• Title/Summary/Keyword: Cognitive Dysfunction

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Apolipoprotein E in Synaptic Plasticity and Alzheimer's Disease: Potential Cellular and Molecular Mechanisms

  • Kim, Jaekwang;Yoon, Hyejin;Basak, Jacob;Kim, Jungsu
    • Molecules and Cells
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    • v.37 no.11
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    • pp.767-776
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    • 2014
  • Alzheimer's disease (AD) is clinically characterized with progressive memory loss and cognitive decline. Synaptic dysfunction is an early pathological feature that occurs prior to neurodegeneration and memory dysfunction. Mounting evidence suggests that aggregation of amyloid-${\alpha}$ ($A{\alpha}$) and hyperphosphorylated tau leads to synaptic deficits and neurodegeneration, thereby to memory loss. Among the established genetic risk factors for AD, the ${\varepsilon}4$ allele of apolipoprotein E (APOE) is the strongest genetic risk factor. We and others previously demonstrated that apoE regulates $A{\alpha}$ aggregation and clearance in an isoform-dependent manner. While the effect of apoE on $A{\alpha}$ may explain how apoE isoforms differentially affect AD pathogenesis, there are also other underexplored pathogenic mechanisms. They include differential effects of apoE on cerebral energy metabolism, neuroinflammation, neurovascular function, neurogenesis, and synaptic plasticity. ApoE is a major carrier of cholesterols that are required for neuronal activity and injury repair in the brain. Although there are a few conflicting findings and the underlying mechanism is still unclear, several lines of studies demonstrated that apoE4 leads to synaptic deficits and impairment in long-term potentiation, memory and cognition. In this review, we summarize current understanding of apoE function in the brain, with a particular emphasis on its role in synaptic plasticity and the underlying cellular and molecular mechanisms, involving low-density lipoprotein receptor-related protein 1 (LRP1), syndecan, and LRP8/ApoER2.

The Effects of Computer-Based Cognitive Rehabilitation Program(CoTras) for Visual Perception and ADL in Stroke (한국형 전산화 인지재활프로그램(CoTras)이 뇌졸중 환자의 시지각 기능 및 일상생활동작에 미치는 효과)

  • Jo, A-Young;Kim, Jung-Mi
    • The Journal of Korean society of community based occupational therapy
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    • v.2 no.1
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    • pp.49-63
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    • 2012
  • Objective : The purpose of study was to verify the clinical effect of a Korean Computer-based cognitive rehabilitation program(called CoTras) for recovering the visual perception function and ADL in stroke. Methods : A CBCRT was applied to 14 Stoke patients who rehabilitation professional medical treatment hospital. All participant were evaluated with four standardized assessment tolls(Motor-Free Visual Perception Test; MVPT, Korean version of Mini-Mental State Examination; MMSE-K, Assesment of Motor and Process Skills: AMPS) before and after the planned computer based cognitive rehabilitation sessions. Results : A significant effect was confirmed (p<.05) from the CBCRT which visual perception function. By each entry comparative result, visual memory, figure ground, visual close, spatial relation, visual discrimination, were the order of treatment. Neither was found any significant effect in improving process skills from AMPS. Conclusion : These results indicate that CoTras have effects on improving visual perception and ADL performance in stroke patients. Will be able to present with the fundamental data CoTras will be able to contribute to increase visual perception function & ADL performance to the stroke patient who has visual perception dysfunction.

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Ethanolic Extract of the Seed of Zizyphus jujuba var. spinosa Ameliorates Cognitive Impairment Induced by Cholinergic Blockade in Mice

  • Lee, Hyung Eun;Lee, So Young;Kim, Ju Sun;Park, Se Jin;Kim, Jong Min;Lee, Young Woo;Jung, Jun Man;Kim, Dong Hyun;Shin, Bum Young;Jang, Dae Sik;Kang, Sam Sik;Ryu, Jong Hoon
    • Biomolecules & Therapeutics
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    • v.21 no.4
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    • pp.299-306
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    • 2013
  • In the present study, we investigated the effect of ethanolic extract of the seed of Zizyphus jujuba var. spinosa (EEZS) on cholinergic blockade-induced memory impairment in mice. Male ICR mice were treated with EEZS. The behavioral tests were conducted using the passive avoidance, the Y-maze, and the Morris water maze tasks. EEZS (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in our present behavioral tasks without changes of locomotor activity. The ameliorating effect of EEZS on scopolamine-induced memory impairment was significantly reversed by a sub-effective dose of MK-801 (0.0125 mg/kg, s.c.). In addition, single administration of EEZS in normal naive mouse enhanced latency time in the passive avoidance task. Western blot analysis was employed to confirm the mechanism of memory-ameliorating effect of EEZS. Administration of EEZS (200 mg/kg) increased the level of memory-related signaling molecules, including phosphorylation of extracellular signal-regulated kinase or cAMP response element-binding protein in the hippocampal region. Also, the time-dependent expression level of brain-derived neurotrophic factor by the administration of EEZS was markedly increased from 3 to 9 h. These results suggest that EEZS has memory-ameliorating effect on scopolamine-induced cognitive impairment, which is mediated by the enhancement of the cholinergic neurotransmitter system, in part, via NMDA receptor signaling, and that EEZS would be useful agent against cognitive dysfunction such as Alzheimer's disease.

The Effect of Treadmill Exercise and Environmental Enrichment on Cognitive Function, Muscle Function, and Levels of tight junction protein in an Alzheimer's Disease Animal Model (트레드밀 운동 및 환경강화가 알츠하이머 질환 동물 모델의 인지기능, 근 기능 및 밀착연접 단백질 수준에 미치는 영향)

  • Hyun-Seob Um;Jong-Hwan Jung;Tae-Kyung Kim;Yoo-Joung Jeon;Joon-Yong Cho;Jung-Hoon Koo
    • Journal of the Korean Applied Science and Technology
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    • v.41 no.1
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    • pp.58-68
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    • 2024
  • The purpose of this study was to investigate the effects of treadmill exercise treadmill exercise (TE) and environmental enrichment (EE) interventions on cognitive function, muscle function, and the expression of tight junction proteins in an Alzheimer's disease (AD) animal model. To create the AD animal model, aluminum chloride (AlCl3) was administered for 90 days (40mg/kg/day), while simultaneously exposing the animals to TE (10-12m/min, 40-60min/day) or EE. The results showed that cognitive impairment and muscle dysfunction induced by AlCl3 administration were alleviated by TE and EE. Furthermore, TE and EE reduced the increased expression of β-amyloid(Aβ), alpha-synuclein, and tumor necrosis factor-α (TNF-α) proteins observed in AD pathology. Additionally, TE and EE significantly increased the expression of decreased adhesive adjacent proteins (Occludin, Claudin-5, and ZO-1) induced by AlCl3 administration. Lastly, correlation analysis between Aβ protein and tight junction proteins showed negative correlations (Occludin: r=-0.853, p=0.001; Claudin-5: r=-0.352, p=0.915; ZO-1: r=-0.424, p=0.0390). In conclusion, TE or EE interventions are considered effective exercise methods that partially alleviate pathological features of AD, improving cognitive and muscle function.

Mild Impairments in Cognitive Function in the Elderly with Restless Legs Syndrome (노인 하지불안증후군에서의 인지기능 저하)

  • Kim, Eun Soo;Yoon, In-Young;Kweon, Kukju;Park, Hye Youn;Lee, Chung Suk;Han, Eun Kyoung;Kim, Ki Woong
    • Sleep Medicine and Psychophysiology
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    • v.20 no.1
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    • pp.15-21
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    • 2013
  • Objectives: Cognitive impairment in restless legs syndrome (RLS) patients can be affected by sleep deprivation, anxiety and depression, which are common in RLS. The objective of this study is to investigate relationship between cognitive impairment and RLS in the non-medicated Korean elderly with controlling for psychiatric conditions. Method: The study sample for this study comprised 25 non-medicated Korean elderly RLS patients and 50 age-, sex-, and education- matched controls. All subjects were evaluated with comprehensive cognitive function assessment tools- including the Korean version of Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K), severe cognitive impairment rating scale (SCIRS), frontal assessment battery (FAB), and clock drawing test (CLOX). Sleep quality and depression were also assessed with Pittsburgh sleep quality index (PSQI) and geriatric depression scale (GDS). Results: PSQI and GDS score showed no difference between RLS and control group. There was no significant difference between two groups in nearly all the cognitive function except in constructional recognition test, in which subjects with RLS showed lower performance than control group (t=-2.384, p=0.02). Subjects with depression ($GDS{\geq}10$) showed significant cognitive impairment compared to control in verbal fluency, Korean version of Mini Mental Status Examination in the CERAD-K (MMSE-KC), word list memory, trail making test, and frontal assessment battery (FAB). In contrast, no difference was observed between subjects who have low sleep quality (PSQI>5) and control group. Conclusions: At the exclusion of the impact of insomnia and depression, cognitive function was found to be relatively preserved in RLS patients compared to control. Impairment of visual recognition in RLS patients can be explained in terms of dopaminergic dysfunction in RLS.

Correlation between Peripheral Neuropathy and Cognitive Factors in Type 2 Diabetic Patients (제2형 당뇨병환자에서 말초신경병증과 인지기능항목의 상관관계)

  • Yang, Wonyul;Kim, Jong Kuk;Park, Kyung Won;Suh, Sunghwan;Lee, Hye-Jeong;Park, Mi-Kyoung
    • Journal of Life Science
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    • v.30 no.3
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    • pp.250-259
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    • 2020
  • Diabetes is a well-known risk factor for dementia and cognitive impairment. Diabetic polyneuropathy (DPN) is the most prevalent microvascular complication in type 2 diabetes mellitus (T2DM) patients. The purpose of this study was to evaluate the relation between diabetic peripheral polyneuropathy and cognitive factors in T2DM patients. Retrospective chart review of type 2 diabetic patients with results of a nerve conduction study (NCS) and a neurocognitive study. A total of 19 patients were included. DPN was defined using data from a nerve conduction study: a score of less than 24 in the Korean version of the Mini-Mental State Examination (K-MMSE) was considered as an indicator of cognitive impairment (CI). The mean age of the 19 patients was 71.6±5.0 years. The mean duration of diabetes was 8.4±9.1 years, and the mean HbA1c level was 8.1±1.8%. DPN was present in 7 of the 19 patients. Based on the K-MMSE score, CI was diagnosed in eight patients. The mean K-MMSE scores and the prevalence of CI was not different between the groups with and without DPN. There was no significant difference in DPN prevalence between the groups with and without CI. Education was significantly correlated with cognitive factors. Only the digit span-forward among the cognitive factors showed a significant negative correlation with nerve conduction velocity. In conclusion, the longer education period was associated with higher cognitive function and no significant correlation was observed between diabetic peripheral neuropathy and cognitive dysfunction in type 2 diabetic patients. Further prospective research is needed in the future.

Effects of Cupping Therapy on Memory Impairment after Hemorrhage in Rats (뇌출혈 동물 모델에서 부항이 뇌 인지기능 회복에 미치는 효과)

  • Lee, Ji Hye;Joh, Day;Choi, Young Ho;Chung, Chan Kyung;Choi, Yoon Suk;Cha, Mi Gyoung;Jung, Ji Wook
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.27 no.6
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    • pp.789-794
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    • 2013
  • Hemorrhage is a devastating type of stroke, accounts for 15-20% of all strokes. This disease can cause cognitive dysfunction with a very high mortality rate. Cupping therapy of Traditional Korean medicine has frequently been used to relieve a variety of diseases or clinical conditions, although not in the memory loss after hemorrhage. This study was designed to evaluate the effects of cupping therapy on learning and memory with Y-maze test, as well as its effects on different molecular changes in hippocampus following the induction of hemorrhage in rats. Cupping, using vacuum cupping machine, was applied at target area for 5 min daily for 7 consecutive days, commencing 1 day after brain impairment. As a result, induction of hemorrhage enhanced memory deficit, suppressed brain-derived neurotrophin factor (BDNF) in the hippocampus. Cupping treatment effectively reversed collagenase-induced cognitive impairment in SD rats which was represented by improvement of spontaneous alterations in Y-maze test. In addition, BDNF expression was enhanced after cupping therapy. The present results suggest that the therapeutic effects of cupping treatment after hemorrhage is involved in expression of BDNF.

The effects of regular exercise on capsaicin-induced pulpal pain and pain-induced changes in passive avoidance learning and memory in rats

  • Raoof, Maryam;Shakoori, Afshin;Kooshki, Razieh;Abbasnejad, Mehdi;Amanpour, Sara
    • The Korean Journal of Pain
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    • v.30 no.4
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    • pp.258-264
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    • 2017
  • Background: Pulpal pain is one of the most common and severe orofacial pain conditions with considerable adverse effects on physiological processes including learning and memory. Regular exercise is known to be effective on cognitive function as well as pain processing in the central nervous system. Here, the possible effects of regular exercise on pulpal pain response as well as pain-induced changes in learning and memory efficiency in rats were investigated. Methods: Twenty-four male Wistar rats were randomly assigned to the control, capsaicin, exercise, and exercise plus capsaicin groups. Rats in exercise groups were forced to run on a treadmill with a moderate exercise protocol for 4 weeks. Capsaicin was used to induce dental pulp pain. Passive avoidance learning and memory performance was assessed by using a shuttle box apparatus. Results: According to the results, regular exercise could decrease the time course of capsaicin-induced pulpal pain (P < 0.001). Moreover, in capsaicin-treated rats, passive avoidance acquisition was impaired as compared to the control (P < 0.05) and exercise (P < 0.001) groups. Additionally, regular exercise before capsaicin injection could attenuate capsaicin-induced memory impairments (P < 0.05). Conclusions: Taken together, the present data showed that regular exercise has inhibitory effects on capsaicin-induced pulpal pain as well as pain-induced cognitive dysfunction in rats.

Comparison of Executive Function in Children with ADHD and Anxiety Disorder (주의력결핍 과잉행동장애, 불안장애 아동의 실행기능 비교)

  • Park, Soon-Mal;Shin, Min-Sup
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.21 no.3
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    • pp.147-152
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    • 2010
  • Objectives : The purpose of this study was to investigate the deficits in executive function in children with ADHD and anxiety disorder, and further, to characterize executive function deficits among the two groups. Methods : Subjects consisted of 60 children between the ages of 5 and 14 (16 Normal, 24 ADHD, 20 Anxiety Disorder). Neuropsychological tests (KEDI-WISC, CCTT, STROOP, WCST, ROCF) for assessing cognitive and executive function were individually administered to all subjects. Results : There were no significant differences in FSIQ or PIQ among the three groups. However, the ADHD group tended to score lower on the VIQ and subtest of similarity, vocabulary, and digit span tests. The three groups did not significantly differ with respect to CCTT test results. On the STROOP test, the ADHD group showed poor performance on the word, color, and color-word subtests. The three groups did not exhibit significant differences in WCST test results ; however, the anxiety group performed poorly belonging to below 25 percentile rank on perseverative response. On the ROCF test, the ADHD group performed poorly with respect to their organization score and in particular, regarding copy and immediate recall. The anxiety group also performed poorly with regard to organization ; however, this was limited only to immediate recall. Conclusion : Children with ADHD displayed poor inhibition and organizational abilities compared to children with anxiety and normal controls. Further, children with anxiety disorder exhibited low cognitive flexibility and voluntary problem-solving abilities compared to ADHD children and normal controls. Based on these results, we suggest that the characteristics of executive dysfunction in ADHD and anxiety disorder in children are different.

Biological Mechanism of Suicide (자살의 생물학적 기전)

  • Cheon, Eun-Jin
    • Journal of the Korean society of biological therapies in psychiatry
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    • v.24 no.3
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    • pp.129-141
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    • 2018
  • Suicide is a behavior that is intended to cause death by itself and requires medical treatment, resulting in suicidal attempt or completion. Suicide causes loss of life, damages the body, costs a lot of medical expenses, and causes families to fall into sorrow and suffering therefore this suicide is a huge loss to family and society. There have been attempts to reduce and prevent suicide by understanding the mechanism of suicide. The mechanism of suicide can be thought of as psychological mechanism and biological mechanism. In the past, if we considered the psychological and biological mechanisms separately, the development of neuroscience now connects and integrates these two. Psychological factors affect biological factors and biological temperaments also affect perception or thinking about the situation and increase psychological vulnerability. Distant factors in suicidal behavior-such as childhood adversity and family and genetic predisposition-increase the lifetime risk of suicide. They alter the response to stress and other processes through changes in gene expression and regulation of emotional and behavioral characteristics. Distant factors affect the biological system and consequently changes in these systems can increase the risk of suicide. In other words, the distal factor does not directly induce suicidal behavior but rather acts indirectly through developmental or mediating factors. These mediating factors are impulsive aggressive and anxious trait, and chronic use of substances. The mechanism of this disorder is the abnormality of the serotonin system and the abnormality of the lipid level. Proximal factors are associated with the onset of suicide events and include changes in the major neurotransmitter systems, inflammatory changes, and dysfunction of glial cells in the brain. A series of studies, including a variety of research methods and postmortem and in-vivo imaging studies, show the impairment of the serotonergic neurotransmitter system and hypothalamic-pituitary-adrenal axis stress response system for suicidal behavior. These disorders lead to suicidal behavior due to difficulty in cognitive control of mood, pessimism, reactive aggression, abnormality in problem solving abilities, excessive response to negative social signals, severe emotional distress, and cognitive dysregulation of suicidal ideation.