Network Analysis Revealed the Role of Helplessness as a Central Feature Among Late-Life Depressive Symptoms in Patients With Mild Cognitive Impairment and Early Stage Dementia.

OBJECTIVE: It has been reported that depressive symptoms in older adults are different from those in younger adults, especially when accompanied by cognitive decline. However, few studies have investigated the network structure of depressive symptoms in this population. METHODS: The participants consisted of 627 older adults (>60 yr) who were diagnosed with mild cognitive impairment (MCI) or early stage dementia. Among them, 36.7% were male and the mean age was 76.20±7.71 years. The Korean form of Geriatric Depression Scale (KGDS) was used to evaluate their depressive symptoms and network analyses were performed using bootnet R-package to identify the central features among depressive symptoms. RESULTS: Of all the KGDS items, we found that KGDS 2 (often feel helpless) had the highest node strength followed by KGDS 21 (in good spirits), KGDS 14 (not confident at all), and KGDS 15 (cheerful and happy). In terms of node betweenness, KGDS 2 also showed the highest value. The edge weights of edges connected to node KGDS 2 were strongest in KGDS 3 (restless and fidgety) and KGDS 28 (easily get tired). CONCLUSION: In this study, we presented which symptoms are central among the elderly with MCI and early stage dementia. This result not only increases the understanding of depressive symptoms in this group but would also help determine target symptoms in the treatment program.

Association of Depression With the Progression of Multimorbidity in Older Adults: A Population-Based Cohort Study.

BACKGROUND: The relationship between depression and the risk of multimorbidity progression has rarely been studied in older adults. This study was aimed to determine whether depression is associated with progression in the severity and complexity of multimorbidity, considering the influence of depression's severity and subtype. METHODS: As a part of the Korean Longitudinal Study on Cognitive Aging and Dementia, this population-based cohort study followed a random sample of community-dwelling Koreans aged 60 and older for 8 years at 2-year intervals starting in 2010. Participants included those who completed mood and multimorbidity assessments and did not exhibit complex multimorbidity at the study's outset. Depression was assessed using the Geriatric Depression Scale, while multimorbidity was evaluated using the Cumulative Illness Rating Scale. The study quantified multimorbidity complexity by counting affected body systems and measured multimorbidity severity by averaging scores across 14 body systems. FINDINGS: The 2,486 participants (age = 69.1 ± 6.5 years, 57.6% women) were followed for 5.9 ± 2.4 years. Linear mixed models revealed that participants with depression had a faster increase in multimorbidity complexity score (ß = .065, SE = 0.019, p = 0.001) than those without depression, but a comparable increase in multimorbidity severity score (ß = .001, SE = .009, p = 0.870) to those without depression. Cox proportional hazard models revealed that depression was associated with the risk of developing highly complex multimorbidity affecting five or more body systems, particularly in severe or anhedonic depression. INTERPRETATION: Depression was associated with the worsening of multimorbidity in Korean older adults, particularly when severe or anhedonic. Early screening and management of depression may help to reduce the burden of multimorbidity in older adults.

Temperament Clusters in Patients With Panic Disorder in Relation to Character Maturity.

OBJECTIVE: This study explored whether temperament profiles are associated with psychological functioning and whether character maturity affects this association in patients with panic disorders (PD). METHODS: A total of 270 patients with PD were enrolled in this study. Measurements included the Temperament and Character Inventory-revised-short (TCI-RS), a self-report version of the Panic Disorder Severity Scale (PDSS-SR), Beck Depression Inventory-II (BDI-II), and Spielberger State-Trait Anxiety Inventory (STAI). Cluster analysis was used to define the patients' temperament profiles, and the differences in discrete variables among temperament clusters were calculated using a one-way analysis of variance. An analysis of covariance was conducted to control for the impact of character maturity on psychological functioning among clusters. RESULTS: We identified four temperament clusters of patients with PD. Significant differences in the PDSS-SR, BDI-II, STAI-state, and STAI-trait scores among the four clusters were detected [F(3, 262)=9.16, p<0.001; F(3, 266)=33.78, p<0.001; F(3, 266)=19.12, p<0.001; F(3, 266)=39.46, p<0.001]. However, after controlling for the effect of character maturity, the effect of cluster type was either eliminated or reduced ([STAI-state] cluster type: F(3, 262)=0.94, p>0.05; SD+CO: F(1, 262)=65.95, p<0.001, ηp2 =0.20). CONCLUSION: This study enabled a more comprehensive and integrated understanding of patients by exploring the configuration of all temperament dimensions together rather than each temperament separately. Furthermore, we revealed that depending on the degree of character maturity, the psychological functioning might differ even within the same temperament cluster. These results imply that character maturity can complement inherently vulnerable temperament expression.

A cross-sectional study of colic and rate of return to racing in Thoroughbreds at Seoul Racecourse in Korea between 2010 and 2020.

BACKGROUND: The incidence of colic and the outcomes of colic surgery have not been surveyed in racetracks in Korea. OBJECTIVES: This study examined the incidence, mortality, and case fatality of colic and investigated the effects of age and sex after an exploratory celiotomy on the long-term survival rate (return to racing), subsequent racing performance, and career longevity. METHODS: The incidence, mortality, and case fatalities of colic were examined over an 11-year period. The records of 40 horses that had undergone a celiotomy, after participating in at least one race and 75 race-matched control horses were analyzed. The racing performance and career length of the horses that returned to racing post-surgery were compared with a control group. RESULTS: The annual incidence, fatality rate of colic, and annual mortality rate at Seoul Racecourse were 6.5, 2.8 per 100 horse-years, and 0.2 deaths cases per 100 horse-years, respectively. Of the 40 horses that underwent colic surgery, 26 (65%) returned to racing. The likelihood of returning to racing decreased with increasing age of the horses, and geldings had a lower probability of returning. While the performance in the five preoperative races between the two groups was not significantly different, a significant decrease in racing performance was observed after the surgery date (p < 0.01). Horses that underwent colic surgery did not show a significant decrease in career length. CONCLUSIONS: Surgical treatment for colic at the age of three and four years had a negative impact on the racing performance. On the other hand, there was no significant difference in career longevity between the two groups.

What is the impact of one's chronic illness on his or her spouse's future chronic illness: a community-based prospective cohort study.

BACKGROUND: Integrating a joint approach to chronic disease management within the context of a couple has immense potential as a valuable strategy for both prevention and treatment. Although spousal concordance has been reported in specific chronic illnesses, the impact they cumulatively exert on a spouse in a longitudinal setting has not been investigated. We aimed to determine whether one's cumulative illness burden has a longitudinal impact on that of their spouse. METHODS: Data was acquired from a community-based prospective cohort that included Koreans aged 60 years and over, randomly sampled from 13 districts nationwide. Data from the baseline assessment (conducted from November 2010 to October 2012) up to the 8-year follow-up assessment was analyzed from October 2021 to November 2022. At the last assessment, partners of the index participants were invited, and we included 814 couples in the analysis after excluding 51 with incomplete variables. Chronic illness burden of the participants was measured by the Cumulative Illness Rating Scale (CIRS). Multivariable linear regression and causal mediation analysis were used to examine the longitudinal effects of index chronic illness burden at baseline and its change during follow-up on future index and spouse CIRS scores. RESULTS: Index participants were divided based on baseline CIRS scores (CIRS < 6 points, n = 555, mean [SD] age 66.3 [4.79] years, 43% women; CIRS ≥ 6 points, n = 259, mean [SD] age 67.7 [4.76] years, 36% women). The baseline index CIRS scores and change in index CIRS scores during follow-up were associated with the spouse CIRS scores (ß = 0.154 [SE: 0.039], p < 0.001 for baseline index CIRS; ß = 0.126 [SE: 0.041], p = 0.002 for change in index CIRS) at the 8-year follow-up assessment. Subgroup analysis found similar results only in the high CIRS group. The baseline index CIRS scores and change in index CIRS scores during follow-up had both direct and indirect effects on the spouse CIRS scores at the 8-year follow-up assessment. CONCLUSIONS: The severity and course of one's chronic illnesses had a significant effect on their spouse's future chronic illness particularly when it was severe. Management strategies for chronic diseases that are centered on couples may be more effective.

A Preliminary Study on the Potential Protective Role of the Antioxidative Stress Markers of Cognitive Impairment: Glutathione and Glutathione Reductase.

Objective: : To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer's dementia and cognitive decline. Methods: : In all, 20 participants with Alzheimer's dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status. Results: : The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer's dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile. Conclusion: : The higher the GR, the lower the prevalence of Alzheimer's dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer's dementia and cognitive decline.

Central features in health-related quality of life in older adults: network analysis using nationwide survey data.

BACKGROUND: Population ageing is a global phenomenon that necessitates consideration of health-related quality of life (HRQoL) in older adults. Previous studies have investigated related factors including mobility, social support and living situations. AIMS: This study aimed to provide a network perspective on factors related to HRQoL. METHOD: Cross-sectional nationwide data were obtained from the Korean National Health and Nutrition Examination Survey conducted from 2018 to 2020 for network analyses. Data for participants aged 65 years or above were analysed, resulting in a total of 4317 eligible cases. The variables included were EQ-5D (a measure of HRQoL), household income, education, living situation, subjective perceived health, Charlson Comorbidity Index (a measure of medical comorbidities), stress, exercise per week, alcohol consumption and smoking. Three networks were produced: (a) EQ-5D dimensions network, (2) EQ-5D dimensions, lifestyle and psychosocial factors network, and (3) overall EQ-5D index, lifestyle and psychosocial factors network. Node centralities, bridge centralities and edges of the networks were examined. RESULTS: The most central EQ-5D dimension was the ability to carry out usual activities. In the second network, subjective health, stress and anxiety/depression were revealed as nodes with high bridge centralities. Subjective health, exercise, and Charlson Comorbidity Index were nodes closely linked to the overall EQ-5D index. CONCLUSIONS: The results emphasise the importance of enhancing functional independence and subjective health cognition, increasing routine exercise and reducing stress as targets for interventions to improve HRQoL in older adults.

The impact of the COVID-19 pandemic on depression in community-dwelling older adults: a prospective cohort study.

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.

Parental history of dementia and the risk of dementia: A cross-sectional analysis of a global collaborative study.

BACKGROUND: Parental history of dementia appears to increase the risk of dementia, but there have been inconsistent results. We aimed to investigate whether the association between parental history of dementia and the risk of dementia are different by dementia subtypes and sex of parent and offspring. METHODS: For this cross-sectional study, we harmonized and pooled data for 17,194 older adults from nine population-based cohorts of eight countries. These studies conducted face-to-face diagnostic interviews, physical and neurological examinations, and neuropsychological assessments to diagnose dementia. We investigated the associations of maternal and paternal history of dementia with the risk of dementia and its subtypes in offspring. RESULTS: The mean age of the participants was 72.8 ± 7.9 years and 59.2% were female. Parental history of dementia was associated with higher risk of dementia (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.15-1.86) and Alzheimer's disease (AD) (OR = 1.72, 95% CI = 1.31-2.26), but not with the risk of non-AD. This was largely driven by maternal history of dementia, which was associated with the risk of dementia (OR = 1.51, 95% CI = 1.15-1.97) and AD (OR = 1.80, 95% CI = 1.33-2.43) whereas paternal history of dementia was not. These results remained significant when males and females were analyzed separately (OR = 2.14, 95% CI = 1.28-3.55 in males; OR = 1.68, 95% CI = 1.16-2.44 for females). CONCLUSIONS: Maternal history of dementia was associated with the risk of dementia and AD in both males and females. Maternal history of dementia may be a useful marker for identifying individuals at higher risk of AD and stratifying the risk for AD in clinical trials.

Shared Risk Factors for Depressive Disorder Among Older Adult Couples in Korea.

Importance: Although 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. Objectives: To 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 Participants: This 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. Exposures: Depressive disorders of the KLOSCAD participants. Main Outcomes and Measures: The 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. Results: A 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 < .001). Social-emotional support mediated the association between depressive disorders in the KLOSCAD participants and their spouses' risk of depressive disorders by itself (ß = 0.012; 95% CI, 0.001-0.024; P = .04; mediation proportion [MP] = 6.1%) and through chronic illness burden (ß = 0.003; 95% CI, 0.000-0.006; P = .04; MP = 1.5%). Chronic medical illness burden (ß = 0.025; 95% CI, 0.001-0.050; P = .04; MP = 12.6%) and presence of a cognitive disorder (ß = 0.027; 95% CI, 0.003-0.051; P = .03; MP = 13.6%) mediated the association. Conclusions and Relevance: The 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.

Evidence of risky driving in Korean older adults: A longitudinal cohort.

OBJECTIVES: 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. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Association between Heart Rate Variability Indices and Depressed Mood in Patients with Panic Disorder.

Objective: Heart rate variability (HRV) reflects the regulation of the autonomic nervous system. Panic disorder is highly associated with autonomic dysfunction, and is often accompanied by depression. The aim of this study is to determine the association between depression and HRV indices in patients with panic disorder. Methods: A total of 110 outpatients diagnosed with panic disorder participated in this study. The medical records of patients with panic disorder who visited the outpatient clinic of Konkuk University Hospital between December 2018 and March 2020 were retrospectively reviewed. Measurements used in this study include the Panic Disorder Severity Scale-Self Report, Beck Depression Inventory (BDI-II), Insomnia Severity Index, and HRV. Patients were divided into depressive and non-depressive groups based on their BDI-II scores. The association between HRV indices and depressive symptoms was statistically analyzed. Results: The low frequency/high frequency (LF/HF) ratio was reduced in patients with depression (mean = -0.095, p = 0.004 in the above moderate depressive group, mean = -0.120, p = 0.020 in the severe depressive group). Significant correlations were found between depressive symptoms and standard deviation of NN interval (SDNN) (ms) (-0.19, p = 0.044), very low frequency (VLF) (ms2/Hz) (-0.22, p = 0.021), LF (-0.25, p = 0.008), HF (-0.19, p = 0.043), and LF/HF (-0.25, p = 0.009). Multiple linear regression analysis showed that BDI predicted SDNN (ms), VLF (ms2/Hz), LF, HF, and LF/HF. Conclusion: We confirmed that the LF/HF ratio decreases when depression is accompanied by panic disorder. HRV indices may be useful markers for detecting depressive symptoms in patients with panic disorder.

Association of Low Emotional and Tangible Support With Risk of Dementia Among Adults 60 Years and Older in South Korea.

Importance: The association between social support and dementia risk has been debated. Most previous prospective studies have not differentiated the subtypes of social support. Objective: To examine whether the association between social support and risk of dementia differs by subtype of social support and by sex. Design, Setting, and Participants: This 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. Exposures: Geriatric 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 Measures: Baseline levels of emotional and tangible support using the Medical Outcomes Survey Social Support Survey. Results: Among 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 Relevance: The 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.

A network analysis of panic symptoms in relation to depression and anxiety sensitivity in patients with panic disorder.

BACKGROUND: Panic disorder is an anxiety disorder presenting panic attacks as a defining feature, with cognitive and behavioral symptoms that are associated with the panic attacks. Recently, the use of network analysis is increasing to determine the symptoms and mutual reinforcing patterns that conceptualize a mental disorder. This study aimed to improve our understanding of panic disorder by estimating a network structure of its symptoms. METHOD: Data from 257 patients diagnosed with panic disorder who visited the outpatient psychiatric clinic from 2018 to 2020 were collected. Panic attacks, cognitive and behavioral symptoms concerning the panic attacks, depression, and anxiety sensitivity dimensions such as fear of cardiovascular symptom, fear of publicly observable anxiety reaction, fear of respiratory symptom, and fear of cognitive dyscontrol were computed. Bootstrapping was applied to estimate the 95% confidence intervals for each edges. RESULTS: The resulting network indicated fear of cognitive dyscontrol, impairment in social functioning, phobic avoidance of situations, and panic-focused anticipatory anxiety to be central symptoms in panic disorder. Interestingly, panic attacks and distress during panic did not emerge as central. Depression was strongly linked to fear of cognitive dyscontrol. LIMITATIONS: The sample size limits network comparison tests between those with comorbid depression or agoraphobia. In addition, the cross-sectional design limits the opportunity to draw causal conclusions regarding the symptoms. CONCLUSIONS: These results have implications in etiology of panic disorder and support the efficaciousness of Cognitive Behavioral Therapy. Future network analyses may employ longitudinal designs to investigate causal relationships between the symptoms.

Mood disorders increase mortality mainly through dementia: A community-based prospective cohort study.

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.

Association Between Plasma Monocyte Trafficking-Related Molecules and Future Risk of Depression in Older Adults.

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.

Exploration of Cognitive Outcomes and Risk Factors for Cognitive Decline Shared by Couples.

Importance: 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. Objective: 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. Design, Setting, and Participants: 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). Exposures: The cognitive disorder of a spouse was defined as mild cognitive impairment or dementia. Main Outcomes and Measures: 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. Results: 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 (ß = 0.50; 95% CI, 0.09-0.90; P = .02) and age (ß = 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 (ß = 0.33, 95% CI, 0.09-0.57, P = .006 for physical inactivity; ß = 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. Conclusions and Relevance: 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.

Hypohomocysteinemia may increases the risk of dementia and Alzheimer's disease: A nationwide population-based prospective cohort study.

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.

Disease Burdens of Alzheimer's Disease, Vascular Dementia, and Mild Cognitive Impairment.

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.