• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.77-83
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• 2024

Alzheimer's disease (AD) is a neurodegenerative disease characterized by neuronal cell death and memory impairment. Corticosterone (CORT) is a glucocorticoid hormone produced by the hypothalamic-pituitary-adrenal axis in response to a stressful condition. Excessive stress and high CORT levels are known to cause neurotoxicity and aggravate various diseases, whereas mild stress and low CORT levels exert beneficial actions under pathophysiological conditions. However, the effects of mild stress on AD have not been clearly elucidated yet. In this study, the effects of low (3 and 30 nM) CORT concentration on Aβ_25-35-induced neurotoxicity in SH-SY5Y cells and underlying molecular mechanisms have been investigated. Cytotoxicity caused by Aβ_25-35 was significantly inhibited by the low concentration of CORT treatment in the cells. Furthermore, CORT pretreatment significantly reduced Aβ_25-35-mediated pro-apoptotic signals, such as increased Bim/Bcl-2 ratio and caspase-3 cleavage. Moreover, low concentration of CORT treatment inhibited the Aβ_25-35-induced cyclooxygenase-2 and pro-inflammatory cytokine expressions, including tumor necrosis factor-α and interleukin-1β. Aβ_25-35 resulted in intracellular accumulation of reactive oxygen species and lipid peroxidation, which were effectively reduced by the low CORT concentration. As a molecular mechanism, low CORT concentration activated the nuclear factor-erythroid 2-related factor 2, a redox-sensitive transcription factor mediating cellular defense and upregulating the expression of antioxidant enzymes, such as NAD(P)H:quinone oxidoreductase, glutamylcysteine synthetase, and manganese superoxide dismutase. These findings suggest that low CORT concentration exerts protective actions against Aβ_25-35-induced neurotoxicity and might be used to treat and/or prevent AD.

• Dementia and Neurocognitive Disorders
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• v.22 no.2
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• pp.85-85
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• 2023

• Korean Journal of Psychosomatic Medicine
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• v.27 no.1
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• pp.60-68
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• 2019

Objectives : The association between thyroid-related hormones and cognitive function has been controversial. The purpose of this study is to compare the levels of thyroid-related hormones in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Furthermore, we investigated the relationship between thyroid-related hormones and cognitive function. Methods : From January 2011 to December 2018, we retrospectively reviewed 105 patients who were diagnosed with AD and MCI by visiting a dementia clinic at Ilsan Paik Hospital. Thyroid-related hormones [triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH)] was measured using chemiluminescent immunoassay. An independent sample t-test was performed to analyze the mean value of thyroid-related hormones in patients of AD and MCI. To investigate whether thyroid-related hormones correlate significantly with Global deterioration scale (GDS), Clinical dementia rating (CDR) and scores of each The Korean version of the consortium to establish a registry for Alzheimer's disease items, we conducted a partial correlation analysis with geriatric depression scale-Korean version (GDS-K) scores as covariates. Results : There was no significant difference in the mean serum T3, T4 and TSH levels between patients of the AD and the MCI, but the Construction Praxis Test (CPT) showed a significant positive correlation with the serum TSH concentration (p-value=0.004). Conclusions : In our study, the positive correlation between serum TSH level and the CPT associated with executive function was found to be helpful in understanding the association between thyroid-related hormones and the pathophysiology of dementia. Prospective studies in regard of the pathophysiology of thyroid-related hormones on cognitive function will be necessary in the future.

• Korean Journal of Psychosomatic Medicine
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• v.29 no.1
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• pp.67-76
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• 2021

Objectives : The aim of this study was to compare activities of daily living (ADLs) according to degenerative changes in brain [i.e., medial temporal lobe atrophy (MTA), white matter hyperintensities] and to examine the association between neurocognitive functions and ADLs in Korean patients with dementia due to Alzheimer's disease (AD) and mild cognitive impairment (MCI). Methods : Participants were 111 elderly subjects diagnosed with AD or MCI in this cross-sectional study. MTA in brain MRI was rated with standardized visual rating scales (Scheltens scale) and the subjects were divided into two groups according to Scheltens scale. ADLs was evaluated with the Korean version of Blessed Dementia Scale-Activity of daily living (BDS-ADL). Neurocognitive function was evaluated with the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease assessment packet (CERAD-K). Independent t-test was performed to compare ADLs with the degree of MTA. Pearson correlation and hierarchical multiple regression analyses were performed to analyze the relationship between ADLs and neurocognitive functions. Results : The group with high severity of the MTA showed significantly higher BDS-ADL scores (p<0.05). The BDS-ADL score showed the strongest correlation with the word list recognition test among sub-items of the CERAD-K test (r=-0.568). Findings from the hierarchical multiple regression analysis revealed that the scores of MMSE-K and word list recognition test were factors that predict ADLs (F=44.611, p<0.001). Conclusions : ADLs of AD and MCI patients had significant association with MTA. Our study, which identifies factors correlated with ADLs can provide useful information in clinical settings. Further evaluation is needed to confirm the association between certain brain structures and ADLs.

• Korean Journal of Psychosomatic Medicine
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• v.22 no.1
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• pp.40-45
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• 2014

Objectives : Mild cognitive impairment(MCI) and dementia of Alzheimer's type(AD) are characterized by progressive decline of cognitive abilities and a wide range of neuropsychiatric symptoms like depression. Among various diagnostic tools of AD, many studies showed that elevated levels of serum total homocysteine are associated with increased risk of developing Alzheimer's disease, depression and other neuropsychiatric disorders. We investigated whether elevated homocysteine concentrations are associated with depressive symptoms in MCI and AD. Methods : A total of 86 patients diagnosed with MCI or AD participated. Total serum homocysteine levels in fasting blood samples were measured. We examined cognitive symptoms by MMSE-KC, Global Deterioration Scale(GDS), Clinical dementia rating(CDR) and depressive symptoms by Korean version of Geriatric Depression Scale(K-GDS). Results : The total serum homocysteine levels were significantly higher in MCI with depression than in MCI without depression. There was no significant difference in the mean homocysteine levels between AD patients with depression and AD patients without depression. The total homocysteine levels showed a negative correlation with MMSE-KC and a positive correlation with CDR, GDS. Conclusions : These findings suggest that elevated homocysteine level is a risk factor for the decline of cognitive function and depression. We found a significant relationship between elevated serum homocysteine level and depressive symptoms in MCI. But our study had several limitations, thus more research is needed to confirm this finding.

• Korean Journal of Biological Psychiatry
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• v.22 no.4
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• pp.223-232
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• 2015

Objectives In this study, the authors evaluated the correlation between levels of serum lipid, homocysteine, and folate with volumes of hippocampus, amygdala, corpus callosum, and in patients with amnestic mild cognitive impairment (aMCI) or Alzheimer's disease (AD) type. Methods The study recruited patients who visited the dementia clinic of Haeundae Paik Hospital in Korea between March 2010 and June 2014. Among those, patients who had taken the neurocognitive test, brain magnetic resonance imaing, tests for serum lipid, homocysteine, folate, and apolipoprotein E (APOE) genotyping and diagnosed with aMCI or AD were included for analysis. Bilateral hippocampus, entorhinal cortex, amygdala and corpus callosum were selected for region of interest (ROI). The cross-sectional relationships between serum lipid, homocysteine, folate and ROI were assessed by partial correlation analysis and multiple linear regression analysis. Results In patients with aMCI, old age (> 80) and APOE ${\varepsilon}4$ carrier were associated with AD [odds ration (OR) : 12.80 ; 95% confidence interval (CI) : 2.25-72.98 and OR : 4.48 ; 95% CI : 1.58-12.67, respectively]. In patients with aMCI or AD, volumes and thickness of ROI were inversely correlated with levels of serum lipid and homocysteine. In multiple linear regression analyses, higher total cholesterol level was related to lower left, right hippocampus volume and left amygdala volume ; higher low-density lipoprotein cholesterol was related to lower right entorhinal cortex thickness ; higher homocysteine level was related to lower corpus callosum volume. Conclusions Higher serum lipid and homocysteine levels are associated with decreased volume of hippocampus, amygdala, corpus callosum and entorhinal cortex thickness in patients with aMCI or AD. These findings suggest that serum lipid and homocysteine levels are associated with AD as a modifiable risk factor.

• Journal of Biomedical Engineering Research
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• v.39 no.6
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• pp.237-242
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• 2018

$^{18}F$-fludeoxyglucose PET (FDG-PET) can help finding an abnormal metabolic activity in brain. In this study, we evaluated an efficiency of volume- and cortical surface-based analysis which were used to determine whether standardized uptake value ratio (SUVR) of FDG-PET was different among Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy control (HC). Each PET image was rigidly co-registered to the corresponding magnetic resonance imaging (MRI) using mutual information. All voxels of the co-registered PET images were divided by the mean FDG uptake of the cerebellum cortex which was thresholded by partial volume effect (>0.9). Also, the SUVR value of each vertex was linearly interpolated from volumetric SUVR image which was thresholded by gray matter partial volume effect (>0.1). Lobar mean values were calculated from both volume- and cortical surface-based SUVRs. Statistical analysis was conducted to compare two measures for AD, MCI and HC groups. Even though the results of volume (SUVR_vol) and cortical surface-based SUVR (SUVR_surf) analysis were not significantly different from each other, the latter would be better for detecting group differences in SUVR of PET.

• Dementia and Neurocognitive Disorders
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• v.22 no.4
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• pp.148-157
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• 2023

Background and Purpose: Episodic memory is a system that receives and stores information about temporally dated episodes and their interrelations. Our study aimed to investigate the relevance of episodic memory to time perception, with a specific focus on simultaneity/order judgment. Methods: Experiment 1 employed the simultaneity judgment task to discern differences in time perception between patients with mild cognitive impairment or dementia, and age-matched normals. A mathematical analysis capable of estimating subjects' time processing was utilized to identify the sensory and decisional components of temporal order and simultaneity judgment. Experiment 2 examined how differences in temporal perception relate to performance in temporal order memory, in which time delays play a critical role. Results: The temporal decision windows for both temporal order and simultaneity judgments exhibited marginal differences between patients with episodic memory impairment, and their healthy counterparts (p = 0.15, t(22) = 1.34). These temporal decision windows may be linked to the temporal separation of events in episodic memory (Pearson's ρ = -0.53, p = 0.05). Conclusions: Based on our findings, the frequency of visual events accumulated and encoded in the working memory system in the patients' and normal group appears to be approximately (5.7 and 11.2) Hz, respectively. According to the internal clock model, a lower frequency of event pulses tends to result in underestimation of event duration, which phenomenon might be linked to the observed time distortions in patients with dementia.

• Korean Journal of Cognitive Science
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• v.20 no.1
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• pp.79-107
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• 2009

Episodic memory, i.e. memorization of information within a spatiotemporal environment, is affected Alzheimer's disease(AD), but its impairment may also be occurred in the normal aging process. The purpose of this study is to analyze and evaluate memory in with Dementia of Alzheimer Type by examining their cognitive skills in episodic memory using the technique. This new method involves assessing the mental images the subject's own past in the mind like projected and movies. Three patients in the early stage of Dementia of Alzheimer Type, one with mild depression, and 2 healthy controls for comparison were asked to retrieve their episodic memory of the previous day, week, month, and a day testing day. The answers were then analyzed with regards to their specific features as emotional state, color, and time order. In the following day, the subjects were tasked to recall again the images they reproduced in the day's test order to observe of memory. Results showed that all 3 patients failed to arrange the retrieved images in time order and their images of the previous day were unclear in color and were stationary like photographs, even when they reproduced the mental images at much quantity as controls. patients could not remember particular events of yesterday, and only recalled the general occurrences of every day life. These results suggest that in the early stage of Dementia of Alzheimer Type, difficulties in the retrieval of recent episodic memory begin to primarily occur, and qualitative impairment happens earlier than quantitative.

• Journal of Microbiology and Biotechnology
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• v.33 no.10
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• pp.1376-1383
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• 2023

Recent studies have confirmed that gut microbiota differs according to race or country in many diseases, including mild cognitive impairment (MCI) and Alzheimer's disease. However, no study has analyzed the characteristics of Korean MCI patients. This study was performed to observe the association between gut microbiota and MCI in the Korean elderly and to identify potential markers for Korean MCI patients. For this purpose, we collected fecal samples from Korean subjects who were divided into an MCI group (n = 40) and control group (n = 40) for 16S rRNA gene amplicon sequencing. Although no significant difference was observed in the overall microbial community profile, the relative abundance of several genera, including Bacteroides, Prevotella, and Akkermansia, showed significant differences between the two groups. In addition, the relative abundance of Prevotella was negatively correlated with that of Bacteroides (r = 0.733). This study may provide Korean-specific basic data for comparing the characteristics of the gut microbiota between Korean and non-Korean MCI patients.