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We report a case of an 80-year-old Korean man with chronic cerebral paragonimiasis who presented with progressive memory impairment. He suffered from pulmonary paragonimiasis 60 years ago and has been experiencing epilepsy since the age of 45. He began experiencing memory and cognitive deterioration 3 years ago. He visited the neuropsychiatric department of our hospital to check his symptoms and health from a year ago. Contrast-enhanced brain magnetic resonance imaging study revealed calcifications and cystic lesions encompassing the right temporo-occipital region. Encephalomalatic changes were also observed in the right occipital and temporal areas. The anti-Paragonimus specific IgG antibodies in his serum showed a strong positive response. The neuropsychological test results showed a Global Deterioration Scale of 4 and a Clinical Dementia Rating Scale of 1. The chronic cerebral paragonimiasis lesions in the patient’s right temporo-occipital region might induce the dementic change.

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.

Alzheimer's disease (AD), the most prevalent form of dementia, affects 6.5 million Americans and over 50 million people globally. Clinical, genetic, and phenotypic studies of dementia provide some insights of the observed progressive neurodegenerative processes, however, the mechanisms underlying AD onset remain enigmatic.This paper examines late-onset dementia-related cognitive impairment utilizing neuroimaging-genetics biomarker associations.The participants, ages 65-85, included 266 healthy controls (HC), 572 volunteers with mild cognitive impairment (MCI), and 188 Alzheimer's disease (AD) patients. Genotype dosage data for AD-associated single nucleotide polymorphisms (SNPs) were extracted from the imputed ADNI genetics archive using sample-major additive coding. Such 29 SNPs were selected, representing a subset of independent SNPs reported to be highly associated with AD in a recent AD meta-GWAS study by Jansen and colleagues.We identified the significant correlations between the 29 genomic markers (GMs) and the 200 neuroimaging markers (NIMs). The odds ratios and relative risks for AD and MCI (relative to HC) were predicted using multinomial linear models.In the HC and MCI cohorts, mainly cortical thickness measures were associated with GMs, whereas the AD cohort exhibited different GM-NIM relations. Network patterns within the HC and AD groups were distinct in cortical thickness, volume, and proportion of White to Gray Matter (pct), but not in the MCI cohort. Multinomial linear models of clinical diagnosis showed precisely the specific NIMs and GMs that were most impactful in discriminating between AD and HC, and between MCI and HC.This study suggests that advanced analytics provide mechanisms for exploring the interrelations between morphometric indicators and GMs. The findings may facilitate further clinical investigations of phenotypic associations that support deep systematic understanding of AD pathogenesis.

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.

Objective Recently, rational polypharmacy approaches have been proposed, regardless of the lower risk and cost of monotherapy. Considering monotherapy as first-line treatment and polypharmacy as rational treatment, a balanced attitude toward polypharmacy is recommended. However, the high prevalence of polypharmacy led the Japanese government to establish a polypharmacy reduction policy. Based on this, the association between the policy and psychiatrists’ attitude toward polypharmacy has been under debate.Methods We developed an original questionnaire about Psychiatrists’ attitudes toward polypharmacy (PAP). We compared the PAP scores with the treatment decision-making in clinical case vignettes. Multiple regression analyses were performed to quantify associations of explanatory variables including policy factors and PAP scores. The anonymous questionnaires were administered to psychiatrists worldwide.Results The study included 347 psychiatrists from 34 countries. Decision-making toward polypharmacy was associated with high PAP scores. Multiple regression analysis revealed that low PAP scores were associated with the policy factor (β=-0.20, p=0.004). The culture in Korea was associated with high PAP scores (β=0.34, p

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.

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.

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 The correlation among the thyroid-related hormones, Apolipoprotein E ε4 (APOE ε4) and cognitive function has been reported despite controversial results. This study was designed to investigate this correlation among cognitively-normal elderly dwellers.Methods This study assessed 507 cognitively normal individuals aged over 60 who underwent comprehensive hematological and neuropsychological assessments including the quantification of serum free thyroxine and thyroid stimulating hormone (TSH) as well as the Korean version of the Consortium Establish a Registry for Alzheimer’s disease. The Korean version of Geriatric Depression Scale was also employed to evaluate the severity of depression. Age, gender, education, and the presence of APOE ε4 were taken into account as covariates.Results There was a significant positive association between verbal fluency test (VFT), Word List Memory Test (WLMT), and Word List Recall Test (WLRT) score and serum TSH levels (p=0.007, 0.031, and 0.023 respectively). The further analysis adding the interaction between APOE ε4 and TSH level, however, revealed only VFT score was significantly influenced by this interaction (p=0.026).Conclusion Lower serum TSH levels had impacts on both semantic memory (VFT) and episodic memory (WLMT, WLRT) among cognitively-normal elderly, whereas the interaction of TSH and APOE ε4 influenced only the task of semantic memory (VFT) in this group.

BackgroundAnkle-brachial index (ABI), an indicator of atherosclerosis or arterial stiffness, has been associated with Alzheimer’s disease (AD) dementia and related cognitive impairment. Nevertheless, only limited information is yet available for its contribution to brain alterations related to cognitive decline in late-life. We aimed to investigate the relationship of ABI with in vivo AD pathologies and cerebrovascular injury in cognitively impaired older adults.MethodsTotal 127 cognitively impaired (70 mild cognitive impairment and 57 AD dementia) individuals, who participated in an ongoing prospective cohort study, were included. All participants underwent comprehensive clinical and neuropsychological assessment, ABI measurement, apolipoprotein E (APOE) ε4 genotyping, and multi-modal brain imaging including [11C] Pittsburgh Compound B (PiB)-positron emission tomography (PET) and [18F] fludeoxyglucose (FDG)-PET, and MRI.ResultsGeneral linear model analysis showed significant relationship between ABI strata (low ABI: < 1.00, normal ABI: 1.00–1.29, and high ABI: ≥ 1.30) and AD-signature region cerebral glucose metabolism (AD-CM), even after controlling age, sex, clinical dementia rating–sum of box (CDR-SOB), and APOE ε4 positivity (p = 0.029). Post hoc comparison revealed that low ABI had significantly lower AD-CM than middle and high ABI, while no difference of AD-CM was found between middle and high ABI. There was no significant difference of global Aβ deposition, AD-signature region cortical thickness, and white matter hyperintensity volume between the three ABI strata.ConclusionOur findings suggest that lower ABI, probably related to atherosclerosis, may contribute to the aggravation of AD-related regional neurodegeneration in cognitively impaired older adults.

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.

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 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: 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.

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.

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.

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.

Objective The aim of this study was to examine the change in the hippocampal volume and shape in early-onset mild cognitive impairment (EO-MCI) associated with the APOE e4 carrier state. Methods This study had 50 subjects aged 55-63 years, all of whom were diagnosed with MCI at baseline via the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet. The EO-MCI patients were divided into the MCI continued (MCIcont) and Alzheimer's disease (AD) converted (ADconv) groups 2 years later. The hippocampal volume and shape were measured for all the subjects. The local shape analysis (LSA) was used to conduct based on the 2-year-interval magnetic resonance imaging scans. Results There was a significant correlation between APOE e4 allele and hippocampal volume atrophy. Over two years, the volume reduction in the left hippocampus was found to be faster than that in the right hippocampus, especially in the APOE e4 carriers. LSA showed that the 2 subfields were significantly affected in the left hippocampus. Conclusion These results suggest that the possession of APOE e4 allele may lead to greater predilection for left hippocampal atrophy in EO-MCI, and some specific subfields of the hippocampus may be more prominently involved.

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.

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.

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.

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.

Objective Lack of knowledge about a disease could impede early diagnosis and may lead to delays in seeking appropriate medical care. The aim of this study was to explore knowledge of dementia (KOD) and to find the determinants of KOD among three groups: older adults with normal cognition, mild cognitive impairment (MCI), and dementia. Methods A representative nationwide sample of 6141 Korean elders aged 65 years or older participated in face-to-face interviews and answered 14 questions pertaining to general information, etiology, symptoms, and treatment of dementia. Stepwise multiple regressions and path analyses probed the relationships between various sociodemographic variables and KOD. Results The percentage of correct responses was only 62%. The item ‘A person who remembers things that happened in the past does not have dementia’ was answered correctly (false) by only 24.8–27% of the respondents in all groups. Older adults with normal cognition had higher KOD scores than those with MCI or dementia. In the normal-cognition group, KOD scores were higher among highly educated, younger, and literate women with no depression and a family history of dementia. In contrast with the determinants in the normal-cognition group, only the ability to read and write predicted KOD scores in the dementia group. Conclusions Efforts to enhance KOD in elder adults are needed. Public education regarding the differences between dementia and healthy aging may increase KOD among normal elders and those with MCI. Among elders with dementia, educational materials that do not require literacy may be more helpful in increasing KOD with the aim of preventing treatment delay.