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Background: Genome-wide association studies (GWAS) have identified a number of genetic variants for Alzheimer's disease (AD). However, most GWAS were conducted in individuals of European ancestry, and non-European populations are still underrepresented in genetic discovery efforts. Here, we performed GWAS to identify single nucleotide polymorphisms (SNPs) associated with amyloid β (Aβ) positivity using a large sample of Korean population., Methods: One thousand four hundred seventy-four participants of Korean ancestry were recruited from multicenters in South Korea. Discovery dataset consisted of 1190 participants (383 with cognitively unimpaired [CU], 330 with amnestic mild cognitive impairment [aMCI], and 477 with AD dementia [ADD]) and replication dataset consisted of 284 participants (46 with CU, 167 with aMCI, and 71 with ADD). GWAS was conducted to identify SNPs associated with Aβ positivity (measured by amyloid positron emission tomography). Aβ prediction models were developed using the identified SNPs. Furthermore, bioinformatics analysis was conducted for the identified SNPs., Results: In addition to APOE, we identified nine SNPs on chromosome 7, which were associated with a decreased risk of Aβ positivity at a genome-wide suggestive level. Of these nine SNPs, four novel SNPs (rs73375428, rs2903923, rs3828947, and rs11983537) were associated with a decreased risk of Aβ positivity (p < 0.05) in the replication dataset. In a meta-analysis, two SNPs (rs7337542 and rs2903923) reached a genome-wide significant level (p < 5.0 × 10 -8 ). Prediction performance for Aβ positivity increased when rs73375428 were incorporated (area under curve = 0.75; 95% CI = 0.74-0.76) in addition to clinical factors and APOE genotype. Cis-eQTL analysis demonstrated that the rs73375428 was associated with decreased expression levels of FGL2 in the brain., Conclusion: The novel genetic variants associated with FGL2 decreased risk of Aβ positivity in the Korean population. This finding may provide a candidate therapeutic target for AD, highlighting the importance of genetic studies in diverse populations.

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: 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.

Objective: This study aimed to investigate the different clinical characteristics among elderly coronavirus disease 2019 (COVID-19) patients with and without mental disorders in South Korea and determine if these characteristics have an association with underlying mental disorders causing mortality., Method: A population-based comparative cohort study was conducted using the national claims database. Individuals aged ≥65 years with confirmed COVID-19 between January 1, 2020 and April 10, 2020 were assessed. The endpoints for evaluating mortality for all participants were death, 21 days after diagnosis, or April 10, 2020. The risk of mortality associated with mental disorders was estimated using Cox hazards regression., Results: We identified 814 elderly COVID-19 patients (255 [31.3%] with mental disorder and 559 [68.7%] with nonmental disorder). Individuals with mental disorders were found more likely to be older, taking antithrombotic agents, and had diabetes, hypertension, chronic obstructive lung disease, and urinary tract infections than those without mental disorders. After propensity score stratification, our study included 781 patients in each group (236 [30.2%] with mental disorder and 545 [69.8%] with nonmental disorder). The mental disorder group showed higher mortality rates than the nonmental disorder group (12.7% [30/236] versus 6.8% [37/545]). However, compared to patients without mental disorders, the hazard ratio (HR) for mortality in elderly COVID-19 patients with mental disorders was not statistically significant (HR: 1.57, 95%CI: 0.95-2.56)., Conclusion: Although the association between mental disorders in elderly individuals and mortality in COVID-19 is unclear, this study suggests that elderly patients with comorbid conditions and those taking psychiatric medications might be at a higher risk of COVID-19., (Copyright © 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

We compared the efficacy and safety of transcranial direct current stimulation (tDCS) vs. Sertraline in the treatment of Major Depressive Disorder (MDD) in South Korean participants. This was a multi-center, double blind, active controlled study with non-inferiority testing. Patients were randomly assigned to receive tDCS (n = 45) or Sertraline (n = 47). tDCS was administered in 30-min, 2 mA prefrontal stimulation sessions for 10 consecutive weekdays, followed by 2 treatments at 4 and 6 weeks. Sertraline was administered at a dose of 50 mg per day for 6 weeks. The primary outcome measure was a change in the Montgomery-Asberg Depression Rating Scale (MADRS) score at six weeks. Mean MADRS scores decreased by 14.58 ± 8.51 points in the tDCS group and 12.32 ± 8.56 points in the Sertraline group. There was no significant main effect of group (p = 0.5877) or time by group interaction across weeks 0, 3, and 6 (p = 0.1539). Noninferiority of tDCS compared with Sertraline was not demonstrated. The mean difference between the Sertraline and tDCS group was -2.258 (95% confidence interval [CI], -5.795 to 1.27811), and the lower boundary of the CI was lower than the prespecified noninferiority margin of -3.56. There were no significant group differences in the rate of adverse events. In the present study, the noninferiority of tDCS to Sertraline for the treatment of depression was not found in this Korean population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: The purpose of the Korean Frailty and Aging Cohort Study (KFACS) is to initiate a nationwide, population-based prospective cohort study of older adults living in the community to assess their frailty status and explore transitions between frailty states over time in Korea., Participants: The KFACS is a multicentre longitudinal study with the baseline survey conducted from May 2016 to November 2017. Each centre recruited participants using quota sampling stratified by age and sex. The number of participants recruited through 2 years of baseline study from 10 centres was 3014, with each site accounting for approximately 300 participants. The inclusion criteria were: having an age of 70-84 years, currently living in the community, having no plans to move out in the next 2 years, having no problems with communication and no prior dementia diagnosis., Findings to Date: To define physical frailty, the KFACS used a modified version of the Fried Frailty Phenotype (FFP) consisting of five components of frailty: unintended weight loss, weakness, self-reported exhaustion, slowness and low physical activity. In the baseline study of 2016-2017, 2907 of 3014 individuals fulfilled all five components of FFP. The results indicated that 7.8% of the participants (n=228) were frail, 47.0% (n=1366) were prefrail and 45.2% (n=1313) were robust. The prevalence of frailty increased with age in both sexes; in the group aged 70-74 years, 1.8% of men and 3.7% of women were frail, whereas in the 80-84 years age group, 14.9% of men and 16.7% of women were frail. Women tended to exhibit a higher prevalence of frailty than men in all age groups., Future Plans: The KFACS plans to identify outcomes and risk factors associated with frailty by conducting a 10-year cohort study, with a follow-up every 2 years, using 3014 baseline participants., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The leading causes of death among the elderly with cognitive impairment are unknown. This study aims to estimate the suicide and accidental death rates on the basis of a clinical case registry of patients diagnosed with cognitive impairment., Methods: The target sample consisted of 10,169 patients diagnosed with dementia or mild cognitive impairment (MCI), who were evaluated at the Clinical Research Center for Dementia of Korea (CREDOS) from January 2005 to December 2013. Information about whether the patients had died from suicide or in any kind of accident by December 31, 2016, was obtained from the database of the National Statistical Office (NSO). The standardized mortality ratio (SMR) and Cox-regression analysis were performed for evaluating the risk of suicide and accidental death as identified by the ICD-10., Results: The average of the Clinical Dementia Rating Scale (CDR) score (0.68 vs 0.93) was lower, and the age at the time of study registration (71.42 vs 75.68 years) was younger in the suicidal death group, as compared to the accidental death group. The overall SMR for accidental death in cognitively impaired patients (1.44, 95% CI 1.22-1.71) was significantly higher than the general population. Later onset (1.43, 95% CI 1.20-1.71) and older age (2.21, 95% CI 1.04-4.68) increased the risk of accidental death in cognitively impaired patients. According to the dementia subtypes, the SMR for accidental death was higher in both Alzheimer's disease (1.72, 95% CI 1.36-2.14) and vascular dementia (2.14, 95% CI 1.27-3.38). Additionally, the SMR for accidental death showed an increasing tendency as the CDR score increased (mild 1.80, 95% CI 1.32-2.42, moderate 1.86, 95% CI 1.07-3.03, severe 3.32, 95% CI 1.08-7.76). Unemployment increased the risks of both suicide (3.71, 95% CI 1.54-8.95) and accidental death (2.09, 95% CI 1.20-3.63)., Conclusions: Among people with cognitive impairment, the risk of death by suicide did not increase, whereas that of accidental death increased significantly. Preventive strategies for premature mortality in those with cognitive impairment should be implemented from the early stages and should include careful evaluation of the individual risk factors for each type of death.

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.

Background: The study's aim was to examine the association of alcohol consumption with verbal and visuospatial memory impairment in older people., Methods: Participants were 1,572, aged ≥60 years, in the hospital-based registry of the Clinical Research Center for Dementia of South Korea (CREDOS). Moderate drinking was defined as no more than seven drinks per week and three drinks per day. Memory impairment was defined as performance with more than 1 standard deviation below the mean value on the Seoul Verbal Learning Test and Rey Complex Figure Test., Results: Those who consumed alcohol moderately, compared with abstainers, had a lower odds of verbal memory impairment (Odds Ratio [OR] = 0.64; 95% Confidence Interval [CI]: 0.46-0.87), adjusting for covariates. Visuospatial memory, however, was not significantly associated with alcohol consumption., Conclusions: Moderate alcohol drinking is associated with a reduced likelihood of verbal memory impairment among older people attending memory clinics.

Background: A healthy lifestyle may protect against cognitive decline. We examined outcomes in elderly individuals after 18 months of a five-group intervention program consisting of various modalities to prevent cognitive decline., Methods: We conducted a cluster randomized controlled trial assessing 460 community-dwelling individuals aged 60 years and older in a geriatric community mental health center in Suwon, Republic of Korea, between 2008 and 2010. We developed an intervention program based on the principles of contingency management, which could be delivered by ordinary primary health workers. Group A (n = 81) received standard care services. Group B (n = 80) received bimonthly (once every 2 months) telephonic care management. Group C (n = 111) received monthly telephonic care management and educational materials similar to those in group B. Group D (n = 93) received bimonthly health worker-initiated visits and counseling. Group E (n = 94) received bimonthly health worker-initiated visits, counseling, and rewards for adherence to the program., Results: The primary outcome was the change in Mini-Mental State Examination (MMSE) scores from baseline to the final follow-up visit at 18 months. Group E showed superior cognitive function to group A (adjusted coefficient β = 0.99, p = 0.044), with participation in cognitive activities being the most important determining factor among several health behaviors (adjusted coefficient β = 1.04, p < 0.01)., Conclusions: Engaging in cognitive activities, in combination with positive health behaviors, may be most beneficial in preserving cognitive abilities in community-dwelling older adults.