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1.  IQ in childhood and vegetarianism in adulthood: 1970 British cohort study 
BMJ : British Medical Journal  2006;334(7587):245.
Objective To examine the relation between IQ in childhood and vegetarianism in adulthood.
Design Prospective cohort study in which IQ was assessed by tests of mental ability at age 10 years and vegetarianism by self-report at age 30 years.
Setting Great Britain.
Participants 8170 men and women aged 30 years participating in the 1970 British cohort study, a national birth cohort.
Main outcome measures Self-reported vegetarianism and type of diet followed.
Results 366 (4.5%) participants said they were vegetarian, although 123 (33.6%) admitted eating fish or chicken. Vegetarians were more likely to be female, to be of higher social class (both in childhood and currently), and to have attained higher academic or vocational qualifications, although these socioeconomic advantages were not reflected in their income. Higher IQ at age 10 years was associated with an increased likelihood of being vegetarian at age 30 (odds ratio for one standard deviation increase in childhood IQ score 1.38, 95% confidence interval 1.24 to 1.53). IQ remained a statistically significant predictor of being vegetarian as an adult after adjustment for social class (both in childhood and currently), academic or vocational qualifications, and sex (1.20, 1.06 to 1.36). Exclusion of those who said they were vegetarian but ate fish or chicken had little effect on the strength of this association.
Conclusion Higher scores for IQ in childhood are associated with an increased likelihood of being a vegetarian as an adult.
doi:10.1136/bmj.39030.675069.55
PMCID: PMC1790759  PMID: 17175567
2.  Modifiable cardiovascular disease risk factors as predictors of dementia death: pooling of ten general population-based cohort studies 
Background
With drug treatment for dementia being of limited effectiveness, the role of primary prevention, in particular the predictive value of modifiable cardiovascular disease risk factors, may warrant exploration. The evidence base is, however, characterised by discordant findings and is modest in size. Accordingly, we examined the association of modifiable cardiovascular disease risk factors with dementia death.
Design and methods
We pooled raw data from 10 UK general population-based prospective cohort studies within the context of an individual participant meta-analysis.
Results
A total of 103,764 men and women were followed up for a mean of 8 years giving rise to 443 dementia-related deaths and 2612 cardiovascular disease deaths. Cardiovascular disease mortality was, as anticipated, associated with the full range of risk factors under study, including raised blood pressure, smoking, diabetes, physical inactivity. By contrast, dementia death was related to very few of the cardiovascular disease risk factors: of those classified as modifiable, only smoking was associated with a raised risk and higher levels of non-HDL with a lower risk.
Conclusions
In the present individual participant meta-analysis, there was limited evidence that cardiovascular disease risk factors were related to dementia death.
doi:10.1186/1477-5751-13-8
PMCID: PMC4036694  PMID: 24886432
3.  Metabolically healthy obesity: What is the role of sedentary behaviour?☆ 
Preventive Medicine  2014;62(100):35-37.
Objective
The role of sedentary behaviour in metabolically healthy obesity is unknown. We examined cross-sectional differences in television viewing time across metabolic and obesity phenotypes, hypothesizing that healthy obese individuals spend less time viewing television than their unhealthy counterparts.
Methods
A nationally representative sample of 4931 older adults in England (mean age 65.1; SD = 8.9 years) was drawn from the 2008/9 wave of the English Longitudinal Study of Ageing. Average weekly television viewing time was derived from two questions about weekday and weekend viewing. Obesity was defined as body mass index ≥ 30 kg/m2, and metabolically healthy as having < 2 metabolic abnormalities (low HDL-cholesterol, high triglycerides, high blood pressure, hyperglycaemia, high inflammation).
Results
After adjusting for covariates including chronic illness, functional limitations and physical activity, mean weekly viewing times were 4.7 (95% confidence interval 2.9, 6.5), 5.8 (2.5, 9.0) and 7.8 (5.7, 9.8) h higher in unhealthy non-obese, healthy obese, and unhealthy obese groups respectively, compared to the healthy non-obese group (p for heterogeneity < 0.001).
Conclusions
A common type of leisure-time sedentary behaviour varies across metabolic and obesity phenotypes. However, healthy obesity is not explained through differences in leisure-time sedentary behaviour.
doi:10.1016/j.ypmed.2014.01.028
PMCID: PMC3995089  PMID: 24513171
Sedentary behaviour; Television viewing; Obesity; Metabolic health
4.  Reaction Time and Incident Cancer: 25 Years of Follow-Up of Study Members in the UK Health and Lifestyle Survey 
PLoS ONE  2014;9(4):e95054.
Objectives
To investigate the association of reaction time with cancer incidence.
Methods
6900 individuals aged 18 to 94 years who participated in the UK Health and Lifestyle Survey in 1984/1985 and were followed for a cancer registration for 25 years.
Results
Disease surveillance gave rise to 1015 cancer events from all sites. In general, there was essentially no clear pattern of association for either simple or choice reaction time with cancer of all sites combined, nor specific malignancies. However, selected associations were found for lung cancer, colorectal cancer and skin cancer.
Conclusions
In the present study, reaction time and its components were not generally related to cancer risk.
doi:10.1371/journal.pone.0095054
PMCID: PMC3991647  PMID: 24747801
6.  Socioeconomic status as a risk factor for dementia death: individual participant meta-analysis of 86 508 men and women from the UK* 
Background
Life-course socioeconomic factors may have a role in dementia aetiology but there is a current paucity of studies. Meta-analyses of individual participant data would considerably strengthen this evidence base.
Aims
To examine the association between socioeconomic status in early life and adulthood with later dementia death.
Method
Individual participant meta-analysis of 11 prospective cohort studies (1994-2004, n = 86 508).
Results
Leaving full-time education at an earlier age was associated with an increased risk of dementia death in women (fully adjusted hazard ratio (HR) for age ⩽14 v. age ⩾16: HR = 1.76, 95% CI 1.23-2.53) but not men. Occupational social class was not statistically significantly associated with dementia death in men or women.
Conclusions
Lower educational attainment in women was associated with an increased risk of dementia-related death independently of common risk behaviours and comorbidities.
doi:10.1192/bjp.bp.112.119479
PMCID: PMC3696876  PMID: 23818534
8.  Study protocol for examining job strain as a risk factor for severe unipolar depression in an individual participant meta-analysis of 14 European cohorts 
F1000Research  2014;2:233.
Background: Previous studies have shown that gainfully employed individuals with high work demands and low control at work (denoted “job strain”) are at increased risk of common mental disorders, including depression. Most existing studies have, however, measured depression using self-rated symptom scales that do not necessarily correspond to clinically diagnosed depression. In addition, a meta-analysis from 2008 indicated publication bias in the field.
 
Methods: This study protocol describes the planned design and analyses of an individual participant data meta-analysis, to examine whether job strain is associated with an increased risk of clinically diagnosed unipolar depression based on hospital treatment registers.  The study will be based on data from approximately 120,000 individuals who participated in 14 studies on work environment and health in 4 European countries. The self-reported working conditions data will be merged with national registers on psychiatric hospital treatment, primarily hospital admissions. Study-specific risk estimates for the association between job strain and depression will be calculated using Cox regressions. The study-specific risk estimates will be pooled using random effects meta-analysis.
 
Discussion: The planned analyses will help clarify whether job strain is associated with an increased risk of clinically diagnosed unipolar depression. As the analysis is based on pre-planned study protocols and an individual participant data meta-analysis, the pooled risk estimates will not be influenced by selective reporting and publication bias. However, the results of the planned study may only pertain to severe cases of unipolar depression, because of the outcome measure applied.
doi:10.12688/f1000research.2-233.v2
PMCID: PMC3938244  PMID: 24627793
9.  Influence of maternal and paternal IQ on offspring health and health behaviours: evidence for some trans-generational effects using the 1958 British birth cohort study 
Purpose
Individuals scoring poorly on tests of intelligence (IQ) have been reported as having increased risk of morbidity, premature mortality, and risk factors such as obesity, high blood pressure, poor diet, alcohol and cigarette consumption. Very little is known about the impact of parental IQ on the health and health behaviours of their offspring.
Methods
We explored associations of maternal and paternal IQ scores with offspring television viewing, injuries, hospitalisations, long standing illness, height and BMI at ages 4 to 18 using data from the National Child Development Study (1958 birth cohort).
Results
Data were available for 1,446 mother-offspring and 822 father-offspring pairs. After adjusting for potential confounding/mediating factors, the children of higher IQ parents were less likely to watch TV (odds ratio (95% confidence interval) for watching 3+ vs. <3 hours per week associated with a standard deviation increase in maternal or paternal IQ: 0.75 (0.64, 0.88) or 0.78 (0.64, 0.95) respectively) and less likely to have one or more injuries requiring hospitalisation (0.77 (0.66, 0.90) or 0.72 (0.56, 0.91) respectively for maternal or paternal IQ).
Conclusions
Children whose parents have low IQ scores may have poorer selected health and health behaviours. Health education might usefully be targeted at these families.
doi:10.1016/j.eurpsy.2012.01.005
PMCID: PMC3696866  PMID: 22541368
Intelligence; Life course; Birth cohort; Trans-generational
10.  Common Genetic Variants Explain the Majority of the Correlation Between Height and Intelligence: The Generation Scotland Study 
Behavior Genetics  2014;44:91-96.
Greater height and higher intelligence test scores are predictors of better health outcomes. Here, we used molecular (single-nucleotide polymorphism) data to estimate the genetic correlation between height and general intelligence (g) in 6,815 unrelated subjects (median age 57, IQR 49–63) from the Generation Scotland: Scottish Family Health Study cohort. The phenotypic correlation between height and g was 0.16 (SE 0.01). The genetic correlation between height and g was 0.28 (SE 0.09) with a bivariate heritability estimate of 0.71. Understanding the molecular basis of the correlation between height and intelligence may help explain any shared role in determining health outcomes. This study identified a modest genetic correlation between height and intelligence with the majority of the phenotypic correlation being explained by shared genetic influences.
Electronic supplementary material
The online version of this article (doi:10.1007/s10519-014-9644-z) contains supplementary material, which is available to authorized users.
doi:10.1007/s10519-014-9644-z
PMCID: PMC3938855  PMID: 24554214
Height; Intelligence; Molecular genetics; Genetic correlation; Generation Scotland
11.  Extending Employment beyond the Pensionable Age: A Cohort Study of the Influence of Chronic Diseases, Health Risk Factors, and Working Conditions 
PLoS ONE  2014;9(2):e88695.
Background
In response to the economic consequences of ageing of the population, governments are seeking ways with which people might work into older age. We examined the association of working conditions and health with extended employment (defined as >6 months beyond the pensionable age) in a cohort of older, non-disabled employees who have reached old-age retirement.
Methods
A total of 4,677 Finnish employees who reached their old-age pensionable date between 2005 and 2011 (mean age 59.8 years in 2005, 73% women) had their survey responses before pensionable age linked to national health and pension registers, resulting in a prospective cohort study.
Results
In all, 832 participants (17.8%) extended their employment by more than 6 months beyond the pensionable date. After multivariable adjustment, the following factors were associated with extended employment: absence of diagnosed mental disorder (OR 1.25, 95% confidence interval = 1.01–1.54) and psychological distress (OR 1.68; 1.35–2.08) and of the work characteristics, high work time control (OR 2.31; 1.88–2.84). The projected probability of extended employment was 21.3% (19.5–23.1) among those free of psychiatric morbidity and with high work time control, while the corresponding probability was only 9.2% (7.4–11.4) among those with both psychiatric morbidity and poor work time control. The contribution of chronic somatic diseases was modest.
Conclusions
In the present study, good mental health in combination with the opportunity to control work time seem to be key factors in extended employment into older age. In addition, high work time control might promote work life participation irrespective of employees' somatic disease status.
doi:10.1371/journal.pone.0088695
PMCID: PMC3929527  PMID: 24586372
12.  Job Strain and the Risk of Inflammatory Bowel Diseases: Individual-Participant Meta-Analysis of 95 000 Men and Women 
PLoS ONE  2014;9(2):e88711.
Background and Aims
Many clinicians, patients and patient advocacy groups believe stress to have a causal role in inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis. However, this is not corroborated by clear epidemiological research evidence. We investigated the association between work-related stress and incident Crohn's disease and ulcerative colitis using individual-level data from 95 000 European adults.
Methods
We conducted individual-participant data meta-analyses in a set of pooled data from 11 prospective European studies. All studies are a part of the IPD-Work Consortium. Work-related psychosocial stress was operationalised as job strain (a combination of high demands and low control at work) and was self-reported at baseline. Crohn's disease and ulcerative colitis were ascertained from national hospitalisation and drug reimbursement registers. The associations between job strain and inflammatory bowel disease outcomes were modelled using Cox proportional hazards regression. The study-specific results were combined in random effects meta-analyses.
Results
Of the 95 379 participants who were free of inflammatory bowel disease at baseline, 111 men and women developed Crohn's disease and 414 developed ulcerative colitis during follow-up. Job strain at baseline was not associated with incident Crohn's disease (multivariable-adjusted random effects hazard ratio: 0.83, 95% confidence interval: 0.48, 1.43) or ulcerative colitis (hazard ratio: 1.06, 95% CI: 0.76, 1.48). There was negligible heterogeneity among the study-specific associations.
Conclusions
Our findings suggest that job strain, an indicator of work-related stress, is not a major risk factor for Crohn's disease or ulcerative colitis.
doi:10.1371/journal.pone.0088711
PMCID: PMC3928274  PMID: 24558416
13.  Reaction Time and Mortality from the Major Causes of Death: The NHANES-III Study 
PLoS ONE  2014;9(1):e82959.
Objective
Studies examining the relation of information processing speed, as measured by reaction time, with mortality are scarce. We explored these associations in a representative sample of the US population.
Methods
Participants were 5,134 adults (2,342 men) aged 20–59 years from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–94).
Results
Adjusted for age, sex, and ethnic minority status, a 1 SD slower reaction time was associated with a raised risk of mortality from all-causes (HR = 1.25, 95% CI 1.12, 1.39) and cardiovascular disease (CVD) (HR = 1.36, 95% CI 1.17, 1.58). Having 1 SD more variable reaction time was also associated with greater risk of all-cause (HR = 1.36, 95% CI 1.19, 1.55) and CVD (HR = 1.50, 95% CI 1.33, 1.70) mortality. No associations were observed for cancer mortality. The magnitude of the relationships was comparable in size to established risk factors in this dataset, such as smoking.
Interpretation
Alongside better-established risk factors, reaction time is associated with increased risk of premature death and cardiovascular disease. It is a candidate risk factor for all-cause and cause-specific mortality.
doi:10.1371/journal.pone.0082959
PMCID: PMC3906008  PMID: 24489645
14.  Physical activity and inflammatory markers over 10 years follow up in men and women from the Whitehall II cohort study 
Circulation  2012;126(8):928-933.
Background
Inflammatory processes are putative mechanisms underlying the cardio-protective effects of physical activity. An inverse association between physical activity and inflammation has been demonstrated but no long-term prospective data are available. We therefore examined the association between physical activity and inflammatory markers over a 10-year follow-up period.
Methods and Results
Participants were 4289 men and women (mean age 49.2 years) from the Whitehall II cohort study. Self-reported physical activity and inflammatory markers (serum high-sensitivity C-reactive protein [CRP] and interleukin-6 [IL-6]) were measured at baseline (1991) and follow-up (2002). Forty-nine percent of the participants adhered to standard physical activity recommendations for cardiovascular health (2.5 hours per week moderate to vigorous physical activity) across all assessments. Physically active participants at baseline had lower CRP and IL6 levels and this difference remained stable over time. In comparison to participants that rarely adhered to physical activity guidelines over the 10 years follow-up, the high adherence group displayed lower logeCRP (β=−0.07, 95% CI, −0.12, −0.02) and logeIL-6 (β=−0.07, 95% CI, −0.10, −0.03) at follow up after adjustment for a range of covariates. Compared to participants that remained stable, those that reported an increase in physical activity of at least 2.5 hours/wk displayed lower loge CRP (B coefficient =−0.05, 95% CI, −0.10, −0.001) and loge IL-6 (B coefficient =−0.06, 95% CI, −0.09, −0.03) at follow up.
Conclusions
Regular physical activity is associated with lower markers of inflammation over 10 years of follow-up and thus may be important in preventing the pro-inflammatory state seen with ageing.
doi:10.1161/CIRCULATIONAHA.112.103879
PMCID: PMC3890998  PMID: 22891048
Ageing; C-reactive protein; exercise; physical activity; inflammation
15.  A Questionnaire-Wide Association Study of Personality and Mortality: The Vietnam Experience Study 
Journal of psychosomatic research  2013;74(6):523-529.
Objective
We examined the association between the Minnesota Multiphasic Personality Inventory (MMPI) and all-cause mortality in 4462 middle-aged Vietnam-era veterans.
Methods
We split the study population into half samples. In each half, we used proportional hazards (Cox) regression to test the 550 MMPI items’ associations with mortality over 15 years. In all participants, we subjected significant (p < .01) items in both halves to principal-components analysis (PCA). We used Cox regression to test whether these components predicted mortality when controlling for other predictors (demographics, cognitive ability, health behaviors, mental/physical health).
Results
Eighty-nine items were associated with mortality in both half-samples. PCA revealed Neuroticism/Negative Affectivity, Somatic Complaints, Psychotic/Paranoia, and Antisocial components, and a higher-order component, Personal Disturbance. Individually, Neuroticism/Negative Affectivity (HR = 1.55, 95% CI = 1.39,1.72), Somatic Complaints (HR = 1.66; 95% CI = 1.52,1.80), Psychotic/Paranoid (HR = 1.44; 95% CI = 1.32,1.57), Antisocial (HR = 1.79; 95% CI = 1.59,2.01), and Personal Disturbance (HR = 1.74; 95% CI = 1.58,1.91) were associated with risk. Including covariates attenuated these associations (28.4 to 54.5%), though they were still significant. After entering Personal Disturbance into models with each component, Neuroticism/Negative Affectivity and Somatic Complaints were significant, although Neuroticism/Negative Affectivity’s were now protective (HR = 0.73, 95% CI = 0.58,0.92). When the four components were entered together with or without covariates, Somatic Complaints and Antisocial were significant risk factors.
Conclusions
Somatic Complaints and Personal Disturbance are associated with increased mortality risk. Other components’ effects varied as a function of variables in the model.
doi:10.1016/j.jpsychores.2013.02.010
PMCID: PMC3697823  PMID: 23731751
Minnesota Multiphasic Personality Inventory; Mortality; Negative Affect Personality; Vietnam Experience Study; Somatic Complaints
16.  IQ in childhood and atherosclerosis in middle-age: 40 Year follow-up of the Newcastle Thousand Families Cohort Study 
Atherosclerosis  2013;231(2):234-237.
Objective
Carotid intima-media thickness (IMT) is a known precursor to coronary heart disease (CHD) and other relevant health outcomes such as stroke and cognitive impairment. In addition, higher childhood intelligence has been associated with lower risk of coronary heart disease events in later life, although the mechanisms of effect are unclear. We therefore examined the association between childhood intelligence and atherosclerosis using carotid IMT as a marker of the atherosclerotic process.
Approach
Participants were 412 members of the Newcastle Thousand Families Study, a prospective cohort study of all 1142 births in the city of Newcastle in May and June 1947, who took an IQ test and English and arithmetic tests at age 11 years. Study members participated in a medical examination and lifestyle assessment at age 49–51 years during which IMT was measured using ultrasound techniques.
Results
Individuals with higher childhood IQ score had a lower mean IMT in middle-age. A standard deviation higher score in childhood overall IQ was associated with a 0.053 mm (95% CI −0.102, −0.004) lower IMT in men and a 0.039 mm (95% CI −0.080, −0.002) lower IMT in women. Similar levels of association were found for the English and arithmetic tests. After adjustment for a range of covariates including education, the size of effect was undiminished in men but increased in women.
Conclusions
In the present study, higher childhood IQ scores were associated with a lower degree of atherosclerosis by middle-age.
doi:10.1016/j.atherosclerosis.2013.09.018
PMCID: PMC3918147  PMID: 24267233
Childhood IQ; Atherosclerosis; Intima-media thickness; Cognitive epidemiology; CHD, coronary heart disease, IMT, intima-media thickness
17.  Influence of retirement on nonadherence to medication for hypertension and diabetes 
Background:
The extent to which common life transitions influence medication adherence among patients remains unknown. We examined whether retirement is associated with a change in adherence to medication in patients with hypertension or type 2 diabetes.
Methods:
Participants in the Finnish Public Sector study were linked to national registers. We included data for the years 1994–2011. We identified and followed 3468 adult patients with hypertension and 412 adult patients with type 2 diabetes for medication adherence for the 3 years before their retirement and the 4 years after their retirement (mean follow-up 6.8 yr). Our primary outcome was proportion of patients with poor adherence to medication, which we defined as less than 40% of days covered by treatment. We determined these proportions before and after retirement using data from filled prescriptions.
Results:
The preretirement prevalence of poor adherence to medication was 6% in men and women with hypertension, 2% in men with diabetes and 4% in women with diabetes. Among men, retirement was associated with an increased risk of poor adherence to both antihypertensive agents (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.03–1.68) and antidiabetic drugs (OR 2.40, 95% CI 1.37–4.20). Among women, an increased risk of poor adherence was seen only for antihypertensive agents (OR 1.25, 95% CI 1.07–1.46). Similar results were apparent for alternative definitions of poor adherence. Our results did not differ across strata of age, socioeconomic status or comorbidity.
Interpretation:
We found a decline in adherence to medication after retirement among men and women with hypertension and men with type 2 diabetes. If these findings can be confirmed, we need randomized controlled trials to determine whether interventions to reduce poor adherence after retirement could improve clinical outcomes of treatments for hypertension and diabetes.
doi:10.1503/cmaj.122010
PMCID: PMC3832579  PMID: 24082018
18.  The Alcohol Hangover Research Group Consensus Statement on Best Practice in Alcohol Hangover Research 
Current drug abuse reviews  2010;3(2):116-126.
Alcohol-induced hangover, defined by a series of symptoms, is the most commonly reported consequence of excessive alcohol consumption. Alcohol hangovers contribute to workplace absenteeism, impaired job performance, reduced productivity, poor academic achievement, and may compromise potentially dangerous daily activities such as driving a car or operating heavy machinery. These socioeconomic consequences and health risks of alcohol hangover are much higher when compared to various common diseases and other health risk factors. Nevertheless, unlike alcohol intoxication the hangover has received very little scientific attention and studies have often yielded inconclusive results. Systematic research is important to increase our knowledge on alcohol hangover and its consequences. This consensus paper of the Alcohol Hangover Research Group discusses methodological issues that should be taken into account when performing future alcohol hangover research. Future research should aim to (1) further determine the pathology of alcohol hangover, (2) examine the role of genetics, (3) determine the economic costs of alcohol hangover, (4) examine sex and age differences, (5) develop common research tools and methodologies to study hangover effects, (6) focus on factor that aggravate hangover severity (e.g., congeners), and (7) develop effective hangover remedies.
PMCID: PMC3827719  PMID: 20712593
Alcohol hangover; methodology; guidelines; research
19.  Chronic inflammation as a determinant of future aging phenotypes  
Background:
The importance of chronic inflammation as a determinant of aging phenotypes may have been underestimated in previous studies that used a single measurement of inflammatory markers. We assessed inflammatory markers twice over a 5-year exposure period to examine the association between chronic inflammation and future aging phenotypes in a large population of men and women.
Methods:
We obtained data for 3044 middle-aged adults (28.2% women) who were participating in the Whitehall II study and had no history of stroke, myocardial infarction or cancer at our study’s baseline (1997–1999). Interleukin-6 was measured at baseline and 5 years earlier. Cause-specific mortality, chronic disease and functioning were ascertained from hospital data, register linkage and clinical examinations. We used these data to create 4 aging phenotypes at the 10-year follow-up (2007–2009): successful aging (free of major chronic disease and with optimal physical, mental and cognitive functioning), incident fatal or nonfatal cardiovascular disease, death from noncardiovascular causes and normal aging (all other participants).
Results:
Of the 3044 participants, 721 (23.7%) met the criteria for successful aging at the 10-year follow-up, 321 (10.6%) had cardiovascular disease events, 147 (4.8%) died from noncardiovascular causes, and the remaining 1855 (60.9%) were included in the normal aging phenotype. After adjustment for potential confounders, having a high interleukin-6 level (> 2.0 ng/L) twice over the 5-year exposure period nearly halved the odds of successful aging at the 10-year follow-up (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.38–0.74) and increased the risk of future cardiovascular events (OR 1.64, 95% CI 1.15–2.33) and noncardiovascular death (OR 2.43, 95% CI 1.58–3.80).
Interpretation:
Chronic inflammation, as ascertained by repeat measurements, was associated with a range of unhealthy aging phenotypes and a decreased likelihood of successful aging. Our results suggest that assessing long-term chronic inflammation by repeat measurement of interleukin-6 has the potential to guide clinical practice.
doi: 10.1503/cmaj.122072
PMCID: PMC3826354  PMID: 24043651
20.  Study protocol for examining job strain as a risk factor for severe unipolar depression in an individual participant meta-analysis of 14 European cohorts 
F1000Research  2013;2:233.
Background: Previous studies have shown that gainfully employed individuals with high work demands and low control at work (denoted “job strain”) are at increased risk of common mental disorders, including depression. Most existing studies have, however, measured depression using self-rated symptom scales that do not necessarily correspond to clinically diagnosed depression. In addition, a meta-analysis from 2008 indicated publication bias in the field.
 
Methods: This study protocol describes the planned design and analyses of an individual participant data meta-analysis, to examine whether job strain is associated with an increased risk of clinically diagnosed unipolar depression based on hospital treatment registers.  The study will be based on data from approximately 120,000 individuals who participated in 14 studies on work environment and health in 4 European countries. The self-reported working conditions data will be merged with national registers on psychiatric hospital treatment, primarily hospital admissions. Study-specific risk estimates for the association between job strain and depression will be calculated using Cox regressions. The study-specific risk estimates will be pooled using random effects meta-analysis.
 
Discussion: The planned analyses will help clarify whether job strain is associated with an increased risk of clinically diagnosed unipolar depression. As the analysis is based on pre-planned study protocols and an individual participant data meta-analysis, the pooled risk estimates will not be influenced by selective reporting and publication bias. However, the results of the planned study may only pertain to severe cases of unipolar depression, because of the outcome measure applied.
doi:10.12688/f1000research.2-233.v1
PMCID: PMC3938244  PMID: 24627793
21.  Diabetes Risk Factors, Diabetes Risk Algorithms, and the Prediction of Future Frailty: The Whitehall II Prospective Cohort Study 
Objective
To examine whether established diabetes risk factors and diabetes risk algorithms are associated with future frailty.
Design
Prospective cohort study. Risk algorithms at baseline (1997–1999) were the Framingham Offspring, Cambridge, and Finnish diabetes risk scores.
Setting
Civil service departments in London, United Kingdom.
Participants
There were 2707 participants (72% men) aged 45 to 69 years at baseline assessment and free of diabetes.
Measurements
Risk factors (age, sex, family history of diabetes, body mass index, waist circumference, systolic and diastolic blood pressure, antihypertensive and corticosteroid treatments, history of high blood glucose, smoking status, physical activity, consumption of fruits and vegetables, fasting glucose, HDL-cholesterol, and triglycerides) were used to construct the risk algorithms. Frailty, assessed during a resurvey in 2007–2009, was denoted by the presence of 3 or more of the following indicators: self-reported exhaustion, low physical activity, slow walking speed, low grip strength, and weight loss; “prefrailty” was defined as having 2 or fewer of these indicators.
Results
After a mean follow-up of 10.5 years, 2.8% of the sample was classified as frail and 37.5% as prefrail. Increased age, being female, stopping smoking, low physical activity, and not having a daily consumption of fruits and vegetables were each associated with frailty or prefrailty. The Cambridge and Finnish diabetes risk scores were associated with frailty/prefrailty with odds ratios per 1 SD increase (disadvantage) in score of 1.18 (95% confidence interval: 1.09–1.27) and 1.27 (1.17–1.37), respectively.
Conclusion
Selected diabetes risk factors and risk scores are associated with subsequent frailty. Risk scores may have utility for frailty prediction in clinical practice.
doi:10.1016/j.jamda.2013.08.016
PMCID: PMC3820037  PMID: 24103860
Aging; frailty; diabetes risk scores; diabetes risk factors
22.  The Role of Health Behaviours Across the Life Course in the Socioeconomic Patterning of All-Cause Mortality: The West of Scotland Twenty-07 Prospective Cohort Study 
Annals of Behavioral Medicine  2013;47:148-157.
Background
Socioeconomic differentials in mortality are increasing in many industrialised countries.
Purpose
This study aims to examine the role of behaviours (smoking, alcohol, exercise, and diet) in explaining socioeconomic differentials in mortality and whether this varies over the life course, between cohorts and by gender.
Methods
Analysis of two representative population cohorts of men and women, born in the 1950s and 1930s, were performed. Health behaviours were assessed on five occasions over 20 years.
Results
Health behaviours explained a substantial part of the socioeconomic differentials in mortality. Cumulative behaviours and those that were more strongly associated with socioeconomic status had the greatest impact. For example, in the 1950s cohort, the age-sex adjusted hazard ratio comparing respondents with manual versus non-manual occupational status was 1.80 (1.25, 2.58); adjustment for cumulative smoking over 20 years attenuated the association by 49 %, diet by 43 %, drinking by 13 % and inactivity by only 1%.
Conclusions
Health behaviours have an important role in explaining socioeconomic differentials in mortality.
doi:10.1007/s12160-013-9539-x
PMCID: PMC3964290  PMID: 24072618
Mortality; Socioeconomic status; Health behaviours; Cohort
23.  Parental education as a predictor of offspring behavioural and physiological cardiovascular disease risk factors 
Background: Childhood socio-economic disadvantage has been shown to be associated with an elevated rate of cardiovascular disease (CVD) events in adulthood. The objective of this study is to examine associations between mothers’ and fathers’ education and offspring CVD risk factors. Methods: The Oslo Youth Study (n = 498) was initiated in 1979. Children (age 11–15 years) attending six schools and their parents were included. Information on education was collected for parents and participants. Participants were followed through 2006 (age 40 years). Information about physical activity, diet, smoking, binge drinking, body mass index (BMI), s-cholesterol, s-triglycerides and blood pressure was collected in 1981, 1991 and 2006. Results: Fathers’ education was inversely associated with participants’ BMI at 15 and 25 years, cholesterol at 25 and 40 years, triglycerides at 25 years and systolic blood pressure at 15 and 25 years (regression coefficients −0.18 to −0.11; P < 0.05 for all). The effects were weakened after adjusting for participants’ own education. Maternal education showed no association with these risk factors. After controlling for participants’ own education, associations between parental education and behavioural risk factors in adulthood were few. Conclusion: Any impact of parental education on offspring CVD risk factors seemed to be mediated via subject’s own education. Parental education offered little predictive capacity for offspring CVD risk factors.
doi:10.1093/eurpub/ckr106
PMCID: PMC3402716  PMID: 21893507
24.  Geographical variation in dementia: systematic review with meta-analysis 
Background Geographical variation in dementia prevalence and incidence may indicate important socio-environmental contributions to dementia aetiology. However, previous comparisons have been hampered by combining studies with different methodologies. This review systematically collates and synthesizes studies examining geographical variation in the prevalence and incidence of dementia based on comparisons of studies using identical methodologies.
Methods Papers were identified by a comprehensive electronic search of relevant databases, scrutinising the reference sections of identified publications, contacting experts in the field and re-examining papers already known to us. Identified articles were independently reviewed against inclusion/exclusion criteria and considered according to geographical scale. Rural/urban comparisons were meta-analysed.
Results Twelve thousand five hundred and eighty records were reviewed and 51 articles were included. Dementia prevalence and incidence varies at a number of scales from the national down to small areas, including some evidence of an effect of rural living [prevalence odds ratio (OR) = 1.11, 90% confidence interval (CI) 0.79–1.57; incidence OR = 1.20, 90% CI 0.84–1.71]. However, this association of rurality was stronger for Alzheimer disease, particularly when early life rural living was captured (prevalence OR = 2.22, 90% CI 1.19–4.16; incidence OR = 1.64, 90% CI 1.08–2.50).
Conclusions There is evidence of geographical variation in rates of dementia in affluent countries at a variety of geographical scales. Rural living is associated with an increased risk of Alzheimer disease, and there is a suggestion that early life rural living further increases this risk. However, the fact that few studies have been conducted in resource-poor countries limits conclusions.
doi:10.1093/ije/dys103
PMCID: PMC3429875  PMID: 22798662
Dementia; Alzheimer disease; epidemiology; geography; disease clustering
25.  Is bipolar disorder more common in highly intelligent people? A cohort study of a million men 
Molecular psychiatry  2012;18(2):190-194.
Anecdotal and biographical reports have long suggested that bipolar disorder is more common in people with exceptional cognitive or creative ability. Epidemiological evidence for such a link is sparse. We investigated the relationship between intelligence and subsequent risk of hospitalisation for bipolar disorder in a prospective cohort study of 1,049,607 Swedish men. Intelligence was measured on conscription for military service at a mean age of 18.3 years and data on psychiatric hospital admissions over a mean follow-up period of 22.6 years was obtained from national records. Risk of hospitalization with any form of bipolar disorder fell in a stepwise manner as intelligence increased (p for linear trend <0.0001). However, when we restricted analyses to men with no psychiatric comorbidity, there was a ‘reversed-J’ shaped association: men with the lowest intelligence had the greatest risk of being admitted with pure bipolar disorder, but risk was also elevated among men with the highest intelligence (p for quadratic trend = 0.03), primarily in those with the highest verbal (p for quadratic trend=0.009) or technical ability (p for quadratic trend <0.0001). At least in men, high intelligence may indeed be a risk factor for bipolar disorder, but only in the minority of cases who have the disorder in a pure form with no psychiatric comorbidity.
doi:10.1038/mp.2012.26
PMCID: PMC3705611  PMID: 22472877

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