Socioeconomic status and the 25 × 25 risk factors as determinants of premature mortality: a multicohort study and meta-analysis of 1·7 million men and women.

BACKGROUND: In 2011, WHO member states signed up to the 25 × 25 initiative, a plan to cut mortality due to non-communicable diseases by 25% by 2025. However, socioeconomic factors influencing non-communicable diseases have not been included in the plan. In this study, we aimed to compare the contribution of socioeconomic status to mortality and years-of-life-lost with that of the 25 × 25 conventional risk factors. METHODS: We did a multicohort study and meta-analysis with individual-level data from 48 independent prospective cohort studies with information about socioeconomic status, indexed by occupational position, 25 × 25 risk factors (high alcohol intake, physical inactivity, current smoking, hypertension, diabetes, and obesity), and mortality, for a total population of 1 751 479 (54% women) from seven high-income WHO member countries. We estimated the association of socioeconomic status and the 25 × 25 risk factors with all-cause mortality and cause-specific mortality by calculating minimally adjusted and mutually adjusted hazard ratios [HR] and 95% CIs. We also estimated the population attributable fraction and the years of life lost due to suboptimal risk factors. FINDINGS: During 26·6 million person-years at risk (mean follow-up 13·3 years [SD 6·4 years]), 310 277 participants died. HR for the 25 × 25 risk factors and mortality varied between 1·04 (95% CI 0·98-1·11) for obesity in men and 2 ·17 (2·06-2·29) for current smoking in men. Participants with low socioeconomic status had greater mortality compared with those with high socioeconomic status (HR 1·42, 95% CI 1·38-1·45 for men; 1·34, 1·28-1·39 for women); this association remained significant in mutually adjusted models that included the 25 × 25 factors (HR 1·26, 1·21-1·32, men and women combined). The population attributable fraction was highest for smoking, followed by physical inactivity then socioeconomic status. Low socioeconomic status was associated with a 2·1-year reduction in life expectancy between ages 40 and 85 years, the corresponding years-of-life-lost were 0·5 years for high alcohol intake, 0·7 years for obesity, 3·9 years for diabetes, 1·6 years for hypertension, 2·4 years for physical inactivity, and 4·8 years for current smoking. INTERPRETATION: Socioeconomic circumstances, in addition to the 25 × 25 factors, should be targeted by local and global health strategies and health risk surveillance to reduce mortality. FUNDING: European Commission, Swiss State Secretariat for Education, Swiss National Science Foundation, the Medical Research Council, NordForsk, Portuguese Foundation for Science and Technology.

Subjective social status and mortality: the English Longitudinal Study of Ageing.

Self-perceptions of own social position are potentially a key aspect of socioeconomic inequalities in health, but their association with mortality remains poorly understood. We examined whether subjective social status (SSS), a measure of the self-perceived element of social position, was associated with mortality and its role in the associations between objective socioeconomic position (SEP) measures and mortality. We used Cox regression to model the associations between SSS, objective SEP measures and mortality in a sample of 9972 people aged ≥ 50 years from the English Longitudinal Study of Ageing over a 10-year follow-up (2002-2013). Our findings indicate that SSS was associated with all-cause, cardiovascular, cancer and other mortality. A unit decrease in the 10-point continuous SSS measure increased by 24 and 8% the mortality risk of people aged 50-64 and ≥ 65 years, respectively, after adjustment for age, sex and marital status. The respective estimates for cardiovascular mortality were 36 and 11%. Adjustment for all covariates fully explained the association between SSS and cancer mortality, and partially the remaining associations. In people aged 50-64 years, SSS mediated to a varying extent the associations between objective SEP measures and all-cause mortality. In people aged ≥ 65 years, SSS mediated to a lesser extent these associations, and to some extent was associated with mortality independent of objective SEP measures. Nevertheless, in both age groups, wealth partially explained the association between SSS and mortality. In conclusion, SSS is a strong predictor of mortality at older ages, but its role in socioeconomic inequalities in mortality appears to be complex.

Social and Behavioural Determinants of the Difference in Survival among Older Adults in Japan and England.

BACKGROUND: A rapidly ageing population presents major challenges to health and social care services. Cross-country comparative studies on survival among older adults are limited. In addition, Japan, the country with the longest life expectancy, is rarely included in these cross-country comparisons. OBJECTIVE: We examined the relative contributions of social and behavioural factors on the differences in survival among older people in Japan and England. METHODS: We used data from the Japan Gerontological Evaluation Study (JAGES; n = 13,176) and the English Longitudinal Study of Ageing (ELSA; n = 5,551) to analyse all-cause mortality up to 9.4 years from the baseline. Applying Laplace regression models, the 15th survival percentile difference was estimated. RESULTS: During the follow-up, 31.3% of women and 38.6% of men in the ELSA died, whereas 19.3% of women and 31.3% of men in the JAGES died. After adjusting for age and baseline health status, JAGES participants had longer survival than ELSA participants by 318.8 days for women and by 131.6 days for men. Family-based social relationships contributed to 105.4 days longer survival in JAGES than ELSA men. Fewer friendship-based social relationships shortened the JAGES men's survival by 45.4 days compared to ELSA men. Currently not being a smoker contributed to longer survival for JAGES women (197.7 days) and ELSA men (46.6 days), and having lower BMI reduced the survival of JAGES participants by 129.0 days for women and by 212.2 days for men. CONCLUSION: Compared to participants in England, Japanese older people lived longer mainly because of non-smoking for women and family-based social relationships for men. In contrast, a lower rate of underweight, men's better friendship-based social relationships, and a lower smoking rate contributed to survival among participants in England.

Contribution of cognitive performance and cognitive decline to associations between socioeconomic factors and dementia: A cohort study.

BACKGROUND: Socioeconomic disadvantage is a risk factor for dementia, but longitudinal studies suggest that it does not affect the rate of cognitive decline. Our objective is to understand the manner in which socioeconomic disadvantage shapes dementia risk by examining its associations with midlife cognitive performance and cognitive decline from midlife to old age, including cognitive decline trajectories in those with dementia. METHODS AND FINDINGS: Data are drawn from the Whitehall II study (N = 10,308 at study recruitment in 1985), with cognitive function assessed at 4 waves (1997, 2002, 2007, and 2012). Sociodemographic, behavioural, and cardiometabolic risk factors from 1985 and chronic conditions until the end of follow-up in 2015 (N dementia/total = 320/9,938) allowed the use of inverse probability weighting to take into account data missing because of loss to follow-up between the study recruitment in 1985 and the introduction of cognitive tests to the study in 1997. Generalized estimating equations and Cox regression were used to assess associations of socioeconomic markers (height, education, and midlife occupation categorized as low, intermediate, and high to represent hierarchy in the socioeconomic marker) with cognitive performance, cognitive decline, and dementia (N dementia/total = 195/7,499). In those with dementia, we examined whether retrospective trajectories of cognitive decline (backward timescale) over 18 years prior to diagnosis differed as a function of socioeconomic markers. Socioeconomic disadvantage was associated with poorer cognitive performance (all p < 0.001). Using point estimates for the effect of age, the differences between the high and low socioeconomic groups corresponded to an age effect of 4, 15, and 26 years, for height, education, and midlife occupation, respectively. There was no evidence of faster cognitive decline in socioeconomically disadvantaged groups. Low occupation, but not height or education, was associated with risk of dementia (hazard ratio [HR] = 2.03 [95% confidence interval (CI) 1.23-3.36]) in an analysis adjusted for sociodemographic factors; the excess risk was unchanged after adjustment for cognitive decline but was completely attenuated after adjustment for cognitive performance. In further analyses restricted to those with dementia, retrospective cognitive trajectories over 18 years prior to dementia diagnosis showed faster cognitive decline in the high education (p = 0.006) and occupation (p = 0.001) groups such that large differences in cognitive performance in midlife were attenuated at dementia diagnosis. A major limitation of our study is the use of electronic health records rather than comprehensive dementia ascertainment. CONCLUSIONS: Our results support the passive or threshold cognitive reserve hypothesis, in that high cognitive reserve is associated with lower risk for dementia because of its association with cognitive performance, which provides a buffer against clinical expression of dementia.

Alcohol, drinking pattern and all-cause, cardiovascular and alcohol-related mortality in Eastern Europe.

Alcohol has been implicated in the high mortality in Central and Eastern Europe but the magnitude of its effect, and whether it is due to regular high intake or episodic binge drinking remain unclear. The aim of this paper was to estimate the contribution of alcohol to mortality in four Central and Eastern European countries. We used data from the Health, Alcohol and Psychosocial factors in Eastern Europe is a prospective multi-centre cohort study in Novosibirsk (Russia), Krakow (Poland), Kaunas (Lithuania) and six Czech towns. Random population samples of 34,304 men and women aged 45-69 years in 2002-2005 were followed up for a median 7 years. Drinking volume, frequency and pattern were estimated from the graduated frequency questionnaire. Deaths were ascertained using mortality registers. In 230,246 person-years of follow-up, 2895 participants died from all causes, 1222 from cardiovascular diseases (CVD), 672 from coronary heart disease (CHD) and 489 from pre-defined alcohol-related causes (ARD). In fully-adjusted models, abstainers had 30-50% increased mortality risk compared to light-to-moderate drinkers. Adjusted hazard ratios (HR) in men drinking on average ≥60 g of ethanol/day (3% of men) were 1.23 (95% CI 0.95-1.59) for all-cause, 1.38 (0.95-2.02) for CVD, 1.64 (1.02-2.64) for CHD and 2.03 (1.28-3.23) for ARD mortality. Corresponding HRs in women drinking on average ≥20 g/day (2% of women) were 1.92 (1.25-2.93), 1.74 (0.76-3.99), 1.39 (0.34-5.76) and 3.00 (1.26-7.10). Binge drinking increased ARD mortality in men only. Mortality was associated with high average alcohol intake but not binge drinking, except for ARD in men.

Mortality risk attributable to smoking, hypertension and diabetes among English and Brazilian older adults (The ELSA and Bambui cohort ageing studies).

BACKGROUND: The main aim of this study was to quantify and compare 6-year mortality risk attributable to smoking, hypertension and diabetes among English and Brazilian older adults. This study represents a rare opportunity to approach the subject in two different social and economic contexts. METHODS: Data from the data from the English Longitudinal Study of Ageing (ELSA) and the Bambuí Cohort Study of Ageing (Brazil) were used. Deaths in both cohorts were identified through mortality registers. Risk factors considered in this study were baseline smoking, hypertension and diabetes mellitus. Both age-sex adjusted hazard ratios and population attributable risks (PAR) of all-cause mortality and their 95% confidence intervals for the association between risk factors and mortality were estimated using Cox proportional hazards models. RESULTS: Participants were 3205 English and 1382 Brazilians aged 60 years and over. First, Brazilians showed much higher absolute risk of mortality than English and this finding was consistent in all age, independently of sex. Second, as a rule, hazard ratios for mortality to smoking, hypertension and diabetes showed more similarities than differences between these two populations. Third, there was strong difference among English and Brazilians on attributable deaths to hypertension. CONCLUSIONS: The findings indicate that, despite of being in more recent transitions, the attributable deaths to one or more risk factors was twofold among Brazilians relative to the English. These findings call attention for the challenge imposed to health systems to prevent and treat non-communicable diseases, particularly in populations with low socioeconomic level.

Social patterning in grip strength, chair rise, and walk speed in an aging population: the Czech HAPIEE Study.

BACKGROUND: The aim was to examine the association of objective measures of physical functioning (PF) with education and material circumstances and the decline in PF with age by socioeconomic position (SEP). METHODS: In 3,205 subjects (60-75 years) from the Czech Republic, we assessed relationship between PF, SEP, and age. Linear regression was used to assess PF measures and SEP measures. RESULTS: Cross-sectional decline in PF by age was similar in all individuals. Differences between SEP groups were similar across age groups, except for the difference in walk speed by material circumstances in men-bigger at older ages (p = .004). Men and women with the highest education were about 2 s faster at the chair rise test than those with the lowest education. DISCUSSION: Findings suggest strong educational gradient in PF, an inconsistent role of self-assessed material circumstances, and virtually no interaction of SEP with the cross-sectional decline in PF by age.

Inequalities in non-communicable diseases and effective responses.

In most countries, people who have a low socioeconomic status and those who live in poor or marginalised communities have a higher risk of dying from non-communicable diseases (NCDs) than do more advantaged groups and communities. Smoking rates, blood pressure, and several other NCD risk factors are often higher in groups with low socioeconomic status than in those with high socioeconomic status; the social gradient also depends on the country's stage of economic development, cultural factors, and social and health policies. Social inequalities in risk factors account for more than half of inequalities in major NCDs, especially for cardiovascular diseases and lung cancer. People in low-income countries and those with low socioeconomic status also have worse access to health care for timely diagnosis and treatment of NCDs than do those in high-income countries or those with higher socioeconomic status. Reduction of NCDs in disadvantaged groups is necessary to achieve substantial decreases in the total NCD burden, making them mutually reinforcing priorities. Effective actions to reduce NCD inequalities include equitable early childhood development programmes and education; removal of barriers to secure employment in disadvantaged groups; comprehensive strategies for tobacco and alcohol control and for dietary salt reduction that target low socioeconomic status groups; universal, financially and physically accessible, high-quality primary care for delivery of preventive interventions and for early detection and treatment of NCDs; and universal insurance and other mechanisms to remove financial barriers to health care.

Association of lifecourse socioeconomic status with chronic inflammation and type 2 diabetes risk: the Whitehall II prospective cohort study.

BACKGROUND: Socioeconomic adversity in early life has been hypothesized to "program" a vulnerable phenotype with exaggerated inflammatory responses, so increasing the risk of developing type 2 diabetes in adulthood. The aim of this study is to test this hypothesis by assessing the extent to which the association between lifecourse socioeconomic status and type 2 diabetes incidence is explained by chronic inflammation. METHODS AND FINDINGS: We use data from the British Whitehall II study, a prospective occupational cohort of adults established in 1985. The inflammatory markers C-reactive protein and interleukin-6 were measured repeatedly and type 2 diabetes incidence (new cases) was monitored over an 18-year follow-up (from 1991-1993 until 2007-2009). Our analytical sample consisted of 6,387 non-diabetic participants (1,818 women), of whom 731 (207 women) developed type 2 diabetes over the follow-up. Cumulative exposure to low socioeconomic status from childhood to middle age was associated with an increased risk of developing type 2 diabetes in adulthood (hazard ratio [HR] = 1.96, 95% confidence interval: 1.48-2.58 for low cumulative lifecourse socioeconomic score and HR = 1.55, 95% confidence interval: 1.26-1.91 for low-low socioeconomic trajectory). 25% of the excess risk associated with cumulative socioeconomic adversity across the lifecourse and 32% of the excess risk associated with low-low socioeconomic trajectory was attributable to chronically elevated inflammation (95% confidence intervals 16%-58%). CONCLUSIONS: In the present study, chronic inflammation explained a substantial part of the association between lifecourse socioeconomic disadvantage and type 2 diabetes. Further studies should be performed to confirm these findings in population-based samples, as the Whitehall II cohort is not representative of the general population, and to examine the extent to which social inequalities attributable to chronic inflammation are reversible.

Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant data.

BACKGROUND: Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies. METHODS: We used individual records from 13 European cohort studies (1985-2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. FINDINGS: 30,214 (15%) of 197,473 participants reported job strain. In 1·49 million person-years at risk (mean follow-up 7·5 years [SD 1·7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1·23 (95% CI 1·10-1·37). This effect estimate was higher in published (1·43, 1·15-1·77) than unpublished (1·16, 1·02-1·32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1·31, 1·15-1·48) and 5 years (1·30, 1·13-1·50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3·4%. INTERPRETATION: Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking. FUNDING: Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health.

Social relationships and oral health among adults aged 60 years or older.

OBJECTIVE: This study assessed associations between social relationships and oral health outcomes and whether these associations were explained by demographic, socioeconomic, and behavioral factors, and physical health. METHODS: We used the National Health and Nutrition Examination Survey (1999-2004) data on 4014 adults aged 60 years or older. Oral health outcomes were edentulism, number of decayed teeth, root decay, number of sound or filled teeth, and self-rated oral health. Social relationships referred to social networks (marital status, number of close friends) and social support (emotional support need, provision of financial support). Analyses consisted of regression models sequentially adjusting for demographic, socioeconomic, behavioral, and physical health confounders. RESULTS: In fully adjusted models, widowed or divorced/separated individuals had fewer sound or filled teeth than those married or living with a partner: rate ratio (95% confidence interval)=0.89 (0.82 to 0.97) and 0.90 (0.83 to 0.97), respectively. People with four to six close friends had fewer decayed teeth and lower probability for root decay than those with fewer friends. Emotional support need was associated with 1.41 (1.05 to 1.90) higher odds for root decay and 1.18 (1.04 to 1.35) higher odds for poorer self-rated oral health. Lack of financial support was associated with more decayed teeth. Edentulism was not related to any social network and social support markers. CONCLUSIONS: Social relationships are associated with clinical measures of current disease, markers of good oral function, and subjective oral health, but not with clinical measures of a lifetime history of oral disease among older Americans.

Job strain and health-related lifestyle: findings from an individual-participant meta-analysis of 118,000 working adults.

OBJECTIVES: We examined the associations of job strain, an indicator of work-related stress, with overall unhealthy and healthy lifestyles. METHODS: We conducted a meta-analysis of individual-level data from 11 European studies (cross-sectional data: n = 118,701; longitudinal data: n = 43,971). We analyzed job strain as a set of binary (job strain vs no job strain) and categorical (high job strain, active job, passive job, and low job strain) variables. Factors used to define healthy and unhealthy lifestyles were body mass index, smoking, alcohol intake, and leisure-time physical activity. RESULTS: Individuals with job strain were more likely than those with no job strain to have 4 unhealthy lifestyle factors (odds ratio [OR] = 1.25; 95% confidence interval [CI] = 1.12, 1.39) and less likely to have 4 healthy lifestyle factors (OR = 0.89; 95% CI = 0.80, 0.99). The odds of adopting a healthy lifestyle during study follow-up were lower among individuals with high job strain than among those with low job strain (OR = 0.88; 95% CI = 0.81, 0.96). CONCLUSIONS: Work-related stress is associated with unhealthy lifestyles and the absence of stress is associated with healthy lifestyles, but longitudinal analyses suggest no straightforward cause-effect relationship between work-related stress and lifestyle.

Education is associated with lower levels of abdominal obesity in women with a non-agricultural occupation: an interaction study using China's Four Provinces survey.

BACKGROUND: The prevalence of obesity is increasing rapidly in low- and middle-income countries (LMICs) as their populations become exposed to obesogenic environments. The transition from an agrarian to an industrial and service-based economy results in important lifestyle changes. Yet different socioeconomic groups may experience and respond to these changes differently. Investigating the socioeconomic distribution of obesity in LMICs is key to understanding the causes of obesity but the field is limited by the scarcity of data and a uni-dimensional approach to socioeconomic status (SES). This study splits socioeconomic status into two dimensions to investigate how educated women may have lower levels of obesity in a context where labour market opportunities have shifted away from agriculture to other forms of employment. METHODS: The Four Provinces Study in China 2008/09 is a household-based community survey of 4,314 people aged ≥60  years (2,465 women). It was used to investigate an interaction between education (none/any) and occupation (agricultural/non-agricultural) on high-risk central obesity defined as a waist circumference ≥80 cm. An interaction term between education and occupation was incorporated in a multivariate logistic regression model, and the estimates adjusted for age, parity, urban/rural residence and health behaviours (smoking, alcohol, meat and fruit & vegetable consumption). Complete case analyses were undertaken and results confirmed using multiple imputation to impute missing data. RESULTS: An interaction between occupation and education was present (P = 0.02). In the group with no education, the odds of central obesity in the sedentary occupation group were more than double those of the agricultural occupation group even after taking age group and parity into account (OR; 95%CI: 2.21; 1.52, 3.21), while in the group with any education there was no evidence of such a relationship (OR; 95%CI: 1.25; 0.92, 1.70). Health behaviours appeared to account for some of the association. CONCLUSION: These findings suggest that education may have a protective role in women against the higher odds of obesity associated with occupational shifts in middle-income countries, and that investment in women's education may present an important long term investment in obesity prevention. Further research could elucidate the mechanisms behind this association.

Job strain as a risk factor for leisure-time physical inactivity: an individual-participant meta-analysis of up to 170,000 men and women: the IPD-Work Consortium.

Unfavorable work characteristics, such as low job control and too high or too low job demands, have been suggested to increase the likelihood of physical inactivity during leisure time, but this has not been verified in large-scale studies. The authors combined individual-level data from 14 European cohort studies (baseline years from 1985-1988 to 2006-2008) to examine the association between unfavorable work characteristics and leisure-time physical inactivity in a total of 170,162 employees (50% women; mean age, 43.5 years). Of these employees, 56,735 were reexamined after 2-9 years. In cross-sectional analyses, the odds for physical inactivity were 26% higher (odds ratio = 1.26, 95% confidence interval: 1.15, 1.38) for employees with high-strain jobs (low control/high demands) and 21% higher (odds ratio = 1.21, 95% confidence interval: 1.11, 1.31) for those with passive jobs (low control/low demands) compared with employees in low-strain jobs (high control/low demands). In prospective analyses restricted to physically active participants, the odds of becoming physically inactive during follow-up were 21% and 20% higher for those with high-strain (odds ratio = 1.21, 95% confidence interval: 1.11, 1.32) and passive (odds ratio = 1.20, 95% confidence interval: 1.11, 1.30) jobs at baseline. These data suggest that unfavorable work characteristics may have a spillover effect on leisure-time physical activity.

Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.

Blood lipids are important cardiovascular disease (CVD) risk factors with both genetic and environmental determinants. The Whitehall II study (n=5592) was genotyped with the gene-centric HumanCVD BeadChip (Illumina). We identified 195 SNPs in 16 genes/regions associated with 3 major lipid fractions and 2 apolipoprotein components at p<10(-5), with the associations being broadly concordant with prior genome-wide analysis. SNPs associated with LDL cholesterol and apolipoprotein B were located in LDLR, PCSK9, APOB, CELSR2, HMGCR, CETP, the TOMM40-APOE-C1-C2-C4 cluster, and the APOA5-A4-C3-A1 cluster; SNPs associated with HDL cholesterol and apolipoprotein AI were in CETP, LPL, LIPC, APOA5-A4-C3-A1, and ABCA1; and SNPs associated with triglycerides in GCKR, BAZ1B, MLXIPL, LPL, and APOA5-A4-C3-A1. For 48 SNPs in previously unreported loci that were significant at p<10(-4) in Whitehall II, in silico analysis including the British Women's Heart and Health Study, BRIGHT, ASCOT, and NORDIL studies (total n>12,500) revealed previously unreported associations of SH2B3 (p<2.2x10(-6)), BMPR2 (p<2.3x10(-7)), BCL3/PVRL2 (flanking APOE; p<4.4x10(-8)), and SMARCA4 (flanking LDLR; p<2.5x10(-7)) with LDL cholesterol. Common alleles in these genes explained 6.1%-14.7% of the variance in the five lipid-related traits, and individuals at opposite tails of the additive allele score exhibited substantial differences in trait levels (e.g., >1 mmol/L in LDL cholesterol [approximately 1 SD of the trait distribution]). These data suggest that multiple common alleles of small effect can make important contributions to individual differences in blood lipids potentially relevant to the assessment of CVD risk. These genes provide further insights into lipid metabolism and the likely effects of modifying the encoded targets therapeutically.

Does cognitive reserve shape cognitive decline?

OBJECTIVE: Cognitive reserve is associated with a lower risk of dementia, but the extent to which it shapes cognitive aging trajectories remains unclear. Our objective is to examine the impact of 3 markers of reserve from different points in the life course on cognitive function and decline in late adulthood. METHODS: Data are from 5,234 men and 2,220 women, mean age 56 years (standard deviation = 6) at baseline, from the Whitehall II cohort study. Memory, reasoning, vocabulary, and phonemic and semantic fluency were assessed 3× over 10 years. Linear mixed models were used to assess the association between markers of reserve (height, education, and occupation) and cognitive decline, using the 5 cognitive tests and a global cognitive score composed of these tests. RESULTS: All 3 reserve measures were associated with baseline cognitive function; the strongest associations were with occupation and the weakest with height. All cognitive functions except vocabulary declined over the 10-year follow-up period. On the global cognitive test, there was greater decline in the high occupation group (-0.27; 95% confidence interval [CI], -0.28 to -0.26) compared to the intermediate (-0.23; 95% CI, -0.25 to -0.22) and low groups (-0.21; 95% CI, -0.24 to -0.19); p = 0.001. The decline in reserve groups defined by education (p = 0.82) and height (p = 0.55) was similar. INTERPRETATION: Cognitive performance over the adult life course was remarkably higher in the high reserve groups. However, rate of cognitive decline did not differ between reserve groups with the exception of occupation, where there was some evidence of greater decline in the high occupation group.