Heterogeneity of factors associated with cognitive decline and cortical atrophy in early- versus late-onset Alzheimer's disease.

The objectives of this study were to investigate the variable factors associated with cognitive function and cortical atrophy and estimated variable importance of those factors in affecting cognitive function and cortical atrophy in patients with EOAD and LOAD. Patients with EOAD (n = 40), LOAD (n = 34), and healthy volunteers with normal cognition were included (n = 65). All of them performed 3T MRI, [18F]THK5351 PET (THK), [18F]flutemetamol PET (FLUTE), and detailed neuropsychological tests. To investigate factors associated with neuropsychological test results and cortical thickness in each group, we conducted multivariable linear regression models, including amyloid, tau, cerebral small vessel disease markers on MRI, and vascular risk factors. Then, we estimated variable importance in associating cognitive functions and cortical thickness, using relative importance analysis. In patients with EOAD, global THK retention was the most important contributor to the model variances for most neuropsychological tests, except for memory. However, in patients with LOAD, multiple contributors beyond tau were important in explaining variance of neuropsychological tests. In analyses with mean cortical thickness, global THK retention was the main contributor in patients with EOAD, while in LOAD patients, multiple factors contributed equally to mean cortical thickness. Therefore, EOAD and LOAD may have different pathomechanistic courses.

Estimation of Attributable Risk and Direct Medical and Non-Medical Costs of Major Mental Disorders Associated With Air Pollution Exposures Among Children and Adolescents in the Republic of Korea, 2011-2019.

BACKGROUND: Recent studies have reported the burden of attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and depressive disorder. Also, there is mounting evidence on the effects of environmental factors, such as ambient air pollution, on these disorders among children and adolescents. However, few studies have evaluated the burden of mental disorders attributable to air pollution exposure in children and adolescents. METHODS: We estimated the risk ratios of major mental disorders (ADHD, ASD, and depressive disorder) associated with air pollutants among children and adolescents using time-series data (2011-2019) obtained from a nationwide air pollution monitoring network and healthcare utilization claims data in the Republic of Korea. Based on the estimated risk ratios, we determined the population attributable fraction (PAF) and calculated the medical costs of major mental disorders attributable to air pollution. RESULTS: A total of 33,598 patients were diagnosed with major mental disorders during 9 years. The PAFs for all the major mental disorders were estimated at 6.9% (particulate matter < 10 µm [PM10]), 3.7% (PM2.5), and 2.2% (sulfur dioxide [SO2]). The PAF of PM10 was highest for depressive disorder (9.2%), followed by ASD (8.4%) and ADHD (5.2%). The direct medical costs of all major mental disorders attributable to PM10 and SO2 decreased during the study period. CONCLUSION: This study assessed the burden of major mental disorders attributable to air pollution exposure in children and adolescents. We found that PM10, PM2.5, and SO2 attributed 7%, 4%, and 2% respectively, to the risk of major mental disorders among children and adolescents.

Effect of polycyclic aromatic hydrocarbon exposure on amnestic mild cognitive impairment and Alzheimer's disease: A matched case-control study.

There is an emerging body of evidence concerning the neurological effect of air pollutants on cognitive function and increased risk of neurodegeneration. Although previous studies have suggested that polycyclic aromatic hydrocarbons (PAHs) are neurotoxic, the effect of PAHs exposure on neurodegeneration remains unclear. This study aimed to investigate the association between PAH exposure and the risk of developing amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). For this matched case-control cross-sectional study, we recruited patients aged ≥50 years diagnosed with aMCI and AD from the Samsung Medical Center, Seoul, Korea, between 2014 and 2019. For each patient, we randomly selected four cognitively healthy controls through frequency matching based on sex, age group, and education level. Urinary levels of four PAH metabolites, 1-hydroxypyrene (1-OHP), 1-hydroxyphenanthrene (1-OHPhe), 2-hydroxyfluorene (2-OHFlu), and 2-naphthol (2-NAP), were measured. A conditional logistic regression model was used to evaluate the association, adjusting for potential confounders. A total of 212 patients with aMCI with 848 matched controls, and 267 patients with AD with 1068 matched controls were included in the analyses to estimate the risk of PAH exposure. We found that elevated urinary levels of PAH metabolites (specifically, 1-OHP and 2-NAP) were significantly associated with an increased risk of aMCI and AD. An increase of one unit in log-transformed level of urinary 1-OHP was associated with a 1.15- and 1.16-times higher risk of aMCI and AD, respectively. An increase of one unit in log-transformed level of urinary 2-NAP was associated with a 1.11- and 1.13-times higher risk of aMCI and AD, respectively. These findings indicate that PAH exposure may increase the risk of aMCI and AD, especially for the elderly population. Considering the widespread distribution of PAHs in the environment, reducing PAH exposure may be an effective strategy for the prevention of neurodegenerative diseases.

Epidemiology of post-pancreatitis diabetes mellitus: insights from the COSMOS program.

INTRODUCTION: Post-pancreatitis diabetes mellitus (PPDM) has long been recognized as one of the most challenging sub-types of diabetes to manage. Part of the problem is that the earlier literature on epidemiology of PPDM was confusing because of the presence of selection bias. AREAS COVERED: A concerted series of population-based nationwide studies on PPDM from New Zealand has recently been published as part of the COSMOS (Clinical and epidemiOlogical inveStigations in Metabolism, nutritiOn, and pancreatic diseaseS) program and is the main focus of the present article. EXPERT OPINION: The foundational knowledge on epidemiology of PPDM generated by the COSMOS program is generalizable to the population at large. It brings the field closer to a comprehensive narrative of risk factors, burden, mortality, and morbidity outcomes of PPDM. In producing new knowledge on epidemiology of PPDM, it will be important to adhere to the guidelines on identification of PPDM in population-based datasets advanced in the present article.

Association of 1-bromopropane exposure with asthma prevalence: A Korean National health and Nutritional examination survey (2020-2021)-based study.

Exposure to 1-bromopropane (1-BP) is an emerging environmental and health concern due to its increasing environmental prevalence. Although the health effects of 1-BP exposure have been under-recognized, current evidence suggests the possibility of adverse pulmonary health effects due to 1-BP exposure. However, the association between 1-BP exposure and asthma prevalence remains unclear. Thus, we aimed to examine the association between 1-BP exposure and asthma prevalence in the general population. Using nationally representative data, we explored the potential impacts of indoor air quality (IAQ)-related behavioral factors on the level of 1-BP exposure. This study included 1506 adults from the 2020-2021 Korea National Health and Nutrition Examination Survey. The prevalence of asthma was based on self-reported physician-diagnosed asthma. Urinary N-acetyl-S-(n-propyl)-L-cysteine (BPMA) levels were measured as a biomarker of 1-BP exposure, using high-performance liquid chromatography-mass spectrometry. Multiple logistic regression models were performed to investigate the associations between urinary BPMA metabolite and asthma prevalence after adjusting for potential confounders. Log-linear multiple regression models were used to examine the association between IAQ-related behavior and urinary BPMA concentration. Forty-seven individuals with asthma and 1459 without asthma were included. Individuals in the highest quartile of urinary BPMA concentration had a 2.9 times higher risk of asthma than those in the lowest quartile (odds ratio [OR]: 2.85, 95% confidence interval [CI]: 1.02-7.98). The combination of natural and mechanical ventilation was associated with a reduced urinary BPMA concentration. Our findings suggest that 1-BP exposure is associated with the prevalence of asthma in adults and revealed higher urinary levels of BPMA in our study population compared to those in other countries. Given the emerging importance of IAQ, actively managing and modifying behavioral patterns to reduce 1-BP exposure in indoor environments could substantially attenuate the risk of asthma-related to 1-BP exposure.

Diverging Relationships among Amyloid, Tau, and Brain Atrophy in Early-Onset and Late-Onset Alzheimer's Disease.

PURPOSE: Alzheimer's disease (AD) dementia may not be a single disease entity. Early-onset AD (EOAD) and late-onset AD (LOAD) have been united under the same eponym of AD until now, but disentangling the heterogeneity according to the age of sonset has been a major tenet in the field of AD research. MATERIALS AND METHODS: Ninety-nine patients with AD (EOAD, n=54; LOAD, n=45) and 66 cognitively normal controls completed both [18F]THK5351 and [18F]flutemetamol (FLUTE) positron emission tomography scans along with structural magnetic resonance imaging and detailed neuropsychological tests. RESULTS: EOAD patients had higher THK retention in the precuneus, parietal, and frontal lobe, while LOAD patients had higher THK retention in the medial temporal lobe. Intravoxel correlation analyses revealed that EOAD presented narrower territory of local FLUTE-THK correlation, while LOAD presented broader territory of correlation extending to overall parieto-occipito-temporal regions. EOAD patients had broader brain areas which showed significant negative correlations between cortical thickness and THK retention, whereas in LOAD, only limited brain areas showed significant correlation with THK retention. In EOAD, most of the cognitive test results were correlated with THK retention. However, a few cognitive test results were correlated with THK retention in LOAD. CONCLUSION: LOAD seemed to show gradual increase in tau and amyloid, and those two pathologies have association to each other. On the other hand, in EOAD, tau and amyloid may develop more abruptly and independently. These findings suggest LOAD and EOAD may have different courses of pathomechanism.

Increased risk of developing cerebro-cardiovascular diseases in police officers: a nationwide retrospective cohort study.

BACKGROUND: Police officers face an increased risk of developing cerebro-cardiovascular diseases (CVD). However, current literature lacks population-based cohort studies specifically focusing on this association. This study aimed to investigate the association between police officers and the risk of developing CVD compared with education officers, while accounting for socioeconomic and demographic factors. METHODS: We used the Korean National Health Insurance Service data spanning from 2009 to 2020. In this population-based retrospective matched cohort study, we identified age, sex, and calendar years of job-enrollment-matched education officers for each police officer. This study evaluated the CVD occurrence, including acute myocardial infarction, ischemic stroke, and hemorrhagic stroke. Using multivariable Cox regression analysis, we determined the risk of developing CVD, expressed as a hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Among 104,134 police officers and 104,134 education officers, 4,391(42.2%) cases and 3,631(34.9%) cases of CVD occurred, respectively. The mean ± standard deviation age was 38.4 ± 9.4 years in police officers and 38.6 ± 9.5 years in education officers. The proportion of men was 84.8 % in both groups. Police officers were significantly associated with a higher risk of developing CVD compared with education officers, with an adjusted HR of 1.15 (95% CI, 1.09-1.22). In addition, police officers had significantly higher risks for acute myocardial infarction (adjusted HR, 1.16; 95% CI, 1.06-1.26) and ischemic stroke (adjusted HR, 1.17; 95% CI, 1.09-1.25). CONCLUSIONS: The findings of our study highlight a significant increase in the risk of developing CVD among police officers, particularly among those aged 45 years and older and those with uncontrolled blood pressure compared to their education officer counterparts. Future cohort studies are required to confirm this association.

Effects of Ambient Air Pollution on Brain Cortical Thickness and Subcortical Volume: A Longitudinal Neuroimaging Study.

INTRODUCTION: Several cross-sectional studies have shown that long-term exposures to air pollutants are associated with smaller brain cortical volume or thickness. Here, we investigated longitudinal associations of long-term air pollution exposures with cortical thickness and subcortical volume. METHODS: In this longitudinal study, we included a prospective cohort of 361 adults residing in four cities in the Republic of Korea. Long-term concentrations of particulate matter with aerodynamic diameters of ≤10 µm (PM10) and ≤2.5 µm (PM2.5) and nitrogen dioxide (NO2) at residential addresses were estimated. Neuroimaging markers (cortical thickness and subcortical volume) were obtained from brain magnetic resonance images at baseline (August 2014 to March 2017) and at the 3-year follow-up (until September 2020). Linear mixed-effects models were used, adjusting for covariates. RESULTS: A 10-µg/m3 increase in PM10 was associated with reduced whole-brain mean (ß = -0.45, standard error [SE] = 0.10; p < 0.001), frontal (ß = -0.53, SE = 0.11; p < 0.001) and temporal thicknesses (ß = -0.37, SE = 0.12; p = 0.002). A 10-ppb increase in NO2 was associated with a decline in the whole-brain mean cortical thickness (ß = -0.23, SE = 0.05; p < 0.001), frontal (ß = -0.25, SE = 0.05; p < 0.001), parietal (ß = -0.12, SE = 0.05; p = 0.025), and temporal thicknesses (ß = -0.19, SE = 0.06; p = 0.001). Subcortical structures associated with air pollutants included the thalamus. CONCLUSIONS: Long-term exposures to PM10 and NO2 may lead to cortical thinning in adults.

Physical Activity-Induced Modification of the Association of Long-Term Air Pollution Exposure with the Risk of Depression in Older Adults.

PURPOSE: Evidence suggests that long-term air pollution exposures may induce depression; however, the influence of physical activity on this effect is unclear. We investigated modification of the associations between air pollution exposures and depression by the intensity of physical activity. MATERIALS AND METHODS: This cross-sectional study included 1454 Korean adults. Depression was defined as a Geriatric Depression Scale score ≥8. Concentrations of particulate matter (PM10 and PM2.5: diameter ≤10 µm and ≤2.5 µm, respectively) and nitrogen dioxide (NO2) level at each participant's residential address were estimated. Based on metabolic equivalents, physical activity intensity was categorized as inactive, minimally active, or health-enhancing physical activity (HEPA). RESULTS: Each 1-part per billion (ppb) NO2 concentration increase was significantly associated with a 6% [95% confidence interval (CI), 4%-8%] increase in depression risk. In older adults (≥65 years), a 1-ppb NO2 increase was associated (95% CI) with a 4% (1%-7%), 9% (5%-13%), and 21% (9%-33%) increase in depression risk in the inactive, minimally active, and HEPA groups, respectively. Compared with the inactive group, the minimally active (p=0.039) and HEPA groups (p=0.004) had higher NO2 exposure-associated depression risk. Associations of PM10 and PM2.5 with depression did not significantly differ by the intensity of physical activity. CONCLUSION: We suggest that older adults who vigorously exercise outdoors may be susceptible to air pollution-related depression.

Association between exposure to heavy metals in atmospheric particulate matter and sleep quality: A nationwide data linkage study.

BACKGROUND: Recent studies have demonstrated that long-term exposure to particulate matter (PM) is associated with poor sleep quality. However, no studies have linked PM constituents, particularly heavy metals, to sleep quality. OBJECTIVE: This study investigated the association between exposure to heavy metals in PM and sleep quality. METHODS: We obtained nationwide data from the Korean Community Health Survey conducted in 2018 among adults aged 19-80 years. Sleep quality was evaluated using Pittsburgh Sleep Quality Index (PSQI). Poor sleep quality was defined as PSQI ≥5. One-year and three-month average concentrations of heavy metals (lead, manganese, cadmium, and aluminum) in PM with diameter ≤10 µm were obtained from nationwide air quality monitoring data and linked to the survey data based on individual district-level residential addresses. Logistic regression analyses were performed after adjusting for age, gender, education level, marital status, smoking status, alcohol consumption, history of hypertension, and history of diabetes mellitus. RESULTS: Of 32,050 participants, 17,082 (53.3%) reported poor sleep quality. Increases in log-transformed one-year average lead (odds ratio, 1.14; 95% confidence interval, 1.08-1.20), manganese (1.31; 1.25-1.37), cadmium (1.03; 1.00-1.05), and aluminum concentrations (1.17; 1.10-1.25) were associated with poor sleep quality. Increases in log-transformed three-month average manganese (odds ratio, 1.13; 95% confidence interval, 1.09-1.17) and aluminum concentrations (1.28; 1.21-1.35) were associated with poor sleep quality. CONCLUSION: We showed for the first time that exposure to airborne lead, manganese, cadmium, and aluminum were associated with poor sleep quality. This study may be limited by self-reported sleep quality and district-level exposure data.

Remnant cholesterol, but not low-density lipoprotein cholesterol, is associated with intra-pancreatic fat deposition.

AIM: To investigate the associations of components of the lipid panel (and its derivatives) with intra-pancreatic fat deposition (IPFD). METHODS: All participants underwent abdominal magnetic resonance imaging on the same 3.0-Tesla scanner and IPFD was quantified. Blood samples were collected in the fasted state for analysis of lipid panel components. A series of linear regression analyses was conducted, adjusting for age, sex, ethnicity, body mass index, fasting plasma glucose, homeostatic model assessment of insulin resistance, and liver fat deposition. RESULTS: A total of 348 participants were included. Remnant cholesterol (P = 0.010) and triglyceride levels (P = 0.008) were positively, and high-density lipoprotein cholesterol level (P = 0.001) was negatively, associated with total IPFD in the most adjusted model. Low-density lipoprotein cholesterol and total cholesterol were not significantly associated with total IPFD. Of the lipid panel components investigated, remnant cholesterol explained the greatest proportion (9.9%) of the variance in total IPFD. CONCLUSION: Components of the lipid panel have different associations with IPFD. This may open up new opportunities for improving outcomes in people at high risk for cardiovascular diseases (who have normal low-density lipoprotein cholesterol) by reducing IPFD.

Heavy metal exposure linked to metabolic syndrome in Korean male firefighters: FRESH cohort cross-sectional analysis.

This study aimed to identify the relationship between blood lead and Cadmium (Cd) concentrations and metabolic syndromes (MetS), including its components (central obesity, hypertriglyceridemia, low high-density lioioritein, hypertension, and hyperglycemia) among Korean firefighters. A total of 965 firefighters of the Enhancement of Safety and Health cohort were analyzed in this study. MetS was defined according to the 2005 revised National Cholesterol Education Program-Adult Treatment Panel III criteria and the Korean Society for the Study of Obesity criteria for waist circumference. The collected data were analyzed using a logistic regression model. Of the 965 participants, 190 (19.7%) had MetS. After adjusting for age, body mass index, smoking, drinking, exercise, shift duty, and main duty position, the Cd level was significantly associated with an increased risk of MetS in the Korean firefighter population (odds ratio [OR] = 1.62, 95% confidence interval [CI] 1.07, 2.46). This association was significant among non-smokers and ex-smokers (OR = 1.58, 95% CI 1.03, 2.43), non-drinkers and ex-drinkers (OR = 1.77, 95% CI 1.06, 2.94), firefighters aged 40 year or older (OR = 1.77, 95% CI 1.10, 2.86), and office administrators (OR = 3.85, 95% CI 1.42, 10.39). This outcome suggests that exposure to Cd is likely to increase risk of MetS among firefighters.

Polycyclic aromatic hydrocarbons and changes in brain cortical thickness and an Alzheimer's disease-specific marker for cortical atrophy in adults: A longitudinal neuroimaging study of the EPINEF cohort.

Although several epidemiological studies have suggested that exposure to polycyclic aromatic hydrocarbons (PAHs) may induce brain atrophy, no longitudinal study has investigated the effect of PAH exposure on brain structural changes. This study examined the longitudinal associations between urinary PAH metabolites and brain cortical thickness. We obtained urinary concentrations of PAH metabolites and brain magnetic resonance images from 327 adults (≥50 years of age) without dementia at baseline and 3-year follow-up. We obtained whole-brain and regional cortical thicknesses, as well as an Alzheimer's disease (AD)-specific marker for cortical atrophy (a higher score indicated a greater similarity to patients with AD) at baseline and follow-up. We built a linear mixed-effect model including each of urinary PAH metabolites as the time-varying exposure variable of interest. We found that increases in urinary concentrations of 1-hydroxypyrene (ß = -0.004; 95% CI, -0.008 to -0.001) and 2-hydroxyfluorene (ß = -0.011; 95% CI, -0.015 to -0.006) were significantly associated with a reduced whole-brain cortical thickness. A urinary concentration of 2-hydroxyfluorene was significantly associated with an increased AD-specific cortical atrophy score (ß = 2.031; 95% CI, 0.512 to 3.550). The specific brain regions showing the association of urinary concentrations of 1-hydroxypyrene, 2-naphthol, 1-hydroxyphenanthrene, or 2-hydroxyfluorene with cortical thinning were the frontal, parietal, temporal, and cingulate lobes. These findings suggested that exposure to PAHs may reduce brain cortical thickness and increase the similarity to AD-specific cortical atrophy patterns in adults.

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.

Associations of ambient manganese exposure with brain gray matter thickness and white matter hyperintensities.

Manganese (Mn) exposure is associated with increased risks of dementia and cerebrovascular disease. However, evidence regarding the impact of ambient Mn exposure on brain imaging markers is scarce. We aimed to investigate the association between ambient Mn exposure and brain imaging markers representing neurodegeneration and cerebrovascular lesions. We recruited a total of 936 adults (442 men and 494 women) without dementia, movement disorders, or stroke from the Republic of Korea. Ambient Mn concentrations were predicted at each participant's residential address using spatial modeling. Neurodegeneration-related brain imaging markers, such as the regional cortical thickness, were estimated using 3 T brain magnetic resonance images. White matter hyperintensity volume (an indicator of cerebrovascular lesions) was also obtained from a certain number of participants (n = 397). Linear regression analyses were conducted after adjusting for potential confounders. A log-transformed ambient Mn concentration was associated with thinner parietal (ß = -0.02 mm; 95% confidence interval [CI], -0.05 to -0.01) and occipital cortices (ß = -0.03 mm; 95% CI, -0.04 to -0.01) after correcting for multiple comparisons. These associations remained statistically significant in men. An increase in the ambient Mn concentration was also associated with a greater volume of deep white matter hyperintensity in men (ß = 772.4 mm3, 95% CI: 36.9 to 1508.0). None of the associations were significant in women. Our findings suggest that ambient Mn exposure may induce cortical atrophy in the general adult population.

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 microplastics 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 monitoring the occurrence, distribution, and movement of microplastics in the environment, as well as developing microplastic substitutes; 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.

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.

Metabolic traits affecting the relationship between liver fat and intrapancreatic fat: a mediation analysis.

AIMS/HYPOTHESIS: The clinical importance of fat deposition in the liver and pancreas is increasingly recognised. However, to what extent deposition of fat in these two depots is affected by intermediate variables is unknown. The aim of this work was to conduct a mediation analysis with a view to uncovering the metabolic traits that underlie the relationship between liver fat and intrapancreatic fat deposition (IPFD) and quantifying their effect. METHODS: All participants underwent MRI/magnetic resonance spectroscopy on the same 3.0 T scanner to determine liver fat and IPFD. IPFD of all participants was quantified manually by two independent raters in duplicate. A total of 16 metabolic traits (representing markers of glucose metabolism, incretins, lipid panel, liver enzymes, pancreatic hormones and their derivatives) were measured in blood. Mediation analysis was conducted, taking into account age, sex, ethnicity and BMI. Significance of mediation was tested by computing bias-corrected bootstrap CIs with 5000 repetitions. RESULTS: A total of 353 individuals were studied. Plasma glucose, HDL-cholesterol and triacylglycerol mediated 6.8%, 17.9% and 24.3%, respectively, of the association between liver fat and IPFD. Total cholesterol, LDL-cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, insulin, glucagon, amylin, C-peptide, HbA1c, glucagon-like peptide-1 and gastric inhibitory peptide did not mediate the association between liver fat and IPFD. CONCLUSIONS/INTERPRETATION: At least one-quarter of the association between liver fat and IPFD is mediated by specific blood biomarkers (triacylglycerol, HDL-cholesterol and glucose), after accounting for potential confounding by age, sex, ethnicity and BMI. This unveils the complexity of the association between the two fat depots and presents specific targets for intervention.

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 (ß = -1.13; 95 % CI, -1.73 to -0.53) and a 10 ppb increase in NO2 (ß = -1.09; 95 % CI, -1.40 to -0.78) were significantly associated with a lower MoCA score. PM10 (ß = 0.27; 95 % CI, 0.06 to 0.48) and NO2 (ß = 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.

Factors Affecting the Circulating Levels of Oxyntomodulin in Health and After Acute Pancreatitis.

OBJECTIVES: To investigate the factors associated with the circulating levels of oxyntomodulin in healthy individuals and individuals after an episode of acute pancreatitis (AP). METHODS: Blood samples were collected from all participants after an overnight fast and analyzed for 28 biomarkers. Participants also underwent comprehensive body composition analysis on a 3-T magnetic resonance imaging scanner. Regression analyses were done to investigate the associations between oxyntomodulin and the studied factors. RESULTS: The study included 105 individuals who had a primary diagnosis of AP and 58 healthy individuals. Peptide YY (B coefficient, 0.094; 95% confidence interval [95% CI], 0.164-0.123), pancreatic polypeptide (0.048; 95% CI, 0.030-0.066), and leptin (0.394; 95% CI, 0.128-0.661) had significant associations with oxyntomodulin in healthy individuals. Peptide YY was the most prominent factor associated with oxyntomodulin, explaining 60% of its variance in health. Cholecystokinin (0.014; 95% CI, 0.010-0.018), amylin (-0.107; 95% CI, -0.192 to -0.021), and glycated hemoglobin (-0.761; 95% CI, -1.249 to -0.273) had significant associations with oxyntomodulin in individuals after AP. Cholecystokinin was the most prominent factor associated with oxyntomodulin, explaining 44% of its variance after AP. CONCLUSIONS: Factors affecting the circulating levels of oxyntomodulin are different in health and after AP. These insights will enable the determination of populations that benefit from oxyntomodulin therapeutics in the future.