Association of Tumor Necrosis Factor-α Inhibitors with Incident Dementia: Analysis Based on Population-Based Cohort Studies.

BACKGROUND AND OBJECTIVE: Preliminary evidence suggests a possible preventive effect of tumor necrosis factor-α inhibitors (TNFi) on incident dementia. The objective of the analysis was to investigate the association between TNFi and the risk of incident dementia in a population undergoing treatment for rheumatological disorders. METHODS: We followed patients aged ≥ 65 years with dementia and rheumatological conditions in two cohort studies, DANBIO (N = 21,538), a Danish clinical database, and AOK PLUS (N = 7112), a German health insurance database. We defined incident dementia using diagnostic codes and/or medication use and used Cox regression to compare the associations of TNFi with other rheumatological therapies on the risk of dementia. To ensure that the patients were receiving long-term medication, we included patients with rheumatic diseases and systemic therapies. RESULTS: We observed similar trends towards a lower risk of dementia associated with TNFi versus other anti-inflammatory agents in both cohorts (hazard ratios were 0.92 [95% confidence interval 0.76, 1.10] in DANBIO and 0.89 [95% confidence interval 0.63, 1.24] in AOK PLUS, respectively). CONCLUSIONS: Tumor necrosis factor-α inhibitors may decrease the risk of incident dementia although the association did not reach statistical significance in this analysis. Further research, ideally with randomization, is needed to gauge the potential of repurposing TNFi for dementia prevention and/or treatment.

Long-Term Exposure to Air Pollution and Risk of Acute Lower Respiratory Infections in the Danish Nurse Cohort.

RATIONALE: Air pollution is a major risk factor for chronic cardiorespiratory diseases, affecting both the immune and respiratory systems' functionality, while the epidemiological evidence on respiratory infections remains sparse. OBJECTIVE: We aimed to assess the association of long-term exposure to ambient air pollution with risk of developing new and recurrent ALRIs that characterized by persistently severe symptoms necessitating hospital contact, and identify the potential susceptible populations by socio-economic status (SES), smoking, physical activity status, overweight, and co-morbidity with chronic lung disease. METHODS: We followed 23,912 female nurses from the Danish Nurse Cohort (> 44 years) from baseline (1993 or 1999) until 2018 for the incident and recurrent ALRIs defined by hospital contact (in-, outpatient, and emergency room) data from the National Patient Register. Residential annual mean concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), and black carbon (BC) were modelled using Danish DEHM/UBM/AirGIS system. We used marginal Cox models with time-varying exposures to assess the association of 3-year running-mean air pollution with incident and recurrent ALRIs and examine effect modification by age, socio-economic status (SES), smoking, physical activity, body mass index, and comorbidity with asthma or chronic obstructive pulmonary disease (COPD). RESULTS: During a 21.3 years mean follow-up, 4,746 ALRIs were observed, of which 2,553 were incident. We observed strong positive associations of all three pollutants with incident ALRIs, with hazard ratios and 95% confidence intervals of 1.19 (1.08-1.31) per 2.5 µg/m3 for PM2.5, 1.17 (1.11-1.24) per 8.0 µg/m3 for NO2, and 1.09 (1.05-1.12) per 0.3 µg/m3 for BC, and slightly stronger associations with recurrent ALRIs. Associations were strongest in COPD patients and nurses with low physical activity. CONCLUSION: Long-term exposure to air pollution at low levels was associated with risk of new and recurrent ALRIs, with COPD patients and physically inactive subjects most vulnerable. Primary Source of Funding: This study was supported by the Novo Nordisk Foundation Challenge Programme (NNF17OC0027812).

Long-term exposure to air pollution and risk of SARS-CoV-2 infection and COVID-19 hospitalisation or death: Danish nationwide cohort study.

BACKGROUND: Early ecological studies have suggested links between air pollution and risk of coronavirus disease 2019 (COVID-19), but evidence from individual-level cohort studies is still sparse. We examined whether long-term exposure to air pollution is associated with risk of COVID-19 and who is most susceptible. METHODS: We followed 3 721 810 Danish residents aged ≥30 years on 1 March 2020 in the National COVID-19 Surveillance System until the date of first positive test (incidence), COVID-19 hospitalisation or death until 26 April 2021. We estimated residential annual mean particulate matter with diameter ≤2.5 µm (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone (O3) in 2019 by the Danish DEHM/UBM model, and used Cox proportional hazards regression models to estimate the associations of air pollutants with COVID-19 outcomes, adjusting for age, sex, individual- and area-level socioeconomic status, and population density. RESULTS: 138 742 individuals were infected, 11 270 were hospitalised and 2557 died from COVID-19 during 14 months. We detected associations of PM2.5 (per 0.53 µg·m-3) and NO2 (per 3.59 µg·m-3) with COVID-19 incidence (hazard ratio (HR) 1.10 (95% CI 1.05-1.14) and HR 1.18 (95% CI 1.14-1.23), respectively), hospitalisations (HR 1.09 (95% CI 1.01-1.17) and HR 1.19 (95% CI 1.12-1.27), respectively) and death (HR 1.23 (95% CI 1.04-1.44) and HR 1.18 (95% CI 1.03-1.34), respectively), which were strongest in the lowest socioeconomic groups and among patients with chronic respiratory, cardiometabolic and neurodegenerative diseases. We found positive associations with BC and negative associations with O3. CONCLUSION: Long-term exposure to air pollution may contribute to increased risk of contracting severe acute respiratory syndrome coronavirus 2 infection as well as developing severe COVID-19 disease requiring hospitalisation or resulting in death.

Long-term exposure to elemental components of fine particulate matter and all-natural and cause-specific mortality in a Danish nationwide administrative cohort study.

BACKGROUND: Fine particulate matter (PM2.5) is a well-recognized risk factor for premature death. However, evidence on which PM2.5 components are most relevant is unclear. METHODS: We evaluated the associations between mortality and long-term exposure to eight PM2.5 elemental components [copper (Cu), iron (Fe), zinc (Zn), sulfur (S), nickel (Ni), vanadium (V), silicon (Si), and potassium (K)]. Studied outcomes included death from diabetes, chronic kidney disease (CKD), dementia, and psychiatric disorders as well as all-natural causes, cardiovascular disease (CVD), respiratory diseases (RD), and lung cancer. We followed all residents in Denmark (aged ≥30 years) from January 1, 2000 to December 31, 2017. We used European-wide land-use regression models at a 100 × 100 m scale to estimate the residential annual mean levels of exposure to PM2.5 components. The models were developed with supervised linear regression (SLR) and random forest (RF). The associations were evaluated by Cox proportional hazard models adjusting for individual- and area-level socioeconomic factors and total PM2.5 mass. RESULTS: Of 3,081,244 individuals, we observed 803,373 death from natural causes during follow-up. We found significant positive associations between all-natural mortality with Si and K from both exposure modeling approaches (hazard ratios; 95% confidence intervals per interquartile range increase): SLR-Si (1.04; 1.03-1.05), RF-Si (1.01; 1.00-1.02), SLR-K (1.03; 1.02-1.04), and RF-K (1.06; 1.05-1.07). Strong associations of K and Si were detected with most causes of mortality except CKD and K, and diabetes and Si (the strongest associations for psychiatric disorders mortality). In addition, Fe was relevant for mortality from RD, lung cancer, CKD, and psychiatric disorders; Zn with mortality from CKD, RD, and lung cancer, and; Ni and V with lung cancer mortality. CONCLUSIONS: We present novel results of the relevance of different PM2.5 components for different causes of death, with K and Si seeming to be most consistently associated with mortality in Denmark.

Long-term air pollution exposure and Parkinson's disease mortality in a large pooled European cohort: An ELAPSE study.

BACKGROUND: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson's Disease (PD) remains limited. OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. METHODS: Within the project 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3), as well as 8 PM2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. RESULTS: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM2.5 (hazard ratio per 5 µg/m3: 1.25; 95% confidence interval: 1.01-1.55), NO2 (1.13; 0.95-1.34 per 10 µg/m3), and BC (1.12; 0.94-1.34 per 0.5 × 10-5m-1), and a negative association with O3 (0.74; 0.58-0.94 per 10 µg/m3). Associations of PM2.5, NO2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM2.5 remained robust when adjusted for NO2 (1.24; 0.95-1.62) or BC (1.28; 0.96-1.71), whereas associations with NO2 or BC attenuated to null. O3 associations remained negative, but no longer statistically significant in models with PM2.5. We detected suggestive positive associations with the potassium component of PM2.5. CONCLUSION: Long-term exposure to PM2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality.

Long-term exposure to air pollution and mortality in a Danish nationwide administrative cohort study: Beyond mortality from cardiopulmonary disease and lung cancer.

BACKGROUND: The association between long-term exposure to air pollution and mortality from cardiorespiratory diseases is well established, yet the evidence for other diseases remains limited. OBJECTIVES: To examine the associations of long-term exposure to air pollution with mortality from diabetes, dementia, psychiatric disorders, chronic kidney disease (CKD), asthma, acute lower respiratory infection (ALRI), as well as mortality from all-natural and cardiorespiratory causes in the Danish nationwide administrative cohort. METHODS: We followed all residents aged ≥ 30 years (3,083,227) in Denmark from 1 January 2000 until 31 December 2017. Annual mean concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (warm season) were estimated using European-wide hybrid land-use regression models (100 m × 100 m) and assigned to baseline residential addresses. We used Cox proportional hazard models to evaluate the association between air pollution and mortality, accounting for demographic and socioeconomic factors. We additionally applied indirect adjustment for smoking and body mass index (BMI). RESULTS: During 47,023,454 person-years of follow-up, 803,881 people died from natural causes. Long-term exposure to PM2.5 (mean: 12.4 µg/m3), NO2 (20.3 µg/m3), and/or BC (1.0 × 10-5/m) was statistically significantly associated with all studied mortality outcomes except CKD. A 5 µg/m3 increase in PM2.5 was associated with higher mortality from all-natural causes (hazard ratio 1.11; 95% confidence interval 1.09-1.13), cardiovascular disease (1.09; 1.07-1.12), respiratory disease (1.11; 1.07-1.15), lung cancer (1.19; 1.15-1.24), diabetes (1.10; 1.04-1.16), dementia (1.05; 1.00-1.10), psychiatric disorders (1.38; 1.27-1.50), asthma (1.13; 0.94-1.36), and ALRI (1.14; 1.09-1.20). Associations with long-term exposure to ozone (mean: 80.2 µg/m3) were generally negative but became significantly positive for several endpoints in two-pollutant models. Generally, associations were attenuated but remained significant after indirect adjustment for smoking and BMI. CONCLUSION: Long-term exposure to PM2.5, NO2, and/or BC in Denmark were associated with mortality beyond cardiorespiratory diseases, including diabetes, dementia, psychiatric disorders, asthma, and ALRI.

Long-term Air Pollution Exposure and Pneumonia-related Mortality in a Large Pooled European Cohort.

Rationale: Ambient air pollution exposure has been linked to mortality from chronic cardiorespiratory diseases, while evidence on respiratory infections remains more limited. Objectives: We examined the association between long-term exposure to air pollution and pneumonia-related mortality in adults in a pool of eight European cohorts. Methods: Within the multicenter project ELAPSE (Effects of Low-Level Air Pollution: A Study in Europe), we pooled data from eight cohorts among six European countries. Annual mean residential concentrations in 2010 for fine particulate matter, nitrogen dioxide (NO2), black carbon (BC), and ozone were estimated using Europe-wide hybrid land-use regression models. We applied stratified Cox proportional hazard models to investigate the associations between air pollution and pneumonia, influenza, and acute lower respiratory infections (ALRI) mortality. Measurements and Main Results: Of 325,367 participants, 712 died from pneumonia and influenza combined, 682 from pneumonia, and 695 from ALRI during a mean follow-up of 19.5 years. NO2 and BC were associated with 10-12% increases in pneumonia and influenza combined mortality, but 95% confidence intervals included unity (hazard ratios, 1.12 [0.99-1.26] per 10 µg/m3 for NO2; 1.10 [0.97-1.24] per 0.5 10-5m-1 for BC). Associations with pneumonia and ALRI mortality were almost identical. We detected effect modification suggesting stronger associations with NO2 or BC in overweight, employed, or currently smoking participants compared with normal weight, unemployed, or nonsmoking participants. Conclusions: Long-term exposure to combustion-related air pollutants NO2 and BC may be associated with mortality from lower respiratory infections, but larger studies are needed to estimate these associations more precisely.

Long-term exposure to road traffic noise and all-cause and cause-specific mortality: a Danish Nurse Cohort study.

BACKGROUND: Long-term road traffic noise exposure is linked to cardio-metabolic disease morbidity, whereas evidence on mortality remains limited. OBJECTIVES: We investigated association of long-term exposure to road traffic noise with all-cause and cause-specific mortality. METHODS: We linked 22,858 females from the Danish Nurse Cohort (DNC), recruited into the Danish Register of Causes of Death up to 2014. Road traffic noise levels since 1970 were modelled by Nord2000 as the annual mean of a weighted 24 h average (Lden). Cox regression models examined the associations between Lden (5-year and 23-year means) and all-cause and cause-specific mortalities, adjusting for lifestyle and exposure to PM2.5 (particulate matter with diameter < 2.5 µm) and NO2 (nitrogen dioxide). RESULTS: During follow-up (mean 17.4 years), 3902 nurses died: 1622 from cancer, 922 from CVDs (289 from stroke), 338 from respiratory diseases (186 from chronic obstructive pulmonary disease, 114 from lower respiratory tract infections [ALRIs]), 234 from dementia, 95 from psychiatric disorders, and 79 from diabetes. Hazard ratios (95% confidence intervals) for all-cause mortality from fully-adjusted models were 1.06 (1.01, 1.11) and 1.09 (1.03, 1.15) per 10 dB of 5-year and 23-year mean Lden, respectively, which attenuated slightly in our main model (fully-adjusted plus PM2.5: 1.04 [1.00, 1.10]; 1.08 [1.02, 1.13]). Main model estimates suggested the strongest associations between 5-year mean Lden and diabetes (1.14: 0.81, 1.61), ALRIs (1.13: 0.84, 1.54), dementia (1.12: 0.90, 1.38), and stroke (1.10: 0.91, 1.31), whereas associations with 23-year mean Lden were suggested for respiratory diseases (1.15: 0.95, 1.39), psychiatric disorders (1.11: 0.78, 1.59), and all cancers (1.08: 0.99, 1.17). DISCUSSION: Among the female nurses from the DNC, we observed that long-term exposure to road traffic noise led to premature mortality, independently of air pollution, and its adverse effects may extend well beyond those on the cardio-metabolic system to include respiratory diseases, cancer, neurodegenerative and psychiatric disorders.

Time trends in incidence and prevalence of chronic pancreatitis: A 25-year population-based nationwide study.

BACKGROUND: Updated population-based estimates on incidence and prevalence of chronic pancreatitis are scarce. METHODS: We used nationwide healthcare registries to identify all Danish patients diagnosed with chronic pancreatitis and computed crude and standardised incidence rates and prevalence estimates in 1994-2018. Incidence and prevalence were evaluated in relation to patients age and gender, aetiology (alcoholic vs. non-alcoholic) and smoking and alcohol consumption in the general Danish population. RESULTS: The mean incidence rate of chronic pancreatitis during the study period was 12.6 per 100,000 person years for the total population, for women it was 8.6 per 100,000 person years and for men it was 16.7 per 100,000 person years. The standardised incidence rate was stable from 1994 to 2018, remaining at 12.5 per 100,000 person years in the last observation period (2014-2018). The point prevalence of chronic pancreatitis in 2016 was 153.9 per 100,000 persons. A gradual increase in standardised prevalence estimates was observed during the study period from 126.6 in 1996 to 153.9 in 2016. The mean age at chronic pancreatitis diagnosis increased from 52.1 to 60.0 years during the study period. CONCLUSION: The prevalence of chronic pancreatitis is increasing in the Danish population despite a stable incidence level. Improved management strategies and changes in the underlying patient population may explain these observations.

Outdoor light at night and breast cancer incidence in the Danish Nurse Cohort.

BACKGROUND: Knowledge of the role of melatonin, xenograft experiments, and epidemiological studies suggests that exposure to light at night (LAN) may disturb circadian rhythms, possibly increasing the risk of developing breast cancer. OBJECTIVES: We examined the association between residential outdoor LAN and the incidence of breast cancer: overall and subtypes classified by estrogen (ER) and progesterone (PR) receptor status. METHODS: We used data on 16,941 nurses from the Danish Nurse Cohort who were followed-up from the cohort baseline in 1993 or 1999 through 2012 in the Danish Cancer Registry for breast cancer incidence and the Danish Breast Cancer Cooperative Group for breast cancer ER and PR status. LAN exposure data were obtained from the U.S. Defense Meteorological Satellite Program (DMSP) available for 1996, 1999, 2000, 2003, 2004, 2006, and 2010 in nW/cm2/sr unit, and assigned to the study participants' residence addresses during the follow-up. Time-varying Cox regression models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between LAN and breast cancer, adjusting for individual characteristics, road traffic noise, and air pollution. RESULTS: Of 16,941 nurses, 745 developed breast cancer in total during 320,289 person-years of follow-up. We found no association between exposure to LAN and overall breast cancer. In the fully adjusted models, HRs for the highest (65.8-446.4 nW/cm2/sr) and medium (22.0-65.7 nW/cm2/sr) LAN tertiles were 0.97 (95% CI: 0.77, 1.23) and 1.09 (95% CI: 0.90, 1.31), respectively, compared to the lowest tertile of LAN exposure (0-21.9 nW/cm2/sr). We found a suggestive association between LAN and ER-breast cancer. CONCLUSION: This large cohort study of Danish female nurses suggests weak evidence of the association between LAN and breast cancer incidence.

The importance of early life family factors in the association between cardiovascular risk factors and early cardiovascular mortality.

OBJECTIVE: To explore the importance of early life factors shared by siblings, such as parental socioeconomic position, parental practices, housing and neighbourhood, for the association between cardiovascular disease (CVD) risk factors and mortality from CVD, ischaemic heart disease (IHD) and cerebrovascular disease. METHODS: Norwegian health surveys (1974-2003) were linked with data from the Norwegian Family Based Life Course Study and the Cause of Death Registry. Participants with at least one full sibling among survey participants (n=2 71 643) were included. Data on CVD risk factors, body mass index (BMI), height, systolic blood pressure (SBP) and total cholesterol (TC) were stratified into 'low', 'medium' and 'high' risk, and smoking to 'daily smoking' and 'not daily smoking'. RESULTS: Mean age of participants was 41 years, mean follow-up time was 19 years and during follow-up 2512 died from CVD. For each category of increased risk factor level, the per step HR of CVD mortality was increased by 1.91 (95% CI 1.78 to 2.05) for SBP, 1.67 (1.58 to 1.76) for TC, 1.44 (1.36 to 1.53) for BMI, 1.26 (1.18 to 1.35) for height and 2.89 (2.66 to 3.14) for smoking. In analyses where each sibship (groups of full siblings) had a group-specific baseline hazard, these associations were attenuated to 1.74, 1.51, 1.29, 1.18 and 2.63, respectively. The associations between risk factors and IHD mortality followed the same pattern. CONCLUSION: Early life family factors explained a small part of the association between risk factors and mortality from CVD and IHD in a relatively young sample.

Offspring sex and parental health and mortality.

Increased mortality has been observed in mothers and fathers with male offspring but little is known regarding specific diseases. In a register linkage we linked women born 1925-1954 having survived to age 50 (n = 661,031) to offspring and fathers (n = 691,124). Three approaches were used: 1) number of total boy and girl offspring, 2) sex of the first and second offspring and 3) proportion of boys to total number of offspring. A sub-cohort (n = 50,736 mothers, n = 44,794 fathers) from survey data was analysed for risk factors. Mothers had increased risk of total and cardiovascular mortality that was consistent across approaches: cardiovascular mortality of 1.07 (95% CI: 1.03-1.11) per boy (approach 2), 1.04 (1.01-1.07) if the first offspring was a boy, and 1.06 (1.01-1.10) if the first two offspring were boys (approach 3). We found that sex of offspring was not associated with total or cardiovascular mortality in fathers. For other diseases or risk factors no robust associations were seen in mothers or fathers. Increased cardiovascular risk in mothers having male offspring suggests a maternal disease specific mechanism. The lack of consistent associations on measured risk factors could suggest other biological pathways than those studied play a role in generating this additional cardiovascular risk.

Family of origin and educational inequalities in mortality: Results from 1.7 million Swedish siblings.

Circumstances in the family of origin have short- and long-term consequences for people's health. Family background also influences educational achievements - achievements that are clearly linked to various health outcomes. Utilizing population register data, we compared Swedish siblings with different levels of education (1,732,119 individuals within 662,095 sibships) born between 1934 and 1959 and followed their death records until the end of 2012 (167,932 deaths). The educational gradient in all-cause mortality was lower within sibships than in the population as a whole, an attenuation that was strongest at younger ages (< 50 years of age) and for those with a working class or farmer background. There was substantial variation across different causes of death with clear reductions in educational inequalities in, e.g., lung cancer and diabetes, when introducing shared family factors, which may indicate that part of the association can be ascribed to circumstances that siblings have in common. In contrast, educational inequalities in suicide and, for women, other mental disorders increased when adjusting for factors shared by siblings. The vast variation in the role of childhood conditions for the education-mortality association may help us to further understand the interplay between family background, education, and mortality. The increase in the education gradient in suicide when siblings are compared may point towards individually oriented explanations ('non-shared environment'), perhaps particularly in mental disorders, while shared family factors primarily seem to play a more important role in diseases in which health behaviors are most significant.

Education and adult cause-specific mortality--examining the impact of family factors shared by 871 367 Norwegian siblings.

OBJECTIVE: To estimate the impact family factors shared by siblings has on the association between length of education and cause-specific mortality in adulthood. METHODS: The study population (n = 871 367) was all Norwegians born 1940-59 having one or more sibling within the cohort and alive in 1990. Length of education was obtained in 1990. Follow-up of deaths was from 1991 to 2008 when participants were aged 32-68 years. RESULTS: Sixty-five per cent of participants had one or more siblings who had completed a different number of years of formal education. A one-category difference in education was associated with a 30% increase in the hazard rate of death by all causes among men in the cohort analysis and 23% in within siblings analysis, and in women, increases were 22% and 14%, respectively. For cardiovascular disease, increases were 36% and 25% in men and 51% and 36% in women. For lung cancer, they were 48% and 29% in men and 53% and 22% in women. External causes and alcohol-related causes in men were generally similar in both analyses. CONCLUSIONS: This study suggests that at least some of the educational inequalities in all-cause, cardiovascular disease and lung cancer, external and alcohol-related mortality are explained by factors shared by siblings.

Does shared family background influence the impact of educational differences on early mortality?

The mechanisms behind social differences in mortality rates have been debated. The authors examined the extent to which shared family background and health in early life could explain the association between educational status and all-cause mortality rates using a sibling design. The study was register-based and included all individuals born in Denmark between 1950 and 1979 who had at least 1 full sibling born in the same time period (n = 1,381,436). All individuals were followed from 28 years of age until death, emigration, or December 2009. The authors used Cox regression analyses to estimate hazard ratios for mortality according to educational level. Conventional cohort and intersibling analyses were carried out and conducted separately for deaths occurring before and after the age of 45 years, respectively. The cohort analyses showed an inverse association between educational status and all-cause mortality that was strongest for males, increased with younger birth cohorts, and tended to be strongest in the analyses of death before 45 years of age. The associations were attenuated slightly in the intersibling analyses and after adjustment for serious health conditions in early life. Hence, health selection and confounding by factors shared by siblings explained only a minor part of the association between educational level and all-cause mortality.

Cognitive ability in early adulthood as a predictor of habitual drug use during later military service and civilian life: the Vietnam Experience Study.

BACKGROUND: Recent reports have linked cognitive ability (IQ) with alcohol dependency, but the relationship with illegal drug use is not well understood. METHODS: Participants were 14,362 male US Vietnam veterans with IQ test results at entry into military service in 1965-1971 (mean age 22.58) who participated in a telephone interview in 1985-1986. A structured diagnostic telephone interview was used to ascertain habitual drug use during military service (for once a week, ≥ 3 months) and in civilian life (in the past 12 months, ≥ once a week), combat exposure, and post-traumatic stress disorder according to established Diagnostic and Statistical Manual of Mental disorders criteria (version III). RESULTS: In unadjusted analysis, men with high IQ scores were less likely to be habitual users of cannabis (OR=0.89, 95% CI=0.86, 0.93), cocaine (OR=0.69, 95% CI=0.61, 0.78), heroin (OR=0.80, 95% CI=0.73, 0.88), amphetamines (OR=0.90, 95% CI=0.83, 0.98), barbiturates (OR=0.79, 95% CI=0.72, 0.86) and LSD (OR=0.91, 95% CI=0.82, 0.99) during military service and civilian life. These associations were markedly attenuated after adjustment for socioeconomic status in early and later civilian life. CONCLUSION: In this cohort, socioeconomic position might lie on the pathway linking earlier IQ and later habitual drug use but might also act as a surrogate for IQ. This suggests interventions to prevent drug use could attempt to improve early life IQ and opportunities for employment.

Low cognitive ability in early adulthood is associated with reduced lung function in middle age: the Vietnam experience study.

OBJECTIVE: Reduced lung function has been linked to poorer cognitive ability later in life. In the present study, the authors examined the converse: whether there was a prospective association between cognitive ability in early adulthood and lung function in middle age. METHODS: Participants were 4256 male Vietnam-era US veterans. Cognitive ability was assessed by the Army General Technical Test on enlistment when participants were, on average, 20 years old (range: 17-34). Data on ethnicity and place of service were extracted from army files. Smoking behaviour, alcohol consumption, basic socio-demographics and whether participants had a physician-diagnosed chronic disease were determined by telephonic interview in middle age in 1985. Forced expiratory volume in one second (FEV(1)) was measured by spirometry at a 3-day medical examination in 1986. Height and weight were also measured. RESULTS: In linear regression models, poor cognitive ability in early adulthood was associated with reduced lung function in middle age, first adjusting for age and height, ß=0.17, p<0.001, then additionally adjusting for circumstantial, socio-demographic, lifestyle and health factors, ß=0.12, p=0.001. The same results were obtained when the analysis was confined to non-smokers. CONCLUSION: Not only is lung function related to subsequent cognitive ability, but poor cognitive ability earlier in life is also associated with reduced lung function in middle age.

Cognitive ability in early adulthood is associated with systemic inflammation in middle age: the Vietnam experience study.

We examined the prospective association between cognitive ability in early adulthood and erythrocyte sedimentation rate, a marker of inflammation, in middle age. Participants were 4256 male Vietnam era US veterans. Data on cognitive ability, assessed by the Army General Technical Test, ethnicity, and place of service were extracted from enlistment files. Smoking behaviour, alcohol consumption, basic socio-demographics, and whether participants suffered from a physician diagnosed chronic disease were determined by telephone interview in middle-age in 1985. Erythrocyte sedimentation rate, cholesterol, blood pressure, height, and weight were measured at a 3-day medical examination in 1986. In linear regression models that adjusted for age and then additionally for circumstantial, socio-demographic, lifestyle, and health factors, poor cognitive ability in early adulthood was associated with greater erythrocyte sedimentation rate in middle age, ß=-.09. Thus, it would appear that not only does systemic inflammation influence cognition, but also that poor cognitive ability earlier in life is associated with inflammation in middle-age.

Does IQ explain socio-economic differentials in total and cardiovascular disease mortality? Comparison with the explanatory power of traditional cardiovascular disease risk factors in the Vietnam Experience Study.

AIMS: The aim of this study was to examine the explanatory power of intelligence (IQ) compared with traditional cardiovascular disease (CVD) risk factors in the relationship of socio-economic disadvantage with total and CVD mortality, that is the extent to which IQ may account for the variance in this well-documented association. METHODS AND RESULTS: Cohort study of 4289 US male former military personnel with data on four widely used markers of socio-economic position (early adulthood and current income, occupational prestige, and education), IQ test scores (early adulthood and middle-age), a range of nine established CVD risk factors (systolic and diastolic blood pressure, total blood cholesterol, HDL cholesterol, body mass index, smoking, blood glucose, resting heart rate, and forced expiratory volume in 1 s), and later mortality. We used the relative index of inequality (RII) to quantify the relation between each index of socio-economic position and mortality. Fifteen years of mortality surveillance gave rise to 237 deaths (62 from CVD and 175 from 'other' causes). In age-adjusted analyses, as expected, each of the four indices of socio-economic position was inversely associated with total, CVD, and 'other' causes of mortality, such that elevated rates were evident in the most socio-economically disadvantaged men. When IQ in middle-age was introduced to the age-adjusted model, there was marked attenuation in the RII across the socio-economic predictors for total mortality (average 50% attenuation in RII), CVD (55%), and 'other' causes of death (49%). When the nine traditional risk factors were added to the age-adjusted model, the comparable reduction in RII was less marked than that seen after IQ adjustment: all-causes (40%), CVD (40%), and 'other' mortality (43%). Adding IQ to the latter model resulted in marked, additional explanatory power for all outcomes in comparison to the age-adjusted analyses: all-causes (63%), CVD (63%), and 'other' mortality (65%). When we utilized IQ in early adulthood rather than middle-age as an explanatory variable, the attenuating effect on the socio-economic gradient was less pronounced although the same pattern was still present. CONCLUSION: In the present analyses of socio-economic gradients in total and CVD mortality, IQ appeared to offer greater explanatory power than that apparent for traditional CVD risk factors.

The social gradient in birthweight at term: quantification of the mediating role of maternal smoking and body mass index.

BACKGROUND: Maternal education is associated with the birthweight of offspring. We sought to quantify the role of maternal body mass index (BMI) and smoking as intermediary variables between maternal education and birthweight at term. METHODS: We examined the association between maternal education, BMI, smoking and offspring's birthweight among women who delivered at term in the Danish National Birth Cohort (n = 75,085). RESULTS: Compared with mothers with more than 12 years of education, women with 10-12 years of education had babies that were 12 (4-19) g lighter. Mothers with 9 years of education had babies that were 51 (95% CI; 39-62) g lighter. BMI and smoking affected the association between maternal education and birthweight, albeit in different directions. If all mothers had the BMI of the highest educated mothers, the deficits would be larger: -20 (-22 to -19) and -74 (-80 to -68) g, respectively. If all mothers smoked like the highest educated mothers, mothers with a shorter education would have the heaviest babies: the difference would be 9 (2-16) and 23 (11-36) g, respectively. In combination, smoking and BMI all but explained the educational gradient in birthweight at term. CONCLUSION: Maternal smoking and BMI are important intermediates of the educational gradient in birthweight at term. As the prevalence of smoking is dropping and the prevalence of obesity is increasing the educational gradient will likely reverse, but it seems unlikely that this will translate into a health advantage for the children of the least educated mothers.