• Biomolecules & Therapeutics
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• v.27 no.3
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• pp.327-335
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• 2019

As the elderly population is increasing, Alzheimer's disease (AD) has become a global issue and many clinical trials have been conducted to evaluate treatments for AD. As these clinical trials have been conducted and have failed, the development of new theraphies for AD with fewer adverse effects remains a challenge. In this study, we examined the effects of Theracurmin on cognitive decline using 5XFAD mice, an AD mouse model. Theracurmin is more bioavailable form of curcumin, generated with submicron colloidal dispersion. Mice were treated with Theracurmin (100, 300 and 1,000 mg/kg) for 12 weeks and were subjected to the novel object recognition test and the Barnes maze test. Theracurmin-treated mice showed significant amelioration in recognition and spatial memories compared those of the vehicle-treated controls. In addition, the antioxidant activities of Theracurmin were investigated by measuring the superoxide dismutase (SOD) activity, malondialdehyde (MDA) and glutathione (GSH) levels. The increased MDA level and decreased SOD and GSH levels in the vehicle-treated 5XFAD mice were significantly reversed by the administration of Theracurmin. Moreover, we observed that Theracurmin administration elevated the expression levels of synaptic components, including synaptophysin and post synaptic density protein 95, and decreased the expression levels of ionized calcium-binding adapter molecule 1 (Iba-1), a marker of activated microglia. These results suggest that Theracurmin ameliorates cognitive function by increasing the expression of synaptic components and by preventing neuronal cell damage from oxidative stress or from the activation of microglia. Thus, Theracurmin would be useful for treating the cognitive dysfunctions observed in AD.

• Korean Journal of Psychosomatic Medicine
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• v.24 no.2
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• pp.200-207
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• 2016

Objectives : Alzheimer's disease(AD) is characterized by progressive decline of cognitive function and also by various behavioral psychological symptoms of dementia(BPSD) which causes distress to their caregivers. The purpose of this study was to investigate association between each AD patients' behavioral psychological symptoms and their caregivers' burden. Methods : Participants were 80 AD patients and their caregivers. We used Korean neuropsychiatric inventory (K-NPI) to assess the symptoms of patients and Korean version of Zarit Burden Interview(ZBI) to evaluate caregivers' burden. Results : The results showed ZBI score, which is the index for caregivers' burden, had a statistically significant positive correlation with the frequency of delusion, hallucination, agitation/aggression, depression, anxiety, disinhibition and irritability, the severity of hallucination, agitation/aggression, anxiety, disinhibition, aberrant motor, and sleep, and the global score(frequency${\times}$severity) for delusion, hallucination, agitation/aggression, depression, anxiety, disinhibition, aberrant motor, and sleep. There were significant correlations between each scale for cognitive function(i.e. MMSE-KC, CDR, GDS) and ZBI scale. Correlations between each scale for activity of daily living(i.e. Barthel -ADL, K-ADL) and ZBI scale were also significant. Conclusions : There were a significant correlation between BPSD and caregiver burden. Caregiver burden was also correlated with cognitive function and activity of daily living. Early detection and preventive treatment of these symptoms in BPSD might make improvement of caregivers' quality of life as well as AD patients'.

• Journal of Life Science
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• v.28 no.11
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• pp.1386-1395
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• 2018

Over recent years, it has become evident that the central nervous system bidirectionally interacts with the gastrointestinal tract along the gut-brain axis. A series of preclinical studies indicate that the gut microbiota can modulate central nervous system function through a multitude of physiological functions. Polyphenols are ubiquitous plant chemicals included in foods such as fruits, vegetables, tea, coffee and wine, and their consumption is directly responsible for beneficial health effects due to antioxidant, anti-inflammatory, antimicrobial, immunomodulatory, anticancer, vasodilating, and prebiotic-like effects. There is increasing evidence that dietary polyphenol can contribute to beneficial effects in neuronal protection acting against oxidative stress and inflammatory injury as well as in cognitive functions. In this paper, we overview the neuroprotective role of dietary polyphenols especially focusing on the neuroinflammation and neurovascular function by interaction with the gut microbiome. Polyphenol metabolites could directly act as neurotransmitters crossing the blood-brain barrier and modulating the cerebrovascular system or indirectly modulating gut microbiota. In addition, evidence suggests that dietary polyphenols are effective in preventing and managing neurological disorders, such as age-related cognitive decline and neurodegeneration, through a multitude of physiological functions. Dietary polyphenols are increasingly envisaged as a potential nutraceuticals in the prevention and treatment of neurological disorders, because they possess the ability to reduce neuroinflammation, to improve memory and cognitive function and to modulate the gut microbiota.

• Korean Journal of Psychosomatic Medicine
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• v.20 no.2
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• pp.105-111
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• 2012

Objectives : We investigated the prevalence and composite score of the neuropsychiatric symptoms in patients with mild cognitive impairment(MCI), and dementia of Alzheimer's type(AD). The aim of this study is to analyze the correlation between the result of Korean Neuropsychiatric Inventory(K-NPI) and cognitive function. Methods : A total of 163 patients diagnosed with MCI or AD was divided into three groups(55 MCI patients, 56 dementia patients with mild stage, and 52 dementia patients with moderate, severe stage). We examined neuro-psychiatric symptoms by K-NPI and compared the prevalence and composite score of each subdomain in K-NPI among three groups. Results : The most common symptoms in the MCI group were depression/dysphoria, sleep/night-time behavior, anxiety, and irritability/lability. In mild AD group, the most frequent disturbance was agitation/aggression, depression/dysphoria, anxiety, apathy/indifference, and sleep/night-time behavior. In moderate to severe AD group, the most frequent disturbance was apathy/indifference, depression/dysphoria, agitation/aggression, and delusion. The frequencies of delusion, hallucination, agitation/aggression, apathy/indifference, aberrant motor behavior, appetite/eating change were statistically significant. The total NPI score showed a negative correlation with MMSE-KC and a positive correlation with GDS. Conclusions : Neuropsychiatric symptoms are common features of MCI and AD. These symptoms observed in MCI are similar to those of mild AD. Psychosis is most common in moderate to severe AD, leading to a faster rate of cognitive decline. Therefore, proper management according to the neuropsychiatric symptoms of MCI and three stages of dementia is needed.

• Journal of Oriental Neuropsychiatry
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• v.32 no.2
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• pp.81-93
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• 2021

Objectives: Mild cognitive impairment (MCI) is condition of cognitive decline shown in transition from normal aging to dementia. Hominis placenta pharmacopuncture (HPP) is a treatment that combines effects of medication and acupuncture by injecting Hominis placenta into acupoints. The objective of this study was to evaluate the efficacy and safety of HPP for MCI. Methods: This was a randomized, double-blind, placebo-controlled, two-center clinical trial. Eligible patients were randomly allocated to either the HPP group or the placebo group. HPP or saline as placebo was administered to participants for eight weeks. Changes in symptoms were observed. The primary outcome was difference in mean change of Korean Version of the Montreal Cognitive Assessment (MoCA-K) score between the HPP group and the placebo group. Cognitive function, overall status of mood and sleep, and quality of life (QoL) were also assessed. Safety assessment and economic analysis were then conducted. Results: Thirty participants were enrolled. One participant in the placebo group dropped out. The score of MoCA-K increased after treatment. Its mean change was smaller in the HPP group than in the control group. HPP ameliorated Global Deterioration Scale and Korean Dementia Rating Scale subtests for attention, organization, and memory compared to the placebo. However, none of them was significantly different between the two groups. Mood, sleep, and QoL all improved more in the HPP group than in the placebo group, although differences between the two groups were not statistically significant. There was no adverse event probably related to the drug. HPP treatment needed KRW 345,000 more than the placebo group in improving Geriatric Quality of Life scale-Dementia score by one point for one year. Conclusions: Although HPP treatment did not significantly improve cognition, it changed behavioral and psychological symptoms in MCI.

• Korean Journal of Psychosomatic Medicine
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• v.24 no.2
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• pp.184-190
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• 2016

Objectives : This study analyzed the differences of body mass index(BMI) in Korean patients with Alzheimer's diseases(AD), Mild Cognitive Impairment(MCI), and healthy controls to verify whether low BMI is associated with cognitive impairment. Furthermore, this study also sought to examine any association between BMI and Mini Mental State Examination-Korean version(MMSE-K), Clinical Dementia Rating(CDR), and Global Deterioration Scale(GDS). Methods : A total of 257 subjects were included in the study. History taking, mental status examination, physical examination and neurocognitive function test were carried out for the diagnosis of AD and MCI. The subjects' demographic data and presence of diseases were also surveyed. The overall cognitive function and severity of diseases were assessed using MMSE-K, GDS, and CDR. Results : The order of BMI was found to be healthy controls>MCI>AD, with statistically significant differences among the groups. The order of MMSE-K scores was similar, with healthy controls>MCI>AD in statistically significant differences. The healthy controls had the lowest CDR and GDS scores, and AD patients had the highest scores. There was a significant positive correlation between BMI and MMSE scores(r=0.238, p=0.000). BMI was negatively correlated with CDR(r=-0.174, p=0.008) as well as with GDS(r=-0.233, p= 0.000). Conclusions : Measuring BMI of patients with AD or MCI is expected to be meaningful in that BMI could be a clinical indicator of AD. We expect this to be beneficial for the diagnosis, prevention, and therapeutic approach of AD and also expect large-scale, long-term longitudinal studies to follow.

• Sleep Medicine and Psychophysiology
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• v.24 no.2
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• pp.86-96
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• 2017

Objectives: This study aimed to analyze causality among sleep apnea, depression and cognitive function in patients with obstructive sleep apnea. Methods: We reviewed the medical records of 105 patients with sleep apnea and snoring who underwent overnight polysomnography (PSG). We analyzed various biological data, sleep variables (sleep duration and percentage) and respiratory variables [arousal index (AI), periodic leg movement index (PLM index), snoring Index (SI), mean SpO2, minimum SpO2, apnea-hypopnea index (AHI), and respiratory disturbance index (RDI)]. We also analyzed various data by sleep, cognition, and mood related scales: Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), snoring index by scale (SIS), Montreal Cognitive Assessment-Korean (Moca-K), Mini-mental State Examination-Korean (MMSE-K), clinical dementia rating (CDR), and Beck Depression Inventory (BDI). We analyzed causation among sleep, and respiratory, mood, and cognition related scales in obstructive sleep apnea patients. We analyzed the mediating effects of depression on sleep apnea patient cognition. Results: As Duration N1 increased and Total sleep time (TST) decreased, MOCA-K showed negative causality (p < 0.01). As BDI and supine RDI increased, causality was negatively related to MOCA-K (p < 0.01). As PSQI (p < 0.001) and SIS (p < 0.01) increased and as MMSE-K (p < 0.01) decreased, causality was positively related to BDI. BDI was found to mediate the effect of age on MOCA-K in patients with obstructive sleep apnea. Conclusion: Duration N1, total sleep time, BDI, and supine RDI were associated with cognitive function in obstructive sleep apnea patients. Depression measured by BDI partially mediated cognitive decline in obstructive sleep apnea patients.

• 한국노년학
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• v.40 no.3
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• pp.429-442
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• 2020

The purpose of this research was to examine changes in the physical fitness, activities of daily living performance, and cognitive status of the frail elderly by combined exercise programs. The combined exercise program consisted of an aerobic exercise for the elderly and a four-color ladder exercise for improving of cognitive ability and physical fitness. Twenty-one frail elderly participated in this study, they were divided into 12 exercise groups and nine control groups. The exercise group conducted the combined exercise program of 60 minutes, twice a week, for10 weeks, while the control group maintained their normal lives. Strength, flexibility, agility, coordination, ADL and MMSE-K were measured. Exercise group showed significant improvement in grip strength compared to control group. In addition, ADL showed significant improvement only in the exercise group. The results of this study showed that participation in the combined exercise program of the el derl y was effective in improving the grip strength, and in preventing various physical functions and cognitive conditions decline.

• Journal of the Society of Disaster Information
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• v.18 no.3
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• pp.622-635
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• 2022

Purpose: Due to the change of demography, the ratio of senior drivers has increased and the transition to a super-aged society is expected to make more seniors drive in the future. Method: In this research, we analyzed medical characteristics of the driver's age-specific decline in body function and saw that both the function of the physical as well as mental capacities deteriorates as people age. Among them, various functions are precipitously weakened after reaching 70, implying that those over the age of 70 are classified as seniors in a medical sense. In this context, we also could identify that based on such age criteria, various safety policies for senior drivers should be developed and set up in Korea. Result: We could find a steep fall in the physical function of body after reaching 70 from the chronological change of cognitive function and judgment ability. In particular, it is revealed that the driving license institution and aptitude test for drivers over 70 should be thoroughly examined, as physical functions necessary for driving such as eyesight and hearing ability is not strong enough in many drivers over 70. Conclusion: Focusing on the physical capacity to drive, we tried to find the hazardous age bracket of senior drivers which might influence driving behaviors. Going forward, we expect this work would help to understand the policies for senior drivers and drivers' physical differences.

• 한국약용작물학회:학술대회논문집
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• 2011.09a
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• pp.31-45
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• 2011

The amyloid ${\beta}$-peptide ($A{\beta}$), which originates from the proteolytic cleavage of amyloid precursor protein (APP), plays a central role in the pathogenesis of Alzheimer's disease (AD). Mounting evidence indicates that different species of $A{\beta}$, such as $A{\beta}$ oligomers and fibrils, may contribute to AD pathogenesis via distinct mechanisms at different stages of the disease. Importantly, elevation and accumulation of soluble $A{\beta}$ oligomers closely correlate with cognitive decline and/or disease progression in animal models of AD. In agreement with these studies, oligomers of $A{\beta}$ have been shown to directly affect synaptic plasticity, a neuronal process that is known to be essential for memory formation. Our previous studies showed that $A{\beta}$ induces the breakdown of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), a phospholipid that regulates key aspects of neuronal function. PI(4,5)P2 breakdown was found to be a key step toward synaptic and memory dysfunction in a mouse model of AD. To this end, we seek to identify small molecules that could elevate the levels of PI(4,5)P2 and subsequently block $A{\beta}$ oligomer-induced breakdown of PI(4,5)P2 and synaptic dysfunction.. We found that (20S)Rg3, an active triterpene glycoside from heat-processed ginseng, serves as an agonist for phosphatidylinositol 4-kinase IIalpha (PI4KIIalpha), which is a lipid kinase that mediates a rate-limiting step in PI(4,5)P2 synthesis. Consequently, (20S)Rg3 stimulates PI(4,5)P2 synthesis by directly stimulating the activity of PI4KIIalpha. Interestingly, treatment of a mouse model of AD with (20S)Rg3 leads to reversal of memory deficits. Our data suggest that the PI(4,5)P2-promoting effects of (20S)Rg3 may help mitigate the cognitive symptoms associated with AD.