Correlation of Androgen Deprivation Therapy with Cognitive Dysfunction in Patients with Prostate Cancer: A Nationwide Population-Based Study Using the National Health Insurance Service Database

태범식,전병조,신승훈,최훈,배재현,박재영 대한암학회 2019 Cancer Research and Treatment Vol.51 No.2

Purpose The purpose of this study was to evaluate the association of androgen deprivation therapy (ADT) with cognitive dysfunction. Materials and Methods Using the National Health Insurance Service database of the entire Korean adult prostate cancer population (n=236,391), data on ADT and cognitive dysfunction between 2008 and 2015 were analyzed. We excluded patients previously diagnosed with cognitive dysfunction, dementia, or a cerebral event history. We tested the effect of ADT on the risk of cognitive dysfunction using propensity score–matched Cox proportional hazards regression models and Kaplan-Meier survival analysis. Our final cohort comprised of 35,401 individuals with prostate cancer, including 24,567 men (70.6%) who underwent ADT. Results During a mean follow-up period of 4.1 years, 4,741 patients were newly diagnosed with cognitive dysfunction. A statistically significant association was found between ADT and the risk of cognitive dysfunction (hazard ratio, 1.169; p=0.002). Meanwhile, age ( 70 years), diabetes, hypertension, cardiovascular history, and peripheral vascular disease were identified as factors that contribute to the increased risk of cognitive dysfunction. In contrast, the use of statins and aspirin was associated with a lower risk of cognitive dysfunction. Kaplan-Meier analysis demonstrated that patients aged 70 years or older who underwent ADT had the lowest cumulative probability of remaining cognitive dysfunction-free (log-rank p < 0.001). Conclusion Our results revealed an association between the use of ADT for the treatment of prostate cancer and an increased risk of cognitive dysfunction in a nationwide population-based study. This finding should be further evaluated in prospective studies.

Factors Influencing Cognitive Dysfunction in Korean Patients with Rheumatoid Arthritis

신소영(Shin, So Young) 한국노인간호학회 2020 노인간호학회지 Vol.22 No.3

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.

PCSK9 저해제와 인지 기능 관련 이상사례: 세계보건복지기구 데이터베이스 VigiBase를 활용한 약물감시 연구

박다현,배성호,배지환,이혜성,최영준,신주영 한국에프디시규제과학회 2023 FDC법제연구 Vol.18 No.2

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.

유방암 생존여성의 갱년기 증상과 피로가 삶의 질에 미치는 영향

김경덕(Kim, Gyung Duck) 대한종양간호학회 2014 Asian Oncology Nursing Vol.14 No.2

Purpose: The purpose of this study was to test hypothetical model of quality of life (QOL) in breast cancer survivors and to test the mediating effects of cognitive dysfunction. Methods: This study was conducted from December 1st, 2013 to February 28th, 2014. 164 breast 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 climacteric symptoms and cognitive dysfunction did not effect on QOL directly. Impact of climacteric symptoms on QOL, mediating effect of cognitive dysfunction was not confirmed. In addition, effect of fatigue on the QOL, the mediating effect of cognitive dysfunction was not. Conclusions: Effects of climacteric symptoms on QOL was not mediated by cognitive dysfunction, Furthermore effects of fatigue on QOL was not mediated by cognitive dysfunction.

라이프로그 데이터를 활용한 랜덤포레스트 및 SHAP 기반 인지기능 장애 예측 모델

이명진,이종언,이한준 한국정보기술학회 2024 한국정보기술학회논문지 Vol.22 No.1

본 연구에서는 174명의 인지기능 장애인과 비장애인을 대상으로 최소 35일부터 최대 120일 동안에 걸쳐 추적한 24시간 라이프로그 정보와 간이정신상태검사 데이터를 활용하여 인지기능 장애를 예측하는 머신러닝 모델을 구축하였다. 모델 구축에는 Random Forest 알고리즘을 활용하였고 79.3%의 정확도로 인지기능 장애 여부를 분류할 수 있었다. 또한 SHAP 분석을 통하여 수면 및 신체활동 관련 데이터가 인지기능 장애를 판단하는 중요 변수임을 확인하였다. 이러한 결과는 웨어러블 디바이스를 통해 수집된 데이터를 정량적으로 분석한 결과라는 점에서 응답자의 주관이 담긴 설문 기반의 기존 연구와 차별성을 갖는다. 본 연구의 결과는 인지기능 장애 조기 진단 및 추적관리에 활용될 수 있으며 장애 발생 가능자들의 수면 및 신체 활동 등 생활 습관 개선에도 도움을 줄 수 있을 것이다. In this study, we developed a machine learning model to predict cognitive dysfunction using 24-hour lifelog information tracked over a period ranging from a minimum of 35 days to a maximum of 120 days, as well as Mini-Mental State Examination data, involving 174 individuals with cognitive dysfunction and those without cognitive dysfunction. The model utilized the Random Forest algorithm and achieved an accuracy of 79.3% in classifying cognitive dysfunction status. Additionally, SHAP analysis confirmed that data related to sleep and physical activity were significant variables in determining cognitive dysfunction. These results are different from existing survey-based studies that contain respondents’ opinions in that they were derived through quantitative analysis with data collected from wearable devices. The findings of this study can be applied to early diagnosis and tracking management of cognitive dysfunction, as well as potentially contributing to improvements for the individuals at risk of cognitive dysfunction in their lifestyle habits such as sleep and physical activity.

Cognitive Function of Korean Neurosurgical Patients: Cross-sectional Study Using the Korean Version of the Mini-mental Status Examination

김지하,김치헌,강현승,Chul-Kee Park,정천기 대한뇌혈관외과학회 2012 Journal of Cerebrovascular and Endovascular Neuros Vol.14 No.1

Objective: As interest in life quality and expectancy increases, cognitive dysfunction is becoming an important topic. Although there are many foreign articles on this topic, they require cultural interpretation to be applicable to Koreans. The purpose of this study was to assess cognitive function in Korean neurosurgical patients. Methods: We recruited 214 adult Korean patients with various cerebral pathologies and treatments from an outpatient clinic. The male-to-female ratio was 88:126, and their ages ranged from 28 to 81 years (mean: 57.9 years). The Korean version of the mini-mental status examination (K-MMSE) was adopted as an instrument for measuring cognitive function, and a score ≤23 was defined as cognitive dysfunction. K-MMSE scores were analyzed considering the patients’ gender, age, time elapsed since treatments, pathology and treatment modality. A serial analysis was performed for 59 patients who completed the K-MMSE more than once. Results: The mean K-MMSE score of 214 patients was 22.3, and 133 patients (62.1%) had a score ≤23. Cognitive dysfunction was common regardless of age, gender, pathology or treatment modality. Serial analysis revealed K-MMSE score improvement in 45 of 59 patients (76.3%). The mean time interval between two tests was 11.9 months, and the mean K-MMSE score improvement was 2.7, which was statistically significant (P = 0.000). However, many still had cognitive impairment. Conclusion: Most Korean neurosurgical patients showed cognitive dysfunction despite improvement after several months. Patients with trauma or ischemic disease were more vulnerable. More attention should be paid to neuropsychological complications such as cognitive dysfunction.

Angelica keiskei ameliorates chemotherapy induced cognitive dysfunction

Jihye Lee,Ji Wook Jung 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Chemotherapy-induced cognitive dysfunction is a frequent complication secondary to the use of anthracyclines for several types of cancer patients treated with chemotherapy such as Doxorubicin (DOX). However, its clinical use is induced oxidative stress and neuroinflammation. Angelica keiskei Koidzumi (A. keiskei) has a variety of biological activities due to the presence of numerous active compounds. This study aimed to examine the protective effects of A. keiskei extract in DOX-induced cognitive dysfunction in mouse models. Acute cognitive dysfunction was established by injecting female C57BL/6J mice with a single dose of DOX (20 mg/kg, intraperitoneal). Cognitive function were determined by Y-maze, passive avoidance and Morris water maze. DOX produced significant dysfunction in learning and memory as indicated by the data generated from Y-maze, passive avoidance and Morris water maze tests. A. keiskei extract (5, 10 or 20 mg/kg, p.o.) ameliorated spontaneous alternation versus the DOX-treated group in the Y-maze test, reversed DOX-induced cognitive dysfunction in the passive avoidance test and prolonged swimming time in the target zone in the Morris water maze test. These findings suggest that A. keiskei extract administration can effectively alleviate DOX-induced cognitive dysfunction, suggesting that A. keiskei should be further investigated for the mechanism of DOX-induced cognitive dysfunction.

3차원 가상현실 프로그램을 이용한 뇌졸중 환자의 인지기능 장애 평가

김덕용,박태훈,이장한,박창일,주소영,박기덕,정강재 대한재활의학회 2009 Annals of Rehabilitation Medicine Vol.33 No.1

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. 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.

시설 거주 노인 우울증의 인지기능저하

이정식(Jung Sik Lee),이원혜(Won Hye Lee),이우경(Woo Kyeong Lee),오홍석(Hong Seok Oh) 대한노인정신의학회 2006 노인정신의학 Vol.10 No.1

Objectives : There is a wide spectrum of cognitive dysfunction in geriatric depression due to heterogeneity. The Authors tried to investigate cognitive dysfunction in the elderly with depression and the association between geriatric depression and demographic variables such as sex, age, and education. Methods : Total 101 non-demented participants living in the asylum for the aged had completed frontal lobe function test (executive function and conceptualization) and CERAD-K (the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease) to evaluate neuropsychological function. Symptoms of depression were evaluated by SGDS-K (Short Geriatric Depression Scale of Korean version). We divided the elderly into two groups (depressed, non-depressed group) to evaluate the differences in cognitive function. Results : 30 (29.7%) of the subjects suffered depression and 50 (49.5%) had cognitive decline. Geriatric depression is not associated with age, sex, and education. Depressed older adults had lower executive function score in total group and cognitive decline group than non-depressed. Within cognitive decline group, subject with geriatric depression had lower scores in word fluency and word delayed recall than non-depressed. There was significant correlation between SGDS-K score and executive function. Conclusion : Subjects with geriatric depression had significant executive dysfunction. Executive dysfunction in depressed older adults may provide the basis for further investigation of mechanisms of geriatric depression. Timely identification of executive dysfunction fundamental to daily activities of depressed older adults may lead to coping strategies that will improve the prognosis of geriatric depression.

Effects of Cognitive-Physical Dual-Task Training on Executive Function and Activity in the Prefrontal Cortex of Older Adults with Mild Cognitive Impairment

박진혁 대한뇌신경재활학회 2021 뇌신경재활 Vol.14 No.3

Effects of cognitive-physical dual-task training on prefrontal cortex (PFC)-dependent function remain unclear. This study investigated the effects of dual-task training on executive function and activity in the PFC of older adults with mild cognitive impairment (MCI). Thirty-six older adults with MCI randomly assigned to the experimental group (EG) performing cognitive-physical dual-task training requiring for simultaneous cognitive tasks and physical exercise (n = 18) or the control group (CG) receiving sing-cognitive training using the computerized cognitive training program focusing on executive function (n = 18) for 16 sessions lasting 40 minutes a session. For the primary outcomes, the Trail Making Test Part B (TMT-B) was used, and for the secondary outcome, activity in the PFC using functional near infrared spectroscopy and the Korean version of instrumental activities of daily living (K-IADL) were evaluated at pre-and post-intervention. After the intervention, the EG achieved a significantly higher improvement in the TMT-B and decreased activity in the PFC during TMT-B testing than the CG. However, there were no significant differences in the K-IADL in both groups. These findings indicate that dual-task training is more effective in improving executive process and decreasing activity in the PFC during cognitive testing than single-cognitive training with limitations of its transfer effect to daily life