• The Journal of Korean Medicine
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• v.26 no.3 s.63
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• pp.27-42
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• 2005

Objectives : Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease characterized by amyloid plaques and neurofibrillary tangles. These plaques are associated with degenerating neuronal processes and consist primarily of fibrillary aggregates of beta-amyloid$ protein, generated from amyloid precursor protein (APP). Another amyloidogenic fragment, the carboxyl terminus (CT) of APP, which is composed of 99-105 amino acid residues containing the complete $A{\beta}$ sequence, also appears to be toxic to neurones. Recent evidence suggest that CT105, carboxy terminal 105 amino acids peptide fragment of APP, may be an important factor causing neurotoxicity in AD. Methods : Although a variety of oriental prescriptions including Pinelliae rhizoma have traditionally been utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet been fully elucidated. In the present study, we investigated effects of the dichloromethane extract of Pinelliae rhizoma (PINR) on neurotoxicity and the formation of reactive oxygen species (ROS) and nitric oxide (NO) in SK-N-SH cells overexpressed with CT105. In addition, we evaluated its radical scavenging activity and effects on acetylcholinesterase (AChE) activity. Furthermore, effects on cognitive deficits induced by scopolamine treatment in rats were evaluated. Results ; We found in this study that PINR significantly inhibited apoptotic neuronal death induced by CT105 overexpression in SK-N-SH cells. Based on morphological examinations by phase-contrast microscopy, PINR reversed apoptotic changes of CT105-expressed cells. It was also found that PINR significantly promoted neurite outgrowth and inhibited formation of ROS nd NO. PINR was shown to scavenge DPPH radicals and noncompetitively inhibit AChE activity. Furthermore, it reduced scopolamine-induced memory impairment in rata, assessed by passive avoidance test. Conclusions : Taken together, these results demonstrate that PINR exhibits neuroprotective, antioxidant, and memory enhancing effects, and therefore may bs beneficial for the treatment of AD.

• Journal of Life Science
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• v.17 no.11
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• pp.1464-1471
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• 2007

Diabetes mellitus is a chronic metabolic disorder, leading to many complications including cognitive deficit. Regular exercise has often been recommended as a therapeutic maneuver to the diabetic patients for the prevention of secondary complications. In the present study, the effects of treadmill exercise on memory and brain-derived neurotrophic factor (BDNF) in the hippocampus of streptozotocin (STZ)-induced diabetic rats were investigated. Male SD rats, aged 6 weeks, were randomly assigned to the following three groups: control group(n=8), STZ-induced diabetic group(n=8), and STZ-induced diabetes and exercise group(n=8). Diabetes was induced by a single injection of STZ (50 mg/kg body weight). Treadmill running was conducted with duration and frequency of 30 minutes and 5 times per week, respectively, for 8 weeks. Memories were tested in the Morris water maze. Western blotting was performed to detect BDNF expression in the hippocampus. In this study, we found that compared to the control group, the STZ-induced diabetes group had a significantly impaired cognitive performance along with suppressed BDNF expression in the hippocampus and the exercise group had a higher cognitive function in diabetic rats. Therefore, the current findings of the study show that a treadmill running exercise can improve diabetes-induced impairment of cognitive function. And the improved cognitive function appears to be related to an alleviation in diabetes-induced BDNF expression in hippocampus.

• Journal of Biomedical Engineering Research
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• v.42 no.4
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• pp.150-158
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• 2021

Intracranial hemorrhage (ICH) refers to acute bleeding inside the intracranial vault. Not only does this devastating disease record a very high mortality rate, but it can also cause serious chronic impairment of sensory, motor, and cognitive functions. Therefore, a prompt and professional diagnosis of the disease is highly critical. Noninvasive brain imaging data are essential for clinicians to efficiently diagnose the locus of brain lesion, volume of bleeding, and subsequent cortical damage, and to take clinical interventions. In particular, computed tomography (CT) images are used most often for the diagnosis of ICH. In order to diagnose ICH through CT images, not only medical specialists with a sufficient number of diagnosis experiences are required, but even when this condition is met, there are many cases where bleeding cannot be successfully detected due to factors such as low signal ratio and artifacts of the image itself. In addition, discrepancies between interpretations or even misinterpretations might exist causing critical clinical consequences. To resolve these clinical problems, we developed a diagnostic model predicting intracranial bleeding and its subtypes (intraparenchymal, intraventricular, subarachnoid, subdural, and epidural) by applying deep learning algorithms to CT images. We also constructed a visualization tool highlighting important regions in a CT image for predicting ICH. Specifically, 1) 27,758 CT brain images from RSNA were pre-processed to minimize the computational load. 2) Three different CNN-based models (ResNet, EfficientNet-B2, and EfficientNet-B7) were trained based on a training image data set. 3) Diagnosis performance of each of the three models was evaluated based on an independent test image data set: As a result of the model comparison, EfficientNet-B7's performance (classification accuracy = 91%) was a way greater than the other models. 4) Finally, based on the result of EfficientNet-B7, we visualized the lesions of internal bleeding using the Grad-CAM. Our research suggests that artificial intelligence-based diagnostic systems can help diagnose and treat brain diseases resolving various problems in clinical situations.

• The Korean Journal of Nuclear Medicine
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• v.30 no.3
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• pp.299-314
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• 1996

The purpose of the present study was to validate the use of tissue radioactivity ratios instead of regional metabolic rates for the assessment of regional metabolic changes in Alzheimer's disease(AD) with [$^{18}F$]FDG PET and to examine the correlation of ratio indices with the severity of cognitive impairment in AD. Thirty-seven AD Patients(age $68{\pm}9 yrs$, $mean{\pm}s.d.$; 36 probable and 1 definite AD), 28 patients with dementia of non-Alzheimer type(age $66{\pm}7 yrs$), and 17 healthy controls(age $66{\pm}4 yrs$) underwent [$^{18}F$]FDG PET imaging. Two simplified radioactivity ratio indices were calculated from 37-66 min image: region-to-cerebellar radioactivity ratio(RCR) and a composite radioactivity ratio(a ratio of radioactivity in the most typically affected regions over the least typically affected regions: CRR). Local cerebral metabolic rate for glucose(LCMRglu) was also measured using a three-compartment, five-parameter tracer kinetic model. The ratio indices were significantly lower in AD patients than in controls(RCR in temporoparietal cortex, $0.949{\pm}0.136$ vs. $1.238{\pm}0.129$, p=0.0004; RCR in frontal cortex, $1.027{\pm}0.128$ vs. $1.361{\pm}0.151$, p<0.0001; CRR, $0.886{\pm}0.096$ vs. $1.032{\pm}0.042$. p=0.0024). On the RCR analysis, 86% of AD patients showed a pattern of bilateral temporoparietal hypometabolism with or without frontal involvement; hypometabolism was unilateral in 11% of the patients. When bilateral temporoparietal hypometabolism was considered to be suggestive of AD, the sensitivity and specificity of the RCR analysis for the differential diagnosis of AD were 86% and 73%, respectively. The RCR was correlated significantly with the macroparameter K [$K_1k_3/(k_2+k_3)$] (r=0.775, p<0.0001) and LCMRglu(r=0.633, p=0.0002) measured using the kinetic model. In patients with AD, both average RCR of cortical association areas and CRR were correlated with Mini-Mental Status Examination(r=0.565, p=0.0145; r=0.642, p=0.0031, respectively), Clinical Dementia Rating(r=-0.576, p=0.0124; r=-0.591, p=0.0077), and total score of Mattis Dementia Rating Scale (r=0.574, p=0.0648; r=0.737, p=0.0096). There were also significant correlations between memory and language impairments and corresponding regional RCRs. The results suggest that the [$^{18}F$]FDG PET ratio indices, RCR and CRR, reflect global and regional metabolic rates and correlate with the severity of cognitive impairment in AD. The simplified ratio analysis may be clinically useful for the differential diagnosis and serial monitoring of the disease.

• Korean Journal of Psychosomatic Medicine
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• v.27 no.2
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• pp.155-163
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• 2019

Objectives : The aim of this study was to compare severity, neurocognitive functions, and behavioral and psychological symptoms of dementia (BPSD) according to the degree of temporal lobe atrophy (MTA) in Korean patients with dementia due to Alzheimer's disease and mild cognitive impairment due to Alzheimer's disease. Methods : Participants were 114 elderly subjects diagnosed with Alzheimer's disease or mild cognitive impairment 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. Severity was evaluated with Clinical Dementia Rating (CDR) and Global Deterioration Scale (GDS). Neurocognitive functions was evaluated with the Korean version of Short Blessed Test (SBT-K) and the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease assessment packet (CERAD-K). BPSD was evaluated with the Korean version of the Neuropsychiatric Inventory (K-NPI). Independent t-test was performed to compare severity, neurocognitive functions, and BPSD between two groups. Results : The group with high severity of MTA showed significantly lower scores in CDR, SBT-K, MMSE-KC, modified Boston naming test, word list recognition, and word list memory (p<0.05). There were no differences in K-NPI scores between two groups. Conclusions : Severity and neurocognitive functions of dementia had significant positive association with MTA, but BPSD had no association with MTA. Evaluating MTA seems to have potential benefit in diagnosing and treating neurocognitive impairments in the elderly. Further evaluation is needed to confirm the association between certain brain structures and BPSD.

• Korean Journal of Food Science and Technology
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• v.47 no.3
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• pp.373-379
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• 2015

This study aimed to investigate the anti-amnesic effect of perilla oil against trimethyltin (TMT)-induced learning and memory impairment in ICR mice. Perilla oil (2.5 mL/kg of body weight) and soybean oil (2.5 mL/kg of body weight) were administered orally to mice for 3 weeks, and at the end of the experimental period, cognitive behavior was examined by Y-maze and Morris water maze (MWM) tests. Behavioral tests showed that the mice treated with perilla oil had improved cognitive function compared to that in mice administered soybean oil. Analysis of brain tissue showed that perilla oil significantly lowered acetylcholinesterase activity and malondialdehyde (MDA) levels. Oxidized glutathione (GSH)-to-total GSH ratio also decreased from 10.4% to 5.3% in perilla oil-treated mice, but superoxide dismutase (SOD) activity increased from 11.7 to 14.2 U/mg protein. Therefore, these results suggest that the perilla oil could be a potential functional substance for improving cognitive function.

• Sleep Medicine and Psychophysiology
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• v.11 no.1
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• pp.44-49
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• 2004

Objectives: The purpose of this study was to investigate whether longitudinal changes in positive and negative symptoms affect cognitive functioning in chronic schizophrenia. Methods: Sixty-eight patients diagnosed with DSM-IV schizophrenia were examined on two occasions over 6 months for symptoms and cognitive changes. Symptoms were measured by PANSS. Cognitive functions were examined for sustained attention, executive function, concentration and attention, and verbal memory and learning using Degraded Stimulus Continuous Performance Test, Wisconsin Card Sorting Test, Digit Span, and Rey Auditory Verbal Learning Test, respectively. Twenty control subjects were assessed to compare the cognitive scores of remitted schizophrenic patients. Results: Patients showed significant improvement in symptoms and all cognitive tests after 6 months treatments. Significant improvements in positive and negative symptoms did not predict improvements in any aspect of cognitive functioning measured. Normal controls performed significantly better than remitted schizophrenic patients on all cognitive tests. The results show no relationship between change in symptoms and change in cognition in chronic schizophrenia. Conclusion: We suggest that symptomatic and cognitive impairment may be a distinct construct. These findings highlight the importance of treating cognitive impairment in addition to the clinical symptoms of schizophrenia.

• Journal of Applied Biological Chemistry
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• v.64 no.3
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• pp.299-307
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• 2021

Accumulation of amyloid beta (Aβ) and oxidative stress are the most common reason of Alzheimer's disease (AD). In the present study, we investigated the cognitive improvement effects of butanol (BuOH) fraction from Momordica charantia in Aβ_25-35-induced AD mouse model. To develop an AD mouse model, mice were received injection of Aβ_25-35, and then orally administered BuOH fraction from M. charantia at doses of 100 and 200 mg/kg/day during 14 days. In the T-maze and novel object recognition test, administration of BuOH fraction from M. charantia L. at doses of 100 and 200 mg/kg/day improved spatial ability and novel object recognition by increased explorations of novel route and new object. In addition, BuOH fraction of M. charantia-administered groups improved learning and memory abilities by decreased time to reach hidden platform in Morris water maze test. Oral administration of BuOH fraction from M. charantia significantly inhibited lipid peroxidation and nitric oxide levels in the brain, liver, and kidney compared with Aβ_25-35-induced control group. These results indicated that BuOH fraction of M. charantia improved Aβ_25-35-induced cognitive impairment by attenuating oxidative stress. Therefore, M. charantia could be useful for protection from Aβ_25-35-induced cognitive impairment.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.5
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• pp.241-251
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• 2019

In the present study, we investigated the effect of microcurrent against cognitive impairment in Alzheimer's disease (AD) mice model. The cognitive impairment was induced by intracerebroventricularly injection of amyloid beta ($A{\beta}$) to ICR mouse brain, and four kinds of micorocurrent wave were applied to AD mice. We observed the improved cognitive ability in microcurrent-applied AD mice through novel object recognition test and Morris water maze test, compared to $A{\beta}$-injected control group. The contents of malondialdehyde generated by $A{\beta}$ in the brain were also reduced by microcurrent application. These effects of microcurrent were related to the modulation of $A{\beta}$ producing and brain-derived neurotrophic factor (BDNF). Microcurrent down-regulated ${\beta}$-secretase, presenilin 1, and presenilin 2 which were related amyloidogenic pathway, and up-regulated human brain-derived neurotrophic factor in the mice brain, especially Wave4 group [STEP FORM wave form (0, 1.5, 3, 5V), wave superposition]. These results suggest that microcurrent application could provide help for improvement learning and memory ability, at least partly.

• Dementia and Neurocognitive Disorders
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• v.22 no.3
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• pp.100-108
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• 2023

Background and Purpose: The efficacy and safety of GV1001 have been demonstrated in patients with moderate-to-severe Alzheimer's disease (AD). In this study, we aimed to further demonstrate the effectiveness of GV1001 using subscales of the Severe Impairment Battery (SIB), which is a validated measure to assess cognitive function in patients with moderate-to-severe AD. Methods: We performed a post hoc analysis of data from a 6 month, multicenter, phase 2, randomized, double-blind, placebo-controlled trial with GV1001 (ClinicalTrials.gov, NCT03184467). Patients were randomized to receive either GV1001 or a placebo for 24 weeks. In the current study, nine subscales of SIB-social interaction, memory, orientation, language, attention, praxis, visuospatial ability, construction, and orientation to name-were compared between the treatment (GV1001 1.12 mg) and placebo groups at weeks 12 and 24. The safety endpoints for these patients were also determined based on adverse events. Results: In addition to the considerable beneficial effect of GV1001 on the SIB total score, GV1001 1.12 mg showed the most significant effect on language function at 24 weeks compared to placebo in both the full analysis set (FAS) and per-protocol set (PPS) (p=0.017 and p=0.011, respectively). The rate of adverse events did not differ significantly between the 2 groups. Conclusions: Patients with moderate-to-severe AD receiving GV1001 had greater language benefits than those receiving placebo, as measured using the SIB language subscale.