알쯔하이머 질환의 신경신호전달계 이상소견

김영훈(Young-Hoon Kim),이상경(Sang-Kyeong Lee),김성수(Sung-Su Kim) 대한생물치료정신의학회 1997 생물치료정신의학 Vol.3 No.2

There are accumulating evidences that aging is regulated by different genes through several lines of biochemical processes simultaneously or independently. Aging of brain is accompanied with changes of several neurotransmitter systems. Most of all, abnormalities in the cholinergic system are remarkable. There are reductions in the number of neurons of Meynert's basal nucleus and activities of choline acetyltransferase in some areas of brain. Although reductions in other neurotransmitter systems such as dopaminergic, serotonergic and GABAergic system are also investigated, their involvement in the process of aging is still not throughly evaluated. However the brain levels of some of neuropeptides are decreased or increased, changes of them are less remakable than those of classical neurotransmitters. It is also suggested that functional abnormalities of G-protein and dysregulations of intracellular free calcium mobility are involved in the process of aging. Alzheimer's disease is a heterogenous disorder. Mutations of APP gene on chromosome 21, gene encoding preseinlin 1 on chromosome 14 and gene encoding presenilin 2 on chromosome 1 are thought to be causative factors in familial type of early-onset Alzheimer's disease(familial EOAD). There are several theories about the pathophysiology of Alzheimer's disease : cholinergic theory, β-amyloid protein theory, excitotoxicity theory and etc. Reductions in the cholinergic system are most remakable and consistently reported among several neurotransmitter abnormalities in Alzheimer's disease. Reduction in the activity of choline acetyltransferase is related to the impairment of cognitive functions in patients with Alzheimer's disease. Abnormalities in other neurotransmitter systems are also noticed, but the significance of those in the pathogenesis of Alzheimer's disease is not clear. In cases of neuropeptides, reduction in levels of somatostatin in some of brain areas involved in Alzheimer's disease is consistently reported in most of studies. Studies which investigated the nature of neurotransmitter receptors in Alzheimer's disease had several methodological limitations and were very scanty in amout. It is known that there are selective reductions of M2 muscarinic receptor and reductions in nicotinic receptors in general. Studies about other neurotansmitter receptors such as catecholaminergic, serotonergic and GABAergic receptors showed mixed and inconsistent results. Because the phenomenon of longterm potentiation regulated by NMDA receptor is regarded as a important model of memory processing and endogenous excitotoxic molecules binds to excitatory amino acid(EAA) receptors such as kainate receptors, further investigations about EAA receptors in Alzheimer's disease should be needed. Biological markers in Alzheimer's disease can be subdivided into cerebrospinal markers, peripheral markers and the findings obtained in brain imaging studies. The most remarkable is the reduction in levels of CSF somatostatin which is consistent with the findings in postmortem studies. The activity of platelet monoamine oxidase(MAO) is elevated in Alzheimer's disease, but that is also found in normal aging. To search the functional aspects of brain in patients with Alzheimer's disease using brain imaging techniques will be promising in the future. The finding of metabolic reduction in parietal cortex in positron emission tomography(PET)-scan is expected to have a role as a potent biological marker in early stage of Alzheimer's disease. The final goal of these researches is to ameliorate sufferings of the patients with Alzheimer's disease. At present, cholinergic therapy is the most expanding. it is more needed to define the exact nature of cholinergic abnormalities in Alzheimer's disease to reach easily the goals of pharmacological approaches. 노화는 여러 유전자들에 의해 조절되는 동시 진행적인 혹은 종속적인 일련의 생화학적 과정에 의해 진행된다는 근거가 있다. 뇌의 노화는 많은 신경전달계의 변화를 유발한다. 특히 콜린계 장애가 가장 현저하다. Meynert’s basal nucleus의 신경세포가 소실되고, choline acetyl transferase의 활성도가 감소한다. 도파민계, 세로토닌계,GABA계 등 대부분의 신경전달계의 저하가 알려져 있지만, 이들의 노화에의 원인적 기여에 대한 역할은 확실치 않다. 신경펲타이드계는 일부 저하되고 일부는 증가하나, 이들의 변화는 전형적 신경전달계의 변화에 비해 미미하다고 생각된다. 그 외 G 단백질의 기능 장애 및 세포내 유리 칼슘 이온의 조절 기능의 장애도 노화와 관련된 것으로 생각된다. 알쯔하이머 질환은 유전성 질환이다. 염색체 21번의 APP 유전자 돌연변이와 염색체 14번, 1번의 presenilin 1, 2 유전자 돌연변이가 특히 조기발병 알쯔하이머 질환과 관련이 있다. 현재 알쯔하이머 질환의 병인에 대해 cholinergic theory, β-amyloid protein theory, excitotoxicity theory 등 여러 가설이 있다. 알쯔하이머 질환의 신경전달계 장애로 가장 일관성 있게 보고된 것은 역시 콜린계 장애이다. 특히 choline acetyltransferase의 활성도 감소는 이 질환의 인지기능 저하소견과 상관성이 있다. 기타 신경전달계의 장애도 발견되나, 알쯔하이머 병인에의 기여 여부는 확실치 않다. 신경?타이드들 중에는 somatostatin의 감소 소견이 일관성 있게 보고되고 있다. 수용체에 대한 연구들은 아직 미미하다. 콜린계 수용체중 muscarinic receptor type 2(M2) 수용체의 저하가 선택적으로 일어나며, 전체적으로 nicotinic receptor의 수도 감소하는 것으로 보고된다. 기타 카테콜아민, 세로토닌, GABA 수용체 등은 큰 변화가 없다고 보고되고 있다. 향후 NMDA 수용체에 대한 연구가 주목된다. 알쯔하이머 질환에 있어서의 생물학적 지표로서 뇌척수액이나 말초혈액에서 보고되고 있는 것에는 특별한 게 없다. 단 뇌척수액내 somatostatin이 감소되어 있다는 것이 일관성 있게 보고되고 있고, 또한 혈소판 MAO 활성도가 증가된다. 하지만 MAO 활성도 증가는 정상 노화에서도 관찰되는 소견이다. 향후 뇌영상기법을 통한 연구들이 알쯔하이머 질환을 연구하는데 중요한 역할을 할 것이다. 현재 PET 검사로 발견되는 두정엽의 대사감소는 이 질환의 초기 생물학적 지표로 상정되고 있다. 이러한 연구들의 최종 목적은 환자들의 증상을 완화시키는데 있다. 현재로서는 콜린계 장애의 성상을 보다 정확히 규명하고 이에 대한 약물학적 접근을 해 나가는 것이 가장 이 목적에 접근해 있다고 생각된다.

Alzheimer형 치매 의심의 기억기능

박종환,김남수 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

목 적 : 초기 Alzheimer병의 본질을 밝히는 것은 발병율이나 유병율과 같은 역학적 조사나 질병의 진행 양상 파악을 위해서 중요하다. QDAT, MiDAT, 정상 대조군간에 기억 장애의 정도를 비교함으로서 QDAT의 특성을 밝히는 것이 본 연구의 목적이다. 대상과 방법 어느 농촌 지역에서 행해진 치매의 역학적 연구에서 DSM-Ⅲ-R의 진단 기준에 의해서 MiDAT로 진단된 노인 14명, QDAT로 진단된 노인 14명, 그리고 이들과 연령, 성, 교육 수준을 통제한 비치매 대조군 14명을 대상으로 하였다. 이들에게 실시된 여러 가지 신경심리 검사 성적 중에서 본 연구에서는 KWIS에서 숫자 따라 외우기, 인지기능장애진단도구의 하위 검사 중에서 기억 등록, 단기 기억 그리고 장기 기억이, Wechsler 기억 검사 중에서 짝 연상 학습, 즉각적 회상, 그리고 지연성 회상에 관한 자료들이 분석되었다. 결 과 : 장기 기억, 단기 기억, 논리적 기억의 즉각적 회상과 지연성 회상, 그리고 쉬운 짝 연상 학습에서는 QDAT와 정상 대조군 간에 유의한 차이가 있었다. 반면에 QDAT와 MiDAT은 장기 기억을 제외한 각종 기억 검사 성적이 비슷했다. 결 론 : 상기 결과는 QDAT는 비치매와는 다르며 초기 Alzheimer형 치매일 가능성이 높다는 것을 시사한다. Objective : Exploration of the questionable Alzheimer disease is important for accurate estimation of prevalence and incidence, understanding the natural history, and evaluation of treatment strategies for the Alzheimer disease. Subjects and Methods : We compared neuropsychological test performances among 14 non-demented controls, 14 elderly persons with questionable dementia of the Alzheimer type and 14 elderly persons with mild dementia of the Alzheimer type. The test performances analyzed were the digit span of the Korean Adult Wechsler Intelligence Scale, registration, short term memory and long term memory of the Cognitive Impairment Diagnosing Instrument, and paired association learning and logical memory of the Wechsler Memory Scale. Results : There was significant difference between questionable dementia of the Alzheimer type and controls in the long-term memory, short-term memory, immediate and delayed recalls of the logical memory, and easy association. But the subjects with questionable and mild dementia of the Alzheimer type scored similarly on all tests except the long-term memory. Conclusion : These findings suggest that questionable Alzheimer disease may be the very early Alzheimer disease.

알쯔하이머 치매·혈관성 치매·아밀로이드·면역·IL-1β·TNF-α, Alzheimer's discase·Vascular dementia·Amyloid·Immunity·IL-1β·Tnf-α.

채정호,백인호 대한신경정신의학회 1999 신경정신의학 Vol.38 No.1

연구목적 : 알쯔하이머 치매의 병인론에 면역성 기전이 개입된다는 가설을 확인하고자 본 연구를 행하였다. 방 법 : 알쯔하이머 치매 19명, 혈관성 치매 22명, 정상노인 19명에서 말초 혈액 단핵세포를 분리하여 phyohemagglutinin-P(PHA-P) 및 1-40의 β-아밀로이드(Aβ)로 자극하여 세포 증식 정도를 비교하였으며, 배양 상청액에서 interleukin-1β(IL-1β)와 tumor necrosis factor-α(TNF-α)를 효소결합면역흡착분석법으로 측정하였다. 결 과 : 1) PHA-P 자극에 의한 단핵 세포의 증식은 세 군에서 차이가 없었다. 2) Aβ 자극은 단핵세포의 증식에 현저한 영향이 없었으나, 알쯔하이머 치매군이 혈관성 치매군과 대조군에 비하여 유의하게 많이 증식되었다. 3) 배양한 단핵세포 알쯔하이머 치매상청액의 IL-1β는 혈관성 치매군이 가장 높았으며, Aβ자극 후에도 혈관성 치매군에서 가장 높았으나 자극 전후를 비교할 때, 알쯔하이머 치매군에서 가장 현저하게 자극 후 IL-1β 생성이 증가되었다. 4) 배양한 단핵세포 상청액의 TNF-α는 알쯔하이머 치매군이 대조군보다 유의하게 높았으며, Aβ 자극 후에도 알쯔하이머 치매군이 대조군보다 유의하게 높았다. 결 론 : 이상의 실험을 통하여 알쯔하이머 치매군의 말초 혈액 단핵세포가 Aβ 자극에 따라 나타내는 과도한 면역 반응을 관찰하였다. 이는 알쯔하이머 치매의 병태생리에서 Aβ침착에 따른 면역성 반응이 중요한 역할을 한다는 것을 시사한다. Objectives : Deposition of the β-amyloid(Aβ) peptide in the senile plaque has been thought as a major etiologic factor for the development of Alzheimer's disease. Among the hypotheses suggested to explain the mechanism by which Aβ causes Alzheimer's disease, the immune processes have been considered as crucial events in the pathophysiology of the Alzheimer's disease. This study examined the effects of Aβ on the proliferation and production of IL-1β(interleukin-1β) and TNF-α(tumor necrosis factor-α) in peripheral blood mononuclear cells isolated from the patients with Alzheimer's disease, vascular dementia, and normal elderly control subjects. Method : Nineteen patient with Alzheimer's disease, 22 patients with vascular dementia, and 19 controls were participated in this study. Peripheral blood mononuclear cells were obtained from each donors, and subjected to the proliferation assays in response to the stimulation of phytohemagglutinin-P(PHA-P) and Aβ. The levels of IL-1β and TNF-α from the culture supernatant of the cells before and after the stimulation of Aβ were also determined by enzyme linked immunosorbent assay. Results : The results were as follows : 1) The proliferation of mononuclear cells in response to PHA-P were not different among three groups. 2) When compared to PHA-P, the proliferation responses of mononuclear cells to Aβ were insignificant in all experimental groups. However Alzheimer's disease group showed greater stimulation index than vascular dementia and controls. 3) IL-1β production was higher in the vascular dementia group than Alzheimer's disease and control groups both before and after the stimulation of Aβ. However the stimulation ratio of before and after Aβ stimulation was highest in Alzheimer's disease group. 4) TNF-α production was higher in Alzheimer's disease group than controls both before and after the stimulation of Aβ. Conclusion : These finding suggest that the immune responses to the stimulation of Aβ may be enhanced in patients with Alzheimer's disease compared to vascular dementia and control groups, supporting the immune hypothesis for th epathophysiology of Alzheimer's disease.

Recent advances in Alzheimer’s disease pathogenesis and therapeutics from an immune perspective

Nguyen Thai-Duong,Dang Loi Nguyen,Jang Jung-Hee,박소연 한국약제학회 2023 Journal of Pharmaceutical Investigation Vol.53 No.5

Background The prevalence of Alzheimer’s disease, the most common type of dementia, is continuously increasing. Many recent reports have indicated that immune-related mechanisms play a vital role in Alzheimer’s disease pathogenesis, such that the imbalance between the immune response and central nervous system leads to neuroinflammation. Area covered The inflammatory response in Alzheimer’s disease is a “double-edged sword”. Neuroinflammation protects neuronal cells in the initial stages of Alzheimer’s disease, while sustained inflammation promotes neurodegeneration. Alterations in the peripheral immune system, such as increased inflammation, lead to the activation of the central immune response, which in turn causes neuroinflammation and neuronal damage. Additionally, an imbalance between pro- and anti-inflammatory cytokines, which are secreted by the central and peripheral immune systems, induces complex immune responses and contributes to Alzheimer’s disease pathogenesis. In this review, we aimed to summarize our current knowledge of the role of the immune system in Alzheimer’s disease pathology. We performed an in-depth investigation on the contribution of each immune system component to Alzheimer’s disease progression at different disease stages. More importantly, we discuss novel immune-related therapeutic strategies for Alzheimer’s disease treatment currently being investigated via clinical trials. Expert opinion The scrutinized observations of immune responses in different brain regions at various stages of Alzheimer’s disease might help identify potential treatment strategies for Alzheimer’s disease. The modulation of immune components in the brain by targeting cytokines and other factors, which compromise immune response and neuroinflammation, is recommended as a promising alternative for Alzheimer’s disease treatment. Clinical trials are currently investigating the efficacies of numerous vaccines and monoclonal antibodies targeting amyloid beta peptide and tau protein for Alzheimer’s disease treatment. Moreover, aducanumab and lecanemab were approved by the Food and Drug Administration as monoclonal antibody-based drugs for Alzheimer’s disease treatment in 2021 and 2023, respectively. However, these drugs are effective only against mild symptoms due to the irreversible neuronal damage found in patients with Alzheimer’s disease progression. In addition, side effects including amyloid-related imaging abnormalities (such as vasogenic edema, microhemorrhages, and hemosiderosis) were reported in patients undergoing Alzheimer’s disease treatment using monoclonal antibodies. Thus, the future development of therapeutic agents for Alzheimer’s disease requires more sophisticated and multi-plunged approaches considering various biomarkers and immune landscapes characterizing the different stages of Alzheimer’s disease.

자하거(紫河車) 약침(藥鍼)이 βA로 유도(誘導)된 Alzheimer`s Disease 병태(病態) 모델에 미치는 영향(影響)

이병훈 ( Byung Hun Lee ),박선영 ( Sun Young Park ),최철홍 ( Cheol Hong Choi ),이은경 ( Eun Kyung Lee ),정대규 ( Dae Kyoo Chung ) 대한한방신경정신과학회 2008 동의신경정신과학회지 Vol.19 No.2

Objective: Hominis Placenta is used in many cure, mainly treats a weak, chronic disease, especially senile. This research investigates the effect of the Hominis Placenta Herbal-Acupuncture Solution on Alzheimer`s disease. Method: The effects of the Hominis Placenta Herbal-Acupuncture Solution on (1) IL-1β protein, TNF-α protein, MDA, and CD68/CD11b (2) the behavior (3) the infarction area of the hippocampus, and brain tissue injury in Alzheimer`s diseased mice induced with βA were investigated. Results: 1. For the Hominis Placenta Herbal-Acupuncture Solution group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer`s disease induced by βA in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 2. The Hominis Placenta Herbal-Acupuncture Solution group suppressed the over-expression of IL-1β protein, TNF-α protein, MDA, and CD68/CD11b, in the mice with Alzheimer`s disease induced by βA. 3. The Hominis Placenta Herbal-Acupuncture Solution group reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer`s disease induced by βA. 4. The Hominis Placenta Herbal-Acupuncture Solution group reduced the Tau protein, GFAP protein, and presenilin1/2 protein, beta-secretase protein, (immunohistochemistry) of hippocampus in the mice with Alzheimer`s disease induced by βA. Conclusion: These results suggest that the Hominis Placenta Herbal-Acupuncture Solution group may be effective for the prevention and treatment of Alzheimer`s disease. Investigation into the clinical use of the Hominis Placenta Herbal-Acupuncture Solution for Alzheimer`s disease is suggested for future research. Objective: Hominis Placenta is used in many cure, mainly treats a weak, chronic disease, especially senile. This research investigates the effect of the Hominis Placenta Herbal-Acupuncture Solution on Alzheimer`s disease. Method: The effects of the Hominis Placenta Herbal-Acupuncture Solution on (1) IL-1β protein, TNF-α protein, MDA, and CD68/CD11b (2) the behavior (3) the infarction area of the hippocampus, and brain tissue injury in Alzheimer`s diseased mice induced with βA were investigated. Results: 1. For the Hominis Placenta Herbal-Acupuncture Solution group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer`s disease induced by βA in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 2. The Hominis Placenta Herbal-Acupuncture Solution group suppressed the over-expression of IL-1β protein, TNF-α protein, MDA, and CD68/CD11b, in the mice with Alzheimer`s disease induced by βA. 3. The Hominis Placenta Herbal-Acupuncture Solution group reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer`s disease induced by βA. 4. The Hominis Placenta Herbal-Acupuncture Solution group reduced the Tau protein, GFAP protein, and presenilin1/2 protein, beta-secretase protein, (immunohistochemistry) of hippocampus in the mice with Alzheimer`s disease induced by βA. Conclusion: These results suggest that the Hominis Placenta Herbal-Acupuncture Solution group may be effective for the prevention and treatment of Alzheimer`s disease. Investigation into the clinical use of the Hominis Placenta Herbal-Acupuncture Solution for Alzheimer`s disease is suggested for future research.

Platelets as a Source of Peripheral Aβ Production and Its Potential as a Blood-based Biomarker for Alzheimer’s Disease

Jae Seon Kang(강재선),Yun-Sik Choi(최윤식) 한국생명과학회 2020 생명과학회지 Vol.30 No.12

알츠하이머병은 점진적인 신경세포의 손상과 이로 인해 인지기능 장애를 유발하는 질병이다. 이 질환은 현재로서는 치료할 수 있는 질환이 아니고 진행을 멈추게 할 수 있는 방법이 없다. 그러나 초기에 알츠하이머병을 치료하는 것이 가장 효과적이므로 초기 진단은 증상을 관리할 수 있는 가장 좋은 기회를 제공할 수 있다. 알츠하이머병을 진단하기 위한 바이오마커로는 아밀로이드 베타(Aβ), 병적인 타우, 그리고 신경퇴화가 있고, Aβ의 축적, 인산화 타우는 뇌척수액이나 양전자 방출 단층촬영술을 통해 분석할 수 있다. 그러나 뇌척수액의 채취는 매우 침습적이고 양전자 방출 단층촬영술은 전문적인 고가의 장비가 필요하다. 지난 수십년 동안 빠르고 최소한의 침습성을 가진 바이오마커 분석법을 개발하기 위하여 혈액에 기반한 바이오마커 분석 기술이 연구되어 왔다. 그 중 주목할 만 한 발견이 혈장에서 Aβ의 주요 원천으로 혈소판과의 관련성이다. 아밀로이드 베타는 혈액-뇌 장벽을 통과할 수 있고 정상 상태에서는 뇌와 혈액 간 평형을 이루게 된다. 흥미롭게도, 여러 임상시험 결과 혈장에서 Aβ42/Aβ40 비율이 가벼운 인지장애 질환과 알츠하이머병에서 감소되어 있는 것을 증명하였다. 종합하면, 이러한 최근의 발견들은 침습성을 최소화한 알츠하이머병의 초기 진단 기술을 개발하는 데 이용될 수 있다. 본 총설에서, 저자들은 알츠하이머병의 바이오마커에 대한 최근 연구결과들, 특히 말초에서 Aβ를 생산하는 혈소판의 역할과 혈액 기반 바이오마커로서의 개발 가능성에 대해 고찰하였다. Alzheimer’s disease causes progressive neuronal loss that leads to cognitive disturbances. It is not currently curable, and there is no way to stop its progression. However, since medical treatment for Alzheimer’s disease is most effective in the early stages, early detection can provide the best chance for symptom management. Biomarkers for the diagnosis of Alzheimer’s disease include amyloid β (Aβ) deposition, pathologic tau, and neurodegeneration. Aβ deposition and phosphorylated tau can be detected by cerebrospinal fluid (CSF) analysis or positron emission tomography (PET). However, CSF sampling is quite invasive, and PET analysis needs specialized and expensive equipment. During the last decades, blood-based biomarker analysis has been studied to develop fast and minimally invasive biomarker analysis method. And one of the remarkable findings is the involvement of platelets as a primary source of Aβ in plasma. Aβ can be transported across the blood–brain barrier, creating an equilibrium of Aβ levels between the brain and blood under normal condition. Interestingly, a number of clinical studies have unequivocally demonstrated that plasma Aβ42/Aβ40 ratios are reduced in mild cognitive impairment and Alzheimer’s disease. Together, these recent findings may lead to the development of a fast and minimally invasive early diagnostic approach to Alzheimer’s disease. In this review, we summarize recent advances in the biomarkers of Alzheimer’s disease, especially the involvement of platelets as a source of peripheral Aβ production and its potential as a blood-based biomarker.

Alzheimer형 치매 의심과 경도 Alzheimer형 치매의 인지기능 비교

박종한 大韓神經精神醫學會 1994 신경정신의학 Vol.33 No.2

QDAT의 본질을 파악하기 위하여 농촌 지역에서 QDAT나 MiDAT로 진단된 노인들의 MMSEK 점수와 임상적 평가에서 얻은 인지기능을 비교했다. 양자간에 치매의 정도는 차이가 있었으나 MMSEK의 각 하위 검사와 대부분의 인지기능 검사에서는 유의한 차이가 없었다. 이러한 소견으로 미루어 보아 Alzheimer병 의심은 초기 혹은 경도의 Alzheimer병일 가능성이 높다. Objective : Exploration of the nature of very early or mild Alzheimer disease is essential in understanding natural history, assessment of therapeutic interventions and accurate estimation of prevalence or incidence of Alzheimer disease. Method : Scores of the Korean version of Mini-Mental State Examination(MMSEK) and a variety of cognitive functions were compared between questionable and mild dementias of the Alzheimer type. Measurements of cognitive functions were derived from semi-structured interview with the subjects. The two groups were controlled for age(±4), sex, and education, but differed regarding the severity of dementia. Results : Total and subtest scores of the MMSEK and all cognitive functions except for long-term memory were similar between the two severities of dementia of the Alzheimer type. Conclusion : These findings suggest that questionable Alzheimer disease may be very early or mild Alzheimer disease.

알쯔하이머병 환자에서 7분 선별검사를 이용한 인지장애의 평가

김인성(Inseong Kim),전진숙(Jin-Sook Cheon),오병훈(Byoung Hoon Oh) 대한임상노인의학회 2001 대한임상노인의학회지 Vol.2 No.4

연구목적 : 알쯔하이머 병은 인지기능이 점차로 저하되는 특징이 있다. 노화와 연관된 인지기능저하(age associated cognitive decline)와 경증 알쯔하이머 병은 구분이 어렵다. 경증 알쯔하이머 병을 선별하는 진단적 도구로서 한국인 알쯔하이머 환자들을 대상으로 7분 선별검사의 진단적 신뢰도와 영역별 특성을 살펴보았다. 방법 : DSM-IV에 의거하여 알쯔하이머 병으로 입원한 노인환자(N=28)에 대해서, 2주 이상의 병동적응 과정을 거친 후, MMSE-K 및 7분 선별검사(The 7 Minute Screen, 이하 7MS)로 인지기능을 평가하고 구조적 면담과 제반검사를 시행하였으며, 연령과 교육수준을 맞춘 건강한 대조군(N=30)에 대해서도 동일한 인지기능검사를 수행하여 그 결과를 비교 분석하였다. 7분 선별검사의 소검사는 Benton Temporal Orientation Test, Enhanced Cued Recall, Clock Drawing 및 Category Fluency 둥 네 가지로 구성되었다. 결과 : 1. 경증 알쯔하이머 병 환자군에서 7분 선별검사상 네 가지 소검사별 평균 점수는 지남력검사 62.07±40.28, 기억력 검사상 전체 8.43±3.04, Cued Recall 4.00±1.98, Uncued Recall 4.43±1.50, 시각ㆍ공간력검사 1.64±2.04, 언어유창성검사 8.79±2.36점이었으며, 네 가지 소검사에서 모두 대조군에 비해서 통계적으로 유의한 차이를 보였다(p<0.01). 2. 경증 알쯔하이머 병 환자군에서 7분 선별검사의 네 가지 소검사별 절취점의 결정은 지남력검사에서는 0, 기억력검사상 전체는 10개, 시각ㆍ공간력검사는 1점, 언어유창성검사 11개를 기준으로 그 이하에서 치매로 구분되었다. 3. 알쯔하이머 병 환자군에서 7분 선별검사의 네 가지 소검사 점수는 MMSE, 교육정도와 유의한 연관성이 있었다 결론 : 경증 알츠하이머 병 환자군에서 지남력, 기억력, 시각ㆍ공간력, 언어유창성 등의 인지영역에서 기능장애를 볼 수 있었다. Background : Alzheimer's disease is a typical neuropsychiatric disorder with declining of various cognitive function. It may be difficult to differentiated age-associated cognitive decline from mild Alzheimer's dementia. This study was done to identify cognitive disorders in Alzheimer's disease using the 7 Minute Screen. The '7 Minute Screen' test developed by Paul S. Soloman shows high sensitivity and specificity for screening of early Alzheimer' disease. Methods : The cognitive deficits were evaluated using the Mini Mental State Examination(MMSE) and the 7 Minute Screen(7 MS) in patients with Alzheimer's disease (N=28) as well as in age and education level matched healthy controls (N=30). Four individual tests of the 7 MS were consisted of the Benton Temporal Orientation Test, the Memory Test, the Clock Drawing and the Category Fluency. Results : 1. The average scores of four individual tests of the 7 MS for the Alzheimer's disease were 62.07±40.28 for the Benton Temporal Orientation Test, 8.43±3.04 for the Memory Test, 1.64±2.04 for the Clock Drawing and 8.79±2.36 for the Category Fluency. There were statistically significant differences between test scores of Alzheimer's disease and controls(p<0.01). 2. Cut-off poimts of individual test scores of the 7 Minute Screen in mild Alzheimer's disease were 0 for the Benton Temporal Orientation Test, 10 for the Memory Test, 1 for the Clock Drawing and 11 for the Category Fluency. Mild Alzheimer's disease obtained the scores below these levels. 3. Four individual test scores of the 7 MS seemed to have statistically significant association with MMSE and education level. Conclusion : Dysfuntion in cognitive areas such as orientation, memory, visuospatial abilities and verbal fluency could be found in mild Alzheimer's disease. 7 MS to be a valuable tool for the screening of Alzheimer's disease in the Korean elderly.

Alzheimer형 치매 의심 환자의 신경심리검사 소견

박종한,이종학 大韓神經精神醫學會 1997 신경정신의학 Vol.36 No.4

목 적 : Alzheimer형 치매의심(QDAT)과 비치매간에 신경심리 검사 성적을 비교함으로서 QDAT의 특성을 밝히는 것이 본 연구의 목적이다. 대상과 방법 : 어느 농촌 지역에서 행해진 역학적 연구에서 QDAT로 진단된 노인들 14명, 그리고 이들과 연령, 성, 교육 수준을 통제한 비치매 대조군 14명이었다. 사용된 신경심리 검사는 한국판 Wechsler 지능검사의 이해 문제, 숫자 외우기, 산수 문제, 공통성 문제와 토막 짜기. Wechsler 기억 검사의 즉각적 회상, 지연성 회상과 연상 학습, 그리고 언어 유창성 검사이였다. 결 과 : 이해 문제와 숫자 외우기 성적은 양 집단간에 유의한 차이는 없었고, 산수 문제, 공통성 문제 및 토막 짜기의 성적은 QDAT 노인들에서 유의하게 더 낮았다. 즉각적 회상, 지연성 회상, 연상 학습 및 쉬운 짝 연상의 성적은 QDAT 노인들에서 유의하게 더 낮았고, 어려운 짝 연상의 성적은 점수는 양 집단 모두에서 매우 낮아 유의한 차이가 없었다. 언어 유창성의 성적은 QDAT 노인들에서 더 낮은 경향을 보여 주었다. 결 론 : QDAT는 비치매와는 전혀 다르며 초기 Alzheimer형 치매일 가능성이 높다는 것을 강력하게 시사한다. Objective : Elucidation of questionable dementia of the Alzheimer type(QDAT) is important for a accurate estimation of prebalance and incidence of dementia of the Alzheimer type, understanding of the its natural history and evaluation of treatment strategies for dementia of the Alzheimer type. Subjects and Methods : Performances neuropsychological tests were compared between non-demented controls and 14 elderly people in a community diagnosed as having questionable senile dementia of the Alzheimer type. They lived a rural community and their sex, age and education were controlled. Results : The two groups were not significantly different comprehension and digit span of the Wechsler Memory Scale. Performances on arithmetic, similarity and block design were significantly lower in QDAT subjects. Scores on associate learning of the Wechsler Memory Scale and immediate and delayed recalls of logical memory were lower in QDAT subjects with statistical significance. Performance on the semantic verbal fluency tended to the lower for the QDAT subjects. Conclusion : These findings suggest that QDAT may be early dementia of the Alzheimer type.

팔미합총명탕(八味合聰明湯) 열수추출물, 초미세분말제형이 Alzheimer`s Disease 병태 모델에 미치는 영향

임정화 ( Jung Hwa Lim ),이상룡 ( Sang Ryong Lee ) 대한한방신경정신과학회 2008 동의신경정신과학회지 Vol.19 No.2

Objective : This experiment was designed to investigate the effects of the PMCMT hot water extract & ultra-fine powder on Alzheimer`s Disease Model Induced by βA. Method : The effects of the PMCMT hot water extract on expression of proinflammatory cytokine mRNA in BV2 microglial cell cell line treated by lipopolysacchaide(LPS). The effects of the PMCMT hot water extract & ultra-fine powder on (1) the behavior (2) AChE in serum (3) the infarction area of the hippocampus, and brain tissue injury in Alzheimer`s diseased mice induced with βA were investigated. Result : 1. The PMCMT hot water extract suppressed the expression of proinflammatory cytokine mRNA in BV2 microglial cell line treated with LPS. 2. The PMCMT hot water extract & ultra-fine powder a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer`s disease induced by βA in the Morris water maze experiment, which measured stop-through latency and distance movement-through latency 3. The PMCMT hot water extract & ultra-fine powder suppressed the over-expression of AChE activity in the serum of the mice with Alzheimer`s disease induced by βA. 5. The PMCMT ultra-fine powder reduced infarction area of hippocampus significantly, and the PMCMT hot water extract & ultra-fine powder controlled the injury of brain tissue in the mice with Alzheimer`s disease induced by βA. Conclusions : These results suggest that the PMCMT hot water extract & ultra-fine powder may be effective for the prevention and treatment of Alzheimer`s disease. Investigation into the clinical use of the PMCMT hot water extract & ultra-fine powder for Alzheimer`s disease is suggested for future research.