Earticle

본 연구는 2020년 노인실태조사 자료를 활용하여 노인의 복합만성질환 유무별 인지기능 저하의 영향 요인을 규명하기 위한 이차자료를 분석한 서술적 조사연구이다. 본 연구는 2020년 노인실태조사 자료를 활용하여 총 조사대상 10,097명 중 대리응답자 및 인지기능 문항의 무응답자 212명을 제외한 9,885명 중에서 의사의 진단을 받은 치매로 응답한 노인 143명을 제외하여 9,742명을 최종 연구대상으로 하였다. 복합만성질환 유무에 따라 SPSS/WIN 29.0 프로그램을 이용하여 카이제곱 검정과 이항로지스틱 회귀분 석을 적용하였다. 연구 결과 인지기능 저하 노인의 비율은 비복합만성질환군 23%에 비해 복합만성질환 군27.7%로 복합만성질환 노인의 인지기능 저하 발생율이 더 높은 것으로 나타났다. 인지기능 저하의 영향요인으로 비복합만성질환군과 복합만성질환군에서 공통으로 교육수준, 사회활동 및 도구적 일상생 활수행능력이 나타난 반면, 비복합만성질환군에서 가구소득과 주관적 건강상태가 나타났고, 복합만성 질환군에서 음주, 운동, 기본적 일상생활수행능력 및 우울증이 나타났다. 이 결과는 복합만성질환 유무에 따라 노인의 인지저하 예방을 위한 간호 중재가 차별되어야 함을 시사한다.

This descriptive study analyzes secondary data from the 2020 National Survey of Older Koreans to identify factors influencing cognitive dysfunction based on multimorbidity in older adults. From 10,097 participants, 212 proxy respondents and non-respondents to cognitive items were excluded, resulting in a final sample of 9,742 after also removing 143 diagnosed with dementia. Chi-square tests and binary logistic regression were conducted using SPSS/WIN 29.0 by multimorbidity status. Findings showed that the prevalence of cognitive dysfunction was higher in the multimorbidity group (27.7%) than the non-multimorbidity group (23%). Common influencing factors were educational status, social participation, and instrumental activities of daily living (IADL) in both groups. However, household income and self-rated health were significant in the non-multimorbidity group, while alcohol consumption, physical activity, basic activities of daily living (ADL), and depression were significant in the multimorbidity group. These findings suggest the need for tailored nursing interventions to prevent cognitive dysfunction in older adults with multimorbidity.

전구단백질 전환효소 서브틸리신/켁신 9형 (PCSK9) 저해제는 심혈관 질환 환자에게 사용되는 새로운 지질 강 하제이다. 임상시험에서 PCSK9 저해제의 인지 기능 장애에 대한 안전성이 검증되었지만 신경인지 기능 장애 사례가 보고되며 실사용 환경에서의 근거가 증가하고 있다. 이는 PCSK9 저해제가 인지 기능 장애의 위험을 증가시킬 수 있 음을 시사한다. 이에 따라, 본 연구는 PCSK9 저해제와 인지 기능 계통의 이상사례 간 연관성을 확인하는 것을 목표 로 한다. 1968년 1월부터 2022년 12월까지의 세계보건기구 VigiBase 데이터를 사용하여 관찰적 약물 감시 연구를 수 행하였다. PCSK9 저해제인 알리로쿠맙과 에볼로쿠맙의 개별 이상사례 보고서(ICSR)를 연구약물로 하여 다른 모든 약 물의 보고오즈비를 비교했다. 1차 평가 지표로 인지 기능 이상 관련 부작용은 규제 활동을 위한 의학 사전 (MedDRA) 시스템의 상위 단계군 용어 중 ‘인지 및 주의 장애’와 ‘정신적 장애’를 사용하여 정의하였으며, 2차 평가 지표로 세부 인지 기능 관련 이상사례를 나타내었다. PCSK9 저해제에 대한 114,293개의 보고서(258,099개의 약물-이상사례 쌍) 중 2094개(7,988개의 약물-이상사례 쌍)가 인지 기능 이상 부작용에 대한 건으로 확인되었다. ICSR 중 54%는 여성 환자 를 포함했으며, 41%는 65세, 대다수 (82%)는 에볼로쿠맙을 투여받았다. PCSK9 저해제와 인지 기능 이상 관련 부 작용에 대해 뷸균형 정보가 관측되었다(ROR 1.70, 95% CI 1.63-1.77). 세부적으로 인지 장애(ROR 1.47, 95% CI 1.28- 1.69), 기억 이상(ROR 2.72, 95% CI 2.56-2.88), 기억 상실증(ROR 1.50, 95% CI 1.36-1.65)가 유의한 실마리 정보로 탐지되었다. 본 약물감시 연구를 통해 PCSK9 저해제의 사용과 관련된 인지 기능 이상에 대한 보고가 증가한 것을 확 인할 수 있었으며, 특히 PCSK9 저해제를 투여받는 고령층 환자 사용에 있어 ‘기억 이상’ 부작용에 대해 주의 깊게 고 려해야 한다. 결과는 PCSK9 저해제 사용자의 인지 기능 이상에 대한 체계적 감시의 필요성을 시사한다.

Protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel lipid-lowering agents used in patients with cardiovascular diseases. Despite reassuring safety data from pivotal trials, increasing evidence from realworld studies suggests that PCSK9 inhibitors may increase the risk for cognitive dysfunction. This study aimed to identify signals of cognitive dysfunction-related adverse events (AEs) associated with PCSK9 inhibitors. We performed an observational pharmacovigilance study using the World Health Organization (WHO) VigiBase data up to December 2022. We included individual case safety reports (ICSRs) of the PCSK9 inhibitors alirocumab and evolocumab and compared them with those of other drugs. As the primary outcome, cognitive dysfunction was defined using the Medical Dictionary for Regulatory Activities (MedDRA) system’s High Level Group Term (HLGT) ‘Cognitive and attention disorders and disturbances’ and ‘Mental impairment disorders’ The secondary outcomes indicated specific classifications of cognitive dysfunction-related AEs. Among 114,293 reports (258,099 drug-AE pairs) on PCSK9 inhibitors, 8464 (31,951 drug-AE pairs) were identified as cognitive dysfunction-related AEs. Among the ICSRs, 54% included female patients, 41% persons aged 65 years, and the majority (82%) were for those who received evolocumab. The study revealed a significant disproportionality for cognitive dysfunction with PCSK9 inhibitors(ROR 1.70, 95% CI 1.63-1.77). Specifically, significant signals were identified for cognitive disorder (ROR 1.47, 95% CI 1.28-1.69), memory impairment (ROR 2.72, 95% CI 2.56-2.88), and amnesia(ROR 1.50, 95% CI 1.36-1.65). This pharmacovigilance study identified an increased reporting of cognitive dysfunction associated with the use of PCSK9 inhibitors, particularly emphasizing caution regarding ‘memory abnormalities’ in elderly patients receiving PCSK9 inhibitors. Our findings support the need for the systematic surveillance of cognitive dysfunctions among PCSK9 inhibitor users.

Background: In South Korea, as an aged society, an understanding of dementia and its risk factors is important from clinical and healthcare policy perspectives. Relationship between cognitive impairment and body weight or weight changes have been reported, but these were contradictory. We have evaluated the association between weight changes and cognitive decline using national level longitudinal data. Methods: Data from the Korean Longitudinal Study of Ageing from 2006 to 2012 were used. Association between weight changes and decline in cognitive function as measured by K-MMSE (the Korean version of the Minimental state examination) score was assessed by multivariate logistic regression. Weight changes were calculated from 1st wave and 3rd wave survey data, and classified into five groups as stable, increases, decreases of >10%, or 5%-10%. Results: About 37% of the total participants (n=4,512) were 65 years or older. These participants made up the largest proportion of the groups with weight change exceeding 10%. Multivariate logistic regression analyses revealed that weight changes exceeding 10% (10% increase vs stable, adjusted OR [aOR] 1.47, 95% confidence interval (CI) 1.11-1.95; 10% decrease vs stable, aOR 1.44, 95% CI 1.11-1.88) were significant predictive factors for decline in cognitive function. In subgroup analyses, the association between weight changes and cognitive decline was significant in males aged over 65 years and in normal BMI groups. Conclusion: Weight changes, both increases and decreases exceeding 10% of baseline, were significantly associated with declines in cognitive function among older adults in South Korea.

Background: Long-term levodopa therapy relieves the motor dysfunction associated with Parkinson’s disease (PD), but has various effects on non-motor symptoms, including cognitive dysfunction, hallucinations, and affective disorders, and can exacerbate certain aspects of dementia-like cognitive dysfunction. Here, we investigated the relationship between levodopa treatment and development of dementia in patients with PD. Methods: This retrospective study analyzed 76 consecutive patients with PD who had taken levodopa between 2011 and 2015. The participants were initially free of dementia and had initial daily levodopa doses of below 600 mg. Patients who did and did not develop comorbid dementia were compared in terms of potential predictor variables, including PD onset age, sex, levodopa doses, and non-dementia comorbidities. Results: Of the 76 patients, 21 (27.6%) developed dementia, which was followed by hallucinations and insomnia. The independent predictors of incident dementia were PD onset age and second-year and third-year average levodopa doses that were higher than the first-year average levodopa dose. Patients who developed dementia had significantly higher average daily levodopa doses and levodopa dose increases over the 6-year treatment period than those who did not develop dementia. In addition, patients with higher levodopa doses were more likely to experience hallucinations. Conclusion: These results suggest that increases in levodopa doses may be associated with a greater risk of cognitive impairment in patients with PD. Therefore, motor and cognitive functions and levodopa dose increases should be evaluated regularly during long-term levodopa therapy in patients with PD.

Objective To investigate the correlation between the Montreal Cognitive Assessment (MoCA) and functional outcome among subacute stroke patients with cognitive dysfunction. Methods Records of 61 inpatients were reviewed. Patients were divided into two groups based on their initial MoCA score. MoCA score of 11 was set as the differentiating criterion. We compared the improvements in Modified Barthel Index (MBI) from initial assessment to discharge between the two groups. Results There were no significant differences between the two groups in relation to age, duration from onset to admission, hospitalization period, or years of education. In a comparison of the results of Mini-Mental Status Examinations (MMSE) administered at admission and again at discharge, there was significantly more improvement in MMSE scores in the group with low MoCA scores than in the group with high MoCA scores. However, the group with high MoCA scores also showed high MBI scores at discharge and exhibited greater MBI improvement. Conclusion Higher initial MoCA scores (which reflect preservation of executive function) indicate better functional outcome in the subacute stroke phase.

Adulthood Attention-Deficit Hyperactivity Disorder (ADHD) debilitates high-level executive functioning, attention and im- pulse control. There is a lack of consensus regarding the specific cognitive markers for ADHD compared with other psychiat- ric disorders that show attention-related problems as secondary symptoms. This study aimed to aid clinicians in utilizing ex- isting tools for intelligence and cognitive function by investigating the key variables that differentiate ADHD from other men- tal disorders. As preliminary research, the study compared the performances of 35 patients with ADHD and 26 patients diag- nosed with other neurotic disorders on the Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV), Conners Continuous Perceptual Test 3rd Edition (CPT 3) and Conners Continuous Auditory Test of Attention (CATA). The ADHD group per- formed significantly lower on the Verbal Comprehension Index (VCI) and Working Memory Index (WMI) of K-WAIS-IV; the difference was significant in Similarity, Vocabulary and Arithmetic subtests. Perceptual Reasoning Index (PRI) and VCI differed significantly in the ADHD group unlike their neurotic counterpart. Of the variables in CPT 3, only detection differ- entiated ADHD from other neurotic disorders. Our results implicate there are novel standards and key variables that should be considered when differentiating ADHD from other psychiatric disorders.

Purpose: This study was conducted to examine the proportion and potential predictors of cognitive dysfunction in Korean patients with rheumatoid arthritis (RA). Methods: Patients with RA enrolled in this study during follow-up checkups at one general hospital in Korea. A trained research nurse examined participants using a variety of physical,psychosocial, and biological measurements. The Computerized Neuropsychological Function Test, consisting of 16 indicators encompassing a variety of cognitive subdomains, evaluated each participant’s cognitive function. Participants were categorized as “impaired” if they performed one standard deviation (SD) below the age-based population standards on each test. Adding the converted scores (range 0~16) generated the total cognitive function score. Multiple linear regression analyses were conducted to identify the significant factors influencing cognitive dysfunction. Results: Sixty-five participants with a M±SD age of 62.3±10.45 years were included in this study. The total cognitive function score was 9.69±3.50 (range 2~16). The final multivariate regression model was statistically significant; the model explained 32.7% of cognitive dysfunction variance. Even after controlling for disease severity, glucocorticoid use, depression, and functional limitations, education level (β=-.35, p=.005), income (β=-.26, p=.041), and cardiovascular disease risk factors (β=.28, p=.016) significantly influenced cognitive dysfunction. Conclusion: The findings suggest that future studies regarding which etiological variables contribute to cognitive impairment and how to best assess cognitive function in RA patients must occur due to the high risk potential of cognitive dysfunction.

Objective To determine whether cognitive function is associated with white matter hyperintensities (WMH) in patients with infratentorial stroke.Methods This was a retrospective, cross-sectional study. Twenty-four first-ever infratentorial stroke patients between 18 and 60 years of age were enrolled. WMH was evaluated by the Fazekas scale and the Scheltens scale. Cognitive functions were assessed using the Korean Mini-Mental Status Examination (K-MMSE), Rey-Osterrieth Complex Figure Test, and the Seoul Computerized Neuropsychological Test Battery (SCNT) at one month after stroke. All participants were divided into two groups based on the presence of WMH (no-WMH group and WMH group). General characteristics and cognitive functions were compared between the groups.Results There were no significant differences in general characteristics, such as age, stroke type, hypertension history, and education level between the two groups. However, K-MMSE in the WMH group was significantly lower compared to the no-WMH group (p<0.05). The verbal learning test score in SCNT was significantly higher in the no-WMH group compared to the WMH group (p<0.05). Executive function in the no-WMH group tended to be higher compared to the WMH group.Conclusion Impairment of cognitive function in patients with infratentorial stroke appeared to be associated with WMH. WMH should be carefully evaluated during rehabilitation of infratentorial stroke patients.

Objective To clarify the profile of cognitive dysfunction and the effects of intensive exercise in spinocerebellar degeneration (SCD). Methods We enrolled 60 healthy controls and 16 patients with purely cerebellar type SCD without gait disturbance or organic changes other than cerebellar changes. To assess cognitive function, we evaluated the participants using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Montreal Cognitive Assessment-Japanese (MoCA-J) at admission and after intensive exercise. Results Compared to the controls, SCD patients showed significant cognitive decline. As a result of intensive exercise, significant improvements in motor and cognitive functions were observed: the MMSE score improved from 27.7±1.9 to 29.0±1.3 points (p<0.001); the FAB score improved from 14.8±2.2 to 15.8±2.0 points (p=0.002); and the MoCA-J score improved from 24.6±2.2 to 26.7±1.9 points (p<0.001). For sub-scores, significant improvements were noted in serial 7, lexical fluency, motor series, and delayed recall. Conclusion Our study indicates that intensive exercise can be effective not only for motor dysfunction but also for cognitive dysfunction (Clinical Trial Registration No. UMIN-CTR: UMIN000040079).

Objective To investigate whether virtual reality (VR) training will help the recovery of cognitive function in brain tumor patients.Methods Thirty-eight brain tumor patients (19 men and 19 women) with cognitive impairment recruited for this study were assigned to either VR group (n=19, IREX system) or control group (n=19). Both VR training (30 minutes a day for 3 times a week) and computer-based cognitive rehabilitation program (30 minutes a day for 2 times) for 4 weeks were given to the VR group. The control group was given only the computer-based cognitive rehabilitation program (30 minutes a day for 5 days a week) for 4 weeks. Computerized neuropsychological tests (CNTs), Korean version of Mini-Mental Status Examination (K-MMSE), and Korean version of Modified Barthel Index (K-MBI) were used to evaluate cognitive function and functional status.Results The VR group showed improvements in the K-MMSE, visual and auditory continuous performance tests (CPTs), forward and backward digit span tests (DSTs), forward and backward visual span test (VSTs), visual and verbal learning tests, Trail Making Test type A (TMT-A), and K-MBI. The VR group showed significantly (p<0.05) better improvements than the control group in visual and auditory CPTs, backward DST and VST, and TMT-A after treatment. Conclusion VR training can have beneficial effects on cognitive improvement when it is combined with computer-assisted cognitive rehabilitation. Further randomized controlled studies with large samples according to brain tumor type and location are needed to investigate how VR training improves cognitive impairment.

Background: Alzheimer’s disease (AD) is a major neurodegenerative disorder and major type of dementia with progressive cognitive deficits, including multifactorial disorders. The present study examined the therapeutic effect of Sedum kamtschaticum leaf extract (SKE) on cognitive dysfunction disorder induced in rats through trimethyltin (TMT) administration. Methods and Results: In the preliminary screening experiment, SKE was selected as an acetylcholinesterase (AChE) inhibitor. Rats in the negative control and SKE groups were intraperitoneally injected with TMT (8 ㎎/㎏ body weight) dissolved in 0.9% saline and normal rats were injected with 0.9% saline alone. Doses of SKE (100, and 300 ㎎/㎏) were orally administered to the rats for 14 days. Normal and control rats were treated with saline for the same period. We performed a behavioral test using a Morris water maze and found that the escape and latency time periods of the SKE300 rats were shorter than those of the control rats. SKE therefore ameliorated cognitive dysfunction in this animal model. Immunohistochemical assay of biomarkers in the hippocampal cells revealed that the cell levels of phosphorylated cAMP response element binding protein (p-CREB) and AChE in the CA3 region of the control group were lower than those in the normal group. However, p-CREB and AChE reactive hippocampal cells in SKE300 group were significantly increased compared to those of the control. The hippocampal cells of brain-derived neurotrophic factor (BDNF) and protein kinase C (PKC) in control rats tended to be lower than the normal group, while the cells in the SKE groups tended to be higher than the control group. Conclusions: These results suggest that SKE ameliorates cognitive disorders through the neuroprotective effects related to p-CREB and AChE in the hippocampal cells.

Various neurodegenerative diseases including dementia and cognitive dysfunction pathogenesis are caused due to oxidative stress. Several studies have proved that molecular hydrogen (H2) acts as a therapeutic and preventive anti-oxidant, however, H2 effect on dementia is poorly documented. In the present study, we investigated the effects of H2 inhalation on trimethyltin (TMT)-induced memory dysfunction in the C57BL/6 mice. For this, mice were intraperitoneally injected a single dosage of TMT 2.6 mg/kg body weight. The subjects were randomly divided into the following groups: normal control without TMT induction, TMT only as a negative control (TMT injection + saline administration), positive control group [TMT injection + lithium chloride (50 mg/kg body weight) injection], H2-2wk group [TMT injection + H2 gas inhalation (once a day for 30 min for 2 weeks) and H2-4wk group [TMT injection + H2 gas inhalation (once a day for 30 min for 4 weeks). As a result, TMT-exposed mice showed symptoms such as tremor, seizure and aggressive behavior. Meanwhile, H2-treated groups after TMT treatment showed significantly increased spatial cognition abilities in the Y-maze test. Likewise, the level of the oxidative stress markers such as ROS, NO and MDA were found to be decreased in H2-2wk and H2-4wk groups as compared to the TMT only group in both serum and brain lysate, coherently, antioxidant enzymatic activities were increased in H2-2wk and H2-4wk groups compared to TMT only group. Moreover, H2 showed prevention effect of neuronal apoptosis through the suppression of apoptotic signaling molecules such as BAX, and cleaved caspase-7. Overall, H2 inhalation exhibited memory enhancing activity and decreased the oxidative stress markers and suppressed apoptotic signaling molecules on TMT-inducd mice. Therefore, H2 might be one of candidates for repairing dementia and neuro-degenerative diseases which shows symptoms such as dysfunction of learning, memory and cognition. However further studies are needed to clarify this notion.

Objective: To test the feasibility of newly developed 3- dimensional virtual reality (VR) program for assessing the post-stroke cognitive dysfunction. Method: Thirty five post-stroke patients and twenty normal healthy subjects were recruited in this study, and post-stroke patients were classified into three groups according to the severity of cognitive dysfunction. We developed three dimensional virtual reality program to assess the cognitive function with virtual subway environment from taking a subway to arriving at one's destination. The total score, number of success and cue were obtained during completing virtual tasks. We investigated the test-retest reliability, and the parameters of the 3-dimensional VR program were compared with Korean Mini-mental status examination. Results: All parameters of the VR program were significantly correlated with MMSE score (p＜0.01), and showed the significant difference between patient subgroups and control group (p＜0.05). The test-retest reliability of the VR program was significantly high (p＜0.01). Conclusion: Three dimensional virtual reality program may be helpful to assess the cognitive function in patients with stroke.

본 연구는 마약류 의존자들이 경험하는 심각한 부작용 중 하나인 ‘쭈라’와 ‘인지장애’에 대하여 살펴보 는 것에 목적을 두고 있다. 구체적으로 의존 및 단약 기간에 연구참여자들이 체험한 쭈라와 인지장애에 대해 살펴보는 데 집중했다. 본 연구의 목적을 달성하고자 연구참여자 7명과 1:1 심층면담을 진행하여 자료를 수집하였다. 수집된 자료는 주제분석 방법을 활용하여 분석하였다. 분석 결과, 약물의존기에 경험했던 쭈라와 인지장애에 대해 총 3가지 차원(심리적 차원, 신체적 차원, 사회적 차원)으로 구분하고 9개의 주제로 분석할 수 있었다. 또한 단약 과정에서 연구참여자들이 경험한 인지장애 경험으로 총 3가지 주제(기억력 감퇴, 집행 기능의 상실, 자기조절 능력 저하)를 도출할 수 있었다. 본 연구에서는 마약류 의존자들에 대한 맞춤형 개입과 건강한 사회복귀를 지원하는 방안에 대해 제언하였다.

This study aims to explore “Jura” and cognitive impairment, which are among the severe side effects experienced by individuals with substance dependence. To achieve this objective, data were collected through one-on-one in-depth interviews with seven research participants. The collected data were analyzed using thematic analysis. The results concerning the experience of “Jura” and cognitive impairment during the period of drug dependency were categorized into three dimensions: psychological, physical, and social, leading to the identification of nine distinct themes. “Jura” is a slang term used by Korean drug users, particularly those using methamphetamine, to describe a state of extreme anxiety, paranoia, and obsessive-compulsive behaviors that occur as a side effect of the drug. Furthermore, the study identified three main themes related to the cognitive impairment experienced by the participants during their withdrawal process: memory loss, a decline in executive function, and decreased self-regulation. Based on these findings, this study proposes tailored interventions and supportive measures to facilitate the healthy social reintegration of individuals with substance dependence.

본 연구는 유방암 생존 여성이 치료 종료 후에도 경험하게 되는증상인 갱년기 증상, 피로, 인지기능장애, 삶의 질 정도를 확인하고,네 변수 간의 상호관련성과 갱년기 증상과 피로가 삶의 질에 미치는 효과에서 인지기능장애의 매개효과 있는지를 확인한 경로분석연구이다. 연구 결과 갱년기 증상과 피로는 상관성이 매우 높았으며, 갱년기 증상과 피로는 인지기능장애 정도에 유의한 영향을 미치는 것으로 확인되었다. 피로는 삶의 질에 매우 큰 영향을 미치는것으로 확인되었으나, 갱년기 증상이 삶의 질에 미치는 영향과 인지기능장애 정도가 삶의 질에 미치는 효과 모두 미미한 것으로 확인되었다. 또한, 본 연구에서는 갱년기 증상이 삶의 질에 미치는 효과에서인지기능장애의 매개효과와 피로가 삶의 질에 미치는 영향에서 인지기능장애의 매개효과는 아주 미미한 것으로 확인되었다. 본 연구를 위해 대상자를 편의추출 하였으므로 그 결과를 유방암 생존 여성 전체에게 일반화하는데는 제한이 있을 수 있겠다. 그러나 본 연구는 유방암 생존 여성이 치료 후에도 경험하게 되는 증상들에 대한 인과관계를 확인하기 위한 경로분석 연구로서 증상 클러스터의세부이론 개발에 도움이 될 것이다.

Purpose: The purpose of this study was to test hypothetical model of quality of life (QOL) in breast cancer survivors and to test themediating effects of cognitive dysfunction. Methods: This study was conducted from December 1st, 2013 to February 28th, 2014. 164breast cancer survivors were recruited from A, D, and Y city in Korea. The instruments used in this study were climacteric symptoms,fatigue, cognitive dysfunction, and the QOL scales. Data were analyzed using descriptive statistics, correlation, and pathway. Results:Cognitive dysfunction was directly affected by climacteric symptoms and fatigue. QOL was directly affected by fatigue, However climactericsymptoms and cognitive dysfunction did not effect on QOL directly. Impact of climacteric symptoms on QOL, mediatingeffect of cognitive dysfunction was not confirmed. In addition, effect of fatigue on the QOL, the mediating effect of cognitive dysfunctionwas not. Conclusions: Effects of climacteric symptoms on QOL was not mediated by cognitive dysfunction, Furthermore effectsof fatigue on QOL was not mediated by cognitive dysfunction.

Repeated sublethal hypoxia exposure is reported to accelerate brain inflammation, and to affect the initiation and progression of cognitive dysfunction. Forskolin, an adenylate cyclase activator, is well-known as an inducer of the cAMP/PKA/CREB signaling. It has been shown that forskolin protects against various neuronal complications and induces long term memory; however, the underlying mechanism remains unclear. In this study, we showed that intraperitoneal administration of 200ng/g forskolin for 5 days on zebrafish notably recovered hypoxia-induced social interaction impairment and learning memory deficit. Forskolin suppressed hypoxia-induced neuroinflammation indicated by the decrease of NF-kB signaling and GFAP expression. On mouse neuroblastoma cell line, forskolin notably rescued hypoxia-induced cell death and dysfunction. The hypoxia model either in vivo or in vitro exerted a downregulation of PKA/CREB signaling and its downstream, c-Fos and BDNF expression, which was restored by forskolin. As previous studies proposed that hypoxia-induced hypo-O-GlcNAcylation could be an important causal factor for cognitive defect, we further investigated whether the HBP/O-GlcNAcylation cycling was changed by forskolin. Intriguingly, we observed that following forskolin treatment, OGT protein level (enzyme controls the addition of GlcNAc group to target proteins) induced considerably, which was accompanied by the upregulated O-GlcNAcylation level. Under forskolin treatment, O-GlcNAcylation flux on hypoxia-exposed zebrafish was reserved in line with the recovery of other inflammation and learning/memory markers. Next, we studied further about potential regulation of O-GlcNAcylation on the neuroprotective effect of forskolin. Zebrafish were treated with 500ng/g 6-diazo-5-oxo-L-norleucine (DON), an inhibitor of GFAT1 (enzyme that catalyzes the reaction from fructose-6-P to glucosamine-6-P), to downregulate the O-GlcNAcylation of proteins. It was observed that DON treatment led to learning/memory impairment, which was rescued by forskolin. Moreover, forskolin conserved hypo-O-GlcNAcylation and neuroinflammation following DON administration. Further experiments are being conducted to examine how HBP/O-GlcNAc flux is involved in the beneficial effect of forskolin on cognitive function.

Traumatic brain injury (TBI) is known as a functional corruption of the brain caused by a bump or blast to the head when an object hits suddenly or pierces the skull and penetrates brain tissues. There is an urgent need of understanding the pathophysiology following TBI because the morbidity and mortality rates worldwide caused by TBI have remained high throughout decades. In this study, we used a novel model of adult zebrafish to study the molecular and physiological changes following TBI. Using T-maze, on the 3rd-day post-stab-lesion injury (dpi), learning and memory deficits and poor social response were observed. Results from mirror biting and novel tank tests also provided us insight into their defective mobility, explorational, and territorial instincts. Neurogenesis impairment and severe brain inflammation were also altered following TBI, especially at 3 dpi. Upon injury, a notable decrease of O-GlcNAc level was remarked at 3dpi. Deregulation of O-GlcNAcylation which led to impaired glucose metabolism was informed to contribute to the pathologies of neurodegenerative diseases. Glucosamine (GlcN), a natural compound found in cartilage, is known as a derivative of the pathway that can increase O-GlcNAcylation by bypassing the reaction catalyzed by a rate liming enzyme GFAT. To further investigate the correlation, after TBI exposure, zebrafish had been recovered 3 days in 0.1g/L glucosamine (GlcN) diluted in water. Under the treatment of GlcN, the inflammation level reduced significantly, indicated by the decrease of Nuclear factor-kappa B and Glial fibrillary acidic protein expression in the telencephalon. TBI-induced downregulation of the cAMP signaling pathway and its relevant proteins in synaptic plasticity were rescued by GlcN. O-GlcNAc deficiency observed previously, as well as L/M capability were retrieved. GlcN also elevated the number of new cells regenerations and neuronal differentiation. As a result, regulation of brain O-GlcNAcylation may hold a potential role in TBI’s recuperation.

Sleep is an evolutionarily conserved physiological process implicated in the consolidation of learning and memory (L/M). Here, we hypothesize that sleep deprivation (SD)-induced cognitive deficits in zebrafish and mouse are mediated through reduction in O-GlcNAcylation in the brain. At the molecular level, SD downregulated mRNA of key enzymes of HBP metabolism and O-GlcNAc transferase (OGT) along with increased O-GlcNAcase (OGA) expression. Fear conditioning (FC) induced an increase in the expression or activities of proteins associated with long term memory (LTM), and at the same time, OGT protein and O-GlcNAcylation were significantly increased in the normalbut not in the SD-group of zebrafish. Suppression of HBP by the GFAT inhibitor, diazo-oxo-norleucine (DON), impaired L/M function and FC-mediated activation of PKA/CREB signaling. Conversely, enhancement of HBP by glucosamine significantly restored cognitive deficits and increased PKA/CREB signaling in the SD group. To our knowledge, the current study has provided valuable insights into the molecular and biochemical changes associated with L/M at the whole-brain level using the zebrafish and mouse system for the first time. Our findings highlight the role of the HBP during the L/M process and provide potential therapeutic targets for cognitive defects.