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Objective Subjective cognitive impairment (SCI) is associated with future cognitive decline. This study aimed to compare cortical thickness and local gyrification index (LGI) between individuals with SCI and normal control (NC) subjects. Methods Forty-seven participants (27 SCI and 20 NC) were recruited. All participants underwent brain magnetic resonance imaging scanning and were clinically assessed using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) battery of tests. We compared cortical thickness and LGI between the two groups and analyzed correlations between cortical thickness/LGI and scores on CERAD protocol subtests in the SCI group for region of interests with significant between-group differences. Results Cortical thickness reduction in the left entorhinal, superior temporal, insular, rostral middle frontal, precentral, superior frontal, and supramarginal regions, and right supramarginal, precentral, insular, postcentral, and posterior cingulate regions was observed in the SCI compared to the NC group. Cortical thickness in these regions correlated with scores of constructional praxis, word list memory, word list recall, constructional recall, trail making test A, and verbal fluency under the CERAD protocol. Significantly decreased gyrification was observed in the left lingual gyrus of the SCI group. In addition, gyrification of this region was positively associated with scores of constructional praxis. Conclusion Our results may provide an additional reference to the notion that SCI may be associated with future cognitive impairment. This study may help clinicians to assess individuals with SCI who may progress to mild cognitive impairment and Alzheimer’s dementia.

Background Amyloid positron emission tomography (PET) makes it possible to diagnose Alzheimer’s disease (AD) in its prodromal phase including mild cognitive impairment (MCI). This study evaluated the cost-effectiveness of including amyloid-PET for assessing individuals with MCI. Methods The target population was 60-year-old patients who were diagnosed with MCI. We constructed a Markov model for the natural history of AD with the amyloid positivity (AP). Because amyloid-PET can detect the AP MCI state, AD detection can be made faster by reducing the follow-up interval for a high-risk group. The health outcomes were evaluated in quality-adjusted life years (QALYs) and the final results of cost-effectiveness analysis were presented in the form of the Incremental Cost-Effectiveness Ratio (ICER). To handle parameter uncertainties, one-way sensitivity analyses for various variables were performed. Results Our model showed that amyloid-PET increased QALYs by 0.003 in individuals with MCI. The estimated additional costs for adopting amyloid-PET amounted to a total of 1250 USD per patient when compared with the cost when amyloid-PET is not adopted. The ICER was 3,71,545 USD per QALY. According to the sensitivity analyses, treatment effect of Donepezil and virtual intervention effect in MCI state were the most influential factors. Conclusions In our model, using amyloid-PET at the MCI stage was not cost-effective. Future advances in management of cognitive impairment would enhance QALYs, and consequently improve cost-effectiveness.

Background: In many high-income Western countries, the prevalence of dementia had been reduced over the past decades. Objective: We investigated whether the prevalence of all-cause dementia, Alzheimer’s disease, vascular dementia, and mild cognitive impairment (MCI) had changed in Korea from 2008 to 2017. Methods: Nationwide Survey on Dementia Epidemiology of Korea (NaSDEK) in 2008 and 2017 was conducted on representative elderly populations that were randomly sampled across South Korea. Both surveys employed a two-stage design (screening and diagnostic phases) and diagnosed dementia and MCI according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders and the consensus criteria from the International Working Group, respectively. The numbers of participants aged 65 years or older in the screening and diagnostic phases were 6,141 and 1,673 in the NaSDEK 2008 and 2,972 and 474 in the NaSDEK 2017, respectively. Results: The age- and sex-standardized prevalence of all-cause dementia and Alzheimer’s disease showed nonsignificant decrease (12.3% to 9.8%, odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.54–1.48 for all-cause dementia; 7.6% to 6.8%, OR [95% CI] = 0.91 [0.58–1.42] for Alzheimer’s disease). Vascular dementia decreased in the young-old population aged less than 75 years (2.7% to 0.001%, OR [95% CI] = 0.04 [0.01–0.15]) and in women (1.9% to 0.5%, OR [95% CI] = 0.27 [0.10–0.72]) while MCI remained stable (25.3% to 26.2%, OR [95% CI] = 1.08 [0.67–1.73]). Conclusion: We found that the prevalence of dementia in Korea showed a nonsignificant decrease between 2008 and 2017.

Background Long working hours can be a risk factor for poor mental health; however, little is known about the potential factors moderating their relation. This study investigates the association between working hours and depressive symptoms, and explores the potential moderating effect of gender, income level, and job status on this association using a nationally representative sample of working population in South Korea. Methods Data of 7,082 workers aged 19 years or above were obtained from the Korea National Health and Nutrition Examination Surveys (KNHANES) conducted in 2014, 2016, and 2018 in South Korea. Working hours were categorized into 35–39, 40, 41–52, 53–68, and ≥69 hours/week. Depressive symptoms were evaluated using the Patient Health Questionnaire-9 (PHQ-9). Results Individuals working ≥69 hours/week were more likely to have moderate to severe depressive symptoms compared to those working 40 hours/week. The association between longer working hours and depressive symptoms was especially prominent in female workers, standard wage workers, and workers with low income levels. We observed significant partial mediation pathways between working hours and PHQ-9 scores through both perceived usual stress level and self-rated health in the total sample. Limitations The cross-sectional design of the study limits causal interpretation of the findings. Conclusion Working longer than the legal upper limit of 52 hours/week puts workers at a greater risk for depression. Females, low-income workers, and wage workers are more vulnerable to the negative consequences of long working hours on mental health.

Objective Many patients with major depressive disorder (MDD) suffer from residual symptoms without achieving remission. However, pharmacologic options for residual symptoms of MDD have been limited. This study aimed to investigate benefit of aripiprazole augmentation in the treatment of residual symptoms in the patients with partially remitted MDD. Methods We retrospectively analyzed the 8-week medical records of the patients. The enrolled patients did respond to treatment of antidepressant but were not remitted. The range of 17-item Hamilton Depression Rating Scale (HAMD) total score of the subjects were 8 to 15 points. All patients were currently taking antidepressants when they started aripiprazole. The primary endpoint was the mean change of Clinically Useful Depression Outcome Scale (CUDOS). Secondary endpoint measures were HAMD, Clinical Global Impression-severity (CGI-S) scores, Patient Health Questionnaire-15 (PHQ-15), Beck Anxiety Inventory (BAI), Perceived Deficit Questionnaire-depression (PDQ-D), Sheehan Disability Scale (SDS) and General Health Questionnaire/Quality of Life-12 (GHQ/QL-12). Results A total of 134 medical records were analyzed. The changes of CUDOS, HAMD, CGI-S, BAI, PHQ-15, PDQ-D, SDS and GHQ/QL-12 from baseline to the endpoint were -7.93, -3.29, -0.80, -4.02, -2.05, -4.35, -4.77 and -2.82, respectively (all p < 0.001). At the endpoint, the newly remitted subjects rate by HAMD score criteria were approximately 46%. Conclusion Our preliminary findings have presented the effectiveness of aripiprazole augmentation for residual symptoms of partially remitted MDD patients in routine practice. This study assures subsequent well-controlled studies of the possibility of generalizing the above promising outcome in the future.

Background Elderly patients with late-life depression (LLD) often report mild cognitive impairment (MCI), so Alzheimer's disease (AD) is hard to identify in these patients. We aimed to identify the structural and functional differences between prodromal AD and LLD-related MCI. Methods We performed voxel-based morphometry and functional connectivity (FC) analyses in elderly patients with both LLD and MCI to compare alterations between those with cerebral amyloidopathy and those without. We subdivided patients into subthreshold depression (STD) and major depressive disorder (MDD) groups. Using florbetaben positron emission tomography (PET), we compared volume and connectivity between healthy controls and four STD and MDD groups with or without amyloid deposition(A): STD-MCI-A(+), MDD-MCI-A(+), STD-MCI-A(-), and MDD-MCI-A(-). Results Subjects with MDD or amyloid deposition showed greater volume reduction in the left middle temporal gyrus. MDD groups had lower FC than STD groups in the frontal, cortical, and limbic areas. The STD-MCI-A(+) group showed greater FC reduction than the MDD-MCI-A(-) and STD-MCI-A(-) groups, particularly in the hippocampus, parahippocampus, and frontal and temporal cortices. The functional differences associated with amyloid plaques were more evident in the STD group than in the MDD group. Limitations Limitations include disproportional sex ratios, inability to determine the longitudinal effects of amyloidopathy in large populations. Conclusions Regional gray matter loss and alterations in brain networks may reflect impairments caused by amyloid deposition and depression. Such changes may facilitate the detection of prodromal AD in elderly patients with both depression and cognitive dysfunction, allowing earlier intervention and more appropriate treatment.

Workplace gender discrimination (WGD) may have long-term negative impacts on female workers' mental health. We aimed to investigate the association between WGD and the prevalence of depressive symptoms using a nationally representative sample of female employees in South Korea.Data of 3190 adult female employees were obtained from the 2018 nationwide Korean Longitudinal Survey of Women and Families. Women's perception of WGD was assessed using a 6-item questionnaire. Respondents were classified into high, medium, and low levels of WGD according to the 25th and 75th percentile scores. A score of ≥10 on the 10-item version of the Center for Epidemiologic Studies for Depression Scale was defined as having significant depressive symptoms.A high level of WGD was significantly associated with a higher odds ratio (OR) for depressive symptoms compared to the low level (OR = 1.87, 95% confidence interval = 1.45-2.41). In the subgroup analyses, high WGD levels were associated with the highest OR for depressive symptoms in the following subgroups: younger age (19-39 years), those with a college degree, non-standard workers, pink collar workers, those with a workplace size of 10-29 employees, those with high levels of job autonomy, or low levels of emotional labor.Causal interpretation is limited owing to the study's cross-sectional design.A high level of perceived WGD was associated with depressive symptoms among female employees. Certain groups of female employees may be particularly vulnerable to the detrimental effects of WGD on depression.

Work-family conflict (WFC), an inter-role conflict between work and family, negatively affects mental health. Using a nationally representative systematic sample, this study aimed to investigate the association between WFC, depressive symptoms, and potential moderators in the association of adult female workers. Data of 4714 female workers (aged ≥19 years) were obtained cross-sectionally from the 2018 nationwide Korean Longitudinal Survey of Women and Families (KLoWF). WFC was assessed using a 7-item questionnaire, based on which scores were classified into high (75th percentile score) and low (≤75th percentile score) levels of WFC. Significant depressive symptoms were defined as a score of ≥10 on the 10-item version of the Center for Epidemiologic Studies for Depression Scale. Female workers with high WFC levels were more likely to have depressive symptoms than those with low WFC levels (odds ratio = 2.29, 95% confidence interval = 1.91-2.74). In stratified analyses, high WFC levels were associated with the highest odds of depressive symptoms in the following groups: young adults (19-39 years), those with a college degree or above or with high income, never-married individuals, those with a family size of three or a single child, nonstandard workers, and pink-collar workers. This study replicated and extended previous findings on the association between WFC and depressive symptoms. The association was moderated by age, education and income levels, marital status, family size, number of children, and job conditions.

Objective Cardiovascular diseases are representative risk factors for the onset of cognitive decline. The purpose of this study was to confirm the relationship between diastolic blood pressure and cognitive function in elderly people in Korea. Methods Data from subjects who were enrolled in the prospective Korean Longitudinal Study on Cognitive Aging and Dementia were used in this study. Data from 701 subjects whose diastolic blood pressure range did not change (≤79 mm Hg or ≥80 mm Hg) over 2 years were analyzed. To analyze the differences in cognitive function between the groups at the 2-year follow-up, an analysis of covariance was performed with covariates, which were significantly different between the two groups, and the baseline cognitive function. Results Significant differences were observed between the two groups, and the mean scores on the constructional praxis (η2=0.010) and word list recall tests (η2=0.018) in the diastolic blood pressure ≥80 mm Hg group were higher than those in the diastolic blood pressure ≤79 mm Hg group at the 2-year follow-up. Conclusion These results indicate that maintaining a DBP below 79 mm Hg presents a greater risk of cognitive decline in Korean elderly people.

Background Changes in parasympathetic activity have been associated with depression; however, it is not well understood whether these changes are a result of depression, or represent a compensatory mechanism protecting against it. We examined the association of autonomic nervous system activity with the risk of depression in euthymic individuals and those with subsyndromal depression using heart rate variability (HRV) analysis. Methods From a community-based longitudinal cohort, 464 subjects from the baseline assessment and 253 who completed the 5-year follow-up visit were included in the cross-sectional and prospective analyses, respectively. Linear regression analysis was used to investigate the association of HRV measures with the current and future GDS scores. Logistic regression analysis examined the effect of HRV on future risk of SSD. Results Low-frequency power (LFN), high-frequency power (HFN), and the LFN/HFN ratio at the baseline assessment were associated with the GDS score at the 5-year follow-up assessment; however, they were not associated with the GDS score at the baseline assessment. High HFN indicated an increased risk of depression at the 5-year follow-up assessment in euthymic subjects (OR = 3.025, 95% CI = 1.184 – 7.726, p = 0.021). Limitations HRV was not measured at the follow-up assessment and the interval between the assessments was comparatively long. Five-minute ECG recordings were used, and all participants were 65 years old or older. Conclusions Parasympathetic predominance may precede the onset of depression in older adults.

Objective This study aimed to examine the association between normal-but-low folate levels and cognitive function in the elderly population using a prospective cohort study. Methods We analyzed 3,910 participants whose serum folate levels were within the normal reference range (1.5-16.9 ng/mL) at baseline evaluation in the population-based prospective cohort study named the "Korean Longitudinal Study on Cognitive Aging and Dementia." The association between baseline folate quartile categories and baseline cognitive disorders [mild cognitive impairment (MCI) or dementia] was examined using binary logistic regression analysis adjusting for confounding variables. The risks of incident MCI and dementia associated with the decline of serum folate level during a 4-year follow-up period were examined using multinomial logistic regression analysis. Results The lowest quartile group of serum folate (≥1.5, ≤5.9 ng/mL) showed a higher risk of cognitive disorders than did the highest quartile group at baseline evaluation (odds ratio 1.314, p=0.012). Over the 4 years of follow-up, the risk of incident dementia was 2.364 times higher among subjects whose serum folate levels declined from the 2nd-4th quartile group to the 1st quartile than among those for whom it did not (p=0.031). Conclusion Normal-but-low serum folate levels were associated with the risk of cognitive disorders in the elderly population, and a decline to normal-but-low serum folate levels was associated with incident dementia. Maintaining serum folate concentration above 5.9 ng/mL may be beneficial for cognitive status.

Objective : The purpose of this study was to examine post-hospitalization outpatient drug adherence in patients with severe psychiatric illness, including bipolar disorder and schizophrenia, and to investigate factors associated with drug adherence. Methods : Eighty-one patients diagnosed with schizophrenia or bipolar disorder who were hospitalized due to aggravation of psychiatric symptoms were monitored. At hospitalization, we conducted clinical assessments such as the Clinical Global Impression-Severity, Drug Attitude Inventory, Contour Drawing Rating Scale, Multidimensional Scale of Perceived Social Support scale, and patients’ demographic factors. We measured drug adherence using the Medication Event Monitoring System (MEMS), pill count, and patients’ self-report upon out-patients visits, 4 and 24 weeks after discharge. Results : The mean values of the various measures of adherence were as follows: MEMS (4 weeks) 84.8%, pill count (4 weeks) 94.6%, self-report (4 weeks) 92.6%, MEMS (24 weeks) 81.6%, pill count (24 weeks) 90.6%, and self-report (24 weeks) 93.6%. The adherence agreement between MEMS, pill count, and self-report was moderate (4 weeks intraclass correlation [ICC]=0.54, 24 weeks ICC=0.52). Non-adherence (MEMS ≤0.08) was observed in 26.4% of the patients at 4 weeks and 37.7% at 24 weeks. There was a negative correlation between drug adherence assessed 4 weeks after discharge and Contour Drawing Rating Scale difference score (r=-0.282, p＜0.05). A positive correlation was found between drug adherence assessed 24 weeks after discharge and Drug Attitude Inventory (r=0.383, p＜0.01). Conclusion : Patients’ attitude towards their medication and their degree of physical dissatisfaction influenced post-hospitalization drug adherence in severe psychiatric patients.

Co-occurring depression and mild cognitive impairment (MCI) in older adults are important because they have a high risk of conversion to dementia. In the present study, task-related F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) was used to analyse older adults with concomitant depression and MCI. We recruited 20 older adults with simultaneous depression and MCI and 10 older adults with normal cognition (NC). The Verbal Paired Associates test and digit span test were used for the task-related FDG-PET. The 20 older adults with depression and MCI were classified into two groups based on the F-18 florbetaben PET results: depressed MCI patients with (LLD-MCI-A[+]; n = 11) and without amyloid accumulation (LLD-MCI-A[-]; n = 9). Reduced regional cerebral glucose metabolism (rCMglc) in the left superior frontal region was observed in the LLD-MCI-A(-) group compared with the NC group. Analyses of the NC and LLD-MCI-A(+) groups showed significantly decreased rCMglc in the right inferior parietal and left middle frontal regions in the LLD-MCI-A(+) group. rCMglc in the left precuneus was lower in the LLD-MCI-A(+) group than in the LLD-MCI-A(-) group. Significant correlations between the rCMglc in the right inferior parietal/left precuneus regions and memory task scores were observed based on correlation analyses of NC and LLD-MCI-A(+) groups. The findings in the present study indicate the presence of amyloid accumulation influences glucose metabolism in depressed elderly subjects with MCI while performing cognitive tasks. Task-related FDG-PET examinations may help differentiate MCI associated with depression from comorbid depression in patients with prodromal Alzheimer's disease.

Background Despite strong evidence of clinical benefit, cardiac rehabilitation (CR) programs are currently underutilized and smartphone-based CR strategies are thought to address this unmet need. However, data regarding the detailed process of development are scarce. Objective This study focused on the development of a smartphone-based, patient-specific, messaging app for patients who have undergone percutaneous coronary intervention (PCI). Methods The AnSim app was developed in collaboration with a multidisciplinary team that included cardiologists, psychiatrists, nurses, pharmacists, nutritionists, and rehabilitation doctors and therapists. First, a focus group interview was conducted, and the narratives of the patients were analyzed to identify their needs and preferences. Based on the results, health care experts and clinicians drafted messages into 5 categories: (1) general information regarding cardiovascular health and medications, (2) nutrition, (3) physical activity, (4) destressing, and (5) smoking cessation. In each category, 90 messages were developed according to 3 simplified steps of the transtheoretical model of behavioral change: (1) precontemplation, (2) contemplation and preparation, and (3) action and maintenance. After an internal review and feedback from potential users, a bank of 450 messages was developed. Results The focus interview was conducted with 8 patients with PCI within 1 year, and 450 messages, including various forms of multimedia, were developed based on the transtheoretical model of behavioral change in each category. Positive feedback was obtained from the potential users (n=458). The mean Likert scale score was 3.95 (SD 0.39) and 3.91 (SD 0.39) for readability and usefulness, respectively, and several messages were refined based on the feedback. Finally, the patient-specific message delivery system was developed according to the baseline characteristics and stages of behavioral change in each participant. Conclusions We developed an app (AnSim), which includes a bank of 450 patient-specific messages, that provides various medical information and CR programs regarding coronary heart disease. The detailed process of multidisciplinary collaboration over the course of the study provides a scientific basis for various medical professionals planning smartphone-based clinical research.

BACKGROUND Despite strong evidence of clinical benefit, cardiac rehabilitation (CR) programs are currently underutilized and smartphone-based CR strategies are thought to address this unmet need. However, data regarding the detailed process of development are scarce. OBJECTIVE This study focused on the development of a smartphone-based, patient-specific, messaging app for patients who have undergone percutaneous coronary intervention (PCI). METHODS The AnSim app was developed in collaboration with a multidisciplinary team that included cardiologists, psychiatrists, nurses, pharmacists, nutritionists, and rehabilitation doctors and therapists. First, a focus group interview was conducted, and the narratives of the patients were analyzed to identify their needs and preferences. Based on the results, health care experts and clinicians drafted messages into 5 categories: (1) general information regarding cardiovascular health and medications, (2) nutrition, (3) physical activity, (4) destressing, and (5) smoking cessation. In each category, 90 messages were developed according to 3 simplified steps of the transtheoretical model of behavioral change: (1) precontemplation, (2) contemplation and preparation, and (3) action and maintenance. After an internal review and feedback from potential users, a bank of 450 messages was developed. RESULTS The focus interview was conducted with 8 patients with PCI within 1 year, and 450 messages, including various forms of multimedia, were developed based on the transtheoretical model of behavioral change in each category. Positive feedback was obtained from the potential users (n=458). The mean Likert scale score was 3.95 (SD 0.39) and 3.91 (SD 0.39) for readability and usefulness, respectively, and several messages were refined based on the feedback. Finally, the patient-specific message delivery system was developed according to the baseline characteristics and stages of behavioral change in each participant. CONCLUSIONS We developed an app (AnSim), which includes a bank of 450 patient-specific messages, that provides various medical information and CR programs regarding coronary heart disease. The detailed process of multidisciplinary collaboration over the course of the study provides a scientific basis for various medical professionals planning smartphone-based clinical research. CLINICALTRIAL

BACKGROUND Apolipoprotein E (APOE) ɛ4 allele carriers have an increased risk of late-onset Alzheimer's disease (AD). However, in the "Choosing Wisely" campaign for avoiding unnecessary medical tests, treatments, and procedures, APOE genetic testing is not recommended as a predictive test for AD. OBJECTIVE The aim of this study was to investigate the potential value of APOE genetic testing in a specific clinical context. METHODS Subjects with poor performance in the Korean version of the Mini-Mental Status Examination for dementia screening (MMSE-DS) with a Z-score of less than -1.5 were recruited from the public health centers. All participants underwent APOE genetic testing. Family history of dementia (FHx) was confirmed if one or more first-degree relatives had dementia. RESULTS Among 349 subjects, 162 (46.4%) were diagnosed with AD. APOEɛ4 allele carriers had a much higher risk of AD in the group with FHx than in the group without FHx (OR = 15.81, 95% CI = 2.74-91.21 versus OR = 1.82, 95% CI = 1.00-3.27, z = 2.293, p = 0.011). The sensitivity, specificity, positive predictive value, and negative predictive value for the APOEɛ4 allele were 47.7%, 90.9%, 91.3%, and 46.5% in the group with FHx. CONCLUSION It would be a wise choice to perform the APOE genetic testing for the diagnosis of AD in subjects with poor performance in a screening test and a family history of dementia.

Background Depression is a risk factor for mild cognitive impairment (MCI) and for the conversion from MCI to Alzheimer's disease (AD). This study investigated regional cerebral glucose metabolism (rCMglc) in older adults with depression and MCI, either with or without amyloidopathy. Methods We recruited 31 older adults diagnosed with depression and MCI, and 21 older adults with normal cognition (NC). All participants completed demographic questionnaires and were examined with a standardized neuropsychological battery, F-18 fluorodeoxyglucose positron emission tomography (PET), and F-18 florbetaben PET. We classified subjects with depression and MCI into amyloid-β-positive (CDAP; n = 16) and amyloid-β-negative (CDAN; n = 15) groups. Pairwise rCMglc analyses were conducted between all three groups (CDAP vs. NC, CDAN vs. NC, and CDAP vs. CDAN). Results In comparison with the NC group, the CDAP group showed reduced rCMglc predominantly in temporoparietal regions, whereas the CDAN group showed lower rCMglc in regions of the frontal lobe, in addition to the temporoparietal regions. The CDAN group also showed lower rCMglc in right anterior cingulate and left inferior orbitofrontal regions, in a comparison between the CDAP and CDAN groups. Limitations The generalizability of the findings is limited because this study has a relatively small number of participants. In addition, this study used cross-sectional design rather than longitudinal design. Conclusions Our findings may provide a reference to assess the risk of future cognitive deterioration. Consequently, this study is expected to contribute to prevention and early identification of dementia associated with AD.

Objective Due to an unprecedented rate of population aging, South Korea is facing a dementia epidemic. For this reason, the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) was launched in 2009 with support from the Korean Health Industry Development Institute to investigate the epidemiology, biopsychosocial risk factors, and outcomes of dementia and dementia-related conditions. Methods The KLOSCAD is the first nationwide multi-center population-based prospective cohort study. In October 2010, 12,694 individuals were randomly sampled from residents aged 60 years or older who lived in 13 districts across South Korea. In the baseline assessment, which was conducted from November 2010 through October 2012, 6,818 (53.7%) individuals participated. Follow-up assessments have been conducted every two years, with the first follow-up assessment conducted between November 2012 and October 2014, and the second between November 2014 and October 2016. The third is now in progress, and will span from November 2016 to October 2018. Diagnosis of cognitive disorders, neuropsychological battery, behavioral and psychological symptoms of dementia, activities of daily living, physical and neurologic examination and laboratory tests, life styles, quality of life, and identification of death were evaluated in each assessment. Results The cumulative drop-out rate at the second follow-up assessment was 38.7%. Dementia and mild cognitive impairment were 5.0% and 27.0%, respectively. Conclusion The KLOSCAD may provide strong scientific evidence for advancing the fight against dementia both in Korea and globally.

Background: The aim of this study was to investigate the association of gait speed and gait variability, an index of how much gait parameters, such as step time, fluctuate step-to-step, with risk of cognitive decline in cognitively normal elderly individuals. While high gait variability is emerging as an early indicator of dementing illnesses, there is little research on whether high gait variability predicts cognitive decline in cognitively normal elderly who have no evidence of cognitive impairment. Methods: In this 4-year prospective cohort study on 91 community-dwelling cognitively normal elderly individuals without cerebral ischemic burden or Parkinsonism, we evaluated gait speed and step time variability using a tri-axial accelerometer placed on the center of body mass, and diagnosed mild cognitive impairment (MCI) according to the International Working Group on MCI. We performed Kaplan-Meier analysis with consecutive log-rank testing for MCI-free survival by cohort-specific tertiles of gait speed; hazard ratios (HR) of incident MCI were estimated using Cox proportional hazards regression analysis adjusted for age, sex, education level, Cumulative Illness Rating Scale score, GDS score, and presence of the apolipoprotein E ε4 allele. Results: Out of the 91 participants in the baseline assessment, 87 completed one or more 2-year follow-up assessments, and the median duration of follow-up was 47.1 months. Kaplan-Meier curves of incident MCI show evident differences in risk by gait variability group (χ2 = 9.64, p = 0.002, log-rank test). Mean MCI-free survival in the high variability group was 12% shorter than in the mid-to-low tertile group (47.4 ± 1.74 [SD] vs. 54.04 ± 0.52 months), while it was comparable between gait speed groups (51.59 ± 0.70 vs. 50.64 ± 1.77 months; χ2 = 1.16, p = 0.281). In multivariate analysis, subjects with high gait variability showed about 12-fold higher risk of MCI (HR = 11.97, 95% CI = 1.29–111.37) than those with mid-to-low variability. However, those with slow gait speed showed comparable MCI risk to those with mid-to-high speed (HR = 5.04, 95% CI = 0.53–48.18). Conclusions: Gait variability may be a better predictor of cognitive decline than gait speed in cognitively normal elderly individuals without cerebral ischemic burden or Parkinsonism.

Objective The pathophysiology of major depressive disorder (MDD) is still not well understood. Conflicting results for surrogate. biomarkers in MDD have been reported, which might be a consequence of the heterogeneity of MDD patients. Therefore, we aim to investigate how the severity of depression and various symptom domains are related to the levels of dehydroepiandrosterone sulfate (DHEA-s) in MDD patients. Methods We recruited 117 subjects from a general practice. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Depressive symptoms were divided into three subdomains according to BDI items; somatic symptoms, guilt and failure, and mood and inhibition. Results In subjects with very-mild-to-moderate depression, the DHEA-s level increased as BDI score did. However, the DHEA-s levels in the subjects with severe depression were significantly lower than in subjects with moderate depression (p=0.003). DHEA-s level was correlated with the BDI subscore for guilt and failure in very-mild-to-moderate depression (r=0.365, p=0.006). Conclusion The DHEA-s level appears to be indicative of MDD severity with respect to depressive symptoms, especially regarding guilt and failure. Our findings suggest that the upregulation of DHEA-s may be a part of a compensatory process in very-mild-to-moderate depression, and the failure of this compensation mechanism may underlie the development of severe depression.

Background Non-adherence in patients with bipolar disorder (BD) results in symptoms, such as aggravation, BD recurrence, emergency room visits, re-hospitalization, and poor psychosocial outcomes. Though non-adherence rates have been reported to range between 30–50% in patients with BD, the problem of adherence is often either overlooked by the physician or denied by the patient. An essential first step to enhancing medication adherence is to objectively estimate adherence. The Medication Event Monitoring System (MEMS), which is a pill bottle cap with a microprocessor, is an accurate device for assessing medication adherence. Using the MEMS, we aimed to measure medication adherence in patients with BD and evaluate the factors associated with and 6-month changes in medication adherence. Methods Participants with BD were recruited from the psychiatric outpatient clinic of the Korea University Guro Hospital. The medication adherence of each participant was assessed using the MEMS, a self-report, pill count, and clinician rating. MEMS-measured adherence was reassessed after 6 months. Patient demographics were recorded and clinical assessments were conducted. Data were analyzed using Kappa statistics and Pearson’s correlation analysis. Results Of the 59 participants, 50 records were included in the analysis. Patient adherence and adherence rate assessed by the MEMS were lower than those assessed by the other measures. MEMS-measured adherence was correlated more closely with pill counts than with self-reports or clinician ratings. MEMS-measured adherence was negatively associated with prescription duration and the Brief Psychiatric Rating Scale—Affect Subscale Score. Six-month changes in MEMS-measured adherence were positively associated with attitude toward drugs and negatively associated with weight gain assessed by the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. Conclusions Clinicians may have to consider the limited accuracy of self-reporting and clinician rating methods and exercise caution when assessing the medication adherence of patients with BD using these methods. Our findings may assist clinicians in the assessment and improvement of medication adherence in patients with BD and, consequently, may be useful for the treatment and prevention of BD recurrence.

Background The 15-item geriatric depression scale (GDS-15) is a short form of GDS and is used to screen, diagnose, and evaluate depression in elderly individuals. Most previous studies evaluated the ability of GDS-15 to discriminate between depressive and non-depressive states. In this study, we investigated the multi-stage discriminating ability of GDS-15. Methods A total of 774 participants, over 65 years of age were included (normal, n = 650; minor depressive disorder [MnDD], n = 94; major depressive disorder [MDD], n = 30). Multi-category receiver operating characteristic (ROC) surfaces were evaluated to identify three stages of geriatric depression. The optimal cutoff points were selected based on the volume under the ROC surface (VUS) and the Youden index. Results In the results of multi-category classification analyses, VUS of the GDS-15 of 0.61 was obtained, and optimal cutoff points of the GDS-15 for multiple stages of depression of 4 (between normal and MnDD) and 11 (between MnDD and MDD) were derived. The Youden index for the GDS-15 was 0.49, and the derived optimal cutoff points were 5 and 10, for the multiple stages, respectively. The overall diagnostic accuracy based on the Youden index was superior to that based on the VUS in the GDS-15. Limitations The participants’ cognitive function has potential to affect the GDS-15 score; nevertheless, the study included those with mild cognitive impairment. Conclusions GDS-15 was a useful tool to classify stages of geriatric depression into either minor or major depressive disorder.

Apoptosis is a prominent feature in the progression of Alzheimer's disease (AD), regulated in part by the activity of p53. As tripartite motif family-like 2 (TRIML2), a member of the TRIM family of proteins, has been implicated in the regulation of p53-mediated apoptosis, we hypothesized that TRIML2 polymorphisms may result in an increased AD susceptibility. Here, we investigated the association between coding region single nucleotide polymorphisms (cSNPs) in TRIML2 and AD in a Korean population. Two cSNPs (rs79698746 and rs2279551) were genotyped using the Sequenom iPLEX(®) Gold assay and direct sequencing in 162 AD patients and 191 controls. Multiple logistic regression models were used to determine the odds ratios, 95% confidence intervals, and p-values. Significant associations were observed between AD and the allelic frequencies of two SNPs (rs79698746, p=0.007; rs2279551, p=0.01); genotype frequencies were also significantly different between the two groups [rs79698746: p=0.003 in the codominant 2 model (CC vs. TT), p=0.01 in the dominant model (TC/CC vs. TT), p=0.016 in the recessive model (CC vs. TT/TC), and p=0.0025 in the log-additive model (TC vs. CC vs. TT); rs2279551: p=0.003 in the codominant 2 model (CC vs. TT), p=0.011 in the dominant model (TC/CC vs. TT), p=0.019 in the recessive model (CC vs. TT/TC), and p=0.0028 in the log-additive model (TC vs. CC vs. TT)]. In the haplotype analyses, CC haplotypes containing two cSNPs were significantly associated with AD (p=0.013). Taken together, these findings indicate that the C allele of both SNPs was associated with an increased risk of AD. These results suggest that TRIML2 may contribute to AD susceptibility.

Some elders with subjective cognitive deficits (SCD) develop prodromal phase of dementia over time; however, little is known about how they differ from those with normal cognition (NC). Thus, we aim to distinguish the differences in the brain network of elders with SCD and NC. Multiple diffusion-weighted images (DWI) and T1-weighted images were obtained from 18 subjects with NC and 26 subjects with SCD. Using network-based statistics (NBS) analysis, we extracted abnormal brain subnetworks and localized abnormal brain connectivity. We also ran correlation analysis to compare the affected regions and the results of the neurocognitive assessments. Altered subnetworks were found in the superior parietal gyrus, angular gyrus, precuneus, posterior cingulum, putamen, precentral gyrus, postcentral gyrus, and paracentral lobule. They were also associated with scores on the word list recall, word list recognition, and Boston naming test. Elders with SCD had distinctive brain network alterations when compared with those of elders with NC. The results are also in line with the previously identified characteristics of mild cognitive impairment (MCI) and of Alzheimer’s disease (AD) in a milder form. We speculate that it may be possible to predict AD progression early in the SCD stage using NBS analysis.

A brain network is the essence of the intelligence where it consists of nodes that are anatomically defined brain regions, and edges that connect a pair of brain regions. The diffusion-weighted magnetic resonance (MR) images and the advances in computer-aided tractography algorithms let us know strong association between human brain networks and cognitive functions. Brain regions dedicated to a certain specific cognitive function were spatially clustered and efficiently connected each other; it is called local functional segregation. However, it is not well known that such a local segregation is associated with a certain sub-network which may act as a building block of the brain network. In this work, using a graph auto-encoder, we extracted building blocks of brain networks and investigate whether they are affected by a neurological disease, Alzheimer’s disease. We found that the brain network of each person is linear summation of the learned building blocks. Also, the activation levels of these building blocks vary in the normal controls and patients with Alzheimer’s disease, showing that network deterioration in the disease group.

Objective Despite robust interest in the association between inflammation and depression, anti-inflammatory markers have been scarcely investigated as predictors of the future risk of depression. The aim of this study is to determine whether up-regulation of plasma adiponectin, an anti-inflammatory adipokine, precedes and predicts the development of depression in the elderly. Methods This prospective cohort study was launched in 2005. Among 1,000 participants who were randomly sampled from community-dwelling individuals 65 years or older, 633 euthymic individuals without prior history of depressive disorders were enrolled for a baseline evaluation and follow-up after 5 years. Incident clinically significant depression, including major and minor depressive disorders (by DSM-IV criteria), subsyndromal depression (by operational criteria), and euthymia after antidepressant treatment, was assessed by clinical interviews. Results Baseline plasma adiponectin values were divided into tertiles (low tertile: ≤ 5.685 μg/mL, middle tertile: 5.686-10.367 μg/mL, high tertile: ≥ 10.368 μg/mL). Among the 261 euthymic individuals who responded to the 5-year follow-up evaluation, 17 developed incident depression (7 from the high tertile, 8 from the middle tertile, and 2 from the low tertile). The risk of incident depression was much higher in the high tertile group than in the low tertile group after adjusting for age, sex, body mass index, burden of chronic medical illnesses, and Mini-Mental State Examination score (odds ratio = 10.64; 95% CI, 1.21-93.84; P = .033). Conclusions Up-regulation of plasma adiponectin may precede the onset of clinically significant depression in the elderly, and thus plasma adiponectin level is a potential candidate marker for the risk of depression.

Background We investigated the effects of lifetime cumulative ginseng intake on cognitive function in a community-dwelling population-based prospective cohort of Korean elders. Methods Community-dwelling elders (N = 6422; mean age = 70.2 ± 6.9 years, education = 8.0 ± 5.3 years, female = 56.8%) from the Korean Longitudinal Study on Cognitive Aging and Dementia were included. Among them, 3918 participants (61.0%) completed the 2-year and 4-year follow-up evaluations. Subjects were categorized according to cumulative ginseng intake at baseline evaluation; no use group, low use (