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author:("Sabia, serine")
1.  Non-Consent to a Wrist-Worn Accelerometer in Older Adults: The Role of Socio-Demographic, Behavioural and Health Factors 
PLoS ONE  2014;9(10):e110816.
Background
Accelerometers, initially waist-worn but increasingly wrist-worn, are used to assess physical activity free from reporting-bias. However, its acceptability by study participants is unclear. Our objective is to assess factors associated with non-consent to a wrist-mounted accelerometer in older adults.
Methods
Data are from 4880 Whitehall II study participants (1328 women, age range = 60–83), requested to wear a wrist-worn accelerometer 24 h every day for 9 days in 2012/13. Sociodemographic, behavioral, and health-related factors were assessed by questionnaire and weight, height, blood pressure, cognitive and motor function were measured during a clinical examination.
Results
210 participants had contraindications and 388 (8.3%) of the remaining 4670 participants did not consent. Women, participants reporting less physical activity and less favorable general health were more likely not to consent. Among the clinical measures, cognitive impairment (Odds Ratio = 2.21, 95% confidence interval: 1.22–4.00) and slow walking speed (Odds Ratio = 1.38, 95% confidence interval: 1.02–1.86) were associated with higher odds of non-consent.
Conclusions
The rate of non-consent in our study of older adults was low. However, key markers of poor health at older ages were associated with non-consent, suggesting some selection bias in the accelerometer data.
doi:10.1371/journal.pone.0110816
PMCID: PMC4208789  PMID: 25343453
2.  Association of body mass index and waist circumference with successful ageing: 16 year follow-up of the Whitehall II study 
Obesity (Silver Spring, Md.)  2013;22(4):1172-1178.
Objective
We examined whether midlife body mass index (BMI) and waist circumference (WC) predict successful ageing.
Design and Methods
BMI/WC were assessed in 4869 persons (mean age 51.2, range 42–63 in 1991/93) and survival and successful ageing (alive, no chronic disease at age >60 years, not in the worst age- and sex-standardized quintile of cognitive, physical, respiratory, and cardiovascular, and mental health) ascertained over a 16-year follow-up, analysed using logistic regression adjusted for socio-demographic factors and health behaviours.
Results
507 participants died, 1008 met the criteria for successful ageing. Those with BMI≥30 kg/m2 had lower odds of successful ageing (Odds Ratio (OR)=0.37; 95% Confidence Interval (CI): 0.27, 0.50) and survival (OR=0.55; 95% CI: 0.41, 0.74) compared to BMI between 18.5–25 kg/m2. Those with a large waist circumference (≥102/88 cm in men/women) had lower odds of successful ageing (OR=0.41; 95% CI: 0.31, 0.54) and survival (OR=0.57; 95% CI: 0.44, 0.73) compared to those with a small waist (<94/80 cm in men/women). Analysis with finer categories showed lower odds of successful ageing starting at BMI ≥23.5 kg/m2 and waist circumference 82/68 cm in men/women.
Conclusions
Optimal midlife BMI and waist circumference for successful ageing might be substantially below the current thresholds used to define obesity.
doi:10.1002/oby.20651
PMCID: PMC3968224  PMID: 24167036
obesity; body mass index; waist circumference; ageing
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.  Combined impact of smoking and heavy alcohol use on cognitive decline in early old age: Whitehall II prospective cohort study 
The British Journal of Psychiatry  2013;203(2):120-125.
Background
Identifying modifiable risk factors for cognitive decline may inform prevention of dementia.
Aims
To examine the combined impact of cigarette smoking and heavy alcohol consumption on cognitive decline from midlife.
Method
Prospective cohort study (Whitehall II cohort) with three clinical examinations in 1997/99, 2002/04 and 2007/09. Participants were 6473 adults (72% men), mean age 55.76 years (s.d. = 6.02) in 1997/99. Four cognitive tests, assessed three times over 10 years, combined into a global z-score (mean 0, s.d. = 1).
Results
Age-related decline in the global cognitive score was faster in individuals who were smoking heavy drinkers than in non-smoking moderate alcohol drinkers (reference group). The interaction term (P = 0.04) suggested that the combined effects of smoking and alcohol consumption were greater than their individual effects. Adjusting for age, gender, education and chronic diseases, 10-year decline in global cognition was –0.42 z-scores (95% CI –0.45 to –0.39) for the reference group. In individuals who were heavy alcohol drinkers who also smoked the decline was –0.57 z-scores (95% CI –0.67 to –0.48); 36% faster than the reference group.
Conclusions
Individuals who were smokers who drank alcohol heavily had a 36% faster cognitive decline, equivalent to an age-effect of 2 extra years over 10-year follow-up, compared with individuals who were non-smoking moderate drinkers.
doi:10.1192/bjp.bp.112.122960
PMCID: PMC3730115  PMID: 23846998
5.  Combined effect of physical activity and leisure time sitting on long-term risk of incident obesity and metabolic risk factor clustering 
Diabetologia  2014;57(10):2048-2056.
Aims/hypothesis
Our study aimed to investigate the combined effects of moderate-to-vigorous physical activity and leisure time sitting on the long-term risk of obesity and clustering of metabolic risk factors.
Methods
The duration of moderate and vigorous physical activity and of leisure time sitting was assessed by questionnaire between 1997 and 1999 among 3,670 participants from the Whitehall II cohort study (73% male; mean age 56 years). Multivariable-adjusted logistic regression models examined associations of physical activity and leisure time sitting tertiles with odds of incident obesity (BMI ≥ 30 kg/m2) and incident metabolic risk factor clustering (two or more of the following: low HDL-cholesterol, high triacylglycerol, hypertension, hyperglycaemia, insulin resistance) at 5 and 10 year follow-ups.
Results
Physical activity, but not leisure time sitting, was associated with incident obesity. The lowest odds of incident obesity after 5 years were observed for individuals reporting both high physical activity and low leisure time sitting (OR = 0.26; 95% CI 0.11, 0.64), with weaker effects after 10 years. Compared with individuals in the low physical activity/high leisure time sitting group, those with intermediate levels of both physical activity and leisure time sitting had lower odds of incident metabolic risk factor clustering after 5 years (OR 0.53; 95% CI 0.36, 0.78), with similar odds after 10 years.
Conclusions/interpretation
Both high levels of physical activity and low levels of leisure time sitting may be required to substantially reduce the risk of obesity. Associations with developing metabolic risk factor clustering were less clear.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-014-3323-8) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
doi:10.1007/s00125-014-3323-8
PMCID: PMC4153972  PMID: 25078481
Epidemiology; Exercise; Metabolic syndrome; Obesity; Weight regulation
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.  Low Conscientiousness and Risk of All-Cause, Cardiovascular and Cancer Mortality over 17 Years: Whitehall II Cohort Study 
Objective
To examine the personality trait conscientiousness as a risk factor for mortality and to identify candidate explanatory mechanisms.
Methods
Participants in the Whitehall II cohort study (N = 6800, aged 34 to 55 at recruitment in 1985) completed two self-reported items measuring conscientiousness in 1991–1993 (‘I am overly conscientious’ and ‘I am overly perfectionistic’, Cronbach's α = .72), the baseline for this study. Age, socio-economic status (SES), social support, health behaviours, physiological variables and minor psychiatric morbidity were also recorded at baseline. The vital status of participants was then monitored for a mean of 17 years. All-cause and cause-specific mortality was ascertained through linkage to a national mortality register until January 2010.
Results
Each 1 standard deviation decrease in conscientiousness was associated with a 10% increase in all-cause (hazard ratio [HR] = 1.10, 95% CI 1.003, 1.20) mortality. Patterns were similar for cardiovascular (HR = 1.17, 95% CI 0.98, 1.39) and cancer mortality (HR = 1.10, 95% CI 0.96, 1.25), not reaching statistical significance. The association with all-cause mortality was attenuated by 5% after adjustment for SES, 13% for health behaviours, 14% for cardiovascular risk factors, 5% for minor psychiatric morbidity, 29% for all variables. Repeating analyses with each item separately and excluding participants who died within five years of personality assessment did not change the results materially.
Conclusion
Low conscientiousness in midlife is a risk factor for all-cause mortality. This association is only partly explained by health behaviours, SES, cardiovascular disease risk factors and minor psychiatric morbidity in midlife.
doi:10.1016/j.jpsychores.2012.05.007
PMCID: PMC3936113  PMID: 22789411
cohort study; conscientiousness; mortality; perfectionism; personality traits; socio-economic status
8.  Association Between Questionnaire- and Accelerometer-Assessed Physical Activity: The Role of Sociodemographic Factors 
American Journal of Epidemiology  2014;179(6):781-790.
The correlation between objective and self-reported measures of physical activity varies between studies. We examined this association and whether it differed by demographic factors or socioeconomic status (SES). Data were from 3,975 Whitehall II (United Kingdom, 2012–2013) participants aged 60–83 years, who completed a physical activity questionnaire and wore an accelerometer on their wrist for 9 days. There was a moderate correlation between questionnaire- and accelerometer-assessed physical activity (Spearman's r = 0.33, 95% confidence interval: 0.30, 0.36). The correlations were higher in high-SES groups than in low-SES groups (P 's = 0.02), as defined by education (r = 0.38 vs. r = 0.30) or occupational position (r = 0.37 vs. r = 0.29), but did not differ by age, sex, or marital status. Of the self-reported physical activity, 68.3% came from mild activities, 25% from moderate activities, and only 6.7% from vigorous activities, but their correlations with accelerometer-assessed total physical activity were comparable (range of r 's, 0.21–0.25). Self-reported physical activity from more energetic activities was more strongly associated with accelerometer data (for sports, r = 0.22; for gardening, r = 0.16; for housework, r = 0.09). High-SES persons reported more energetic activities, producing stronger accelerometer associations in these groups. Future studies should identify the aspects of physical activity that are most critical for health; this involves better understanding of the instruments being used.
doi:10.1093/aje/kwt330
PMCID: PMC3939851  PMID: 24500862
accelerometry; cohort studies; elderly; epidemiologic methods; physical activity; questionnaires
9.  Motor function in the elderly 
Neurology  2013;81(5):417-426.
Objective:
The reserve hypothesis accounts for the lack of direct relationship between brain pathology and its clinical manifestations. Research has mostly focused on cognition; our objective is to examine whether the reserve hypothesis applies to motor function. We investigated whether education, a marker of reserve, modifies the association between white matter lesions (WMLs), a marker of vascular brain damage, and maximum walking speed (WS), an objective measure of motor function. We also examined the cross-sectional and longitudinal association between education and WS.
Methods:
Data are from 4,010 participants aged 65–85 years in the longitudinal Three-City–Dijon Study with up to 4 WS measures over 10 years. We examined the interaction between education and WMLs for baseline WS. We studied the association between education and repeated WS measures using linear mixed models, and the role of covariates in explaining the education-WS association.
Results:
Education was strongly associated with baseline WS; the difference in mean WS between the high and low education groups (0.145 m/s, 95% confidence interval = 0.125–0.165) was equivalent to 7.4 years of age. WMLs were associated with slow WS only in the low education group (p interaction = 0.026). WS declined significantly over time (−0.194 m/s/10 years, 95% confidence interval = −0.206, −0.182), but education did not influence rate of decline. Anthropometric characteristics, parental education, general health, and cognition had the strongest role in explaining the baseline education-WS association.
Conclusions:
Participants with more education were less susceptible to WMLs' effect on motor function. Higher education was associated with better motor performances but not with motor decline. These results are consistent with the passive reserve hypothesis.
doi:10.1212/WNL.0b013e31829d8761
PMCID: PMC3776533  PMID: 23803317
10.  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
11.  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
12.  Does Overall Diet in Midlife Predict Future Aging Phenotypes? A Cohort Study 
The American Journal of Medicine  2013;126(5):411-419.e3.
Background
The impact of diet on specific age-related diseases has been studied extensively, but few investigations have adopted a more holistic approach to determine the association of diet with overall health at older ages. We examined whether diet, assessed in midlife, using dietary patterns and adherence to the Alternative Healthy Eating Index (AHEI), is associated with aging phenotypes, identified after a mean 16-year follow-up.
Methods
Data were drawn from the Whitehall II cohort study of 5350 adults (age 51.3 ± 5.3 years, 29.4% women). Diet was assessed at baseline (1991-1993). Mortality, chronic diseases, and functioning were ascertained from hospital data, register linkage, and screenings every 5 years and were used to create 5 outcomes at follow-up: ideal aging (free of chronic conditions and high performance in physical, mental, and cognitive functioning tests; 4%), nonfatal cardiovascular event (7.3%), cardiovascular death (2.8%), noncardiovascular death (12.7%), and normal aging (73.2%).
Results
Low adherence to the AHEI was associated with an increased risk of cardiovascular and noncardiovascular death. In addition, participants with a “Western-type” diet (characterized by high intakes of fried and sweet food, processed food and red meat, refined grains, and high-fat dairy products) had lower odds of ideal aging (odds ratio for top vs bottom tertile: 0.58; 95% confidence interval, 0.36-0.94; P = .02), independently of other health behaviors.
Conclusions
By considering healthy aging as a composite of cardiovascular, metabolic, musculoskeletal, respiratory, mental, and cognitive function, the present study offers a new perspective on the impact of diet on aging phenotypes.
doi:10.1016/j.amjmed.2012.10.028
PMCID: PMC3743043  PMID: 23582933
Aging; Cognitive functioning; Dietary patterns; Diet quality indices; Mortality; Nutritional epidemiology; Overall diet; Physical functioning
13.  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
14.  Adherence to healthy dietary guidelines and future depressive symptoms: evidence for sex differentials in the Whitehall II study1234 
Background: It has been suggested that dietary patterns are associated with future risk of depressive symptoms. However, there is a paucity of prospective data that have examined the temporality of this relation.
Objective: We examined whether adherence to a healthy diet, as defined by using the Alternative Healthy Eating Index (AHEI), was prospectively associated with depressive symptoms assessed over a 5-y period.
Design: Analyses were based on 4215 participants in the Whitehall II Study. AHEI scores were computed in 1991–1993 and 2003–2004. Recurrent depressive symptoms were defined as having a Center for Epidemiologic Studies Depression Scale score ≥16 or self-reported use of antidepressants in 2003–2004 and 2008–2009.
Results: After adjustment for potential confounders, the AHEI score was inversely associated with recurrent depressive symptoms in a dose-response fashion in women (P-trend < 0.001; for 1 SD in AHEI score; OR: 0.59; 95% CI: 0.47, 0.75) but not in men. Women who maintained high AHEI scores or improved their scores during the 10-y measurement period had 65% (OR: 0.35%; 95% CI: 0.19%, 0.64%) and 68% (OR: 0.32%; 95% CI: 0.13%, 0.78%) lower odds of subsequent recurrent depressive symptoms than did women who maintained low AHEI scores. Among AHEI components, vegetable, fruit, trans fat, and the ratio of polyunsaturated fat to saturated fat components were associated with recurrent depressive symptoms in women.
Conclusion: In the current study, there was a suggestion that poor diet is a risk factor for future depression in women.
doi:10.3945/ajcn.112.041582
PMCID: PMC3545684  PMID: 23283506
15.  Influence of individual and combined healthy behaviours on successful aging 
Background:
Increases in life expectancy make it important to remain healthy for as long as possible. Our objective was to examine the extent to which healthy behaviours in midlife, separately and in combination, predict successful aging.
Methods:
We used a prospective cohort design involving 5100 men and women aged 42–63 years. Participants were free of cancer, coronary artery disease and stroke when their health behaviours were assessed in 1991–1994 as part of the Whitehall II study. We defined healthy behaviours as never smoking, moderate alcohol consumption, physical activity (≥ 2.5 h/wk moderate physical activity or ≥ 1 h/wk vigorous physical activity), and eating fruits and vegetables daily. We defined successful aging, measured over a median 16.3-year follow-up, as good cognitive, physical, respiratory and cardiovascular functioning, in addition to the absence of disability, mental health problems and chronic disease (coronary artery disease, stroke, cancer and diabetes).
Results:
At the end of follow-up, 549 participants had died and 953 qualified as aging successfully. Compared with participants who engaged in no healthy behaviours, participants engaging in all 4 healthy behaviours had 3.3 times greater odds of successful aging (95% confidence interval [CI] 2.1–5.1). The association with successful aging was linear, with the odds ratio (OR) per increment of healthy behaviour being 1.3 (95% CI 1.2–1.4; population-attributable risk for 1–4 v. 0 healthy behaviours 47%). When missing data were considered in the analysis, the results were similar to those of our main analysis.
Interpretation:
Although individual healthy behaviours are moderately associated with successful aging, their combined impact is substantial. We did not investigate the mechanisms underlying these associations, but we saw clear evidence of the importance of healthy behaviours for successful aging.
doi:10.1503/cmaj.121080
PMCID: PMC3519184  PMID: 23091184
16.  Job Strain as a Risk Factor for Leisure-Time Physical Inactivity: An Individual-Participant Meta-Analysis of Up to 170,000 Men and Women 
American Journal of Epidemiology  2012;176(12):1078-1089.
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.
doi:10.1093/aje/kws336
PMCID: PMC3521479  PMID: 23144364
cohort studies; exercise; physical activity; psychosocial factors; working population
17.  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
18.  Combined Effects of Depressive Symptoms and Resting Heart Rate on Mortality: The Whitehall II Prospective Cohort Study 
The Journal of clinical psychiatry  2010;72(9):1199-1206.
Objective
To examine the combined effects of depressive symptoms and resting heart rate (RHR) on mortality.
Methods
Data come from 5936 participants, aged 61 ± 6 years, from the Whitehall II study. Depressive symptoms were assessed in 2002–2004 using the center-for-epidemiologic-studies-depression-scale (score ≥ 16). RHR was measured at the same study phase via electrocardiogram. Participants were assigned to 1 of 6 risk-factor-groups based on depression status (yes/no) and RHR categories (<60, 60 – 80, >80 bpm). Mean follow-up for mortality was 5.6 years.
Results
In mutually adjusted Cox regression models, depression (hazard ratio = 1.93 p<0.001) and RHR>80 bpm (hazard ratio = 1.67, p<0.001) were independent predictors of mortality. After adjustment for potential confounding and mediating variables, participants with both depression and high RHR had a 3.0-fold higher (p<0.001) risk of death compared to depression-free participants with RHR ranging from 60 to 80 bpm. This risk is particularly marked in participants with prevalent CHD.
Conclusions
This study provides evidence that the coexistence of depressive symptoms and elevated RHR is associated with substantially increased risk of death compared to those without these two factors. This finding raises the possibility that treatments that improve both depression and RHR might improve survival.
doi:10.4088/JCP.09m05901blu
PMCID: PMC3226937  PMID: 21208592
depression; resting heart rate and mortality
19.  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
20.  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
21.  Combined effects of depressive symptoms and resting heart rate on mortality: the Whitehall II prospective cohort study 
The Journal of Clinical Psychiatry  2010;72(9):1199-1206.
Objective
To examine the combined effects of depressive symptoms and resting heart rate (RHR) on mortality.
Methods
Data come from 5936 participants, aged 61 ±6 years, from the Whitehall II study. Depressive symptoms were assessed in 2002–2004 using the center-for-epidemiologic-studies-depression-scale (score ≥16). RHR was measured at the same study phase via electrocardiogram. Participants were assigned to 1 of 6 risk-factor-groups based on depression status (yes/no) and RHR categories (<60, 60–80, >80 bpm). Mean follow-up for mortality was 5.6 years.
Results
In mutually adjusted Cox regression models, depression (hazard ratio = 1.93 p<0.001) and RHR>80 bpm (hazard ratio = 1.67, p<0.001) were independent predictors of mortality. After adjustment for potential confounding and mediating variables, participants with both depression and high RHR had a 3.0-fold higher (p<0.001) risk of death compared to depression-free participants with RHR ranging from 60 to 80 bpm. This risk is particularly marked in participants with prevalent CHD.
Conclusions
This study provides evidence that the coexistence of depressive symptoms and elevated RHR is associated with substantially increased risk of death compared to those without these two factors. This finding raises the possibility that treatments that improve both depression and RHR might improve survival.
doi:10.4088/JCP.09m05901blu
PMCID: PMC3226937  PMID: 21208592
depression; resting heart rate and mortality
22.  Association of walking speed in late midlife with mortality: results from the Whitehall II cohort study 
Age  2012;35(3):943-952.
Slow walking speed is associated with increased mortality in the elderly, but it is unknown whether a similar association is present in late midlife. Our aim was to examine walking speed in late midlife as a predictor of mortality, as well as factors that may explain this association. Data are drawn from the Whitehall II longitudinal cohort study of British civil servants. The analyses are based on 6,266 participants (29% women; mean age = 61 years, SD = 6) for whom “walking speed at usual pace” was measured over 8 ft (2.44 m) at baseline. Participants were followed for all-cause and cause-specific mortalities during a mean of 6.4 (SD = 0.8) years. During this period, 227 participants died. Participants in the bottom sex-specific third of walking speed (men, <1.26 m/s; women, <1.09 m/s) had an increased risk of death compared to those in the middle and top thirds (age- and sex-adjusted hazard ratio = 1.89, 95% confidence interval (CI) = 1.45–2.46), with no evidence of effect modification by age or sex (interactions, P ≥ 0.40). The association between walking speed and mortality was partially explained by baseline inflammatory markers (percentage reduction of the association 22.8%), height and body mass index (16.6%), chronic diseases (14.0%), and health behaviors (13.4%). Together these and other baseline factors (socioeconomic status, cardiovascular risk factors, cognitive function) explained 48.5% of the association (adjusted hazard ratio = 1.39, 95% CI = 1.04–1.84). In conclusion, walking speed measured in late midlife seems to be an important marker of mortality risk; multiple factors, in particular inflammatory markers, partially explain this association.
Electronic supplementary material
The online version of this article (doi:10.1007/s11357-012-9387-9) contains supplementary material, which is available to authorized users.
doi:10.1007/s11357-012-9387-9
PMCID: PMC3636402  PMID: 22361996
Walking speed; Mortality; Inflammation; Cohort study; Epidemiology
23.  Rising adiposity curbing decline in the incidence of myocardial infarction: 20-year follow-up of British men and women in the Whitehall II cohort 
European heart journal  2011;33(4):478-485.
Aims
To estimate the contribution of risk factor trends to 20-year declines in myocardial infarction (MI) incidence in British men and women.
Methods and results
From 1985 to 2004, 6379 men and 3074 women in the Whitehall II cohort were followed for incident MI and risk factor trends. Over 20 years, the age–sex-adjusted hazard of MI fell by 74% (95% confidence interval 48–87%), corresponding to an average annual decline of 6.5% (3.2–9.7%). Thirty-four per cent (20–76%) of the decline in MI hazard could be statistically explained by declining non-HDL cholesterol levels, followed by increased HDL cholesterol (17%, 10–32%), reduced systolic blood pressure (13%, 7–24%), and reduced cigarette smoking prevalence (6%, 2–14%). Increased fruit and vegetable consumption made a non-significant contribution of 7% (−1–20%). In combination, these five risk factors explained 56% (34–112%). Rising body mass index (BMI) was counterproductive, reducing the scale of the decline by 11% (5–23%) in isolation. The MI decline and the impact of the risk factors appeared similar for men and women.
Conclusion
In men and women, over half of the decline in MI risk could be accounted for by favourable risk factor time trends. The adverse role of BMI emphasizes the importance of addressing the rising population BMI.
doi:10.1093/eurheartj/ehr142
PMCID: PMC3272419  PMID: 21653562
Myocardial infarction; Incidence; Time Trends; Population; Prevention; Risk factors
24.  High alcohol consumption in middle aged adults is associated with poorer cognitive performance only in the low socioeconomic group. Results from the GAZEL cohort study 
Addiction (Abingdon, England)  2010;106(1):93-101.
Aims
To examine the association of alcohol consumption over 10 years with cognitive performance in different socioeconomic groups.
Design
Prospective cohort study, the French GAZEL study.
Setting
France.
Participants
Employees of France’s national electricity and gas company.
Measurements
Alcohol intake was assessed annually, beginning in 1992, using questions on frequency and quantity of alcoholic beverages consumed in a week; used to define mean consumption and trajectory of alcohol intake over 10 years. Cognitive performance among participants aged ≥55 years (N=4073) was assessed in 2002–2004 using the Digit Symbol Substitution Test (DSST), a measure of psychomotor speed, attention and reasoning. Occupational position at age 35 and education were used as the markers of socioeconomic position.
Findings
All analyses were stratified by socioeconomic position. In the low occupational group, participants consuming a mean of more than 21 drinks per week had 2.1 points lower (95% CI: −3.9, −0.3) DSST score compared to those consuming 4–14 drinks per week. In participants with primary school education, the corresponding difference was 3.6 points (95% CI: −7.1,−0.0). No association between alcohol consumption and cognitive performance was observed in the intermediate and high socioeconomic groups, defined using either occupation or education. Analysis of trajectories of alcohol consumption showed that in the low socioeconomic groups large increase or decrease in alcohol consumption was associated with lower cognitive scores compared to stable consumption.
Conclusions
Our results suggest that high alcohol consumption is associated with poorer cognitive performance only in the low socioeconomic group, possibly due to greater cognitive reserve in the higher socioeconomic groups.
doi:10.1111/j.1360-0443.2010.03106.x
PMCID: PMC3006084  PMID: 20840170
25.  Why Does Lung Function Predict Mortality? Results From the Whitehall II Cohort Study 
American Journal of Epidemiology  2010;172(12):1415-1423.
The authors examined the extent to which socioeconomic position, behavior-related factors, cardiovascular risk factors, inflammatory markers, and chronic diseases explain the association between poor lung function and mortality in 4,817 participants (68.9% men) from the Whitehall II Study aged 60.8 years (standard deviation, 5.9), on average. Forced expiratory volume in 1 second (FEV1) was used to measure lung function in 2002–2004. A total of 139 participants died during a mean follow-up period of 6.4 years (standard deviation, 0.8). In a model adjusted for age and sex, being in the lowest tertile of FEV1/height2 was associated with a 1.92-fold (95% confidence interval: 1.35, 2.73) increased risk of mortality compared with being in the top 2 tertiles. Once age, sex, and smoking history were taken into account, the most important explanatory factors for this association were inflammatory markers (21.3% reduction in the FEV1/height2-mortality association), coronary heart disease, stroke, and diabetes (11.7% reduction), and alcohol consumption, diet, physical activity, and body mass index (9.8% reduction). The contribution of socioeconomic position and cardiovascular risk factors was small (≤3.5% reduction). Taken together, these factors explained 32.5% of the association. Multiple pathways link lung function to mortality; these results show inflammatory markers to be particularly important.
doi:10.1093/aje/kwq294
PMCID: PMC2998200  PMID: 20961971
forced expiratory volume; inflammation; middle aged; mortality; respiratory function tests

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