PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (26)
 

Clipboard (0)
None

Select a Filter Below

Year of Publication
Document Types
1.  Informal Caregiving and the Risk for Coronary Heart Disease: The Whitehall II Study 
Background.
The stress associated with informal caregiving has been shown to be associated with poor health, including coronary heart disease (CHD). However, it is unclear if the risk of CHD is attributable to caregiving or prior poor health of the caregiver.
Methods.
We used data from the Whitehall II cohort study. Caregiving and caregiver’s health (using 3 measures: self-rated health, mental health using the General Health Questionnaire, and physical component score of the SF-36) were assessed in 1991–1993 among 5,468 men and 2,457 women aged 39–63 years. CHD (fatal CHD, clinically verified nonfatal myocardial infarction, and definite angina) incidence was recorded for a mean 17 years; sociodemographic variables, health behaviors, and cardiovascular risk factors were included as covariates.
Results.
Cox regression showed the risk of CHD in caregivers not to be higher (hazard ratio = 1.18; 95% CI: 0.96, 1.45) compared with noncaregivers. Analyses stratified by health status showed that compared with noncaregivers in good health, caregivers with poor self-rated (hazard ratio = 2.00; 95% CI: 1.44, 2.78), mental (hazard ratio = 1.63; 95% CI: 1.16, 2.30), or physical (hazard ratio =1.87; 95% CI: 1.34, 2.62) health had greater risk of CHD. A similar elevated risk was observed in noncaregivers with poor health; no excess risk was observed among caregivers reporting good health, and the combined effect of poor health and caregiving did not exceed their independent effects.
Conclusions.
Caregiving in midlife is not in itself associated with greater risk of CHD, but it is associated with increased risk for CHD among caregivers who report being in poor health.
doi:10.1093/gerona/glt025
PMCID: PMC3779628  PMID: 23525476
Coronary heart disease; Stress; Caregiver.
2.  No evidence of a longitudinal association between diurnal cortisol patterns and cognition☆ 
Neurobiology of Aging  2014;35(10):2239-2245.
We examined the effect of salivary cortisol on cognitive performance and decline in 3229 adults (79% men), mean age 61 years. Six saliva samples over the day along with a cognition test battery were administered twice in 5 years. In fully-adjusted cross-sectional analyses from 2002 to 2004, higher waking cortisol was associated with higher reasoning score (β = 0.08, 95% confidence interval: 0.01, 0.15) but this finding was not replicated using data from 2007 to 2009. Over the mean 5 years follow-up there was decline in all cognitive tests but this decline did not vary as a function of cortisol levels; the exception was among APOE e4 carriers where a flatter diurnal slope and higher bedtime cortisol were associated with faster decline in verbal fluency. Changes in cortisol measures between 2002/2004 and 2007/2009 or chronically elevated levels were not associated with cognitive performance in 2007/2009. These results, based on a large sample of community-dwelling adults suggest that variability in hypothalamic-pituitary-adrenal function is not a strong contributor to cognitive aging.
doi:10.1016/j.neurobiolaging.2014.03.015
PMCID: PMC4099515  PMID: 24735831
Cortisol; Glucocorticoid; Cognitive decline
3.  Midlife stroke risk and cognitive decline: A 10-year follow-up of the Whitehall II cohort study 
Background
Stroke is associated with an increased risk of dementia. However, it is unclear if risk of stroke in those free of stroke, particularly in non-elderly populations, leads to differential rates of cognitive decline. Our aim was to assess whether risk of stroke in midlife was associated with cognitive decline over 10 years of follow-up.
Methods
We studied 4,153 men and 1,657 women, mean age 55.6 years at baseline, from the Whitehall II study, a longitudinal British cohort study. We used the Framingham Stroke Risk Profile (FSRP) that incorporates age, systolic blood pressure, diabetes mellitus, smoking, prior cardiovascular disease, atrial fibrillation, left ventricular hypertrophy, and use of antihypertensive medication. Cognitive tests included reasoning, memory, verbal fluency, and vocabulary assessed three times over ten years. Longitudinal associations between FSRP and its components were tested using mixed effects models and rates of cognitive change over 10 years were estimated.
Results
Higher stroke risk was associated with faster decline in verbal fluency, vocabulary and global cognition. For example, for global cognition there was greater decline in the highest FSRP quartile (−0.25 of a standard deviation; 95% CI: −0.28 to −0.21) compared to the lowest risk quartile (P=0.03). No association was observed for memory and reasoning. Of the individual components of FSRP only diabetes was independently associated with faster cognitive decline (β=−0.06; 95% CI:−0.01, −0.003, P=0.03).
Conclusion
Elevated stroke risk is associated with accelerated cognitive decline over 10 years. Aggregation of risk factors may be especially important in this association.
doi:10.1016/j.jalz.2012.07.001
PMCID: PMC3918666  PMID: 23199495
vascular risk factors; cognitive decline; Framingham Stroke Risk Profile; aging; midlife
4.  Interleukin-6 and C-reactive protein as predictors of cognitive decline in late midlife 
Neurology  2014;83(6):486-493.
Objective:
Peripheral inflammatory markers are elevated in patients with dementia. In order to assess their etiologic role, we examined whether interleukin-6 (IL-6) and C-reactive protein (CRP) measured in midlife predict concurrently assessed cognition and subsequent cognitive decline.
Methods:
Mean value of IL-6 and CRP, assessed on 5,217 persons (27.9% women) in 1991–1993 and 1997–1999 in the Whitehall II longitudinal cohort study, were categorized into tertiles to examine 10-year decline (assessments in 1997–1999, 2002–2004, and 2007–2009) in standardized scores (mean = 0, SD = 1) of memory, reasoning, and verbal fluency using mixed models. Mini-Mental State Examination (MMSE) was administered in 2002–2004 and 2007–2009; decline ≥3 points was modeled with logistic regression. Analyses were adjusted for baseline age, sex, education, and ethnicity; further analyses were also adjusted for smoking, obesity, Framingham cardiovascular risk score, and chronic diseases (cancer, coronary heart disease, stroke, diabetes, and depression).
Results:
In cross-sectional analysis, reasoning was 0.08 SD (95% confidence interval [CI] −0.14, −0.03) lower in participants with high compared to low IL-6. In longitudinal analysis, 10-year decline in reasoning was greater (ptrend = 0.01) among participants with high IL-6 (−0.35; 95% CI −0.37, −0.33) than those with low IL-6 (−0.29; 95% CI −0.31, −0.27). In addition, participants with high IL-6 had 1.81 times greater odds ratio of decline in MMSE (95% CI 1.20, 2.71). CRP was not associated with decline in any test.
Conclusions:
Elevated IL-6 but not CRP in midlife predicts cognitive decline; the combined cross-sectional and longitudinal effects over the 10-year observation period corresponded to an age effect of 3.9 years.
doi:10.1212/WNL.0000000000000665
PMCID: PMC4141998  PMID: 24991031
5.  Metabolically Healthy Obesity and Risk of Mortality 
Diabetes Care  2013;36(8):2294-2300.
OBJECTIVE
To assess the association of a “metabolically healthy obese” phenotype with mortality using five definitions of metabolic health.
RESEARCH DESIGN AND METHODS
Adults (n = 5,269; 71.7% men) aged 39–62 years in 1991 through 1993 provided data on BMI and metabolic health, defined using data from the Adult Treatment Panel-III (ATP-III); criteria from two studies; and the Matsuda and homeostasis model assessment (HOMA) indices. Cross-classification of BMI categories and metabolic status (healthy/unhealthy) created six groups. Cox proportional hazards regression models were used to analyze associations with all-cause and cardiovascular disease (CVD) mortality during a median follow-up of 17.7 years.
RESULTS
A total of 638 individuals (12.1% of the cohort) were obese, of whom 9–41% were metabolically healthy, depending on the definition. Regardless of the definition, compared with metabolically healthy, normal-weight individuals, both the metabolically healthy obese (hazard ratios [HRs] ranged from 1.81 [95% CI 1.16–2.84] for ATP-III to 2.30 [1.13–4.70] for the Matsuda index) and the metabolically abnormal obese (HRs ranged from 1.57 [1.08–2.28] for the Matsuda index to 2.05 [1.44–2.92] for criteria defined in a separate study) had an increased risk of mortality. The only exception was the lack of excess risk using the HOMA criterion for the metabolically healthy obese (1.08; 0.67–1.74). Among the obese, the risk of mortality did not vary as a function of metabolic health apart from when using the HOMA criterion (1.93; 1.15–3.22). Similar results were obtained for cardiovascular mortality.
CONCLUSIONS
For most definitions of metabolic health, both metabolically healthy and unhealthy obese patients carry an elevated risk of mortality.
doi:10.2337/dc12-1654
PMCID: PMC3714476  PMID: 23637352
6.  Predicting cognitive decline 
Neurology  2013;80(14):1300-1306.
Objective:
Our aim was to compare 2 Framingham vascular risk scores with a dementia risk score in relation to 10-year cognitive decline in late middle age.
Methods:
Participants were men and women with mean age of 55.6 years at baseline, from the Whitehall II study, a longitudinal British cohort study. We compared the Framingham general cardiovascular disease risk score and the Framingham stroke risk score with the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) risk score that uses risk factors in midlife to estimate risk of late-life dementia. Cognitive tests included reasoning, memory, verbal fluency, vocabulary, and global cognition, assessed 3 times over 10 years.
Results:
Higher cardiovascular disease risk and higher stroke risk were associated with greater cognitive decline in all tests except memory; higher dementia risk was associated with greater decline in reasoning, vocabulary, and global cognitive scores. Compared with the dementia risk score, cardiovascular and stroke risk scores showed slightly stronger associations with 10-year cognitive decline; these differences were statistically significant for semantic fluency and global cognitive scores. For example, cardiovascular disease risk was associated with −0.06 SD (95% confidence interval [CI] = −0.08, −0.05) decline in the global cognitive scores over 10 years whereas dementia risk was associated with −0.03 SD (95% CI = −0.04, −0.01) decline (difference in β coefficients = 0.03; 95% CI = 0.01, 0.05).
Conclusions:
The CAIDE dementia and Framingham risk scores predict cognitive decline in late middle age but the Framingham risk scores may have an advantage over the dementia risk score for use in primary prevention for assessing risk of cognitive decline and targeting of modifiable risk factors.
doi:10.1212/WNL.0b013e31828ab370
PMCID: PMC3656460  PMID: 23547265
7.  Midlife type 2 diabetes and poor glycaemic control as risk factors for cognitive decline in early old age: a post-hoc analysis of the Whitehall II cohort study 
Summary
Background
Type 2 diabetes increases the risk for dementia, but whether it affects cognition before old age is unclear. We investigated whether duration of diabetes in late midlife and poor glycaemic control were associated with accelerated cognitive decline.
Methods
5653 participants from the Whitehall II cohort study (median age 54·4 years [IQR 50·3–60·3] at first cognitive assessment), were classified into four groups: normoglycaemia, prediabetes, newly diagnosed diabetes, and known diabetes. Tests of memory, reasoning, phonemic and semantic fluency, and a global score that combined all cognitive tests, were assessed three times over 10 years (1997–99, 2002–04, and 2007–09). Mean HbA1c was used to assess glycaemic control during follow-up. Analyses were adjusted for sociodemographic characteristics, health-related behaviours, and chronic diseases.
Findings
Compared with normoglycaemic participants, those with known diabetes had a 45% faster decline in memory (10 year difference in decline −0·13 SD, 95% CI −0·26 to −0·00; p=0·046), a 29% faster decline in reasoning (−0·10 SD, −0·19 to −0·01; p=0·026), and a 24% faster decline in the global cognitive score (−0·11 SD, −0·21 to −0·02; p=0·014). Participants with prediabetes or newly diagnosed diabetes had similar rates of decline to those with normoglycaemia. Poorer glycaemic control in participants with known diabetes was associated with a significantly faster decline in memory (−0·12 [–0·22 to −0·01]; p=0·034) and a decline in reasoning that approached significance (−0·07 [–0·15 to 0·00]; p=0·052).
Interpretation
The risk of accelerated cognitive decline in middle-aged patients with type 2 diabetes is dependent on both disease duration and glycaemic control.
Funding
US National Institutes of Health, UK Medical Research Council.
doi:10.1016/S2213-8587(13)70192-X
PMCID: PMC4274502  PMID: 24622753
8.  Alcohol consumption and cognitive decline in early old age 
Neurology  2014;82(4):332-339.
Objective:
To examine the association between alcohol consumption in midlife and subsequent cognitive decline.
Methods:
Data are from 5,054 men and 2,099 women from the Whitehall II cohort study with a mean age of 56 years (range 44–69 years) at first cognitive assessment. Alcohol consumption was assessed 3 times in the 10 years preceding the first cognitive assessment (1997–1999). Cognitive tests were repeated in 2002–2004 and 2007–2009. The cognitive test battery included 4 tests assessing memory and executive function; a global cognitive score summarized performances across these tests. Linear mixed models were used to assess the association between alcohol consumption and cognitive decline, expressed as z scores (mean = 0, SD = 1).
Results:
In men, there were no differences in cognitive decline among alcohol abstainers, quitters, and light or moderate alcohol drinkers (<20 g/d). However, alcohol consumption ≥36 g/d was associated with faster decline in all cognitive domains compared with consumption between 0.1 and 19.9 g/d: mean difference (95% confidence interval) in 10-year decline in the global cognitive score = −0.10 (−0.16, −0.04), executive function = −0.06 (−0.12, 0.00), and memory = −0.16 (−0.26, −0.05). In women, compared with those drinking 0.1 to 9.9 g/d of alcohol, 10-year abstainers showed faster decline in the global cognitive score (−0.21 [−0.37, −0.04]) and executive function (−0.17 [−0.32, −0.01]).
Conclusions:
Excessive alcohol consumption in men (≥36 g/d) was associated with faster cognitive decline compared with light to moderate alcohol consumption.
doi:10.1212/WNL.0000000000000063
PMCID: PMC3929201  PMID: 24431298
9.  Usefulness of a single-item measure of depression to predict mortality: the GAZEL prospective cohort study 
Background: It remains unknown whether short measures of depression perform as well as long measures in predicting adverse outcomes such as mortality. The present study aims to examine the predictive value of a single-item measure of depression for mortality. Methods: A total of 14 185 participants of the GAZEL cohort completed the 20-item Center-for-Epidemiologic-Studies-Depression (CES-D) scale in 1996. One of these items (I felt depressed) was used as a single-item measure of depression. All-cause mortality data were available until 30 September 2009, a mean follow-up period of 12.7 years with a total of 650 deaths. Results: In Cox regression model adjusted for baseline socio-demographic characteristics, a one-unit increase in the single-item score (range 0–3) was associated with a 25% higher risk of all-cause mortality (95% CI: 13–37%, P < 0.001). Further adjustment for health-related behaviours and physical chronic diseases reduced this risk by 36% and 8%, respectively. After adjustment for all these variables, every one-unit increase in the single-item score predicted a 15% increased risk of death (95% CI: 5–27%, P < 0.01). There is also an evidence of a dose–reponse relationship between reponse scores on the single-item measure of depression and mortality. Conclusion: This study shows that a single-item measure of depression is associated with an increased risk of death. Given its simplicity and ease of administration, a very simple single-item measure of depression might be useful for identifying middle-aged adults at risk for elevated depressive symptoms in large epidemiological studies and clinical settings.
doi:10.1093/eurpub/ckr103
PMCID: PMC3457003  PMID: 21840893
10.  Impact of smoking on cognitive decline in early old age: the Whitehall II cohort study 
Archives of General Psychiatry  2012;69(6):627-635.
Context
Smoking is a possible risk factor for dementia although its impact may have been underestimated in elderly populations due to the shorter lifespan of smokers.
Objective
To examine the association between smoking history and cognitive decline in the transition from midlife to old age.
Design, Setting, and Participants
Data are from 5099 men and 2137 women in the Whitehall II study, mean age 56 years (range=44–69 years) at the first cognitive assessment (1997–1999), repeated over 2002–2004 and 2007–2009.
Main Outcome Measures
The cognitive test battery was composed of tests of memory, vocabulary, executive function (composed of one reasoning and two fluency tests), and a global cognitive score summarising performance across all five tests. Smoking status was assessed over the entire study period. Linear mixed models were used to assess the association between smoking history and 10-year cognitive decline, expressed as z-scores.
Results
In men, 10-year cognitive decline in all tests except vocabulary among never smokers ranged from a quarter to a third of the baseline standard deviation. Faster cognitive decline was observed among current smokers compared to never smokers in men [mean difference in 10-year decline in global cognition=−0.09 (95%CI:−0.15;−0.03) and executive function=−0.11 (−0.17;−0.05)]. Recent ex-smokers had greater decline in executive function (−0.08 (−0.14;−0.02)) while the decline in long-term ex-smokers was similar to that among never smokers. In analyses that additionally took drop-out and death into account, these differences were 1.2 to 1.5 times larger. In women, cognitive decline did not vary as a function of smoking status.
Conclusions
Compared to never smokers, middle-aged male smokers experienced faster cognitive decline in global cognition and executive function. In ex-smokers with at least 10-year cessation there were no adverse effects on cognitive decline.
doi:10.1001/archgenpsychiatry.2011.2016
PMCID: PMC3675806  PMID: 22309970
Adult; Aged; Cognition Disorders; etiology; physiopathology; Cohort Studies; Female; Great Britain; Humans; Male; Middle Aged; Neuropsychological Tests; Smoking; adverse effects; Time Factors
11.  Obesity phenotypes in midlife and cognition in early old age 
Neurology  2012;79(8):755-762.
Objective:
To examine the association of body mass index (BMI) and metabolic status with cognitive function and decline.
Methods:
A total of 6,401 adults (71.2% men), aged 39–63 years in 1991–1993, provided data on BMI (normal weight 18.5–24.9 kg/m2, overweight 25–29.9 kg/m2; and obese ≥30 kg/m2) and metabolic status (abnormality defined as 2 or more of 1) triglycerides ≥1.69 mmol/L or lipid-lowering drugs, 2) systolic blood pressure ≥130 mm Hg, diastolic blood pressure ≥85 mm Hg, or antihypertensive drugs, 3) glucose ≥5.6 mmol/L or medications for diabetes, and 4) high-density lipoprotein cholesterol <1.04 mmol/L for men and <1.29 mmol/L for women). Four cognitive tests (memory, reasoning, semantic, and phonemic fluency) were administered in 1997–1999, 2002–2004, and 2007–2009, standardized to z scores, and averaged to yield a global score.
Results:
Of the participants, 31.0% had metabolic abnormalities, 52.7% were normal weight, 38.2% were overweight, and 9.1% were obese. Among the obese, the global cognitive score at baseline (p = 0.82) and decline (p = 0.19) over 10 years was similar in the metabolically normal and abnormal groups. In the metabolically normal group, the 10-year decline in the global cognitive score was similar (p for trend = 0.36) in the normal weight (−0.40; 95% confidence interval [CI] −0.42 to −0.38), overweight (−0.42; 95% CI −0.45 to −0.39), and obese (−0.42; 95% CI −0.50 to −0.34) groups. However, in the metabolically abnormal group, the decline on the global score was faster among obese (−0.49; 95% CI −0.55 to −0.42) than among normal weight individuals (−0.42; 95% CI −0.50 to −0.34), (p = 0.03).
Conclusions:
In these analyses the fastest cognitive decline was observed in those with both obesity and metabolic abnormality.
doi:10.1212/WNL.0b013e3182661f63
PMCID: PMC3421151  PMID: 22915175
12.  Association of lung function with physical, mental and cognitive function in early old age 
Age  2010;33(3):385-392.
Lung function predicts mortality; whether it is associated with functional status in the general population remains unclear. This study examined the association of lung function with multiple measures of functioning in early old age. Data are drawn from the Whitehall II study; data on lung function (forced expiratory volume in 1 s, height FEV1), walking speed (2.44 m), cognitive function (memory and reasoning) and self-reported physical and mental functioning (SF-36) were available on 4,443 individuals, aged 50–74 years. In models adjusted for age, 1 standard deviation (SD) higher height-adjusted FEV1 was associated with greater walking speed (beta = 0.16, 95% CI: 0.13, 0.19), memory (beta = 0.09, 95% CI: 0.06, 0.12), reasoning (beta = 0.16, 95% CI: 0.13, 0.19) and self-reported physical functioning (beta = 0.13, 95% CI: 0.10, 0.16). Socio-demographic measures, health behaviours (smoking, alcohol, physical activity, fruit/vegetable consumption), body mass index (BMI) and chronic conditions explained two-thirds of the association with walking speed and self-assessed physical functioning and over 80% of the association with cognitive function. Our results suggest that lung function is a good ‘summary’ measure of overall functioning in early old age.
doi:10.1007/s11357-010-9189-x
PMCID: PMC3168608  PMID: 20878489
Ageing; Lung function; Cognitive function; Physical function
13.  Association of lung function with physical, mental and cognitive function in early old age 
Age  2010;33(3):385-392.
Lung function predicts mortality, whether it is associated with functional status in the general population remains unclear. This study examined the association of lung function with multiple measures of functioning in early old age. Data are drawn from the Whitehall II study; data on lung function (forced expiratory volume in one second, height FEV1), walking speed (over 2.44 m), cognitive function (memory and reasoning), and self-reported physical and mental functioning (SF-36) were available on 4443 individuals, aged 50–74 years. In models adjusted for age, one standard deviation (SD) higher height-adjusted FEV1 was associated with greater walking speed (beta=0.16, 95% CI: 0.13, 0.19), memory (beta=0.09, 95% CI: 0.06, 0.12), reasoning (beta=0.16, 95% CI: 0.13, 0.19), and self-reported physical functioning (beta=0.13, 95% CI: 0.10, 0.16). Socio-demographic measures, health behaviours (smoking, alcohol, physical activity, fruit/vegetable consumption), BMI and chronic conditions explained two-thirds of the association with walking speed and self-assessed physical functioning and over 80% of the association with cognitive function. Our results suggest that lung function is a good “summary” measure of overall functioning in early old age.
doi:10.1007/s11357-010-9189-x
PMCID: PMC3168608  PMID: 20878489
Aged; Aging; physiology; psychology; Cognition; physiology; Female; Health Status; Humans; Lung; physiology; Male; Middle Aged; Spirometry; Walking; physiology; ageing; lung function; cognitive function; physical function
14.  Does cognitive reserve shape cognitive decline? 
Annals of neurology  2011;70(2):296-304.
Objectives
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 three markers of reserve from different points in the lifecourse on cognitive function and decline in late adulthood.
Methods
Data are from 5234 men and 2220 women, mean age 56 years (standard deviation=6) at baseline, from the Whitehall II cohort study. Memory, reasoning, vocabulary, phonemic and semantic fluency were assessed three times 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 three reserve measures were associated with baseline cognitive function, with strongest associations 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, −0.26) compared to the intermediate (−0.23; 95% CI: −0.25, −0.22) and low groups (−0.21; 95% CI: −0.24, −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 lifecourse was remarkably higher in the high reserve groups. However, rate of cognitive decline did not differ between reserve groups except occupation where there was some evidence of greater decline in the high occupation group.
doi:10.1002/ana.22391
PMCID: PMC3152621  PMID: 21563209
15.  Socioeconomic Status, Structural and Functional Measures of Social Support, and Mortality 
American Journal of Epidemiology  2012;175(12):1275-1283.
The authors examined the associations of social support with socioeconomic status (SES) and with mortality, as well as how SES differences in social support might account for SES differences in mortality. Analyses were based on 9,333 participants from the British Whitehall II Study cohort, a longitudinal cohort established in 1985 among London-based civil servants who were 35–55 years of age at baseline. SES was assessed using participant's employment grades at baseline. Social support was assessed 3 times in the 24.4-year period during which participants were monitored for death. In men, marital status, and to a lesser extent network score (but not low perceived support or high negative aspects of close relationships), predicted both all-cause and cardiovascular mortality. Measures of social support were not associated with cancer mortality. Men in the lowest SES category had an increased risk of death compared with those in the highest category (for all-cause mortality, hazard ratio = 1.59, 95% confidence interval: 1.21, 2.08; for cardiovascular mortality, hazard ratio = 2.48, 95% confidence interval: 1.55, 3.92). Network score and marital status combined explained 27% (95% confidence interval: 14, 43) and 29% (95% confidence interval: 17, 52) of the associations between SES and all-cause and cardiovascular mortality, respectively. In women, there was no consistent association between social support indicators and mortality. The present study suggests that in men, social isolation is not only an important risk factor for mortality but is also likely to contribute to differences in mortality by SES.
doi:10.1093/aje/kwr461
PMCID: PMC3372313  PMID: 22534202
cohort; longitudinal; mortality; social class; social support
16.  TRAJECTORIES OF DEPRESSIVE EPISODES AND HYPERTENSION OVER 24 YEARS: THE WHITEHALL II PROSPECTIVE COHORT STUDY 
Hypertension  2011;57(4):710-716.
Prospective data on depressive symptoms and blood pressure (BP) are scarce, and the impact of age on this association is poorly understood. The present study examines longitudinal trajectories of depressive episodes and the probability of hypertension associated with these trajectories over time. Participants were 6,889 men and 3,413 women London based civil servants, aged 35–55 years at baseline, followed for 24 years between 1985 and 2009. Depressive episode (defined as scoring 4 or more on the General Health Questionnaire-Depression subscale or using prescribed antidepressant medication) and hypertension (systolic/diastolic blood pressure ≥ 140/90 mm Hg or use of antihypertensive medication) were assessed concurrently at five medical examinations. In the fully adjusted longitudinal logistic regression analyses based on Generalized-Estimating-Equations using age as the time scale, participants in the “increasing depression” group had a 24% (p<0.05) lower risk of hypertension at ages 35–39, compared to those in the “low/transient depression” group. However, there was a faster age-related increase in hypertension in the “increasing depression” group, corresponding to a 7% (p<0.01) greater increase in the odds of hypertension for every each five-year increase in age. A higher risk of hypertension in the first group of participants was not evident before age 55. A similar pattern of association was observed in men and women although it was stronger in men. This study suggests that the risk of hypertension increases with repeated experience of depressive episodes over time and becomes evident in later adulthood.
doi:10.1161/HYPERTENSIONAHA.110.164061
PMCID: PMC3065997  PMID: 21339474
Depression; hypertension; longitudinal analysis; repeated measures
17.  Do different measures of early life socioeconomic circumstances predict adult mortality? Evidence from the British Whitehall II and French GAZEL studies 
Background
Father’s occupational position, education and height have all been used to examine the effects of adverse early life socioeconomic circumstances on health, but it remains unknown whether they predict mortality equally well.
Methods
We used pooled data on 18393 men and 7060 women from the Whitehall-II and GAZEL cohorts to examine associations between early life socioeconomic circumstances and all-cause and cause-specific mortality.
Results
During the 20-year follow-up period, 1487 participants died. Education had a monotonic association with all mortality outcomes, the age, sex and cohort adjusted Hazard Ratio (HR) for the lowest versus the highest educational group was 1.45 (95% Confidence Interval (CI): 1.24,1.69) for all-cause mortality. There was evidence of a U-shaped association between height and all-cause, cancer and cardiovascular mortality, robust to adjustment for the other indicators (HR=1.41; 95% CI: 1.03,1.93 for those shorter-than-average and HR=1.36; 95% CI: 0.98,1.88 for those taller-than-average for cardiovascular (CVD) mortality). Greater all-cause and cancer mortality was observed in participants whose father’s occupational position was manual rather than non-manual (HR=1.11; 95% CI: 1.00,1.23 for all-cause mortality), but the risks were attenuated after adjusting for education and height.
Conclusions
The association between early life socioeconomic circumstances and mortality depends on the socioeconomic indicator used and the cause of death examined. Height is not a straightforward measure of early life socioeconomic circumstances as taller people do not have a health advantage for all mortality outcomes.
doi:10.1136/jech.2009.102376
PMCID: PMC3294283  PMID: 20675701
Body height; early life; cohort studies; education; mortality; occupational position; Adult; Aged; Cardiovascular Diseases; mortality; Cause of Death; Cohort Studies; Female; Follow-Up Studies; France; epidemiology; Great Britain; epidemiology; Humans; Male; Middle Aged; Neoplasms; mortality; Occupations; Proportional Hazards Models; Risk; Risk Factors; Social Class
18.  Predictive utility of the Framingham general cardiovascular disease risk profile for cognitive function: evidence from the Whitehall II study 
European Heart Journal  2011;32(18):2326-2332.
Aims
Vascular risk factors are associated with cognitive impairment and dementia, although most of the research in this domain focuses on cerebrovascular factors. We examined the relationship between the recently developed Framingham general cardiovascular risk profile and cognitive function and 10-year decline in late midlife.
Methods and results
Study sample comprised of 3486 men and 1341 women, mean age 55 years [standard deviation (SD)=6], from the Whitehall II study, a longitudinal British cohort study. The Framingham General Cardiovascular Risk profile, assessed between 1997 and 1999, included age, sex, HDL cholesterol, total cholesterol, systolic blood pressure, smoking status, and diabetes status. Measures of cognitive function consisted of tests of reasoning (Alice Heim 4-I), memory, phonemic and semantic fluency, and vocabulary (Mill-Hill), assessed three times (1997–1999, 2002–2004, 2007–2009) over 10 years. In cross-sectional age-adjusted models, 10% point increments in cardiovascular risk were associated with poor performance in all cognitive domains in both men and women (all P-values <0.001). In models adjusted for age, ethnicity, marital status, and education, 10% higher cardiovascular risk was associated with greater overall 10-year cognitive decline in men, reasoning in particular (−0.47; 95% CI: −0.81, −0.11).
Conclusion
In middle-aged individuals free of cardiovascular disease, an adverse cardiovascular risk profile is associated with poor cognitive function, and decline in at least one cognitive domain in men.
doi:10.1093/eurheartj/ehr133
PMCID: PMC3172575  PMID: 21606085
Framingham General Cardiovascular Profile; Cognitive function; Cardiovascular risk scores; Cognitive decline
19.  Adult education and child mortality in India: the influence of caste, household wealth, and urbanization 
Epidemiology (Cambridge, Mass.)  2008;19(2):294-301.
Objective
To examine the association between adult education and child mortality, and to explore the influence of other socioeconomic markers - caste, household wealth and urbanization - on this association.
Methods
Data were drawn from the 1998–1999 Indian National Family Health Survey from 26 states on 66367 children aged 5 or under. Adult education, head of household and spouse, was categorized into 0, 1–8, and 9 or more years of schooling. Logistic regression was used to estimate associations between measures of education and child mortality in analysis adjusted for other socioeconomic markers. Effect modification by caste, household wealth and urbanization was assessed by fitting an interaction term with education.
Results
Compared to those with no education, 9 or more years of education for the head of household (OR=0.54: 95% CI=0.48–0.62) and the spouse (OR=0.44: 95% CI=0.36–0.54) was associated with lower child mortality in analyses adjusted for age, sex and state of residence. Further adjustments for caste and urbanization attenuated these associations slightly and substantially when adjustments were made for household wealth. Nevertheless, in fully adjusted models, nine or more years of education for the head of household (OR=0.81: 95% CI=0.70–0.93) and the spouse (OR=0.75: 95% CI=0.60–0.94) remained associated with child mortality. There was no effect modification by caste, household wealth and urbanization of the association between adult education and child mortality.
Conclusion
Our results suggest that adult education has a protective association with child mortality in India. Caste, household wealth and urbanization do not modify or completely attenuate this association.
doi:10.1097/EDE.0b013e3181632c75
PMCID: PMC3056118  PMID: 18300716
Censuses; Child Mortality; Child, Preschool; Educational Status; Effect Modifiers (Epidemiology); Female; Health Surveys; Humans; Income; India; epidemiology; Infant; Infant Mortality; Infant, Newborn; Logistic Models; Male; Social Class; Socioeconomic Factors; Urbanization
20.  Health Behaviours, Socioeconomic Status, and Mortality: Further Analyses of the British Whitehall II and the French GAZEL Prospective Cohorts 
PLoS Medicine  2011;8(2):e1000419.
Further analysis of data from two prospective cohorts reveals differences in the extent to which health behaviors attenuate associations between socioeconomic position and mortality outcomes.
Background
Differences in morbidity and mortality between socioeconomic groups constitute one of the most consistent findings of epidemiologic research. However, research on social inequalities in health has yet to provide a comprehensive understanding of the mechanisms underlying this association. In recent analysis, we showed health behaviours, assessed longitudinally over the follow-up, to explain a major proportion of the association of socioeconomic status (SES) with mortality in the British Whitehall II study. However, whether health behaviours are equally important mediators of the SES-mortality association in different cultural settings remains unknown. In the present paper, we examine this issue in Whitehall II and another prospective European cohort, the French GAZEL study.
Methods and Findings
We included 9,771 participants from the Whitehall II study and 17,760 from the GAZEL study. Over the follow-up (mean 19.5 y in Whitehall II and 16.5 y in GAZEL), health behaviours (smoking, alcohol consumption, diet, and physical activity), were assessed longitudinally. Occupation (in the main analysis), education, and income (supplementary analysis) were the markers of SES. The socioeconomic gradient in smoking was greater (p<0.001) in Whitehall II (odds ratio [OR]  = 3.68, 95% confidence interval [CI] 3.11–4.36) than in GAZEL (OR  = 1.33, 95% CI 1.18–1.49); this was also true for unhealthy diet (OR  = 7.42, 95% CI 5.19–10.60 in Whitehall II and OR  = 1.31, 95% CI 1.15–1.49 in GAZEL, p<0.001). Socioeconomic differences in mortality were similar in the two cohorts, a hazard ratio of 1.62 (95% CI 1.28–2.05) in Whitehall II and 1.94 in GAZEL (95% CI 1.58–2.39) for lowest versus highest occupational position. Health behaviours attenuated the association of SES with mortality by 75% (95% CI 44%–149%) in Whitehall II but only by 19% (95% CI 13%–29%) in GAZEL. Analysis using education and income yielded similar results.
Conclusions
Health behaviours were strong predictors of mortality in both cohorts but their association with SES was remarkably different. Thus, health behaviours are likely to be major contributors of socioeconomic differences in health only in contexts with a marked social characterisation of health behaviours.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The influence of the socioeconomic environment on the health of individuals and populations is well known, giving rise to the so-called social determinants of health. The social determinants of health are the conditions in which people are born, grow, live, work, and age, including the health system. These circumstances are shaped by the distribution of money, power, and resources at global, national, and local levels, which are themselves influenced by policy choices. The social determinants of health are mostly responsible for health inequities—the unfair and avoidable differences in health status seen within and between countries. In addition, health-damaging behaviors are often strongly socially patterned. For example, material constraints, lack of knowledge, and limited opportunities to follow health promoting messages often act as barriers that prevent those from lower socioeconomic groups to adopt a healthy lifestyle. Yet the extent to which health behaviors explain social inequalities in health remains unclear and can range from 12% to 72% according to some studies.
Why Was This Study Done?
In a recently published paper using data from the British Whitehall II cohort, the researchers showed that longitudinal assessment of health behaviors accounted for socioeconomic differences in mortality better than a single baseline assessment as used in most previous studies. (The Whitehall II study started in 1985 to examine the socioeconomic gradient in health among 10,308 London-based civil servants [6,895 men and 3,413 women] aged 35–55).
However, it is not clear whether health behaviors are equally important mediators of the socioeconomic-health association in different cultural settings. In this study, the researchers examine this issue by comparing their recent findings of the Whitehall II study with another European cohort, the French GAZEL study. (The GAZEL study started in 1989 among employees of the French national gas and electricity company totaling 20,625 employees [15,011 men and 5,614 women], aged 35–50.) The Whitehall II study and the GAZEL study have comparable designs in the way both assess socioeconomic status, health behaviors, and mortality and have a similar age range and follow-up period.
What Did the Researchers Do and Find?
The researchers included 9,771 participants from the Whitehall II study and 17,760 from the GAZEL study—mean follow up for Whitehall II was 19.5 years and for GAZEL was 16.5 years. The researchers used occupation as the main marker of socioeconomic status, and education and income as supplementary markers of socioeconomic status. Apart from a few exceptions, the researchers analyzed each cohort separately and used statistical techniques to calculate: the mortality rates per 1000 person-years for each socioeconomic group; the age- and sex-adjusted prevalence rates of smoking, heavy alcohol consumption, unhealthy diet, and physical inactivity, at the first and the last follow-up of the study for each socioeconomic group; and the differences in health behaviors prevalence between lowest and highest occupational position. Then the researchers used a statistical model to deduce the contribution of all health behaviors.
The researchers found that the socioeconomic gradient in smoking, unhealthy diet, and physical inactivity was greater in Whitehall II than in GAZEL. Socioeconomic differences in mortality were similar in the two cohorts, a hazard ratio of 1.62 in Whitehall II and 1.94 in GAZEL for lowest versus highest occupational position. Health behaviors weakened the association between socioeconomic status and mortality by 75% in Whitehall II but only by 19% in GAZEL. The supplementary analysis the researchers conducted using education and income as socioeconomic markers gave similar results.
What Do These Findings Mean?
These results suggest that the social patterning of unhealthy behaviors differs between countries. Although in both cohorts socioeconomic status and health behaviors were strong predictors of mortality, major differences in the social patterning of unhealthy behaviors in the two cohorts meant that the causal chains leading from socioeconomic status to health behaviors to mortality were different. Therefore it may be that health behaviors are likely to only be major contributors of socioeconomic differences in health in contexts with a marked social characterization of those behaviors. In order to identify the common and unique determinants of social inequalities in health in different populations, there needs to be further comparative research on the relative importance of different pathways linking socioeconomic status to health.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000419.
WHO provides information on social determinants of health
University College London provides information on the Whitehall study
The GAZEL study is available in an online open access format
doi:10.1371/journal.pmed.1000419
PMCID: PMC3043001  PMID: 21364974
21.  Socioeconomic position and cognitive decline using data from 2 waves: What is the role of the wave 1 cognitive measure? 
Background
Analysis of change in health status using data from two waves can be examined either adjusted or unadjusted for baseline health status. We assess the effect of socioeconomic position (SEP) on cognitive change using both these strategies and discuss the implications of the analyses.
Methods
Data come from 1261 men and 483 women of the Whitehall II cohort study, aged 50-55 years at wave 1. Cognition was assessed at both waves using a test of verbal memory, and two tests of verbal fluency. Analysis of Variance (ANOVA) was used to estimate the effect of SEP on change score and analysis of covariance (ANCOVA) to estimate this effect adjusted for the baseline cognitive score. Then the ANCOVA estimates were corrected for bias due to measurement error (estimated based on 3-month test-retest). Finally, ANCOVA estimates were examined for increasing levels of measurement error.
Results
The results of the ANOVA suggest no effect of SEP on cognitive decline. In contrast, the ANCOVA suggests significantly greater cognitive decline in the lower SEP groups. However, the ANCOVA estimates for the effect of wave 1 cognition show evidence for regression to the mean due to the presence of measurement error. The corrected ANCOVA estimates show no association between SEP and cognitive decline.
Conclusions
We recommend caution when using ANCOVA, or adjustment for baseline, in the analysis of change using two waves of observational data.
doi:10.1136/jech.2008.081281
PMCID: PMC2789968  PMID: 19406741
t-test; ANCOVA; Lord's paradox; cognitive decline
22.  Hostility and Trajectories of Body Mass Index Over 19 Years 
American Journal of Epidemiology  2008;169(3):347-354.
The authors examined the associations of hostility measured in adulthood with subsequent body mass index (BMI; weight (kg)/height (m)2) assessed at 4 time points over a 19-year period (1985–2004) in a United Kingdom cohort study. A total of 6,484 participants (4,494 men and 1,990 women) aged 35–55 years at baseline (1985–1988) completed the Cook-Medley Hostility Scale. BMI was assessed upon medical examination in phases 1 (1985–1988), 3 (1991–1993), 5 (1997–1999), and 7 (2002–2004). Mixed-models analyses of repeated measures showed clear evidence of increasing BMI over follow-up in both sexes. In women, higher levels of hostility were associated with higher BMI at baseline, and this effect remained constant throughout the follow-up period. In men, hostility levels were also strongly associated with BMI at baseline, but results for the interaction between time and hostility also suggested that this association increased over time, with persons in the highest quartile of hostility gaining an excess of 0.016 units (P = 0.023) annually over the follow-up period as compared with persons in the lowest quartile. The authors conclude that the difference in BMI as a function of hostility levels in men is not stable over time.
doi:10.1093/aje/kwn333
PMCID: PMC2720716  PMID: 19022830
body mass index; health behavior; hostility; psychology
23.  Hostility and trajectories of body mass index over 19 years: the Whitehall II Study 
American Journal of Epidemiology  2008;169(3):347-354.
The authors examined the associations of hostility measured in adulthood with subsequent BMI assessed at four time points over a 19-year period in a United-Kingdom cohort study. A total of 6,484 participants (4,494 men and 1,990 women) aged 35–55 years at baseline (1985–1988) completed the Cook-Medley-hostility-scale for hostility. BMI (kg/m2) was assessed at medical examination at phases 1 (1985–1988), 3 (1991–1993), 5 (1997–1999) and 7(2002–2004). Mixed models analyses of repeated-measures showed clear evidence of increasing BMI over the follow-up in both sexes. In women, higher levels of hostility were associated with higher BMI at baseline and this effect remained constant over the follow-up period. In men, hostility levels were also strongly associated with BMI at baseline but results of the interaction term between time and hostility also suggest that this association increased over time, with the highest quartile of hostility gaining an excess of 0.016 kg/m2 (p=0.023) annually over the follow-up period compared to the lowest quartile. The authors conclude that the difference in BMI as function of the hostility levels in men is not stable over time.
doi:10.1093/aje/kwn333
PMCID: PMC2720716  PMID: 19022830
Adult; Body Mass Index; Cohort Studies; Female; Great Britain; Hostility; Humans; Male; Middle Aged; Social Class; body mass index; health behaviours; hostility; mixed models; psychological factors; repeated measures
24.  The role of conventional risk factors in explaining social inequalities in coronary heart disease: the relative and absolute approaches to risk 
Epidemiology (Cambridge, Mass.)  2008;19(4):599-605.
Background
Various methodologic approaches have been used to estimate the role of risk factors in explaining the social gradient in coronary heart disease (CHD).
Objective
Our objective was to examine whether there is a discrepancy in results obtained using the relative and absolute approaches.
Methods
Data are from the Whitehall II prospective cohort study on 5,363 men who were 40–62 years old at the start of the 11-year follow-up period.
Results
One or more of the four conventional risk factors examined (smoking, hypertension, high cholesterol, and diabetes) were present for 77% of individuals in the low compared with 68% in the high socioeconomic group. The relative risk for incident CHD in the low socioeconomic group was 1.66 (95% confidence interval = 1.20 to 2.29) compared with the high group. Standardizing the distribution of risk factors in the low- and high-socioeconomic group to the overall study sample reduced relative risk by 16% and absolute risk by 14%. We also computed the population attributable risk (PAR) to indicate the reduction in CHD if the risk factor was completely removed from the population. The PAR associated with having at least one risk factor was 41% (95% confidence interval = 33% to 57%) in the high and 58% (13% to 91%) in the low socioeconomic group.
Conclusions
In situations where the goal is to remove social differences in the distribution of risk factors, conventional risk factors explain a similar proportion of the social gradient in CHD whether using the relative or absolute approaches to change in risk. This is not comparable to population attributable risk calculations, in which the goal is to completely remove the risk factors from the population. Failure to recognize that these methods address different questions seems to be the reason for discrepancies in previous results.
doi:10.1097/EDE.0b013e3181761cdc
PMCID: PMC2727630  PMID: 18467960
Adult; Cohort Studies; Coronary Disease; epidemiology; physiopathology; Follow-Up Studies; Health Status Disparities; Humans; Male; Middle Aged; Prospective Studies; Risk Assessment; Risk Factors; Role; Socioeconomic Factors
25.  The association between self-rated health and mortality in different socioeconomic groups in the GAZEL cohort study 
Objectives
Self-rated-health (SRH) is considered a valid measure of health status as it has been shown to predict mortality in several studies. We examine whether SRH predicts mortality equally well in different socioeconomic groups.
Methods
Data (14879 men and 5525 women) are drawn from GAZEL, a prospective cohort study of French public utility workers. Data on SRH and the socioeconomic measures (education, occupational position and income) were taken from the baseline questionnaire (1989), when the average age of individuals was 44.2 years (SD = 3.5). Mortality follow-up was available for a mean of 17.2 years and analysed over the first 10 years and over the entire follow-up period. Associations between SRH and mortality were assessed using Cox regression models using the Relative Index of Inequality (RII) to summarize associations.
Results
The RII for the association between SRH and mortality over the first 10 years was 6.78 (95% confidence interval (CI)=3.33–13.81) in the lowest occupational group and 2.10 (95% CI = 0.97–4.54) in the highest. For income, the RIIs were 8.82 (95% CI=4.70–16.54) for the lowest and 1.80 (95% CI=0.86–3.80) for the highest groups respectively. Findings over the full follow-up period were similar. The association between SRH and mortality was weaker in the high occupation and income groups, both in the short and the long term. The results for education were similar but generally weaker than for the other socioeconomic measures.
Conclusions
The predictive ability of SRH for mortality weakens with increasing socioeconomic advantage among middle-aged individuals. Thus SRH appears not to measure “true” health status in a similar way across socioeconomic categories.
doi:10.1093/ije/dym170
PMCID: PMC2610258  PMID: 18025034
Adult; Employment; Female; Follow-Up Studies; Forecasting; France; epidemiology; Health Status; Health Surveys; Humans; Male; Mortality; trends; Proportional Hazards Models; Self Concept; Social Class; socio-economic factors; occupation; income; education

Results 1-25 (26)