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Background: The association between delirium and dementia has been suggested, but mostly in the postoperative setting. This study aims to explore this relationship in a broader inpatient population, leveraging extensive real-world data to provide a more generalized understanding., Methods: In this retrospective cohort study, electronic health records of 11,970,475 hospitalized patients aged over 60 from nine institutions in South Korea were analyzed. Patients with and without delirium were identified, and propensity score matching (PSM) was used to create comparable groups. A 10-year longitudinal analysis was conducted using the Cox proportional hazards model, which calculated the hazard ratio (HR) and 95% confidence interval (CI). Additionally, a meta-analysis was performed, aggregating results from all nine medical institutions. Lastly, we conducted various subgroup and sensitivity analyses to demonstrate the consistency of our study results across diverse conditions., Results: After 1:1 PSM, a total of 47,306 patients were matched in both the delirium and nondelirium groups. Both groups had a median age group of 75-79 years, with 43.1% being female. The delirium group showed a significantly higher risk of all dementia compared with the nondelirium group (HR: 2.70 [95% CI: 2.27-3.20]). The incidence risk for different types of dementia was also notably higher in the delirium group (all dementia or mild cognitive impairment, HR: 2.46 [95% CI: 2.10-2.88]; Alzheimer's disease, HR: 2.74 [95% CI: 2.40-3.13]; vascular dementia, HR: 2.55 [95% CI: 2.07-3.13]). This pattern was consistent across all subgroup and sensitivity analyses., Conclusions: Delirium significantly increases the risk of onset for all types of dementia. These findings highlight the importance of early detection of delirium and prompt intervention. Further research studies are warranted to investigate the mechanisms linking delirium and dementia., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Plasma protein biomarkers have been considered promising tools for diagnosing dementia subtypes due to their low variability, cost-effectiveness, and minimal invasiveness in diagnostic procedures. Machine learning (ML) methods have been applied to enhance accuracy of the biomarker discovery. However, previous ML-based studies often overlook interactions between proteins, which are crucial in complex disorders like dementia. While protein-protein interactions (PPIs) have been used in network models, these models often fail to fully capture the diverse properties of PPIs due to their local awareness. This drawback increases the chance of neglecting critical components and magnifying the impact of noisy interactions. In this study, we propose a novel graph-based ML model for dementia subtype diagnosis, the graph propagational network (GPN). By propagating the independent effect of plasma proteins on PPI network, the GPN extracts the globally interactive effects between proteins. Experimental results showed that the interactive effect between proteins yielded to further clarify the differences between dementia subtype groups and contributed to the performance improvement where the GPN outperformed existing methods by 10.4% on average., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: This study aimed to explore the potential of whole brain white matter patterns as novel neuroimaging biomarkers for assessing cognitive impairment and disability in older adults., Methods: We conducted an in-depth analysis of magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) scans in 454 participants, focusing on white matter patterns and white matter inter-subject variability (WM-ISV)., Results: The white matter pattern ensemble model, combining MRI and amyloid PET, demonstrated a significantly higher classification performance for cognitive impairment and disability. Participants with Alzheimer's disease (AD) exhibited higher WM-ISV than participants with subjective cognitive decline, mild cognitive impairment, and vascular dementia. Furthermore, WM-ISV correlated significantly with blood-based biomarkers (such as glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]), and cognitive function and disability scores., Discussion: Our results suggest that white matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making and determining cognitive impairment and disability., Highlights: The ensemble model combined both magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) and demonstrated a significantly higher classification performance for cognitive impairment and disability. Alzheimer's disease (AD) revealed a notably higher heterogeneity compared to that in subjective cognitive decline, mild cognitive impairment, or vascular dementia. White matter inter-subject variability (WM-ISV) was significantly correlated with blood-based biomarkers (glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]) and with the polygenic risk score for AD. White matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making processes and determining cognitive impairment and disability., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: White matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH's impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes., Methods: Participants aged 49-89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1-2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific., Results: The study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males., Discussion: Elderly females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies., Clinical Trial Registration: The BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14., Competing Interests: Competing interests: Thurston: Astellas, Bayer, Hello Therapeutics (Advisory Board). All other authors declare no competing interests.

Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states., (© 2024. The Author(s).)

Objective: The impact of the government-initiated senior employment program (GSEP) on geriatric depressive symptoms is underexplored. Unearthing this connection could facilitate the planning of future senior employment programs and geriatric depression interventions. In the present study, we aimed to elucidate the possible association between geriatric depressive symptoms and GSEP in older adults., Methods: This study employed data from 9,287 participants aged 65 or older, obtained from the 2020 Living Profiles of Older People Survey. We measured depressive symptoms using the Korean version of the 15-item Geriatric Depression Scale. The principal exposure of interest was employment status and GSEP involvement. Data analysis involved multiple linear regression., Results: Employment, independent of income level, showed association with decreased depressive symptoms compared to unemployment (p<0.001). After adjustments for confounding variables, participation in GSEP jobs showed more significant reduction in depressive symptoms than non-GSEP jobs (β=-0.968, 95% confidence interval [CI]=-1.197 to -0.739, p<0.001 for GSEP jobs, β=-0.541, 95% CI=-0.681 to -0.401, p<0.001 for non-GSEP jobs). Notably, the lower income tertile in GSEP jobs showed a substantial reduction in depressive symptoms compared to all income tertiles in non-GSEP jobs., Conclusion: The lower-income GSEP group experienced lower depressive symptoms and life dissatisfaction compared to non-GSEP groups regardless of income. These findings may provide essential insights for the implementation of government policies and community-based interventions.

Background: As a collaboration model between the International HundredK+ Cohorts Consortium (IHCC) and the Davos Alzheimer's Collaborative (DAC), our aim was to develop a trans-ethnic genomic informed risk assessment (GIRA) algorithm for Alzheimer's disease (AD)., Methods: The GIRA model was created to include polygenic risk score calculated from the AD genome-wide association study loci, the apolipoprotein E haplotypes, and non-genetic covariates including age, sex, and the first three principal components of population substructure., Results: We validated the performance of the GIRA model in different populations. The proteomic study in the participant sites identified proteins related to female infertility and autoimmune thyroiditis and associated with the risk scores of AD., Conclusions: As the initial effort by the IHCC to leverage existing large-scale datasets in a collaborative setting with DAC, we developed a trans-ethnic GIRA for AD with the potential of identifying individuals at high risk of developing AD for future clinical applications., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Increasing numbers of cardiothoracic surgery residents are resigning, without completing their training. This study analyzes how their turnover intention is related to the training environment, and individual psychological factors. Responses by 57 Korean cardiothoracic surgery residents were analyzed. Their levels of depression, anxiety, grit, and empathy, working conditions, the effect of someone's presence to discuss their concerns with, burnout, and turnover intention were identified as the research variables. Descriptive statistical analysis, correlation analysis, and structural equation modeling were used for data analysis. Burnout has the most significant relationship with turnover intention. It has a mediating effect on the influence of depression, grit (sustained interest), and working conditions, over turnover intention. Empathy, and the presence of someone to discuss concerns with, also affect turnover intention directly. The study also confirmed that grit and work satisfaction affect turnover intention indirectly, through burnout. The study identified both individual- and systemic-level factors for an effective training environment, to reduce cardiothoracic surgery residents' tendencies of leaving the residency program, and supporting them for greater satisfaction with their career choice. In order to resolve negative emotions such as burnout and depression, and foster empathy, a human resource development program for the residents' psychological support must be prepared. The program director should be adequately educated to take charge of the training program, oversee the residents' education and welfare, and perform the roles of role-model and mentor., (© 2023. The Author(s).)

Introduction: Although several studies have examined the individual relationships among digital literacy, cognitive function, and depressive symptoms, few have integrated all three factors into a single model. This study aimed to address this gap by investigating the mediating effect of depressive symptoms on the relationship between digital literacy and cognition. In doing so, we hoped to contribute to a more comprehensive understanding of the complex interplay among these variables and their implications for mental health and well-being., Methods: Participants were 7,988 older adults (65 years or older) who participated in the Living Profiles of Older People Survey 2020. The main type of exposure was digital literacy (communication, information, media, and online transaction literacy). The main outcomes were depressive symptoms measured using the Short Geriatric Depression Scale of Korean version and cognitive function measured using the Mini-Mental State Examination score. Multiple linear regression and mediation analyses were also performed., Results: After adjusting for covariates, our analysis found a significant association between digital literacy and both depressive symptoms and cognitive function (β of four types of digital literacy and depressive symptoms = -0.123, -0.172, -0.702, and - 0.639, respectively; β of four types of digital literacy and cognitive function = 2.102, 2.217, 1.711, and 1.436, respectively). Moreover, our study showed that depressive symptoms play a mediating role in the relationship between media and online transaction literacy and cognitive function (95% CI of indirect effects = 0.0647-0.1212 and 0.0639-0.1277, respectively), implying an indirect pathway (digital literacy, depressive symptoms, and cognitive function)., Discussion: This study sheds light on the relationship between digital literacy, depressive symptoms, and cognitive function in older adults. We found that depressive symptoms mediated the association between specific aspects of digital literacy (online transaction and media literacy) and cognitive function. Our results indicate that community-based digital literacy programs could be effective in reducing depression and preserving or improving cognitive function in older adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hong, Nam, Hong and Roh.)

Introduction: The suicide rate of middle-aged adults has increased rapidly, which is a significant public health concern. A depressed mood and suicidal ideation are significant risk factors for suicide, and non-pharmacological interventions such as exercise therapy have been suggested as potential treatments. Walking is a feasible and accessible form of exercise therapy for middle-aged adults., Methods: We conducted a study based on the Seventh Korea National Health and Nutrition Examination Survey (2016-2018) data of 6,886 general middle-aged adults in South Korea to investigate the relationships of walking exercise with depressed mood and suicidal ideation. Multiple logistic regression analysis was used to adjust for confounding variables. Sampling weights were applied to obtain estimates for the general Korean population., Results: Participants who walked ≥5 days per week had a significantly lower odds ratio (OR) for depressed mood [OR = 0.625, 95% confidence interval (CI): 0.424-0.921, p  = 0.018] and suicidal ideation (OR = 0.252, 95% CI: 0.125-0.507, p  < 0.001) compared to those who never walked, regardless of the duration of exercise. The same results were obtained for males after stratifying the data by sex and suicidal ideation was associated with walking in females., Conclusion: Regular walking exercise was associated with diminished mental health problems in middle-aged adults. Light walks may serve as a useful starting point for patients with serious mental health issues, such as suicidal ideation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ko, Cho, Kim, Hong, Son, Roh, Moon and Han.)

Objective: Contact frequency with adult children plays a critical role in late-life depression. However, evidence on possible moderators of this association remains limited. Moreover, considering alterations in contact modes after the coronavirus disease-2019 pandemic, there is a need to investigate this association post-pandemic to develop effective therapeutic interventions., Methods: This study included 7,573 older adults who completed the Living Profiles of the Older People Survey in Korea. Participants' contact frequency and depressive symptoms were analyzed. Regression analysis was performed after adjusting for covariates. The moderating effects of variables were verified using a process macro., Results: Multivariable logistic regression analysis revealed that infrequent face-to-face (odd ratio [OR]=1.86, 95% confidence interval [CI]=1.55-2.22) and non-face-to-face contact (OR=1.23, 95% CI=1.04-1.45) in the non-cohabitating adult children group was associated with a higher risk of late-life depression compared to that in the frequent contact group. Linear regression analysis indicated consistent results for face-to-face and non-face-to-face contact (estimate=0.458, standard error [SE]=0.090, p<0.001 and estimate=0.236, SE= 0.074, p=0.001, respectively). Moderation analysis revealed that the association between late-life depression and frequency of face-toface contact was moderated by age, household income quartiles, number of chronic diseases, physical activity frequency, presence of spouse, nutritional status, and whether the effect of frequency of non-face-to-face contact on late-life depression was increased by participation in social activity, frequent physical activity, and good cognitive function (p for interaction<0.05)., Conclusion: Frequent contact with non-cohabitating children lowers the risk of depression later in life. Several variables were identified as significant moderators of contact frequency and depression symptoms.

Several programs are widely used for clinical and research purposes to automatically quantify the degree of amyloid deposition in the brain using positron emission tomography (PET) images. Given that very few studies have investigated the use of Heuron, a PET image quantification software approved for clinical use, this study aimed to compare amyloid deposition values quantified from 18 F-flutemetamol PET images using PMOD and Heuron. Amyloid PET data obtained from 408 patients were analysed using each quantitative program; moreover, the standardized uptake value ratios (SUVRs) of target areas were obtained by dividing the standardized uptake value (SUV) of the target region by the SUV of cerebellar grey matter as a reference. Compared with PMOD, Heuron yielded significantly higher SUVRs for all target areas (paired sample t-test, p < 0.001), except for the PC/PCC (p = 0.986). However, the Bland-Altman plot analysis indicated that the two quantitative methods may be used interchangeably. Moreover, receiver operating characteristic curve analysis revealed no significant between-method difference in the performance of the SUVRs in evaluating the visual positivity of amyloid deposits (p = 0.948). In conclusion, Heuron and PMOD have comparable performance in quantifying the degree of amyloid deposits in PET images., (© 2023. The Author(s).)

Objectives: As the significance of the early diagnosis of mild cognitive impairment (MCI) has emerged, it is necessary to develop corresponding screening tools with high ecological validity and feasible biomarkers. Virtual reality (VR)-based cognitive assessment program, which is close to the daily life of the older adults, can be suitable screening tools for MCI with ecological validity and accessibility. Meanwhile, dehydroepiandrosterone (DHEA) has been observed at a low concentration in the older adults with dementia or cognitive decline, indicating its potential as a biomarker of MCI. This study aimed to determine the efficacy and usability of a VR cognitive assessment program and salivary DHEA for screening MCI., Methods: The VR cognitive assessment program and the traditional Montreal Cognitive Assessment (MOCA) test were performed on 12 patients with MCI and 108 healthy older adults. The VR program operates in a situation of caring for a grandchild, and evaluates the memory, attention, visuospatial, and executive functions. An analysis of covariance (ANCOVA), a partial correlation analysis, and receiving operating characteristic (ROC) curve analysis were conducted for statistical analysis., Results: According to the ANCOVA, no significant difference in MOCA scores was found between the normal and MCI groups ( F = 2.36, p = 0.127). However, the VR total score of the MCI group was significantly lower than that of the normal group ( F = 8.674, p = 0.004). There was a significant correlation between the MOCA and VR scores in the total and matched subdomain scores. The ROC curve analysis also showed a larger area under the curve (AUC) for the VR test (0.765) than for the MOCA test (0.598), and the sensitivity and specificity of the VR program were 0.833 and 0.722, respectively. Salivary DHEA was correlated with VR total ( R 2 = 0.082, p = 0.01) and attention scores ( R 2 = 0.086, p = 0.009)., Conclusion: The VR cognitive test was as effective as the traditional MOCA test in the MCI classification and safe enough for older adults to perform, indicating its potential as a diagnostic tool. It has also been shown that salivary DHEA can be used as a biomarker for MCI., Competing Interests: J-HS was a professor at Yonsei University and the CEO of Minds.AI Co., Ltd., which was established in November 2019 as a research and development company for mental health in Republic of Korea. SJ, S-WC, I-YK, JK, J-YL, JR, and RA were employed by Research Institute of Minds.AI, Co., Ltd. HC and SK were employed by FNIKorea Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jang, Choi, Son, Oh, Ha, Kim, Roh, Kim, Lee, Jung, Cha, Chae, Kang, Kwon, Kim, Lee, Shin, Ryu, Ahn, Hong and Seok.)

Background: The moderating effect of cognitive function on the association between social support and late-life depressive symptoms has not been thoroughly investigated. Identifying cognitive function as a possible moderator of this association might help plan community-based interventions for late-life depressive symptoms., Methods: Participants were community-dwelling older adults who visited a community-based mental health center. The ENRICHD Social Support Instrument and the Montgomery-Asberg Depression Rating Scale were used to evaluate social support and depressive symptoms, respectively. Cognitive function was assessed using the Korean version of the Mini-Mental State Examination. Data from 1088 and 506 participants were included in the cross-sectional and longitudinal analyses, respectively. Multiple linear regression analysis was performed to assess the effects of social support on depressive symptoms and the possible moderating effect of cognition., Results: After adjusting for possible confounders, greater social support at baseline was associated with fewer depressive symptoms in both cross-sectional (estimate = -0.25 standard error [SE] = 0.03, P < 0.001) and longitudinal analyses (estimate = -0.11, SE = 0.05, P = 0.014). Moreover, the association between social support and depressive symptoms was significantly moderated by cognitive function (P for interaction < 0.001 for cross-sectional analysis, and P for interaction = 0.011 for longitudinal analysis)., Limitations: The tool for assessing social support was self-reported. There may have been a selection bias in the study sample., Conclusions: Greater social support was associated with fewer late-life depressive symptoms in both analyses. However, social support may have less benefits for alleviating depressive symptoms in older adults with cognitive decline., Competing Interests: Conflict of interest None., (Copyright © 2022. Published by Elsevier B.V.)

We previously developed a novel machine-learning-based brain age model that was sensitive to amyloid. We aimed to independently validate it and to demonstrate its utility using independent clinical data. We recruited 650 participants from South Korean memory clinics to undergo magnetic resonance imaging and clinical assessments. We employed a pretrained brain age model that used data from an independent set of largely Caucasian individuals (n = 757) who had no or relatively low levels of amyloid as confirmed by positron emission tomography (PET). We investigated the association between brain age residual and cognitive decline. We found that our pretrained brain age model was able to reliably estimate brain age (mean absolute error = 5.68 years, r(650) = 0.47, age range = 49-89 year) in the sample with 71 participants with subjective cognitive decline (SCD), 375 with mild cognitive impairment (MCI), and 204 with dementia. Greater brain age was associated with greater amyloid and worse cognitive function [Odds Ratio, (95% Confidence Interval {CI}): 1.28 (1.06-1.55), p = 0.030 for amyloid PET positivity; 2.52 (1.76-3.61), p < 0.001 for dementia]. Baseline brain age residual was predictive of future cognitive worsening even after adjusting for apolipoprotein E e4 and amyloid status [Hazard Ratio, (95% CI): 1.94 (1.33-2.81), p = 0.001 for total 336 follow-up sample; 2.31 (1.44-3.71), p = 0.001 for 284 subsample with baseline Clinical Dementia Rating ≤ 0.5; 2.40 (1.43-4.03), p = 0.001 for 240 subsample with baseline SCD or MCI]. In independent data set, these results replicate our previous findings using this model, which was able to delineate significant differences in brain age according to the diagnostic stages of dementia as well as amyloid deposition status. Brain age models may offer benefits in discriminating and tracking cognitive impairment in older adults., (© 2022. The Author(s).)

This cross-sectional, observational study aimed to integrate the analyses of relationships of physical activity, depression, and sleep with cognitive function in community-dwelling older adults using a single model. To this end, physical activity, sleep, depression, and cognitive function in 864 community-dwelling older adults from the Suwon Geriatric Mental Health Center were assessed using the International Physical Activity Questionnaire, Montgomery-Asberg Depression Rating Scale, Pittsburgh Sleep Quality Index, and Mini-Mental State Examination for Dementia Screening, respectively. Their sociodemographic characteristics were also recorded. After adjusting for confounders, multiple linear regression analysis was performed to investigate the effects of physical activity, sleep, and depression on cognitive function. Models 4, 5, 7, and 14 of PROCESS were applied to verify the mediating and moderating effects of all variables. Physical activity had a direct effect on cognitive function (effect = 0.97, p < 0.01) and indirect effect (effect = 0.36; confidence interval: 0.18, 0.57) through depression. Moreover, mediated moderation effects of sleep were confirmed in the pathways where physical activity affects cognitive function through depression (F-coeff = 13.37, p < 0.001). Furthermore, these relationships differed with age. Thus, the associations among physical activity, depression, and sleep are important in interventions for the cognitive function of community-dwelling older adults. Such interventions should focus on different factors depending on age.

Synergistic effects of amyloid deposition and cerebral small vessel disease (CSVD) on the systematic disruption of large-scale brain anatomical organization are not well known. We investigated the brain structural covariance network (SCN) in 245 cognitively impaired older adults with the information of amyloid deposition and CSVD represented by white matter hyperintensities (WMH). We stratified the participants into 4 groups based on amyloid burden (A+/A -) and WMH severity (W+/W-). Using source-based morphometry analysis, we selected 13 independent components (ICs) in functional brain networks. SCNs between ICs were defined using Pearson correlations between individual weights; SCNs of the A+W+ group were compared with those of other groups using Fisher's r-to-z transformation. Our results revealed that SCN characteristics related to amyloid burden with CSVD could be represented by decreased intra- and increased cortico-subcortical inter-network connectivity in the salience (SN) and default mode networks (DMN), decreased cortico-subcortical internetwork connectivity in the central executive network (CEN), and altered internetwork connectivity among DMN-SN-CEN. Amyloid deposition and CSVD maybe associated with altered connectivity in structural networks in the brain and should be considered when assessing network disruption., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Multidomain lifestyle modification is considered an effective intervention for dementia prevention due to its multifactorial nature. Recognizing that participants' activity adherence is crucial for successful lifestyle modification, our team developed a smartphone application to enhance motivation toward brain health behavior based on gamification theory, which influences behaviors by enhancing motivation. The developed smartphone application has two main functions: delivering supporting videos from family, friends, and medical staff, and self-evaluation. We assessed the effectiveness of this smartphone application with regard to brain health behavior. In this eight-week randomized controlled trial, 40 participants were randomly assigned to the smartphone application intervention group or control group. The primary outcome reflected participants' brain health behavior in three categories: physical activity, cognitive activity, and healthy diet. Each brain health behavior was measured by the Korean version of the Global Physical Activity Questionnaire, Cognitive Activity Score, and Mediterranean DASH Intervention for Neurodegenerative Delay Diet Score. Furthermore, we investigated the change in motivation, measured by the Situational Motivation Scale. Additionally, we reviewed participants' self-record diary during the first, fourth, and eighth week of intervention for evaluation of adherence. The intervention group was found to have a positive association with moderate metabolic equivalent activities (P = 0.01) and intrinsic motivation change (P = 0.01). There was a significant difference between the intervention and control groups regarding average physical activity at week 8 (P = 0.037). An eight-week intervention with the smartphone application induced physical activity of moderate intensity through intrinsic motivation enhancement. We suggest that the motivation enhancement application could be an efficient option for maintaining and promoting psychosocial health behavior. This smartphone application can be applied to any other disease that needs behavioral change. Through the application, a broader spectrum of the population, regardless of time, space, and human resources, can benefit from community health services. Trial registration: Korean National Clinical Trial Registry CRIS identifier: KCT0005231., Competing Interests: The authors have no conflicts of interest to declare.

Background: Late-life depression is a complex phenomenon that cannot be fully understood simply as depression occurring in older adults, prompting researchers to suggest that it represents a component of geriatric syndrome. Given the inherent complexity and multifactorial nature of geriatric syndrome, understanding the interactions between the comorbid conditions involved is important for establishing appropriate preventive strategies. While sleep disturbance and malnutrition are common manifestations of geriatric syndrome, they have also been regarded as indicators of late-life depression. However, the differential effects of sleep disturbance and malnutrition on late-life depression and their interrelationships remain unclear., Objective: The objective of this study was to examine the effects of sleep disturbance and malnutrition on depression and the interactions between them among community-dwelling older adults., Methods: Sleep disturbance and malnutrition in 1,029 community-dwelling older adults from Suwon Geriatric Mental Health Center were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Mini Nutritional Assessment (MNA), respectively. The Korean version of the Short Form of the Geriatric Depression Scale (SGDS-K) was used to evaluate depressive symptoms. Sociodemographic parameters were recorded. A multiple linear regression analysis was conducted to examine the effects of sleep and nutrition on depressive symptoms after adjusting for covariates. The effect size and conditional effects of sleep disturbance and malnutrition on late-life depression were assessed using Cohen's f 2 values and the Johnson-Neyman technique, respectively., Results: After possible confounders were adjusted, the SGDS-K score was positively associated with the PSQI score (standardized beta = 0.166, P < 0.001) and negatively associated with the MNA score (standardized beta = -0.480, P < 0.001). The local effect size of the associations was small for PSQI and medium for MNA. A significant interaction was observed between the PSQI and MNA scores. The result of the Johnson-Neyman technique indicated that the influence of PSQI on SGDS-K became weaker and insignificant as nutritional status worsened. However, the association between the MNA and SGDS-K scores was significant regardless of PSQI., Conclusion: Both sleep disturbance and malnutrition were significantly associated with late-life depression, although malnutrition may be more critically associated with depression than sleep disturbance in community-dwelling older adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hwang, Cho, Kim, Woang, Hong, Roh and Son.)

We explored the associations of actigraphy-derived rest-activity patterns and circadian phase parameters with clinical symptoms and level 1 polysomnography (PSG) results in patients with chronic insomnia to evaluate the clinical implications of actigraphy-derived parameters for PSG interpretation. Seventy-five participants underwent actigraphy assessments and level 1 PSG. Exploratory correlation analyses between parameters derived from actigraphy, PSG, and clinical assessments were performed. First, participants were classified into two groups based on rest-activity pattern variables; group differences were investigated following covariate adjustment. Participants with poorer rest-activity patterns on actigraphy (low inter-day stability and high intra-daily variability) exhibited higher insomnia severity index scores than participants with better rest-activity patterns. No between-group differences in PSG parameters were observed. Second, participants were classified into two groups based on circadian phase variables. Late-phase participants (least active 5-h and most active 10-h onset times) exhibited higher insomnia severity scores, longer sleep and rapid eye movement latency, and lower apnea-hypopnea index than early-phase participants. These associations remained significant even after adjusting for potential covariates. Some actigraphy-derived rest-activity patterns and circadian phase parameters were significantly associated with clinical symptoms and PSG results, suggesting their possible adjunctive role in deriving plans for PSG lights-off time and assessing the possible insomnia pathophysiology., (© 2022. The Author(s).)

There is a proven correlation between the severity of dementia and reduced brain volumes. Several studies have attempted to use activity data to estimate brain volume as a means of detecting reduction early; however, raw activity data are not directly interpretable and are unstructured, making them challenging to utilize. Furthermore, in the previous research, brain volume estimates were limited to total brain volume and the investigators were unable to detect reductions in specific regions of the brain that are typically used to characterize disease progression. We aimed to evaluate volume prediction of 116 brain regions through activity data obtained combining time-frequency domain- and unsupervised deep learning-based feature extraction methods. We developed a feature extraction model based on unsupervised deep learning using activity data from the National Health and Nutrition Examination Survey (NHANES) dataset ( n = 14,482). Then, we applied the model and the time-frequency domain feature extraction method to the activity data of the Biobank Innovations for chronic Cerebrovascular disease With ALZheimer's disease Study (BICWALZS) datasets ( n = 177) to extract activity features. Brain volumes were calculated from the brain magnetic resonance imaging of the BICWALZS dataset and anatomically subdivided into 116 regions. Finally, we fitted linear regression models to estimate each regional volume of the 116 brain areas based on the extracted activity features. Regression models were statistically significant for each region, with an average correlation coefficient of 0.990 ± 0.006. In all brain regions, the correlation was > 0.964. Particularly, regions of the temporal lobe that exhibit characteristic atrophy in the early stages of Alzheimer's disease showed the highest correlation (0.995). Through a combined deep learning-time-frequency domain feature extraction method, we could extract activity features based solely on the activity dataset, without including clinical variables. The findings of this study indicate the possibility of using activity data for the detection of neurological disorders such as Alzheimer's disease., Competing Interests: DY is the founder and employee of BUD.on Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Park, Choi, Lee, Jang, Roh, Kim, Hong, Son and Yoon.)

Objective: We aimed to present the study design and baseline cross-sectional participant characteristics of biobank innovations for chronic cerebrovascular disease with Alzheimer's disease study (BICWALZS) participants., Methods: A total of 1,013 participants were enrolled in BICWALZS from October 2016 to December 2020. All participants underwent clinical assessments, basic blood tests, and standardized neuropsychological tests (n=1,013). We performed brain magnetic resonance imaging (MRI, n=817), brain amyloid positron emission tomography (PET, n=713), single nucleotide polymorphism microarray chip (K-Chip, n=949), locomotor activity assessment (actigraphy, n=200), and patient-derived dermal fibroblast sampling (n=175) on a subset of participants., Results: The mean age was 72.8 years, and 658 (65.0%) were females. Based on clinical assessments, total of 168, 534, 211, 80, and 20 had subjective cognitive decline, mild cognitive impairment (MCI), Alzheimer's dementia, vascular dementia, and other types of dementia or not otherwise specified, respectively. Based on neuroimaging biomarkers and cognition, 199, 159, 78, and 204 were cognitively normal (CN), Alzheimer's disease (AD)-related cognitive impairment, vascular cognitive impairment, and not otherwise specified due to mixed pathology (NOS). Each group exhibited many differences in various clinical, neuropsychological, and neuroimaging results at baseline. Baseline characteristics of BICWALZS participants in the MCI, AD, and vascular dementia groups were generally acceptable and consistent with 26 worldwide dementia cohorts and another independent AD cohort in Korea., Conclusion: The BICWALZS is a prospective and longitudinal study assessing various clinical and biomarker characteristics in older adults with cognitive complaints. Details of the recruitment process, methodology, and baseline assessment results are described in this paper.

Accumulating evidence indicates that amyloid-beta (Aβ) deposition and biogenic aldehyde accumulation contribute to the pathogenesis of neurodegenerative diseases. Human aldehyde dehydrogenase 2 (ALDH2) metabolizes biogenic aldehydes produced in the brain to prevent damage. However, r671G>A, a single nucleotide polymorphism of ALDH2, causes aldehyde accumulation and decreased ALDH2 activity. We aimed to investigate whether Aβ deposition and rs671 polymorphism have an interaction effect on cortical thickness (CTh). We grouped 179 participants in the Biobank Innovations for chronic Cerebrovascular disease With ALZheimer's disease Study as follows: amyloid (-) [A(-)] and amyloid (+) [A(+)] groups based on the Aβ deposition degree; A-carrier (AC) and GG (GG) groups based on the presence/absence of the rs671 A allele; and their combinations, i.e., A(-)AC, A(-)GG, A(+)AC, and A(+)GG groups. A multiple regression analysis identified nine regions of interest. Compared with the A(-)GG group, the A(-)AC group showed thinner CTh in all regions. There were no significant differences between the A(+)AC and A(+)GG groups. We observed an interaction effect of amyloid deposition and rs671 polymorphism on CTh. The CTh in the A(-) group appeared to be strongly influenced by rs671 polymorphism, which could have contributed to cortical thinning and biogenic aldehyde accumulation in the AC group. Additionally, CTh in the A(+) group appeared to be strongly influenced by amyloid deposition., (© 2021. The Author(s).)

Background: Suicide has emerged as a serious concern for public health; however, only few studies have revealed the differences between major psychiatric disorders and suicide. Recent studies have attempted to quantify research domain criteria (RDoC) into numeric scores to systematically use them in computerized methods. The RDoC scores were used to reveal the characteristics of suicide and its association with major psychiatric disorders., Objective: We intended to investigate the differences in the dimensional psychopathology among hospitalized suicidal patients and the association between the dimensional psychopathology of psychiatric disorders and length of hospital stay., Methods: This retrospective study enrolled hospitalized suicidal patients diagnosed with major psychiatric disorders (depression, schizophrenia, and bipolar disorder) between January 2010 and December 2020 at a tertiary hospital in South Korea. The RDoC scores were calculated using the patients' admission notes. To measure the differences between psychiatric disorder cohorts, analysis of variance and the Cochran Q test were conducted and post hoc analysis for RDoC domains was performed with the independent two-sample t test. A linear regression model was used to analyze the association between the RDoC scores and sociodemographic features and comorbidity index. To estimate the association between the RDoC scores and length of hospital stay, multiple logistic regression models were applied to each psychiatric disorder group., Results: We retrieved 732 admissions for 571 patients (465 with depression, 73 with schizophrenia, and 33 with bipolar disorder). We found significant differences in the dimensional psychopathology according to the psychiatric disorders. The patient group with depression showed the highest negative RDoC domain scores. In the cognitive and social RDoC domains, the groups with schizophrenia and bipolar disorder scored higher than the group with depression. In the arousal RDoC domain, the depression and bipolar disorder groups scored higher than the group with schizophrenia. We identified significant associations between the RDoC scores and length of stay for the depression and bipolar disorder groups. The odds ratios (ORs) of the length of stay were increased because of the higher negative RDoC domain scores in the group with depression (OR 1.058, 95% CI 1.006-1.114) and decreased by higher arousal RDoC domain scores in the group with bipolar disorder (OR 0.537, 95% CI 0.285-0.815)., Conclusions: This study showed the association between the dimensional psychopathology of major psychiatric disorders related to suicide and the length of hospital stay and identified differences in the dimensional psychopathology of major psychiatric disorders. This may provide new perspectives for understanding suicidal patients., (©Dong Yun Lee, Jimyung Park, Jai Sung Noh, Hyun Woong Roh, Jae Ho Ha, Eun Young Lee, Sang Joon Son, Rae Woong Park. Originally published in JMIR Mental Health (https://mental.jmir.org), 03.09.2021.)

Background: The impact of the interrelationship between depression and cognitive impairment on risk of falls remains unclear. In addition, gender differences should be considered to further understand the relationships between depression, cognitive impairment, and risk of falls., Methods: Older adults who completed the Living Profiles of Older People Survey in Korea were included. In total, 14,055 participants completed the baseline survey, and 7,150 participants completed a follow-up survey after 3 years. We classified participants into 4 groups based on depression and cognitive impairment., Results: Using generalized estimating equation models, older adults with depression but without cognitive impairment had a higher risk of falls (OR=1.49, 95% CI=1.35-1.63), compared to a reference group with neither depression nor cognitive impairment. However, older adults who had cognitive impairment but not depression had a similar risk of falls (OR=1.03, 95% CI=0.91-1.16) to the reference group. Finally, older adults who had both depression and cognitive impairment had the highest risk of falls (OR=1.95, 95% CI=1.73-2.20) compared to the reference group. In addition, depression seemed to have a bigger effect on the risk of falls in men compared to women (p for interaction < 0.001)., Limitations: These results should be interpreted with caution, considering the use of screening tool for defining depression or cognitive impairment, and lack of information on psychotropic medication use., Conclusions: Depression alone or depression combined with cognitive impairment was associated with higher risk of falls in older adults. In addition, gender differences in the risk of falls was noted., (Copyright © 2020. Published by Elsevier B.V.)

Background: We sought to investigate the possible associations of rest-activity patterns with cortical amyloid burden, medial temporal lobe (MTL) neurodegeneration, and cognitive function in patients in the early stage of cognitive impairment., Methods: Rest-activity patterns were assessed in 100 participants (70 with mild cognitive impairment and 30 with mild dementia) using wrist actigraphy. All participants underwent 18 F-flutemetamol positron emission tomography (PET) imaging to quantify cortical amyloid burden, structural brain magnetic resonance imaging (MRI) to quantify MTL grey matter volume, neuropsychological testing, and clinical diagnosis. We used multiple linear regression models adjusted for covariates, including demographics, diabetes, hypertension, depressive symptom, psychotropic medication, sleep medication, weekend effect, and apolipoprotein-ε allele status., Findings: After adjusting for possible confounders, we found that the midline estimation of statistic of rhythm (MESOR) associated positively with frontal/executive function (estimate = 1.17, standard error [SE] = 0.37, p = 0.002). The least active 5-h (L5) onset time associated positively with MTL grey matter volume and memory function (estimate = 1.24, SE = 0.33, p = 0.001, and estimate = 3.77, SE = 1.22, p = 0.003, respectively), particularly in amyloid-negative participants. Additional path analysis revealed that MTL grey matter volume partially mediated the association between L5 onset time and memory function in amyloid-negative participants., Interpretation: Decreased MESOR and advanced L5 onset time may be useful as early signs of cognitive decline or MTL neurodegeneration. Furthermore, amyloid pathology may act as a moderator of the relationships between rest-activity patterns, neurodegeneration, and cognitive function., Funding: Korea Centres for Disease Control and Prevention (#4845-303); National Research Foundation of Korea (2019M3C7A1031905, 2019R1A5A2026045)., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Data collected by an actigraphy device worn on the wrist or waist can provide objective measurements for studies related to physical activity; however, some data may contain intervals where values are missing. In previous studies, statistical methods have been applied to impute missing values on the basis of statistical assumptions. Deep learning algorithms, however, can learn features from the data without any such assumptions and may outperform previous approaches in imputation tasks., Objective: The aim of this study was to impute missing values in data using a deep learning approach., Methods: To develop an imputation model for missing values in accelerometer-based actigraphy data, a denoising convolutional autoencoder was adopted. We trained and tested our deep learning-based imputation model with the National Health and Nutrition Examination Survey data set and validated it with the external Korea National Health and Nutrition Examination Survey and the Korean Chronic Cerebrovascular Disease Oriented Biobank data sets which consist of daily records measuring activity counts. The partial root mean square error and partial mean absolute error of the imputed intervals (partial RMSE and partial MAE, respectively) were calculated using our deep learning-based imputation model (zero-inflated denoising convolutional autoencoder) as well as using other approaches (mean imputation, zero-inflated Poisson regression, and Bayesian regression)., Results: The zero-inflated denoising convolutional autoencoder exhibited a partial RMSE of 839.3 counts and partial MAE of 431.1 counts, whereas mean imputation achieved a partial RMSE of 1053.2 counts and partial MAE of 545.4 counts, the zero-inflated Poisson regression model achieved a partial RMSE of 1255.6 counts and partial MAE of 508.6 counts, and Bayesian regression achieved a partial RMSE of 924.5 counts and partial MAE of 605.8 counts., Conclusions: Our deep learning-based imputation model performed better than the other methods when imputing missing values in actigraphy data., (©Jong-Hwan Jang, Junggu Choi, Hyun Woong Roh, Sang Joon Son, Chang Hyung Hong, Eun Young Kim, Tae Young Kim, Dukyong Yoon. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 23.07.2020.)

Objective: Early detection and proper management of mental illness can help to prevent severe deterioration. However, with limited financial and human resources of community mental health services, it is not practical to carry out all conventional screening tools simultaneously. In this study, we aimed to develop and validate a brief but comprehensive screening questionnaire for four common mental illnesses of the elderly., Methods: The brief screening for four mental illnesses of elderly (BS4MI-elderly) is a 14-item binary response questionnaire that covers dementia, depressive disorder, sleep disorder, and hwa-byung. To test validity, we compared conventional scale scores for three groups of participants classified using the BS4MI-elderly. The sensitivity, specificity, predictive value of positive test, likelihood ratio of positive test and internal consistency of the BS4MI-elderly were assessed. Finally, a correlation analysis between the BS4MI-elderly and general mental health scales was conducted., Results: A total of 254 participants aged over 65 years were recruited. The BS4MI-elderly showed moderate to high sensitivity for the test that distinguishes the normal group from the risk and disorder groups (dementia: 0.61, depressive disorder: 0.88, sleep disorder: 0.85, hwa-byung: 0.94) and high specificity for the test that distinguishes the disorder group from the normal and risk groups (dementia: 0.91, depressive disorder: 0.93, hwa-byung: 0.84, sleep disorder: 0.84). The BS4MI-elderly also exhibited good internal consistency and significant correlations with general mental health scales., Conclusion: The BS4MI-elderly, a brief but comprehensive screening tool, could be a useful instrument for screening the elderly in community mental health services.

Background: Given that current unimodal strategies for treating late-life depression are insufficient, the awareness of the necessity and importance of multidomain intervention has increased. We assessed the efficacy of multidomain intervention in reducing symptoms of late-life depression., Methods: This was a 12-week community-based randomized controlled trial in 78 older adults diagnosed with major depressive disorder. Participants were randomly assigned to the multidomain intervention or supportive therapy group. We provided four home visits and 12 telephone calls over 12 weeks. Four therapeutic approaches (physical activity, healthy diet, social activity, and brief cognitive restructuring) were incorporated into the multidomain intervention. The primary outcome was the change in depressive symptoms, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS). Secondarily, we investigated changes in resting-state functional connectivity., Results: The MADRS total score was reduced more in the multidomain intervention group than in the supportive therapy group during the 12 weeks (intervention × time interaction, P = =0.007). After correction for multiple comparisons, the multidomain intervention group exhibited a lower MADRS total score at week 12 (score difference 5.117; P = =0.029). At follow-up, the multidomain intervention group also exhibited less functional connectivity between the posterior cingulate cortex and left inferior parietal lobule within the default mode network (FDR < 0.1)., Limitations: Caution is needed in the interpretation of the results, considering the small sample size and high percentage of female participants., Conclusions: A 12-week multidomain intervention resulted in a greater reduction of depressive symptoms among the elderly with major depressive disorder than their counterparts who received supportive therapy., Competing Interests: Declaration of Competing Interest All co-authors contributed significantly in this research and approved the final version, and have no conflicts of interest to declare., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Children today are exposed to various media devices, and their usage of these is increasing. Prior studies have outlined forms of harm this can potentially cause. However, there has been little empirical research on the use of media devices among preschool children in Asia. The aim of this study was to examine and analyze longitudinal trends in media device use among Korean preschool children, focusing on the frequency of engagement, time spent with, and ownership of media devices, delineated by sex., Methods: Four hundred parents of children aged 2-5 years were invited to enroll. The baseline assessment, Wave 1, was conducted between December 2015 and June 2016, and follow-up assessments, Wave 2 and Wave 3, were conducted annually for the following 2 years. Time of media use, frequency of media use, and ownership of media devices (TV, tablet PCs, and smartphones) were investigated., Results: Ownership of tablet PCs increased significantly between Wave 1 and Wave 3 for boys and girls (corrected P < 0.001). Frequency of media use increased significantly between Wave 1 and Wave 3 only in boys' use of tablet PCs (mean difference 0.8 day/wk). Time of media use increased significantly between Wave 1 and Wave 3 for both sexes in all devices, measured by mean difference on weekdays and weekends (TV by 0.6 and 0.7 hr/day, tablet PCs by 0.6 and 0.8 hr/day, and smartphones by 0.4 and 0.4 hr/day). Children spent more time using media devices during weekends than on weekdays., Conclusion: This study observed an increase in the tendency of media device use among preschool children in Korea. The patterns of use indicate that paying attention to the types of devices children use is needed, as well as vigilance on weekends., Competing Interests: The authors have no potential conflicts of interest to disclose, (© 2019 The Korean Academy of Medical Sciences.)

Background: It has been suggested that maintaining the efficient organization of the brain's functional connectivity (FC) supports neuroflexibility under neurogenerative stress. This study examined psychological resilience-related FC in 112 older adults with mild cognitive impairment (MCI). Methods: Using a resting-state functional magnetic resonance imaging (fMRI) approach, we investigated reorganization of the orbitofrontal gyrus (OFG)/amygdala (AMG)/hippocampus (HP)/parahippocampal gyrus (PHG) FC according to the different levels of resilience scale. Results: Compared with the low resilient group, the high resilient group had greater connectivity strengths between the left inferior OFG and right superior OFG ( P < 0.05, Bonferroni corrected), between the right inferior OFG and left PHG ( P < 0.05, Bonferroni corrected), and between the right middle OFG and left PHG (false discovery rate < 0.05). Conclusion: Psychological resilience may be associated with enhancement of the orbitofrontal network in the elderly with MCI.

Epigenetic dysregulation has been known to be involved in neurodegenerative diseases, including amnestic mild cognitive impairment (MCI). The aim of this study was to investigate the genome-wide DNA methylation analysis, in order to identify epigenetic dysregulation in blood from patients with MCI. Here, we investigated whether epigenetic dysregulation in MCI and whether such an aberration could be detected in blood circulation. Genome-wide bisulfite sequencing targeted 84 million bases covering 3.7 million CpG sites was comparatively analyzed in MCI and control groups. And correlation between DNA methylation and transcriptomic changes was sought. Significant differentially methylated regions (DMRs) distinguishing the MCI and control groups were identified and functionally annotated. Most DMRs specific to MCI were enriched between - 2 kb and + 2 kb of the CpG island start sites located within or near gene promoters. Representative hypo- and hypermethylated DMRs in MCI were confirmed to be correlated to mRNA expression changes with the comparative delta Ct method. DNA methylation aberrations involving metal ion homeostasis, axon growth, inflammasome, and others in this study may be less-invasive, easily measurable blood biomarker candidates for MCI.

Objective: Motor, perceptual, and cognitive functions are known to affect driving competence. Subcortical ischemic changes on brain magnetic resonance imaging (MRI) can reflect reduction in cognitive and motor performance. However, few studies have reported the relationship between subcortical ischemic changes and driving competence of the elderly. Thus, the objective of this study was to investigate the association between subcortical ischemic changes on MRI and driving abilities of the elderly., Methods: Participants (n=540) were drawn from a nationwide, multicenter, hospital-based, longitudinal cohort. Each participant underwent MRI scan and interview for driving capacity categorized into 'now driving' and 'driving cessation (driven before, not driving now)'. Participants were divided into three groups (mild, n=389; moderate, n=116; and severe, n=35) depending on the degree of white matter hyperintensity (WMH) on MRI at baseline. Driving status was evaluated at follow-up. Statistical analyses were conducted using χ2 test, analysis of variance (ANOVA), structured equation model (SEM), and generalized estimating equation (GEE)., Results: In SEM, greater baseline degree of WMH was directly associated with driving cessation regardless of cognitive or motor dysfunction (β=-0.110, p<0.001). In GEE models after controlling for age, sex, education, cognitive, and motor dysfunction, more severe change in the degree of WMH was associated with faster change from 'now driving' state to 'driving cessation' state over time in the elderly (β=-0.508, p<0.001)., Conclusion: In both cross-sectional and longitudinal results, the degree of subcortical ischemic change on MRI might predict driving cessation in the elderly.

Objective: The objective of this study was to compare the effectiveness of usual care management (UCM) and a newly-developed lifestyle modification with contingency management (LMCM) for geriatric depressive symptoms in the community., Methods: A randomized controlled trial was conducted in 93 older adults with major depressive disorder at community mental health centers. A 12 week multi-domain LMCM was developed by providing positive reinforcement using 'gold medal stickers' as a symbolic incentive to motivate their participation and adherence. Participants were allocated to LMCM (n=47) and UCM (n=46) groups. They were then subjected to the 12 week treatment. Effects of the two intervention methods on Geriatric Depression Scale were determined using mixed model analysis., Results: Participants in the LMCM group had greater decline in GDS score per month than participants in the UCM group after adjusting for age, sex, years of education, living alone, and MMSE scores at baseline examination [coefficient for GDS score (95% CI): -1.08 (-1.51, -0.65), p<0.001, reference: UCM group]., Conclusion: LMCM is safe and easy to use with a low cost. LMCM is suitable as psychosocial intervention for older adults with depressive symptoms in the community.

Background: We compared the validity of models of subcortical ischemic depression (SID) and depression-executive dysfunction syndrome (DED) in predicting functional disability in the elderly., Methods: We obtained data from elderly Korean subjects (n=1356) aged 60 years or older at baseline from the CREDOS study from November 2005 to July 2014. A generalized estimating equation (GEE) model was constructed to measure functional disability using instrumental activity of daily living as a primary outcome. A risk factor of interest was SID and DED evaluated by a visual rating scale of deep white matter hyperintensity in MRI, Stroop test and Geriatric Depression Scale (GDS) score. Receiver-operating-characteristic plots and area under the curve (AUC) test were applied to examine the difference of the two definitions of vascular depression with predicted values of functional disability outcome., Results: The mean (SD) follow-up duration of the participants was 1.7 (0.9) years. The GEE model showed that presence of SID at baseline predicted functional disability compared to non-depressed subjects (GDS score: Odds ratio [OR] 1.76; 95% CI 1.23, 2.53; p=0.002). The association was also statistically significant among the DED group (OR 1.48; 95% CI 1.15, 1.92; p=0.003). There were no significant differences in predicting functional disability (95% CI: -0.003 to 0.009, p=0.366) according to AUC differences between SID and DED., Conclusions: The results will be useful in evaluating the cardinal features of the vascular depression hypothesis in predicting functional disability., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: In keeping with increasing interest in dementia, few recent studies suggest that clinical course of mild cognitive impairment vary across different studies with hospital-based subjects showing higher rates of conversion than community-based subjects., Objective: The main objective of the present study was to assess whether the clinical conversion or reversion rates differ according to recruitment source., Methods: The baseline study subjects comprised of patients who were diagnosed with mild cognitive impairment in community-based GDEMCIS or hospital-based CREDOS. The two studies had nearly the same protocol and were performed over a similar period. We used propensity score matching for baseline comparability. After that, Cox proportional hazards regression analyses were conducted to estimate the hazard ratios and 95% confidence intervals of clinical conversion or reversion., Results: Based on 89 GDEMCIS subjects, 1 : 4 propensity score matching was conducted and 356 CREDOS subjects were selected. After adjusting for covariates including baseline demographics, comorbidity, depression, disability, and neuropsychological result, Cox proportional hazard regression analysis for time to clinical conversion indicated that recruitment from hospital-based CREDOS exhibited hazard ratio of 2.13 (95% CI, 1.08-4.21), as compared to recruitment from community-based GDEMCIS. Similarly, Cox proportional hazard regression analysis for time to reversion indicated that recruitment from hospital-based CREDOS exhibited hazard ratio of 0.34 (95% CI, 0.20-0.59), as compared to recruitment from community-based GDEMCIS., Conclusion: The present study demonstrated that even after the matching process and adjustments for baseline covariates, recruitment source greatly affected the course of mild cognitive impairment.

Background: We aimed to examine differential effects of WMH on progression of depressive symptoms according to APOE ε4 status in the elderly., Methods: We obtained data from elderly Korean subjects (n=707) aged 60 years or older at baseline from the CREDOS study from November 2005 to July 2014. A linear mixed model stratified according to APOE genotype (APOE ε4 carrier vs. non-carrier) was constructed using GDS score as a primary outcome and degree of overall, deep, periventricular WMH evaluated by a visual rating scale as a risk factor of interest. We also tested interaction between APOE ε4, WMH and time as predictors of clinical progression on GDS scores to examine the moderating effect of APOE ε4 allele on the relationship between degree of WMH and progression of geriatric depressive symptoms., Results: The mean (SD) follow-up duration of the participants was 2.0 (0.8) years. Among APOE ε4 carriers, a severe degree of overall and deep WMH, but not periventricular WMH, predicted progression of geriatric depressive symptoms (overall WMH: coefficient=0.96, p=0.010; deep WMH: 0.87, p=0.016). There were significant interaction between APOE ε4, degree of WMH and time in predicting GDS increase (5df, F=2.28, p=0.046)., Limitations: Only subjects seeking medical attention and with follow-up measurements were enrolled in this study. Specific location of WMH and use of antidepressant were uncontrolled., Conclusions: Considering biological markers such as degree of WMH and APOE ε4 status may be clinically relevant to predicting progression of geriatric depressive symptoms., (Copyright © 2015 Elsevier B.V. All rights reserved.)

To determine the association between frontal lobe function and risk of hip fracture in patients with Alzheimer disease (AD).Retrospective cohort study using multicenter hospital-based dementia registry and national health insurance claim data was done. Participants who had available data of neuropsychological test, national health insurance claim, and other covariates were included. A total of 1660 patients with AD were included based on Stroop Test results. A total of 1563 patients with AD were included based on the Controlled Oral Word Association Test (COWAT) results. Hip fracture was measured by validated identification criteria using national health insurance claim data. Frontal lobe function was measured by Stroop Test and COWAT at baseline.After adjusting for potential covariates, including cognitive function in other domains (language, verbal and nonverbal memory, and attention), the Cox proportional hazard regression analysis revealed that risk of a hip fracture was decreased with a hazard ratio (HR) of 0.98 per one point of increase in the Stroop Test (adjusted HR = 0.98, 95% confidence interval [CI]: 0.97-1.00) and 0.93 per one point increase in COWAT (adjusted HR = 0.93, 95% CI: 0.88-0.99).The risk of hip fracture in AD patients was associated with baseline frontal lobe function. The result of this research presents evidence of association between frontal lobe function and risk of hip fracture in patients with AD.

Background: We examined the longitudinal association between participation in individual or combinations of physical, social, and religious activity and risk of depression in the elderly., Methods: Elderly subjects aged ≥ 60 years who completed the Living Profiles of Older People Survey in Korea (n = 6,647) were included. The baseline assessment, Wave 1, was conducted in 2008, and a follow-up assessment, Wave 2, was conducted in 2011. We defined participation in frequent physical activity as ≥ 3 times weekly (at least 30 minutes per activity). Frequent participation in social and religious activity was defined as ≥ 1 activity weekly. The primary outcome was depression at 3-year follow up., Results: Multivariable logistic regression analysis showed that subjects who participated in frequent physical, social, and religious activity had an adjusted odds ratio of 0.81 (95% confidence interval [CI], 0.69-0.96), 0.87 (95% CI, 0.75-1.00), and 0.78 (95% CI, 0.67-0.90), respectively, compared with participants who did not participate in each activity. Participants who participated in only one type of activity frequently and participants who participated in two or three types of activities frequently had an adjusted odds ratio of 0.86 (95% CI, 0.75-0.98) and 0.64 (95% CI, 0.52-0.79), respectively, compared with participants who did not participate in any type of physical, social, and religious activity frequently., Conclusion: Participation in physical, social, and religious activity was associated with decreased risk of depression in the elderly. In addition, risk of depression was much lower in the elderly people who participated in two or three of the above-mentioned types of activity than that in the elderly who did not.

We aimed to examine risk of diabetes mellitus (DM) among older adults with Alzheimer's disease receiving 3 types of psychotropic drugs, that is, antipsychotics, antidepressants, and sedative anxiolytics. We retrospectively analyzed data from a hospital-based Clinical Research Center for Dementia of South Korea (CREDOS) study conducted between January 1, 2008 and December 31, 2012. Participants (n = 3042) with Alzheimer's disease were aged 65 or older and had no preexisting history of DM. Development of DM was identified using claims for initiating at least 1 prescription of antidiabetic medications or a diagnosis of DM during the follow-up period. Cox proportional hazards regression was used to demonstrate the Hazard ratio of DM in use of each psychotropic drug. Among the 3042 participants, 426 patients (14.0%) developed DM, representing an incidence rate of 5.2/100 person-years during an average 2.9 years of follow-up period. Among the 3 types of psychotropic drugs, antipsychotic users had a significantly higher risk of DM (hazard ratio = 1.74, 95% confidence interval = 1.10, 2.76) than nonusers, after adjusting covariates. Antidepressants and sedative anxiolytics did not achieve statistical significance. These results suggested that the diabetes risk was elevated in Alzheimer patients on antipsychotic treatment. Therefore, patients with Alzheimer's disease receiving antipsychotic treatment should be carefully monitored for the development of DM.

Background and Aims: Heat shock proteins (HSPs) have been regarded as cytoprotectants that protect brain cells during the progression of neurodegenerative diseases and from damage resulting from cerebral ischemia. In this study, we assessed the association between plasma HSP 70/27 levels and cognitive decline., Methods: Among participants in the community-based cohort study of dementia called the Gwangju Dementia and Mild Cognitive Impairment Study, subjects without cognitive impairment at baseline, who then either remained without impairment (non-conversion group), or suffered mild cognitive impairment (MCI) (conversion group) (non-conversion group, N = 36; conversion group, N = 30) were analyzed., Results: After a five to six year follow-up period, comparison of the plasma HSP 70 and HSP 27 levels of the two groups revealed that only the plasma HSP 70 level was associated with a conversion to MCI after adjustments for age, gender, years of education, follow-up duration, APOE e4, hypertension, and diabetes (repeated measure analysis of variance: F = 7.59, p = 0.008). Furthermore, an increase in plasma HSP 70 level was associated with cognitive decline in language and executive function (linear mixed model: Korean Boston Naming Test, -0.426 [-0.781, -0.071], p = 0.019; Controlled Oral Word Association Test, -0.176 [-0.328, -0.023], p = 0.024; Stroop Test, -0.304 [-0.458, -0.150], p<0.001)., Conclusions: These findings suggest that the plasma HSP 70 level may be related to cognitive decline in the elderly.

Background & Objective: White matter hyperintensities (WMHs) contribute to aggravation of dementia or geriatric syndrome, thereby resulting in functional impairment. However, evidence of direct association between WMHs and medical resource utilization indicated by length of hospital stay (LOS) is scarce in patients with cognitive impairment. This study aimed to examine the relationship between the severity of WMHs and LOS in patients with cognitive impairment., Methods: 4,253 older adults with cognitive impairment were enrolled in this study. We defined LOS as the total sum of days from January 1, 2008 to December 31, 2012. The severity of periventricular (PVWMHs), deep (DWMHs), and overall white matter hyperintensities (Overall WMHs) was evaluated by a visual rating scale. We conducted multinomial logistic regression to demonstrate the relationship between LOS and severity of PVWHMs, DWHMs, and Overall WMHs, respectively., Results: The median LOS was 20 days. Severe PVWMHs had a higher likelihood of longer LOS (Q3: odd ratio/OR = 1.32, 95% confidence interval/CI = 1.06-1.64; Q4: OR = 1.33, 95% CI = 1.07-1.65; Q5: OR = 1.55, 95% CI = 1.26-1.91). As for DWMHs, moderate DWMHs were related to longer LOS (Q4: OR = 1.33, 95% CI = 1.03-1.71; Q5: OR = 1.63, 95% CI = 1.26-2.11). Finally, severity of overall WMHs was independently associated with LOS, which was similar to the results of DWMHs., Conclusion: These findings would advocate for prevention of WMHs to stave off excess medical resource utilization in patients with cognitive impairment.

Purpose: Our study aimed to assess the longitudinal association of frequency of contact with non-cohabitating adult children and risk of depression in the elderly., Methods: Elderly aged ≥60 years were included from Living Profiles of Older People Survey (LPOPS) in Korea. The baseline assessment, Wave 1, was conducted in 2008, and follow-up assessment, Wave 2, was conducted in 2011. We included participants who completed both waves and excluded those who met the following criteria: no adult children, living with adult children, cognitive impairment at either waves, and depression at baseline (n=4398). We defined infrequent contact as <1 time per month face-to-face contact or <1 time per week phone contact and classified participants into four groups based on contact method and frequency. Depression was measured using the 15-item geriatric depression scales (SGDS-K)., Results: In multivariable logistic regression analysis, infrequent face-to-face and phone contact group had adjusted odds ratio (OR) of 1.86 (95% CI, 1.44-2.42) when compared with frequent face-to-face and phone contact group. Frequent face-to-face contact with infrequent phone contact group and infrequent face-to-face contact with frequent phone contact group had adjusted OR of 1.49 (95% CI, 1.12-1.98) and 1.44 (95% CI, 1.15-1.80), respectively, when compared with frequent face-to-face and phone contact group., Conclusion: These results propose that the risk of subsequent depression in elderly is associated with frequency of contact with non-cohabitating adult children. Moreover, the efficacy of face-to-face contact and that of phone contact were similar, while the group lacking both types of contact demonstrated the highest risk of depression., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Our study aimed to examine the relationship between perceived sleep quality and depression using Pittsburgh Sleep Quality Index (PSQI) and Cole's model to materialize the concept of perceived sleep quality in the non-cognitively impaired elderly. Older adults aged 60+ were recruited from the baseline study of Suwon Project (SP) between 2009 and 2011 (n=2040). Perceived sleep quality was measured using the Korean version of the Pittsburgh Sleep Quality Index (PSQI-K), and depression was accessed using the Korean version of the Geriatric Depression Scale-Short Form (SGDS-K). We excluded the cognitively impaired elderly using the Korean version-Mini Mental Status Examination (K-MMSE) score less than or equal to 17. In multivariable adjusted logistic regression related to PSQI-K components, poor perceived sleep quality, including poor subjective sleep quality (Odds ratio (OR)=1.27, 95% confidence interval (CI)=1.01-1.61), longer sleep latency (OR=1.32, 95% CI=1.13-1.55) and the frequent use of sleeping medication (OR=1.30, 95% CI=1.10-1.53) were significantly associated with depression after adjusting for age, sex, education, living status, current smoking and current alcohol drinking, the number of comorbidity and Beck Anxiety Inventory (BAI). PSQI-K global score also had greater odds of reporting depression (OR=1.12, 95% CI=1.07-1.16). These results suggested that poor perceived sleep quality was associated with a greater level of depression in the elderly., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

In tissue engineering and wound-healing applications, dermal substitutes are used to provide fibroblasts with the mechanical support for their growth and then to facilitate the skin formation. In this study, three-dimensional porous poly(lactic-co-glycolic acid) (PLGA) 65/35 scaffolds were prepared and then the composites of the scaffolds and human fetal dermal fibroblasts were fabricated as a tissue-engineered dermal substitute. The function and tissue compatibility of the artificial dermal substitute were evaluated at the levels of gene expression (by RT-PCR) and protein expression (total collagen quantities), as well as by histological and immunohistochemical analysis. The PCR products indicated that the mRNA of type-I collagen, mainly secreted by the fibroblasts onto the PLGA scaffolds, was clearly expressed after 4 weeks. The amount of total collagen synthesized from the cells was shown to increase gradually during the initial culture period and slightly decreased afterwards. After 8 weeks of culture, the fibroblasts were well attached and migrated entirely throughout the pores of the PLGA scaffold with normal function. Furthermore, the positively stained type-I collagen was intensively detected throughout the pores. These results suggest that the function and tissue compatibility may be important criteria in evaluating an artificial tissue-engineered skin.

The present study in angulated coronary stenosis used human in vivo hemodynamic parameters and computed simulation, both qualitatively and qualitatively, to evaluate the influence of flow velocity and wall shear stress (WSS) on coronary atherosclerosis, the changes of hemodynamic indices following coronary stenting, and their effect on evolving in-stent restenosis. Initial and follow-up coronary angiographies in patients with angulated coronary stenosis were performed (n=60). The optimal degree of coronary stenting for angulated coronary stenosis had two models, the less than 50% angle changed group (model 1, n=33) and the more than 50% angle changed group (model 2, n=27). This angle change was based on the percentage change of vascular angle between pre- and post-intracoronary stenting. The flow-velocity wave obtained from in vivo intracoronary Doppler study data was used for in vitro numerical simulation. Spatial and temporal patterns of the flow-velocity vector and recirculation area were drawn throughout the selected segment of coronary models. WSS of pre- and post-intracoronary stenting was calculated from three-dimensional computer simulation. As results, follow-up coronary angiogram demonstrated significant difference in the percentage of diameter stenosis between the two groups (group 1: 40.3 +/- 30.2 vs. group 2: 25.5 +/- 22.5%, p < 0.05). Negative shear area on 3D simulation, which is consistent with the re-circulation area of flow vector, was noted on the inner wall of the post-stenotic area before stenting. The negative WSS disappeared after stenting. High spatial and temporal WSS before stenting fell within the range of physiologic WSS after stenting. This finding was more prominent in model 2 (p < 0.01). The present study suggests that hemodynamic forces exerted by pulsatile coronary circulation, termed WSS, might affect the evolution of atherosclerosis within the angulated vascular curvature. Moreover, geometric characteristics, such as the angular difference between pre- and post- intracoronary stenting might define optimal rheologic properties for vascular repair after stenting.

Poly(ethylene oxide) (PEO)-grafted polyurethane (PU)/polystyrene (PS) interpenetrating polymer networks (IPNs) were synthesized. The effects of the mobile pendant PEO chains with their microphase separated structure on blood-compatibility were investigated. The morphology of both the fracture surface as well as the top surface indicate that the size of the dispersed domains of the PS-rich phase decreased as the grafting with the PEO was increased. The swelling ratio also decreased as the grafting with the PEO was increased. However, the dynamic contact angle and the interfacial energy between IPN surface and water decreased, due to the structural reorganization of the pendant PEO chains. PU/PS IPNs have an excellent mechanical property as compared with PU homopolymers. The adsorption of bovine plasma fibrinogen (BPF) onto the PU/PS IPNs and PU homopolymers was effectively suppressed by the PEO-grafting. In the platelet adhesion test, the amount of platelets adsorbed, activated, and/or coagulated upon the PEO-grafted PU/PS IPNs were reduced when compared to the ungrafted PU homopolymers.

To investigate the effect of the hydrophilic and hydrophobic microdomain structure on blood compatibility, a series of interpenetrating polymer networks (IPNs) composed of hydrophilic polyurethane (PU) and hydrophobic polystyrene (PS) was prepared. One series was prepared with varying cross-link densities of each network, the other with varying hydrophilicity of the PU component. All PU/PS IPNs exhibited microphase-separated structures that had dispersed PS domains in the continuous PU matrix. The domain size decreased with decreasing the hydrophilicity of the PU component and increasing the cross-link density of each network. As the cross-link density and hydrophobicity of the PU component was increased, an inward shift of Tgs was observed, which was due to the decrease in phase separation between the hydrophobic PS component and hydrophilic PU component. In the in vitro platelet adhesion test, as the microdomain size of PU/PS IPN surface decreased, the number of adhered platelets on the PU/PS IPN surface was reduced and deformation of the adhered platelets decreased. It could be concluded that blood compatibility of PU/PS IPN was mainly affected by the degree of mixing between PU and PS component, which was reflected by the domain size of PS rich phase.

The objectives of this investigation were to evaluate biomechanical factors in the atherosclerotic process using human in vivo hemodynamic parameters and computed numerical simulation qualitatively and quantitatively. The three-dimensional spatial patterns of steady and pulsatile flows in the left coronary artery were simulated, using a finite volume method. Coronary angiogram and Doppler ultrasound measurement of the proximal left coronary flow velocity were performed in humans. Inlet wave velocity distribution obtained from in vivo data of the intravascular Doppler study allowed for input of in vitro numerical simulation. Hemodynamic variables, such as flow velocity, pressure and shear stress of the left anterior descending coronary bifurcation site were calculated. We found that there were spatial fluctuation of flow-velocity and recirculation areas at the curved outer wall of the left anterior descending coronary artery, which were due to the differences of flow-velocity and shear stress, especially during the declaration phase of pulsatile flow. This study suggests that rheologic properties may be a part of the atherogenic process in the coronary bifurcated and curved areas.