[Show abstract][Hide abstract] ABSTRACT: Previous studies have reported an association between circadian disturbances and age-related cognitive impairment. The aim was to study the 24-hour profiles of melatonin and cortisol in relation to cognitive function in middle-aged male subjects. Fifty healthy middle-aged males born in 1953 were recruited from a population-based cohort based on previous cognitive assessments in young adulthood and late midlife. The sample included 24 cognitively high-functioning and 26 cognitively impaired participants. Saliva samples were collected every 4 hours over a 24-hour period and analyzed for cortisol and melatonin levels by immunoassay. All participants exhibited clear circadian rhythms of salivary melatonin and cortisol. Salivary melatonin concentrations had a nocturnal peak at approximately 4 am. The median nocturnal melatonin response at 4 am was significantly lower in the cognitively impaired group than in the high-functioning group (-4.6 pg/mL, 95% CI: -7.84, -1.36, P=0.006). The 24-hour mean melatonin concentration (high-functioning group: 4.80±0.70 pg/mL, vs cognitively impaired group: 4.81±0.76 pg/mL; P>0.05) (or the area under the curve, AUC) was not significantly different between the two groups. Cortisol levels were low during the night, and peaked at approximately 8 am. Median cortisol concentrations were similar at all times, as were the 24-hour mean cortisol concentrations and AUC. To the best of our knowledge, ours is the first study to assess circadian measures (ie, melatonin and cortisol) in healthy middle-aged men with different cognitive trajectories in midlife. We found evidence of altered circadian rhythms with a reduced nocturnal melatonin response at 4 am in men with cognitive impairment. The 24-hour concentration and AUC of melatonin and cortisol were similar in the cognitively high-functioning group and in the cognitively impaired.
Preview · Article · Feb 2016 · Nature and Science of Sleep
[Show abstract][Hide abstract] ABSTRACT: Introduction In the last decade a range of recommendations to increase awareness of depression in acute coronary syndrome patients have been published. To test the impact of those recommendations we examine and compare recent time trends in depression among acute coronary syndrome patients and a reference population. Methods 87 218 patients registered with acute coronary syndrome from 2001-2009 in Denmark and a match reference population were followed through hospital registries and medication prescriptions for early (≤30 days), intermediate (31 days to 6 months) and later (6 months to 2 years) depression in the acute coronary syndrome population and overall depression in the reference population. Cox regression models were used to compare hazard ratios (HRs) for depression over calendar years. Results During the study period, 11.0% and 6.2% were diagnosed with depression in the acute coronary syndrome population and in the reference population, respectively. For the acute coronary syndrome population, the adjusted HRs increased for early (HR (95% CI) 1.04 (1.01-1.06)) and intermediate depression (HR (95% CI) 1.01 (1.00-1.03)), whereas the adjusted HRs did not change for later depression (HR (95% CI) 0.99 (0.98-1.00)). For the reference population the adjusted HRs for depression increased through the study period (HR (95% CI) 1.01 (1.01-1.03)). Conclusion Increase in diagnoses of depressions within 6 months of acute coronary syndrome may be explained by increased focus on depression in this patient group in combination with increased awareness of depression in the general population.
No preview · Article · Jan 2016 · Nordic journal of psychiatry
[Show abstract][Hide abstract] ABSTRACT: We examined incidence of depression after acute coronary syndrome (ACS) and whether the timing of depression onset influenced survival. All first-time hospitalizations for ACS (n = 97,793) identified in the Danish Patient Registry during 2001-2009 and a reference population were followed for depression and mortality via linkage to patient, prescription, and cause-of-death registries until the end of 2012. Incidence of depression (as defined by hospital discharge or antidepressant medication use) and the relationship between depression and mortality were examined using time-to-event models. In total, 19,520 (20.0%) ACS patients experienced depression within 2 years after the event. The adjusted rate ratio for depression in ACS patients compared with the reference population was 1.28 (95% confidence interval (CI): 1.25, 1.30). During 12 years of follow-up, 39,523 (40.4%) ACS patients and 27,931 (28.6%) of the reference population died. ACS patients with recurrent (hazard ratio (HR) = 1.62, 95% CI: 1.57, 1.67) or new-onset (HR = 1.66, 95% CI: 1.60, 1.72) depression had higher mortality rates than patients with no depression. In the reference population, the corresponding relative estimates for recurrent (HR =1.98, 95% CI: 1.92, 2.05) and new-onset (HR = 2.42, 95% CI: 2.31, 2.54) depression were stronger. Depression is common in ACS patients and is associated with increased mortality independently of time of onset, but here the excess mortality associated with depression seemed to be lower in ACS patients than in the reference population.
No preview · Article · Jan 2016 · American journal of epidemiology
[Show abstract][Hide abstract] ABSTRACT: Objective:
The aim was to estimate the effects of ponderal index at birth and body mass index (BMI) in early adulthood on C-reactive protein (CRP) and interleukin-6 (IL-6) and to quantify the effects through subsequent measures of body size. In a subanalysis, the contributions of maternal BMI to the inflammatory status of offspring were investigated.
The study was based on 2,986 Danish males from the Copenhagen Aging and Midlife Biobank. Path analysis was employed to estimate direct and indirect effects.
A 10% higher maternal BMI was associated with 7% higher CRP and 3% higher IL-6 among offspring. A 10% higher ponderal index at birth was associated with 4% lower CRP in late midlife; this effect was only partially mediated by later growth. A 10% higher BMI in early adulthood was associated with 8% higher CRP and 4% higher IL-6 in late midlife. The findings suggest that weight gain in adulthood is associated with low-grade inflammation in late midlife.
Ponderal index at birth is associated with CRP in later life independently of adult BMI. The findings additionally suggest that preventing weight gain in early adulthood would be beneficial for inflammatory status in later life.
[Show abstract][Hide abstract] ABSTRACT: Background:
Patients with low socioeconomic position have higher rates of mortality after diagnosis of acute coronary syndrome (ACS), but little is known about the mechanisms behind this social inequality. The aim of the present study was to examine whether any educational inequality in survival after ACS was influenced by comorbid conditions including depression.
From 2001 to 2009 all first-time ACS patients were identified in the Danish National Patient Registry. This cohort of 83 062 ACS patients and a matched reference population were followed for incident depression and mortality until December 2012 by linkage to person, patients and prescription registries. Educational status was defined at study entry and the impact of potential confounders and mediators (age, gender, cohabitation status, somatic comorbidity and depression) on the relation between education and mortality were identified by drawing a directed acyclic graph and analysed using multiple Cox regression analyses.
During follow-up, 29 583(35.6%) of ACS patients and 19 105(22.9%) of the reference population died. Cox regression analyses showed an increased mortality in the lowest educated compared to those with high education in both ACS patients and the reference population. Adjustment for previous and incident depression or other covariables only attenuated the relations slightly. This pattern of associations was seen for mortality after 30 days, 1 year and during total follow-up.
In this study the relative excess mortality rate in lower educated ACS patients was comparable with the excess risk associated with low education in the background population. This educational inequality in survival remained after adjustment for somatic comorbidity and depression.
[Show abstract][Hide abstract] ABSTRACT: Mitochondrial bioenergetics, mitochondrial reactive oxygen species (ROS) and cellular levels of nucleotides have been hypothesized as early indicators of Alzheimer's disease (AD). Utilizing relative decline of cognitive ability as a predictor of AD risk, we evaluated the correlation between change of cognitive ability and mitochondrial bioenergetics, ROS and cellular levels of deoxyribonucleotides. Change of cognitive abilities, scored at ages of approximately 20 and 57 was determined for a cohort of 1985 male participants. Mitochondrial bioenergetics, mitochondrial ROS and whole-cell levels of deoxyribonucleotide triphosphates were measured in peripheral blood mononuclear cells (PBMCs) from a total of 103 selected participants displaying the most pronounced relative cognitive decline and relative cognitive improvement. We show that relative cognitive decline is associated with higher PBMC content of deoxythymidine-triphosphate (dTTP) (20%), but not mitochondrial bioenergetics parameters measured in this study or mitochondrial ROS. Levels of dTTP in PBMCs are indicators of relative cognitive change suggesting a role of deoxyribonucleotides in the etiology of AD.
[Show abstract][Hide abstract] ABSTRACT: Background
An association between education and preterm delivery has been observed in populations across Europe, but differences in methodology limit comparability. We performed a direct cross-cohort comparison of educational disparities in preterm delivery based on individual-level birth cohort data.Methods
The study included data from 12 European cohorts from Denmark, England, France, Lithuania, the Netherlands, Norway, Italy, Portugal, and Spain. The cohorts included between 2434 and 99 655 pregnancies. The association between maternal education and preterm delivery (22–36 completed weeks of gestation) was reported as risk ratios, risk differences, and slope indexes of inequality with 95% confidence intervals (CIs).ResultsSingleton preterm live delivery proportion varied between 3.7% and 7.5%. There were large variations between the cohorts in the distribution of education and maternal characteristics. Nevertheless, there were similar educational differences in risk of preterm delivery in 8 of the 12 cohorts with slope index of inequality varying between 2.2 [95% CI 1.1, 3.3] and 4.0 [95% CI 1.4, 6.6] excess preterm deliveries per 100 singleton deliveries among the educationally most disadvantaged, and risk ratio between the lowest and highest education category varying from 1.4 [95% CI 1.1, 1.8] to 1.9 [95% CI 1.2, 3.1]. No associations were found in the last four cohorts.Conclusions
Educational disparities in preterm delivery were found all over Europe. Despite differences in the distributions of education and preterm delivery, the results were remarkably similar across the cohorts. For those few cohorts that did not follow the pattern, study and country characteristics did not explain the differences.
[Show abstract][Hide abstract] ABSTRACT: To estimate the association between educational status and alcohol-related somatic and non-somatic morbidity and mortality among full siblings in comparison with non-related individuals.
Approximately 1.4 million full siblings born in Denmark between 1950 and 1979 were followed from age 28 until age 58 or censoring due to alcohol-related hospitalization and mortality.
Cox-regression analyses were used to estimate associations of educational status with alcohol-related outcomes. Results from cohort analyses based on non-related individuals and inter-sibling analyses were compared.
A lower educational status was associated with a higher rate of alcohol-related outcomes, especially among the youngest (28-37 years of age) and individuals born 1970-1979. Compared with the cohort analyses, the associations attenuated slightly in the inter-sibling analysis. For example in the cohort analysis, females with a basic school education born 1970-1979 had an increased rate of alcohol-related non-somatic morbidity and mortality (Hazard rate ratio (HR) =4.05, CI 95% 3.27-5.02) compared to those with a vocational education. In the inter-sibling analysis, the HR attenuated (HR = 2.66, CI 95% 1.95-3.63). For alcohol-related somatic outcomes the corresponding figures were HR = 3.47 (CI 95% 2.63-4.58) and HR = 3.36 (CI 95% 2.10-5.38), respectively. In general, the associations were stronger among females than males (aged 28-37) in the analyses on alcohol-related non-somatic outcomes. Health conditions earlier in life explained only a minor part of the associations.
The association between educational status and alcohol-related somatic and non-somatic morbidity and mortality is only to a small degree driven by familial factors. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Background An educational gradient in preterm birth has been observed in many countries. The distribution of education and other characteristics of women giving birth are the end result of complex processes that play out over the life course. If these processes play out differently in different contexts, cross-cohort comparisons may be helpful in understanding the educational gradient in preterm birth. We performed a cross-cohort comparison of educational disparities in preterm birth based on European birth cohort data.
Methods The study included individual-level data from 12 European cohorts from Denmark, England, France, Lithuania, the Netherlands, Norway, Italy, Portugal and Spain. The studies covered the period 1990 to 2012 and included between 2434 and 99,655 pregnancies each. The association between maternal education and preterm birth for singleton live births was examined separately in each cohort by linear and logistic regression and reported as risk ratios, risk differences and slope indexes of inequality.
Results The percentage of singleton preterm live births varied between 3.7% and 7.5%. There were large variations between the cohorts in the distribution of education and other maternal characteristics. In spite of this, there were similar educational differences in risk of preterm birth in 8 of the 12 cohorts. In these cohorts, the slope index of inequality varied between 2.2 and 3.2 per 100 singleton live births, and relative risk between the lowest and highest education group varied from 1.4 to 1.9. In the remaining 4 cohorts from England, France, Italy and Portugal, one showed a weaker gradient (Slope Index of Inequality =1.5 (-1.0, 3.9)), two showed no educational differences (SII=-0.3 (-2.0, 1.5) and SII=0.9 (-1.3, 3.1)), and the gradient was reversed in the last cohort (SII=-1.2 (-4.6, 2.3)).
Conclusion Educational disparities in risk of preterm birth were found in birth cohorts from all over Europe. Despite differences in the distribution of education and level of preterm birth, the results were remarkably similar across the cohorts. For those few cohorts that did not follow the pattern, study and country characteristics were unable to explain the differences.
No preview · Article · Sep 2014 · Journal of Epidemiology & Community Health