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Background There are growing concerns about the impact of the COVID-19 pandemic on the mental health of older adults. We examined the effect of the pandemic on the risk of depression in older adults. Methods We analyzed data from the prospective cohort study of Korean older adults, which has been followed every 2 years. Among the 2308 participants who completed both the third and the fourth follow-up assessments, 58.4% completed their fourth follow-up before the outbreak of COVID-19 and the rest completed it during the pandemic. We conducted face-to-face diagnostic interviews using Mini International Neuropsychiatric Interview and used Geriatric Depression Scale. We performed generalized estimating equations and logistic regression analyses. Results The COVID-19 pandemic was associated with increased depressive symptoms in older adults [b (standard error) = 0.42 (0.20), p = 0.040] and a doubling of the risk for incident depressive disorder even in euthymic older adults without a history of depression (odds ratio = 2.44, 95% confidence interval 1.18–5.02, p = 0.016). Less social activities, which was associated with the risk of depressive disorder before the pandemic, was not associated with the risk of depressive disorder during the pandemic. However, less family gatherings, which was not associated with the risk of depressive disorder before the pandemic, was associated with the doubled risk of depressive disorder during the pandemic. Conclusions The COVID-19 pandemic significantly influences the risk of late-life depression in the community. Older adults with a lack of family gatherings may be particularly vulnerable.

The aim of this study was to determine the differences in the risk factors for dangerous driving between older adults with normal cognition and those with cognitive impairment.The driving risk questionnaire (DRQ) that was applied to a community-dwelling older adult cohort and 2 years of accident/violation records from the National Police Agency were analyzed. We conducted regression analyses with the presence or absence of risky driving based on records (accidents + violations) 2 years before and after evaluation as a dependent variable and dichotomized scores of each risky driving factor as independent variables.According to four identified factors-crash history, safety concern, reduced mileage, and aggressive driving-significant associations were found between risky driving over the past 2 years and crash history and for aggressive driving in the normal cognition group. In the cognitive impairment group, only crash history was significantly associated, although safety concerns showed a trend toward significance.In this study, it was suggested that the factors of DRQ have a significant association with actual risky driving. Our results are expected to contribute to establishing the evidence for evaluating and predicting risky driving and advising whether to continue driving in clinics.

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 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.

ObjectiveTo investigate the effects of single sensory impairment (SSI; visual or auditory) or dual sensory impairment (DSI; visual and auditory) on dementia and longitudinal changes of neuropsychological test scores.MethodsIn this nationwide, prospective, community-based elderly cohort study, KLOSCAD (the Korean Longitudinal Study on Cognitive Aging and Dementia), 6,520 elderly individuals (58–101 years) representing the general population were included. We defined visual and auditory sensory impairment via self-report questionnaire: 932 had normal sensory function, 2,957 had an SSI, and 2,631 had a DSI. Demographic and clinical variables including cognitive outcomes were evaluated every 2 years over 6 years. Through logistic regression, Cox regression, and linear mixed model analysis, the relationship between SSI or DSI and dementia prevalence, dementia incidence, and change in neuropsychological scores were evaluated.ResultsAt baseline, DSI was significantly associated with increased dementia prevalence compared to normal sensory function (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.17–4.02), but SSI was not (OR 1.27, 95% CI 0.66–2.41). During the 6-year follow-up, the incidence of dementia was significantly higher in the DSI group than in the normal sensory function group (hazard ratio 1.9, 95% CI 1.04–3.46) and neuropsychological scores significantly decreased (β −0.87, 95% CI [−1.17 to −0.58]).ConclusionsOur results suggest that coexisting visual and hearing impairments facilitate dementia prevalence, dementia incidence, and cognitive decline, but visual or hearing impairment alone do not. Visual and hearing impairment may lead to dementia or cognitive decline independent of Alzheimer pathology.

ImportanceAlthough couples may share many risk factors for depressive disorders in their lifetime, whether these factors mediate the shared risk of depressive disorders has rarely been investigated.ObjectivesTo identify the shared risk factors for depressive disorder in couples and investigate their mediating roles in the shared risk of depressive disorders among older adult couples.Design, Setting, and ParticipantsThis nationwide, multicenter, community-based cohort study assessed 956 older adults from the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) and a cohort of their spouses (KLOSCAD-S) between January 1, 2019, to February 28, 2021.ExposuresDepressive disorders of the KLOSCAD participants.Main Outcomes and MeasuresThe mediating roles of shared factors in couples on the association between one spouse’s depressive disorder and the other’s risk of depressive disorders was examined using structural equation modeling.ResultsA total of 956 KLOSCAD participants (385 women [40.3%] and 571 men [59.7%]; mean [SD] age, 75.1 [5.0] years) and their spouses (571 women [59.7%] and 385 men [40.3%]; mean [SD] age, 73.9 [6.1] years) were included. The depressive disorders of the KLOSCAD participants were associated with an almost 4-fold higher risk of depressive disorders in their spouses in the KLOSCAD-S cohort (odds ratio, 3.89; 95% CI, 2.06-7.19; P P = .04; mediation proportion [MP] = 6.1%) and through chronic illness burden (β = 0.003; 95% CI, 0.000-0.006; P = .04; MP = 1.5%). Chronic medical illness burden (β = 0.025; 95% CI, 0.001-0.050; P = .04; MP = 12.6%) and presence of a cognitive disorder (β = 0.027; 95% CI, 0.003-0.051; P = .03; MP = 13.6%) mediated the association.Conclusions and RelevanceThe risk factors shared by older adult couples may mediate approximately one-third of the spousal risk of depressive disorders. Identification of and intervention in the shared risk factors of depression among older adult couples may reduce the risk of depressive disorders in the spouses of older adults with depression.

Objectives:Subsyndromal depression is prevalent and associated with poor outcomes in late life, but its effect on the risk of dementia has barely been investigated. This study is aimed to investigate the effect of subsyndromal depression on dementia risk in cognitively normal older adults and patients with mild cognitive impairment.Methods:Data were collected from a nationwide, population-based, prospective cohort study on a randomly sampled Korean elderly population aged 60 years or older, which has been followed every 2 years. Using 6-year follow-up data of 4456 non-demented elderly, the authors examined the risk of dementia associated with late-onset subsyndromal depression using multivariate Cox proportional hazard models. After standardized diagnostic interviews, subsyndromal depression and dementia were diagnosed by the operational diagnostic criteria and Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria, respectively.Results:Subsyndromal depression tripled the risk of dementia in non-demented elderly individuals (hazard ratio = 3.02, 95% confidence interval = [1.56, 5.85], p Conclusion:Late-onset subsyndromal depression is a potential predictor of incident dementia when it is chronic or recurrent with increasing severity in cognitively normal older adults.

Subjective age-associated changes in sleep (AACS) and sex differences in AACS have never been prospectively investigated in elderly populations. We compared the AACS every 2 years over a total of 6 years between 4,686 community-dwelling healthy men and women aged 60 years or older who participated in the Korean Longitudinal Study on Cognitive Aging and Dementia. Sleep parameters including sleep duration, latency, and efficiency, mid-sleep time, daytime dysfunction, and overall subjective sleep quality were measured using the Pittsburgh Sleep Quality Index at baseline and at each follow-up. The effects of time and sex on subjective sleep parameters were analyzed using linear mixed-effects models. During the 6 years of follow-up, we observed that overall, sleep latency increased, while daytime dysfunction and sleep quality worsened. Significant sex differences in AACS was found, with women showing shortened sleep duration, delayed mid-sleep time, and decreased sleep efficiency over 6 years. Sleep quality worsened in both groups but a more pronounced change was observed in women. Clinicians should be cautious in determining when to treat declared sleep disturbances in this population.

Objectives Inflammation and vascular dysregulation may contribute to the development of depression and impose a burden on erythropoiesis. This study aimed to identify the association of erythrocyte indices with the severity of depressive symptoms and risk of developing depressive disorders in the older people. Design A prospective cohort study on a randomly sampled Korean older population; the baseline assessment from 2010 to 2012, the first follow-up assessment from 2012 to 2014, and the second follow-up assessment from 2014 to 2016 (mean follow-up duration = 3.4 years). Setting A nationwide and community-based cohort. Participants A total of 4451 Koreans aged 60 years or older. Methods We examined the associations of the values and changes in mean corpuscular volume, mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) with the risk of prevalent and incident depression using logistic regression analyses. Results High MCH and MCHC in female participants and high MCHC in male participants were associated with high geriatric depression scale scores and risk of prevalent depression. In female participants, high- and middle-MCH tertile groups showed a 2.68- and 2.34-fold higher risk of incident depression than did the low tertile group. In male participants, the high-MCH tertile group showed a 1.79-fold higher risk of incident depression than did the low tertile group. In both sexes, the participants whose MCV changed to the high or middle tertile or remained in the high or middle tertile during the follow-up period, and whose MCH increased to the high tertile or remained in the high tertile, were at a higher risk of incident depression. Conclusions and Implications Changes in erythrocyte may be associated with the risk of depression in older adults. This prospective study proposes a new perspective of the old hematologic parameters for understanding the pathophysiology of late-life depression.

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.

Although couples could share many risk factors of cognitive disorders in their lifetime, whether shared risk factors mediate the shared risk of cognitive disorders has rarely been investigated.To identify the risk factors of cognitive decline shared within couples and investigate their mediating roles in the shared risk of cognitive disorders and cognitive functions within couples.A prospective cohort study was launched in November 1, 2010, and 784 participants were followed up every 2 years until December 31, 2020. This nationwide, multicenter, community-based study included older couples from the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) and a cohort of their spouses (KLOSCAD-S).The cognitive disorder of a spouse was defined as mild cognitive impairment or dementia.The mediating roles of factors shared within couples on the association between one spouse's cognitive disorder and the other's risk of cognitive disorders was examined with structural equation modeling.Included were 784 KLOSCAD participants (307 women [39.2%] and 477 men [60.8%]; mean [SD] age, 74.8 [4.8] years) and their spouses (477 women [60.8%] and 307 men [39.2%]; mean [SD] age, 73.6 [6.2] years). The cognitive disorder of the KLOSCAD participants was associated with almost double the risk of cognitive disorder of their spouses in the KLOSCAD-S cohort (odds ratio, 1.74; 95% CI, 1.12-2.69; P = .01). History of head injury (β = 0.50; 95% CI, 0.09-0.90; P = .02) and age (β = 2.57; 95% CI, 1.37-3.76; P .001) mediated the association between cognitive disorder in the KLOSCAD participants and their spouses' risk of cognitive disorder. Physical inactivity mediated the association through major depressive disorder (β = 0.33, 95% CI, 0.09-0.57, P = .006 for physical inactivity; β = 0.28, 95% CI, 0.13-0.44, P .001 for major depressive disorder). These factors similarly mediated the association between spousal cognitive disorder and cognitive functions such as memory and executive function.These findings suggest that the risk factors shared within couples may mediate approximately three-quarters of the spousal risk of cognitive disorders. Identification of and intervention in the shared risk factors of dementia within couples may reduce the risk of cognitive disorders in the spouses of people with dementia.

Objective: The effects of mood disorders on mortality may be mediated by their effects on the risk of dementia, and interventions to reduce the occurrence of dementia may reduce their overall mortality. This study aimed to investigate the direct effects of depressive and bipolar disorders on the 6-year risk of mortality and also their indirect effects on mortality due to their effect on the risk of dementia. Methods: A total of 5101 Koreans were selected from a community-based prospective cohort study, and 6-year risks of mortality and dementia in participants with depressive and bipolar disorders were estimated by Cox proportional hazard analysis. The direct and indirect effects of depressive and bipolar disorders on the risk of mortality were estimated using structural equation modeling. Results: The depressive and bipolar disorder groups showed 51% and 85% higher 6-year mortality, and 82% and 127% higher risk of dementia, respectively, compared to euthymic controls. The effects of depressive and bipolar disorders on mortality were mainly mediated by their effects on the risk of dementia in a structural equation model. The direct effects of each mood disorder on mortality were not significant. Conclusion: Both depressive and bipolar disorders increased the risks of mortality and dementia, and the effects of mood disorders on mortality were mainly mediated through dementia. As dementia occurs later in life than mood disorders, measures to prevent it may effectively reduce mortality in individuals with a history of mood disorders, as well as being more feasible than attempting to control other causes of death.

Background: Subsyndromal depression is prevalent and associated with poor outcomes in late life, but its epidemiological characteristics have barely been investigated. The aim of this prospective cohort study is to compare the prevalence, incidence, and risk factors of subsyndromal depression with those of syndromal depression in community-dwelling elderly individuals. Methods: In a nationwide community-based study of randomly sampled Korean elderly population aged 60 years or older (N = 6,640), depression was assessed with standardized diagnostic interviews. At baseline and at 2-year and 4-year follow-ups, the authors diagnosed subsyndromal depression by the operational criteria and syndromal depression by the DSM-IV diagnostic criteria. Multivariate logistic regression analyses were conducted to identify the risk factors for incident depressive disorders. Outcomes: The age- and gender- adjusted prevalence rate of subsyndromal depression was 9·24% (95% CI = 8·54 – 9·93), which was 2·4-fold higher than that of syndromal depression. The incidence rate of subsyndromal depression was 21·70 per 1000 person-years (95% CI = 19·29 – 24·12), which was five-folds higher than that of syndromal depression. The prevalence to incidence ratio of subsyndromal depression was about half that of syndromal depression. The risk for subsyndromal depression was associated with female gender, low socioeconomic status, poor social support, and poor sleep quality while that of syndromal depression was associated with old age and less exercise. Interpretation: Subsyndromal depression should be validated as a clinical diagnostic entity, at least in late life, since it has epidemiological characteristics different from those of syndromal depression. Funding Statement: This study was supported by a grant from the Korean Health Technology R&D Project, Ministry for Health, Welfare, & Family Affairs, Republic of Korea (Grant No. A092077). Declaration of Interests: The authors declare that there are no conflicts of interest. Ethics Approval Statement: This study was approved by the Institutional Review Board of the Seoul National University Bundang Hospital.

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.

ImportanceThe association between social support and dementia risk has been debated. Most previous prospective studies have not differentiated the subtypes of social support.ObjectiveTo examine whether the association between social support and risk of dementia differs by subtype of social support and by sex.Design, Setting, and ParticipantsThis nationwide prospective cohort study included randomly sampled South Korean adults 60 years or older. The study was launched November 1, 2010, with follow-up every 2 years until November 30, 2020. The 5852 participants who completed the assessment for social support and were not diagnosed as having dementia, severe psychiatric disorders including major depressive disorder, or major neurological disorders at the baseline assessment were included in the analysis.ExposuresGeriatric psychiatrists administered the structured diagnostic interviews and physical examinations to every participant based on the Korean version of the Consortium to Establish a Registry for Alzheimer Disease (CERAD-K) Assessment Packet Clinical Assessment Battery.Main Outcomes and MeasuresBaseline levels of emotional and tangible support using the Medical Outcomes Survey Social Support Survey.ResultsAmong the 5852 participants (mean [SD] age, 69.8 [6.6] years; 3315 women [56.6%]; mean [SD] follow-up duration, 5.9 [2.4] years), 237 (4.0%) had incident all-cause dementia and 160 (2.7%) had incident Alzheimer disease (AD) subtype of dementia. Compared with women who reported having emotional support, those with low emotional support had almost a 2-fold higher incidence of all-cause dementia (18.4 [95% CI, 13.6-23.2] vs 10.7 [95% CI, 9.0-12.5] per 1000 person-years) and AD (14.4 [95% CI, 10.2-18.6] vs 7.8 [95% CI, 6.3-9.3] per 1000 person-years). Adjusted Cox proportional hazard analysis revealed that low emotional support was associated with increased risk of all-cause dementia (hazard ratio, 1.61 [95% CI, 1.10-2.36]; P = .02) and AD (hazard ratio, 1.66 [95% CI, 1.07-2.57]; P = .02) only in women. Low tangible support was not associated with a risk of all-cause dementia or AD regardless of sex.Conclusions and RelevanceThe findings of this cohort study suggest that older women with low emotional support constitute a population at risk for dementia. The level of emotional support should be included in risk assessments of dementia.

Background The recruitment of monocytes to the brain plays an important role in the development of depression. However, the association between plasma biomarkers of monocyte trafficking and depression is unclear. This study is aimed to examine the effects of plasma monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) on the risk of depression. Methods Data were acquired from an ongoing prospective cohort study involving randomly sampled, community-dwelling Korean older adults, which has been followed every 2 years. We included 1539 euthymic older adults (age = 68.2 [5.6] years; 51.7% were women) without a history of major psychiatric disorders and dementia and neurological diseases. Geriatric psychiatrists diagnosed incident depression through a structured interview using the Korean version of the Mini-International Neuropsychiatric Interview. Results Depression had developed in 134 (8.7%) participants during the follow-up period of 5.7 (0.8) years. The high-plasma MCP-1 tertile group showed twofold higher risk of depression than the low-plasma MCP-1 tertile group (hazards ratio = 2.00, 95% confidence interval = 1.27–3.13, p = .003). The association between high levels of plasma MCP-1 and future risk of depression was significant in the middle-plasma ICAM-1 and VCAM-1 tertile groups; the high-plasma MCP-1 tertile group showed about fourfold higher risk of depression than the low-plasma MCP-1 tertile group. Conclusions Molecules involved in monocyte trafficking may be good candidates as diagnostic biomarkers and/or therapeutic targets for late-life depression.

Summary Background Hyperhomocysteinemia has been repeatedly found to increase the risk of dementia. However, the effects of hypohomocysteinemia on the risk of dementia have been barely investigated. If hypohomocysteinemia, like hyperhomocysteinemia, increases the risk of dementia, misuse or overuse of homocysteine-lowing agents such as vitamin supplements may increase the risk of dementia. Aims To investigate whether hypohomocysteinemia, like hyperhomocysteinemia, could increase the risk of dementia and Alzheimer's disease (AD) in a large population-based cohort of older adults. Methods This prospective cohort study followed 2655 randomly sampled, community-dwelling, non-demented individuals aged 60 years or older from 2010 to 2018. We measured baseline serum total homocysteine (tHcy) levels and examined the effect of serum tHcy on the risks of dementia and AD using Cox proportional hazards models. Results During the follow-up period (mean = 5.4 years, SD = 0.9), dementia and AD developed in 85 and 64 participants, respectively. Not only the participants with high serum tHcy (≥10.6 μmol/L) but also those with low serum tHcy (≤8.9 μmol/L) were 4–5 times more likely to develop dementia and AD compared to those with serum tHcy levels between 9.0 and 10.5 μmol/L. With the increase in serum tHcy concentration, the use of vitamin supplements decreased, and 41.2% of the participants with low serum tHcy (≤8.9 μmol/L) were taking vitamin supplements. Conclusions Not only hyperhomocysteinemia but also hypohomocysteinemia considerably increased the risk of dementia and AD in older adults. The risk of dementia that results from overuse or misuse of vitamin supplements should be acknowledged and homocysteine-lowering health policies should be tailored to consider dementia risks that are associated with hypohomocysteinemia.

Background Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. Methods We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype. Results Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10–1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38–6.47) and Latin America (OR = 1.49, 95% CI = 1.04–2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33–3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81–26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07–3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44–8.35) in Asia. Conclusion Parity is associated with women’s risk of dementia, though this is not uniform across regions and dementia subtypes.

Aims To investigate the association between parity and the risk of incident dementia in women. Methods We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)). Results Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity. Conclusions Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.

ObjectiveIt is uncertain what factors increases the risk of suicide in older adults without depression, and it is unknown whether executive dysfunction (ED) is one of those factors. We aimed to examine the effect of ED on the risk of suicide in non-demented older adults without depression.MethodsIn an ongoing population-based prospective cohort of Korean older adults, we identified suicide using the National Mortality Database and suicidal ideation or attempt (SIA) based on the Korean version of the Mini International Neuropsychiatric Interview. We defined ED as performing below −1.5 SD of age-adjusted, gender-adjusted and education-adjusted norms in any of following tests: Frontal Assessment Battery, Trail Making Test A, Digit Span Test or Verbal Fluency Test.ResultsThe mean age of the 4791 participants at baseline was 69.7 (SD 6.4) years, and 57.1% of them were women (mean follow-up duration=4.9 years). ED at baseline increased the risk of suicide by about seven times (HR 7.20, 95% CI 1.84 to 28.12, p=0.005) but did not change the risk of SIA. However, cognitive impairment without ED did not change the risks of suicide and SIA. In participants with ED, being aged 75 years or above, living alone, and having a low socioeconomic status were associated with the risk of suicide.ConclusionED is a strong risk factor of late life suicide independent from depression, particularly in very old adults living in disadvantaged environments.

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.

Objective We investigated the prevalence and risk factors of physically abusive behaviors (PhAB) and psychologically abusive behaviors (PsAB) towards people with dementia (PWD) in family caregivers, and compared their prevalences between East Asian and Western countries. Methods We estimated the prevalence and risk factors of PhAB and PsAB in 467 Korean pairs of community-dwelling PWD and their primary family caregivers. We evaluated abusive behaviors using the Modified Conflict Tactics Scale. In addition, we compared the prevalence of abusive behaviors between Asian and Western countries through a meta-analysis on 12 studies including the current one. Results More than a half of the caregivers reported PsAB and about one out of seven caregivers admitted PhAB within past three months. PsAB and PhAB were slightly more prevalent in East Asian countries than in Western countries. Non-Alzheimer type and moderate to severe behavioral and psychological symptoms of dementia were associated with the risk of PhAB but not with the risk of PsAB. Severe care burden and low income were associated with the risk of PhAB and PsAB. Conclusion PhAB and PsAB were as prevalent in the family caregivers of PWD in Asian countries including Korea as in Western countries. Prevention strategies should be implemented according to the type of abusive behaviors.

Background Mild cognitive impairment (MCI) is a cognitive state that lies on the continuum between normal aging and dementia, and the prevalence of MCI is higher than dementia. However, the risk for mortality of people with MCI has been far less studied than that of people with dementia, and the population attributable risk percent (PAR%) of death attributable to MCI has not been estimated yet. Objective To investigate the impact of MCI on mortality and the cause of death in the elderly, and to estimate the PAR% of deaths attributable to MCI. Methods Data came from 7,315 elderly subjects aged ≥60 years without dementia from two cohort studies with diagnostic assessments of MCI at baseline. Deaths among participants were confirmed through the nationwide mortality database of Statistics Korea. Results MCI increased the risk of mortality in a multivariate Cox proportional model adjusting for age, sex, education, smoking, alcohol drinking, chronic illness, depression, vascular components, and cohort (hazard ratio = 1.59, 95% confidence interval 1.30, 1.94). PAR% of death attributable to MCI was 10.7% for age 65-74 years, 16.0% for age 75-84 years, and 24.2% for age ≥85 years. In the elderly with MCI, mortality risks from cerebrovascular disease, respiratory disease, and external causes were higher than in the cognitively normal elderly. Conclusions Our results suggest that the mortality risk of MCI in Asian countries may be comparable to that in Western countries, and MCI can contribute to the death of the elderly as much as dementia.

Objectives Understanding disability-adjusted life-years (DALYs) based on dementia subtypes and mild cognitive impairment (MCI) is essential for optimal resource allocation. This study aimed to investigate disease burdens of various dementias and MCI in a representative South Korean population. Design Retrospective cohort study. Setting and Participants 6481 Korean older adults. Methods We estimated the disease-specific DALYs. Results DALYs due to MCI and all-cause dementia are estimated to increase from 1295 per 100,000 in 2016 to 9501 per 100,000 in 2065. In 2016, DALYs attributed to Alzheimer's dementia, vascular dementia, and MCI accounted for 33% (423 per 100,000), 20% (316 per 100,000), and 24% (123 per 100,000), respectively, of the total DALYs due to MCI and all-cause dementia. In 2065, DALYs due to Alzheimer's dementia, vascular dementia, and MCI will account for 38% (3654 per 100,000), 17% (1654 per 100,000), and 27% (2585 per 100,000) of total DALYs due to MCI and all-cause dementia, respectively. The years of life lived with disability (YLDs) due to MCI and all-cause dementia are estimated to rise from 479 per 100,000 in 2016 to 2807 per 100,000 in 2065. In 2016, YLDs due to Alzheimer's dementia, vascular dementia, and MCI composed 37% (177 per 100,000), 18% (85 per 100,000), and 15% (70 per 100,000), respectively, of the total YLDs due to MCI and all-cause dementia. In 2065, YLDs due to Alzheimer's dementia, vascular dementia, and MCI will account for 48% (1358 per 100,000), 15% (410 per 100,000), and 10% (290 per 100,000), respectively, of total YLDs due to MCI and all-cause dementia. Conclusions and Implications Considering the rapidly growing disease burden, resources should be allocated to continuously monitor and manage the MCI and dementia burden. Particular attention to Alzheimer's dementia is required considering its significant contribution to current and future disease burden, especially to YLD.

Aim: To examine the impact of the revised diagnostic criteria for neurocognitive disorders (NCDs) in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) on the prevalence of dementia and mild cognitive impairment (MCI). Methods: A total of 755 participants aged 65 years or older in the Nationwide Survey on Dementia Epidemiology in Korea 2012 were rediagnosed according to the DSM-5 criteria. Results: The estimated age-, gender-, education-, and urbanicity-standardized prevalence rates of major and mild NCDs were 8.35 and 11.10%, respectively, and those of dementia and MCI were 8.74 and 31.85%, respectively. Cohen's κ for dementia and major NCD was 0.988, and that for MCI and mild NCD was 0.273. Conclusion: Diagnostic discrepancies between major/mild NCDs and dementia/MCI might depend on the operationalization of neuropsychological performance criteria.

Prospective studies concerning sleep architecture and cognitive function have focused on individual sleep measures per se, without considering the complementary role of non-REM (NREM) and REM sleep. We explored the association between NREM/REM cycle-related sleep architecture and cognitive decline. Community-dwelling elderly people in Korea from the Korean Longitudinal Study on Cognitive Aging and Dementia were enrolled. They were cognitively normal and underwent overnight polysomnography at baseline. A NREM/REM cycle is a sequence of NREM and REM sleep, uninterrupted by a waking period of >2 min. After 4 years, the development of mild cognitive impairment (MCI) or dementia was related to the measures of sleep architecture, including NREM/REM cycle parameters by logistic regression analyses. Of 235 participants (mean [SD] age 68 [5] years; 60% female) at baseline, 14 (5.9%) developed MCI/dementia at follow-up. A short average cycle length (OR, 0.97 [95% CI, 0.94-0.99]; p = 0.02) was significantly associated with cognitive decline. When its substructure and NREM and REM sleep outside of cycles were considered simultaneously, the average REM sleep duration per cycle (OR, 0.87 [95% CI, 0.76-0.98]; p = 0.03) was significantly related to the outcome. In conclusion, short average duration of NREM/REM cycles, especially average REM sleep duration in each cycle, in cognitively normal elderly might be used as an early marker of cognitive decline.

OBJECTIVE We investigated the impact of depressed mood (dysphoria) and loss of interest or pleasure (anhedonia)on the risk of dementia in cognitively-normal elderly individuals. METHODS This study included 2,685 cognitively-normal elderly individuals who completed the baseline and 4-year follow-up assessments of the Korean Longitudinal Study on Cognitive Aging and Dementia. We ascertained the presence of dysphoria and anhedonia using the Mini International Neuropsychiatric Inventory. We defined subjective cognitive decline as the presence of subjective cognitive complaints without objective cognitive impairments. We analyzed the association of dysphoria and anhedonia with the risk of cognitive disorders using multinomial logistic regression analysis adjusted for age, sex, education, Cumulative Illness Rating Scale score, Apolipoprotein E genotype, and neuropsychological test performance. RESULTS During the 4-year follow-up period, anhedonia was associated with an approximately twofold higher risk of mild cognitive impairment (OR=2.09, 95% CI=1.20-3.64, p=0.008) and fivefold higher risk of dementia (OR=5.07, 95% CI=1.44-17.92, p=0.012) but was not associated with the risk of subjective cognitive decline. In contrast, dysphoria was associated with an approximately twofold higher risk of subjective cognitive decline (OR=2.06, 95% CI=1.33-3.19, p=0.001) and 1.7-fold higher risk of mild cognitive impairment (OR=1.75, 95% CI=1.00-3.05, p=0.048) but was not associated with the risk of dementia. CONCLUSION Anhedonia, but not dysphoria, is a risk factor of dementia in cognitively-normal elderly individuals.

Background Measurements of patient quality of life (QoL) play a major role in the management of dementia. Objective We investigated the self-proxy discrepancy of QoL ratings in the elderly and the impact of dementia severity on the discrepancy. Methods QoL of 718 patients with dementia and 651 non-demented elderly were rated by themselves and their caregivers (CG) using the Quality of Life-Alzheimer's Disease (QoL-AD). The impact of the rater on the total and item scores of QoL-AD was analyzed using repeated measures ANOVA and differential response patterns between self and proxy were analyzed using differential item functioning (DIF) analysis. Results Self-rated scores were higher than CG-rated scores in all diagnostic groups. The interaction between rater and diagnostic group was significant in total QoL-AD score and 5 item scores ('memory', 'marriage', 'chores around the house', 'do things for fun', and 'life as a whole'). The strength of the DIF increased with advancing dementia in these items. Conclusion Self-proxy rating discrepancy of QoL was influenced by the presence and severity of dementia only in five items.

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 (

To investigate sleep disturbances that induce cognitive changes over 4 years in nondemented elderlies.Data were acquired from a nationwide, population-based, prospective cohort of Korean elderlies (2,238 normal cognition [NC] and 655 mild cognitive impairment [MCI]). At baseline and 4-year follow-up assessments, sleep-related parameters (midsleep time, sleep duration, sleep latency, subjective sleep quality, sleep efficiency, and daytime dysfunction) and cognitive status were measured using the Pittsburgh Sleep Quality Index and Consortium to Establish a Registry for Alzheimer's Disease Assessment, respectively. We used logistic regression models adjusted for covariates including age, sex, education, apolipoprotein E genotype, Geriatric Depression Scale, Cumulative Illness Rating Scale, and physical activity.In participants with NC, long sleep latency (30 minutes), long sleep duration (≥7.95 hours), and late midsleep time (after 3:00 am) at baseline were related to the risk of cognitive decline at 4-year follow-up assessment; odds ratio (OR) was 1.40 for long sleep latency, 1.67 for long sleep duration, and 0.61 for late midsleep time. These relationships remained significant when these variables maintained their status throughout the follow-up period. Newly developed long sleep latency also doubled the risk of cognitive decline. In those with MCI, however, only long sleep latency reduced the chance of reversion to NC (OR = 0.69).As early markers of cognitive decline, long sleep latency can be used for elderlies with NC or MCI, whereas long sleep duration and relatively early sleep time might be used for cognitively normal elderlies only. Ann Neurol 2018;83:472-482.

Background:Social support programs for dementia caregivers were widely used in order to reduce care burden. We investigated which types of social supports can reduce psychological and non-psychological burdens of dementia caregivers, and explored the mechanism of those social supports.Methods:We evaluated 731 community-dwelling dementia patients and their caregivers from the National Survey of Dementia Care in South Korea. We investigated the five types of social supports (emotional support, informational support, tangible support, positive social interaction, affectionate support) using the Medical Outcomes Study Social Support Survey in each caregiver. The mechanisms of specific types of social support on psychological/non-psychological burden were examined using path analysis.Results:Positive social interaction and affectionate support reduced psychological burden via direct and indirect paths. Tangible support reduced the non-psychological burden via direct and indirect paths. Informational support and emotional support were not helpful for reducing psychological or non-psychological burden. A maximum of 20% of psychological burden could be relieved by positive social interaction and 10.3% of that could be reduced by affectionate support. Tangible support was associated with a 15.1% maximal improvement in non-psychological burden.Conclusions:In order to reduce caregiver burden in dementia effectively, psychosocial interventions should be tailored to target type of caregiver burden.

There has been no studies comparing the clinical benefits of aripiprazole augmentation (AT), antidepressant combination (AC), and switching to a different antidepressant (SW) in patients with major depressive disorder (MDD) patients partially or not responding to an initial antidepressant. AT, AC, or SW was chosen by patients. The primary efficacy measure was the proportion of patients showing an improvement in the Clinical Global Impression-Clinical Benefit (CGI-CB) score at week 8. Secondary efficacy measures included changes in CGI-CB, CGI-Severity (S) and subjective satisfaction scores. Remission and responder analysis were also employed. A total of 295 patients were enrolled. The most preferred strategy was AT (n = 156, 52.9%), followed by AC (n = 93, 31.5%) and SW (n = 46, 15.6%). The improver was significantly higher in AT (74.1%) compared with AC (48.1%; p 0.001) and similar to SW (73.5%, p = 0.948), whereas no significant difference was found between AC and SW. Similar results were also found in the most secondary endpoint measures proving a superiority of AT over AC without differences between AT and SW. Tolerability profiles were similar across the three groups; however, the mean weight gain for SW (-0.1 kg) was significantly less than that for AC (1.3 kg, p 0.05). Patients preferred AT to AC or SW when an antidepressant was ineffective in treating their depression. Among the three treatment strategies, overall AT yielded greater clinical benefit than did AC and SW. Adequately powered, well-controlled clinical trials are strongly warranted to confirm our findings due to methodological shortcomings.