of 76 subjects aged 60 years or older who were diagnosed with subjective cognitive decline (SCD) but not mild cognitive impairment (MCI) or AD were measured using Fitbit^® Alta HR, a wristwatch-shaped wearable device. Amyloid deposition was evaluated using brain amyloid plaque load (BAPL) and global standardized uptake value ratio (SUVR) from fluorine-18 florbetaben positron emission tomography. Each component of measured sleep characteristics was analyzed for statistically significant differences between the amyloid-positive group and the amyloid-negative group. Results: Of the 76 subjects included in this study, 49 (64.5%) were female. The average age of the subjects was 70.72±6.09 years when the study started. 15 subjects were classified as amyloid-positive based on BAPL. The average global SUVR was 1.598±0.263 in the amyloid-positive group and 1.187±0.100 in the amyloid-negative group. Time spent in slow-wave sleep (SWS) was significantly lower in the amyloid-positive group (39.4±13.1 minutes) than in the amyloid-negative group (49.5±13.1 minutes) (p=0.009). Conclusions: This study showed that SWS is different between the elderly SCD population with and without amyloid positivity. How SWS affects AD pathology requires further research.