Developing a Dementia Platform Databank Using Multiple Existing Cohorts

This study was conducted as a pilot project to evaluate the feasibility of building an integrate dementia platform converging preexisting dementia cohorts from several variable levels. The following four cohorts were used to develop this pilot platform: 1) Clinical Research Center for Dementia of South Korea (CREDOS), 2) Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's disease (K-BASE), 3) Environmental Pollution-induced Neurological Effects (EPINEF) study, and 4) a prospective registry in Dementia Platform Korea project (DPKR). A total of 29916 patients were included in the platform with 348 integrated variables. Among participants, 13.9%, 31.5%, and 44.2% of patients had normal cognition, mild cognitive impairment, and dementia, respectively. The mean age was 72.4 years. Females accounted for 65.7% of all patients. Those with college or higher education and those without problems in reading or writing accounted for 12.3% and 46.8%, respectively. Marital status, cohabitation, family history of Parkinson's disease, smoking and drinking status, physical activity, sleep status, and nutrition status had rates of missing information of 50% or more. Although individual cohorts were of the same domain and of high quality, we found there were several barriers to integrating individual cohorts, including variability in study variables and measurements. Although many researchers are trying to combine pre-existing cohorts, the process of integrating past data has not been easy. Therefore, it is necessary to establish a protocol with considerations for data integration at the cohort establishment stage.ope

Risk of Cerebro-Cardiovascular Diseases among Police Officers and Firefighters: A Nationwide Retrospective Cohort Study

Purpose: Police officers and firefighters are exposed to risk factors for cerebro-cardiovascular diseases, and the actual risk is expected to increase compared with other occupational groups. The present study aimed to estimate the risks of cerebro-cardiovascular diseases in police officers and firefighters compared to other occupational groups. Materials and methods: Using the National Health Insurance Service data, we constructed a retrospective cohort of public officers. Three-year consecutive health insurance registration data were used to identify police officers and firefighters. Cerebro-cardiovascular diseases consisted of acute myocardial infarction, other ischemic heart disease, cardiac arrhythmia, and stroke. We compared the incidences of cerebro-cardiovascular diseases between each of the two occupational groups (police officers and firefighters) and other public officers by calculating standardized incidence ratios (SIRs). Results: SIRs and 95% confidence intervals of all cerebro-cardiovascular diseases for police officers and firefighters were 1.71 (1.66-1.76) and 1.22 (1.12-1.31), respectively, as compared with all public officers. The incidence ratios remained significantly higher compared to general and education officers. Subgroup analyses for myocardial infarction, stroke, and cardiac arrhythmia exhibited significant increases in incidence ratios among police officers and firefighters. Conclusion: This study suggests that both police officers and firefighters are at high risk of cerebro-cardiovascular diseases. Therefore, medical protection measures for these occupational groups should be improved.ope

Health Effects of Microplastic Exposures: Current Issues and Perspectives in South Korea

Microplastics are environmental pollutants that prevail in the oceans, remote islands, and polar regions. Exposure to microplas tics presents a major emerging threat to the ecosystems due to their potential adverse effects. Herein, we reviewed the literature to provide an up-to-date synopsis of the current understanding of the sources, compositions, and adverse effects of microplastics in humans and the environment. Most studies on microplastics have focused on developing standardized methods for monitor ing the occurrence, distribution, and movement of microplastics in the environment, as well as developing microplastic substi tutes; however, although humans are exposed to microplastics via various routes, research on the adverse effects of microplastics in humans remains limited. Little is known about the impact of microplastics on human health and the toxic effects that may vary depending on the type, size, shape, and concentration of microplastics. Therefore, more research is needed to understand the cellular and molecular mechanisms of microplastic toxicity and related pathologies.ope

All-Cause and Cause-Specific Mortality Attributable to Seasonal Influenza: A Nationwide Matched Cohort Study

Background: Although influenza poses substantial mortality burden, most studies have estimated excess mortality using time-aggregated data. Here, we estimated mortality risk and population attributable fraction (PAF) attributed to seasonal influenza using individual-level data from a nationwide matched cohort. Methods: Individuals with influenza during four consecutive influenza seasons (2013-2017) (n = 5,497,812) and 1:4 age- and sex-matched individuals without influenza (n = 20,990,683) were identified from a national health insurance database. The endpoint was mortality within 30 days after influenza diagnosis. All-cause and cause-specific mortality risk ratios (RRs) attributed to influenza were estimated. Excess mortality, mortality RR, and PAF of mortality were determined, including for underlying disease subgroups. Results: Excess mortality rate, mortality RR, and PAF of all-cause mortality were 49.5 per 100,000, 4.03 (95% confidence interval [CI], 3.63-4.48), and 5.6% (95% CI, 4.5-6.7%). Cause-specific mortality RR (12.85; 95% CI, 9.40-17.55) and PAF (20.7%; 95% CI, 13.2-27.0%) were highest for respiratory diseases. In subgroup analysis according to underlying disorders, PAF of all-cause mortality was 5.9% (95% CI, 0.6-10.7%) for liver disease, 5.8% (95% CI, 2.9-8.5%) for respiratory disease, and 3.8% (95% CI, 1.4-6.1%) for cancer. Conclusion: Individuals with influenza had a 4-fold higher mortality risk than individuals without influenza. Preventing seasonal influenza may lead to 5.6% and 20.7% reductions in all-cause and respiratory mortality, respectively. Individuals with respiratory disease, liver disease, and cancer may benefit from prioritization when establishing influenza prevention strategies.ope

Association Between Visceral Fat and Brain Cortical Thickness in the Elderly: A Neuroimaging Study

Background: Despite emerging evidence suggesting that visceral fat may play a major role in obesity-induced neurodegeneration, little evidence exists on the association between visceral fat and brain cortical thickness in the elderly. Purpose: We aimed to examine the association between abdominal fat and brain cortical thickness in a Korean elderly population. Methods: This cross-sectional study included elderly individuals without dementia (n = 316). Areas of visceral fat and subcutaneous fat (cm2) were estimated from computed tomography scans. Regional cortical thicknesses (mm) were obtained by analyzing brain magnetic resonance images. Given the inverted U-shaped relationship between visceral fat area and global cortical thickness (examined using a generalized additive model), visceral fat area was categorized into quintiles, with the middle quintile being the reference group. A generalized linear model was built to explore brain regions associated with visceral fat. The same approach was used for subcutaneous fat. Results: The mean (standard deviation) age was 67.6 (5.0) years. The highest quintile (vs. the middle quintile) group of visceral fat area had reduced cortical thicknesses in the global [β = -0.04 mm, standard error (SE) = 0.02 mm, p = 0.004], parietal (β = -0.04 mm, SE = 0.02 mm, p = 0.01), temporal (β = -0.05 mm, SE = 0.02 mm, p = 0.002), cingulate (β = -0.06 mm, SE = 0.02 mm, p = 0.01), and insula lobes (β = -0.06 mm, SE = 0.03 mm, p = 0.02). None of the regional cortical thicknesses significantly differed between the highest and the middle quintile groups of subcutaneous fat area. Conclusion: The findings suggest that a high level of visceral fat, but not subcutaneous fat, is associated with a reduced cortical thickness in the elderly.ope

Reduced brain subcortical volumes in patients with glaucoma: a pilot neuroimaging study using the region-of-interest-based approach

Background: While numerous neuroimaging studies have demonstrated that glaucoma is associated with smaller volumes of the visual cortices in the brain, only a few studies have linked glaucoma with brain structures beyond the visual cortices. Therefore, the objective of this study was to compare brain imaging markers and neuropsychological performance between individuals with and without glaucoma. Methods: We identified 64 individuals with glaucoma and randomly selected 128 age-, sex-, and education level-matched individuals without glaucoma from a community-based cohort. The study participants underwent 3 T brain magnetic resonance imaging and neuropsychological assessment battery. Regional cortical thickness and subcortical volume were estimated from the brain images of the participants. We used a linear mixed model after adjusting for potential confounding variables. Results: Cortical thickness in the occipital lobe was significantly smaller in individuals with glaucoma than in the matched individuals (β = - 0.04 mm, P = 0.014). This did not remain significant after adjusting for cardiovascular risk factors (β = - 0.02 mm, P = 0.67). Individuals with glaucoma had smaller volumes of the thalamus (β = - 212.8 mm3, P = 0.028), caudate (β = - 170.0 mm3, P = 0.029), putamen (β = - 151.4 mm3, P = 0.051), pallidum (β = - 103.6 mm3, P = 0.007), hippocampus (β = - 141.4 mm3, P = 0.026), and amygdala (β = - 87.9 mm3, P = 0.018) compared with those without glaucoma. Among neuropsychological battery tests, only the Stroop color reading test score was significantly lower in individuals with glaucoma compared with those without glaucoma (β = - 0.44, P = 0.038). Conclusions: We found that glaucoma was associated with smaller volumes of the thalamus, caudate, putamen, pallidum, amygdala, and hippocampus.ope

Associations of Particulate Matter Exposures With Brain Gray Matter Thickness and White Matter Hyperintensities: Effect Modification by Low-Grade Chronic Inflammation

Background: Numerous studies have shown the effect of particulate matter exposure on brain imaging markers. However, little evidence exists about whether the effect differs by the level of low-grade chronic systemic inflammation. We investigated whether the level of c-reactive protein (CRP, a marker of systemic inflammation) modifies the associations of particulate matter exposures with brain cortical gray matter thickness and white matter hyperintensities (WMH). Methods: We conducted a cross-sectional study of baseline data from a prospective cohort study including adults with no dementia or stroke. Long-term concentrations of particulate matter ≤ 10 µm in diameter (PM10) and ≤ 2.5 µm (PM2.5) at each participant’s home address were estimated. Global cortical thickness (n = 874) and WMH volumes (n = 397) were estimated from brain magnetic resonance images. We built linear and logistic regression models for cortical thickness and WMH volumes (higher versus lower than median), respectively. Significance of difference in the association between the CRP group (higher versus lower than median) was expressed as P for interaction. Results: Particulate matter exposures were significantly associated with a reduced global cortical thickness only in the higher CRP group among men (P for interaction = 0.015 for PM10 and 0.006 for PM2.5). A 10 μg/m3 increase in PM10 was associated with the higher volumes of total WMH (odds ratio, 1.78; 95% confidence interval, 1.07–2.97) and periventricular WMH (2.00; 1.20–3.33). A 1 μg/m3 increase in PM2.5 was associated with the higher volume of periventricular WMH (odds ratio, 1.66; 95% confidence interval, 1.08–2.56). These associations did not significantly differ by the level of high sensitivity CRP. Conclusion: Particulate matter exposures were associated with a reduced global cortical thickness in men with a high level of chronic inflammation. Men with a high level of chronic inflammation may be susceptible to cortical atrophy attributable to particulate matter exposures.ope

Alzheimer’s disease-like cortical atrophy mediates the effect of air pollution on global cognitive function

Little is known about the effect of air pollution on Alzheimer's disease (AD)-specific brain structural pathologies. There is also a lack of evidence on whether this effect leads to poorer cognitive function. We investigated whether, and the extent to which, AD-like cortical atrophy mediated the association between air pollution exposures and cognitive function in dementia-free adults. We used cross-sectional data from 640 participants who underwent brain magnetic resonance imaging and the Montreal Cognitive Assessment (MoCA). Mean cortical thickness (as the measure of global cortical atrophy) and machine learning-based AD-like cortical atrophy score were estimated from brain images. Concentrations of particulate matter with diameters ≤ 10 μm (PM10) and ≤ 2.5 μm (PM2.5) and nitrogen dioxide (NO2) were estimated based on each participant's residential address. Following the product method, a mediation effect was tested by conducting a series of three regression analyses (exposure to outcome; exposure to mediator; and exposure and mediator to outcome). A 10 μg/m3 increase in PM10 (β = -1.13; 95 % CI, -1.73 to -0.53) and a 10 ppb increase in NO2 (β = -1.09; 95 % CI, -1.40 to -0.78) were significantly associated with a lower MoCA score. PM10 (β = 0.27; 95 % CI, 0.06 to 0.48) and NO2 (β = 0.35; 95 % CI, 0.25 to 0.45) were significantly associated with an increased AD-like cortical atrophy score. Effects of PM10 and NO2 on MoCA scores were significantly mediated by mean cortical thickness (proportions mediated: 25 %-28 %) and AD-like cortical atrophy scores (13 %-16 %). The findings suggest that air pollution exposures may induce AD-like cortical atrophy, and that this effect may lead to poorer cognitive function in dementia-free adults.ope

Cost-effectiveness of Direct Oral Anticoagulant vs. Warfarin Among Atrial Fibrillation Patients With Intermediate Stroke Risk

Background: Several studies have shown the cost-effectiveness of direct oral anticoagulants (DOACs), compared with warfarin, to prevent atrial fibrillation (AF) related complications. However, few have reported cost-effectiveness of DOACs in AF patients with intermediate stroke risk. Thus, we investigated the cost-effectiveness of DOACs vs. warfarin in non-valvular AF patients with intermediate stroke risk using national representative data. Methods: We identified 7,954 newly diagnosed non-valvular AF patients (≥18 years) with intermediate stroke risk (CHA2DS2-VASc score: 1 for men and 2 for women) using the national healthcare utilization data from August 1, 2016, to July 31, 2019. Annual incidence rate of AF-related composite outcomes (heat failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, and gastrointestinal bleeding) was estimated. Cost-effectiveness was estimated using a Markov chain model with the transition probability of 1 year. The willingness-to-pay (WTP) was set at $32,000 per quality-adjusted life-year (QALY) gained. Results: The total cost of warfarin, rivaroxaban, apixaban, dabigatran and edoxaban was$2,874, $5,761,$5,151, $5,761 and$5,851, respectively. The QALYs gained were 10.83, 10.95, 11.10, 10.49 and 10.99 years, respectively. The incremental cost-effectiveness ratio of rivaroxaban, apixaban, dabigatran and edoxaban was $29,743.99,$8,426.71, -$8,483.04 and$18,483.55, respectively. The WTP was set at $32,000. DOACs (except dabigatran) were more cost-effective compared with warfarin because they did not exceed the WTP in the base-case analysis. Conclusion: Our findings showed that DOACs were more cost-effective than warfarin in non-valvular AF patients with intermediate stroke risk.ope

Medical Care Expenditure in Suicides From Non-illness-related Causes

Objectives: Several epidemiological studies on medical care utilization prior to suicide have considered the motivation of suicide, but focused on the influence of physical illnesses. Medical care expenditure in suicide completers with non-illness-related causes has not been investigated. Methods: Suicides motivated by non-illness-related factors were identified using the investigator’s note from the National Police Agency, which was then linked to the Health Insurance Review and Assessment data. We investigated the medical care expenditures of cases one year prior to committing suicide and conducted a case-control study using conditional logistic regression analysis after adjusting for age, gender, area of residence, and socioeconomic status. Results: Among the 4515 suicides motivated by non-illness-related causes, medical care expenditures increased in only the last 3 months prior to suicide in the adolescent group. In the younger group, the proportion of total medical expenditure for external injuries was higher than that in the older groups. Conditional logistic regression analysis showed significant associations with being a suicide completer and having a rural residence, low socioeconomic status, and high medical care expenditure. After stratification into the four age groups, a significant positive association with medical care expenditures and being a suicide completer was found in the adolescent and young adult groups, but no significant results were found in the elderly groups for both men and women. Conclusions: Younger adults who committed suicide motivated by non-illness-related causes had a higher proportion of external injuries and more medical care expenditures than their controls did. This reinforces the notion that suicide prevention strategies for young people with suicidal risk factors are needed.ope