• Journal of the Korean Society of Radiology
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• v.84 no.3
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• pp.638-652
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• 2023

Purpose To investigate the MRI markers for the prediction of amyloid β (Aβ)-positivity in mild cognitive impairment (MCI) and Alzheimer's disease (AD), and to evaluate the differences in MRI markers between Aβ-positive (Aβ [+]) and -negative groups using the machine learning (ML) method. Materials and Methods This study included 139 patients with MCI and AD who underwent amyloid PET-CT and brain MRI. Patients were divided into Aβ (+) (n = 84) and Aβ-negative (n = 55) groups. Visual analysis was performed with the Fazekas scale of white matter hyperintensity (WMH) and cerebral microbleeds (CMB) scores. The WMH volume and regional brain volume were quantitatively measured. The multivariable logistic regression and ML using support vector machine, and logistic regression were used to identify the best MRI predictors of Aβ-positivity. Results The Fazekas scale of WMH (p = 0.02) and CMB scores (p = 0.04) were higher in Aβ (+). The volumes of hippocampus, entorhinal cortex, and precuneus were smaller in Aβ (+) (p < 0.05). The third ventricle volume was larger in Aβ (+) (p = 0.002). The logistic regression of ML showed a good accuracy (81.1%) with mini-mental state examination (MMSE) and regional brain volumes. Conclusion The application of ML using the MMSE, third ventricle, and hippocampal volume is helpful in predicting Aβ-positivity with a good accuracy.

• 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.

• Journal of Dairy Science and Biotechnology
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• v.33 no.3
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• pp.179-196
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• 2015

Because of our aging population, there is increasing concern about the impact of dementia and age-related cognitive decline. Intense research efforts on effective dietary interventions for the prevention or amelioration of dementia and age-related cognitive decline have indicated that dairy products affect physiological health and potentially healthy brain function during aging. Milk is a rich source of proteins and peptides with nutritional and immunotropic activities. The preparation of biologically active proteins and peptides generally requires enzymatic degradation, chemical modification, or the addition of specific co-factors. Milk-derived preparations are widely available in the food industry in the form of hygiene products and infant formulas. However, milk-derived products could also be applied as preventive or therapeutic measures for a wide-range of pathological conditions not only in neonates and infants but also in adults, including the elderly. Because they have no adverse side effects, milk-derived proteins and peptides could be used as a supplementary treatment for dementia and age-related cognitive decline.

• Journal of Oriental Neuropsychiatry
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• v.10 no.1
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• pp.17-38
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• 1999

The effects of Sahyangsohapwon on the affective reactivity of rats were studied with open-field behavior. Sample group was treated with the medicine for 8 weeks, whereas control group was treated with the vehicle. The effects of Sahyangsohapwon on the enhancement of learning and memory of AD model rats were studied with two-way avoidance task. Sample group electrically lesioned on nbM(nucleus basalis of Meynert) was treated with the medicine for 8 weeks, whereas control group with nbM lesion and sham group with the sham operation were treated with the vehicle. 1. In the open-field behavior task, the start latency from start box was measured $27.08{\pm}7.51sec$ in control group, $23.15{\pm}5.98sec$ in sample group. Rats in sample group showed a tendency of shortened latency going out to a strange place compared with those in control group, but with no statistical significance(p>0.05). 2. In the open-field behavior task, the number of locomotion crossing the grid lines was measured $84.54{\pm}3.55$ in control group, $116.93{\pm}6.41$ in sample group. There was an increased locomotion in sample group compared with control group with statistical significance(p<0.01). This can be interpreted as rats in sample group showed lowerd anxiety under a strange environment. 3. In the open-field behavior task, the rearing number was measured $7.46{\pm}0.57$ in control group, $10.13{\pm}0.95$ in sample group. There was an increased rearing in sample group compared with control group with statistical significance(p<0.05). This can also be interpreted as rats in sample group showed lowerd anxiety under a strange environment. 4. In the open-field behavior task, the number of crossing behavior was measured $5.54{\pm}1.50$ in control group, $9.20{\pm}1.67$ in sample group. There was a increasing tendency of crossing behavior in sample group compared with control group, but with no statistical significance(p<0.05). 5. In the open-field behavior task, the total activity was measured $97.54{\pm}4.70$ in control group, $136.27{\pm}792$ in sample group. There was an increased total activity in sample group compared with control group with statistical significance(p<0.01). This can also be interpreted as rats in sample group showed lowerd anxiety under a strange environment. 6. In the analysis of effects on the learning and memory in AD model rats with two-way avoidance task, the response latency was measured $6717{\pm}134msec$ in the 1st session, $5416{\pm}160msec$ in the 2nd session, $5252{\pm}148msec$ in the 3rd session in control group. It was measured $6724{\pm}155msec$ in the 1st session, $4642{\pm}139msec$ in the 2nd session, $4914{\pm}148msec$ in the 3rd session in sample group and $4357{\pm}144msec$ in the 1st session, $3125{\pm}115msec$ in the 2nd session, $3091{\pm}98msec$ in the 3rd session in sham group. There were differences between sham group and nbM lesioned groups with statistical significance in post hoc analysis(p<0.000). And in the 2nd session, there was a reduction of latency in sample group compared with control group with statistical significance (p<0.000). This showed that sample group had better learning capacity than control group. 7. In the analysis of effects on the learning and memory in AD model rats with two-way avoidance task, the number of avoidance response was measured $5.85{\pm}1.41$ in the 1st session, $14.23{\pm}2.89$ in the 2nd session, $15.69{\pm}2.56$ in the 3rd session in control group. It was measured $7.92{\pm}1.94$ in the 1st session, $16.83{\pm}2.29$ in the 2nd session, $15.42{\pm}2.81$ in the 3rd session in sample group and $14.38{\pm}1.62$ in the 1st session, $22.88{\pm}0.89$ in the 2nd session, $23.88{\pm}1.64$ in the 3rd session in sham group. There were differences between sham group and nbM lesioned groups with statistical significance in post hoc analysis(p<0.001). But between control and sample group, there was no significant difference. With the experimental results above, Sahyangsohapwon can be supposed to have the enhancing effects on the affect reactivity and learning with memory of AD model rats induced by electrolyte injury of nbM.

• Journal of Ginseng Research
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• v.24 no.1
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• pp.8-17
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• 2000

Estrogen can influence on the expression of behaviors not associated directly with reproduction, including learning and memory. Recently estrogen has received considerable attention for its effects on neuroprotection and neural circuits in brain areas associated with cognition. Although estrogen replacement therapy may be helpful to postmenopausal women, it also results in a number of harmful side effects. Ginseng also has steroidal qualities and contains several ginsenoside components which have similar backbone structure to estrogen. The objectives of this experiment were 1) to examine the effects of estrogen and 2) to investigate the effects of ginsenosides as estrogenic agent on learning and memory using the Morris water maze, a traditional experimental task for spatial memory. In the experiments designed here, ovariectomized mice were implanted subcutaneously with Sila, itic capsules containing 17${\beta}$-estradiol (100∼250 $\mu\textrm{g}$/$m\ell$), panaxadiol (PD) and panaxatriol (PT) saponins (15∼100 $\mu\textrm{g}$/$m\ell$) diluted with sesame oil. In the first set of experiment, the effects of estradiol on learning and memory during the Morris water maze was examined. When estradiol was delivered via Silastic capsules following training improved spatial memory performance in ovariectomized female mice. In the second set of experiment, three different PD and PT saponin concentrations were delivered via Silastic implants to ovariectomized female mice and their effects were compared with estrogenic effects. Results of three separate experiments demonstrated that estradiol, PD and PT administrated by Silastic implants for 2 weeks prior to water maze training significantly improved spatial memory performance compared to ovariectomized (OVX) mice, as indicated by lower escape latency over trial. The positive effect of estradiol suggests that estrogen can affect performance on learning and memory. In addition, the positive effect of PD and PT saponins suggest that ginsenosides have an estrogen-like effects in mediating learning and memory related behavior action.

• Food Science and Preservation
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• v.18 no.1
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• pp.124-129
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• 2011

PC12 neuronal cell-protective effects of hot water extracts of guava fruit and leaf were evaluated. Total phenolic levels in fruit and leaf were 11.75 and 293.25 mg/g, respectively. Gallic acid, the predominant phenoic, was detected in both extracts. Intracellular reactive oxygen species (ROS) accumulation after $H_2O_2$ treatment was significantly reduced when the hot water extract of guava leaf was added to cell medium, compared to PC12 cells treated with $H_2O_2$ only. In a cell viability assay using 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl- tetrazoliumbromide (MTT), the hot water extracts of fruit and leaf protected against $H_2O_2$-induced neurotoxicity. The leaf extract was more effective in terms of inhibition of lactate dehydrogenase (LDH) release into medium, compared to the fruit extract. These in vitro data suggest that hot water extracts of guava fruit and leaf may be useful in treatment of neurodegenerative conditions such as Alzheimer's disease.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.7
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• pp.958-965
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• 2016

The objective of this study was to evaluate the antioxidant activity of green tea seed shell as an industrial byproduct. Green tea seed shell extract (GTSSE) was obtained by ethanol extraction, and the yield was $1.4{\pm}0.22%$. The radical scavenging activities [1,1-diphenyl-picrylhydrazyl and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)], xanthine oxidase inhibition activity, and reducing power of GTSSE dose-dependently increased. To estimate the neuroprotective effect of GTSSE, viability was tested in HT22 mouse hippocampal cells. GTSSE treatment induced cytotoxicity at a concentration higher than $100{\mu}g/mL$ but not at a concentration lower than $50{\mu}g/mL$. Using this optimal concentration range, GTSSE treatment significantly increased cell viability in $H_2O_2$-treated HT22 cells. Further, GTSSE treatment increased superoxide dismutase activity and decreased the malonaldehyde level, a product of lipid peroxidation, in HT22 cells. Therefore, these results indicate that green tea seed shell extract may be useful for the development of antioxidant materials and have potential activity to prevent and treat neuro-degenerative diseases such as Alzheimer's disease.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.3
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• pp.389-396
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• 2014

The physiological properties of 70% ethanol extracts from Portulaca oleracea with different extraction methods (reflux extraction, RE; autoclave extraction, AE; low temperature high pressure extraction, LTPE) were investigated. The freeze-dried powder yields of RE, AE, and LTPE were 33.78%, 30.80%, and 11.05%, respectively. The color values of L and b were higher in LTPE, and the chroma values were higher in AE and LTPE compared to RE. The total polyphenolics and proanthocyanidin contents in LTPE were significantly higher than in other extracts. The amount of substances related to flavonoids contents was highest in RE (4.30 mg/g), followed by AE (4.06 mg/g), and LTPE (4.00 mg/g). DPPH radical scavenging ability with a concentration of 500 mg% (w/v) were in the following order; LTPE (88.87%)> RE (83.84%)> AE (80.67%). Further, the reducing power, ABTS radical scavenging ability, and nitrite scavenging activity was observed in the same tendency as seen with the DPPH radical scavenging ability. However, the ferrous ion chelating activity of RE (85.45%) and AE (83.88%) was significantly higher than that of LTPE (75.60%). ${\alpha}$-Glucosidase inhibitory activities of RE and LTPE with a concentration of 100 mg% were significantly higher than AE. Xanthine oxidase, and acetylcholinesterase inhibitory activities of LTPE were higher than the other extracts. These results suggest that the extracts from Portulaca oleracea have the potential to act as functional materials, and components of Portulaca oleracea could be effective in the prevention of Alzheimer's disease, and may be used to develop various functional food products.

• Journal of Life Science
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• v.29 no.12
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• pp.1371-1377
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• 2019

Oxidative stress induced by the over-production of reactive oxygen species (ROS) in the brain is the most common cause of neurodegenerative diseases such as Alzheimer's. In the present study, we investigated the protective effects of flavonoids and their glycosides, namely kaempferol, kaempferol-3-O-glucoside, quercetin, and quercetin-3-β-D-glucoside, against H₂O₂-induced oxidative stress in the C6 glial cells. The H₂O₂-treated glial cells exhibited decreased cell viability and increased ROS production when compared with normal cells. However, cells treated with each of the four flavonoids/glycosides demonstrated significantly increased viability and suppressed ROS production when compared with the H₂O₂-treated control group. These results indicate that flavonoids/glycosides attenuate oxidative stress induced by H₂O₂ in C6 glial cells. To confirm the protective molecular mechanisms, we measured pro-inflammatory factors such as inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-1β. H₂O₂ treatment was seen to elevate these factors and decrease IκB-α in the C6 glial cells, while the flavonoids/glycosides induced a down-regulation of the pro-inflammatory factors and increased IκB-α, indicating a neuroprotective effects through attenuation of the inflammation. In particular, quercetin and its glycoside showed a higher neuroprotective effect than the kaempferol treatments. These results suggest that these flavonoids and their glycosides could be promising therapeutic agents for neurodegenerative diseases via the attenuation of oxidative stress.

• Sleep Medicine and Psychophysiology
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• v.21 no.1
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• pp.5-13
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• 2014

Objectives: Depression, sleep complaints and cognitive impairments are commonly observed in the elderly. Elderly subjects with depressive symptoms have been found to show both poor cognitive performances and sleep disturbances. However, the relationship between sleep complaints and cognitive dysfunction in elderly depression is not clear. The aim of this study is to identify the association between sleep disturbances and cognitive decline in late-life depression. Methods: A total of 282 elderly people who underwent nocturnal polysomnography in a sleep laboratory were enrolled in the study. The Korean version of the Neuropsychological Assessment Battery developed by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K) was applied to evaluate cognitive function. Depressive symptoms were assessed with the geriatric depression scale (GDS) and subjective sleep quality was measured using the Pittsburg sleep quality index (PSQI). Results: The control group ($GDS{\leq}9$) when compared with mild ($10{\leq}GDS{\leq}16$) and severe ($17{\leq}GDS$) depression groups, had significantly different scores in the Trail making test part B (TMT-B), Benton visual retention test part A (BVRT-A), and Stroop color and word test (SCWT)(all tests p<0.05). The PSQI score, REM sleep duration, apnea-hypopnea index and oxygen desaturation index were significantly different across the three groups (all indices, p<0.05). A stepwise multiple regression model showed that educational level, age and GDS score were predictive for both TMT-B time (adjusted $R^2$=35.6%, p<0.001) and BVRT-A score (adjusted $R^2$=28.3%, p<0.001). SCWT score was predicted by educational level, age, apnea-hypopnea index (AHI) and GDS score (adjusted $R^2$=20.6%, p<0.001). Poor sleep quality and sleep structure alterations observed in depression did not have any significant effects on cognitive deterioration. Conclusion: Older adults with depressive symptoms showed mild sleep alterations and poor cognitive performances. However, we found no association between sleep disturbances (except sleep apnea) and cognitive difficulties in elderly subjects with depressive symptoms. It is possible that the impact of sleep disruptions on cognitive abilities was hindered by the confounding effect of age, education and depressive symptoms.