Psychosocial factors and cancer incidence (PSY-CA): Protocol for individual participant data meta-analyses.

OBJECTIVES: Psychosocial factors have been hypothesized to increase the risk of cancer. This study aims (1) to test whether psychosocial factors (depression, anxiety, recent loss events, subjective social support, relationship status, general distress, and neuroticism) are associated with the incidence of any cancer (any, breast, lung, prostate, colorectal, smoking-related, and alcohol-related); (2) to test the interaction between psychosocial factors and factors related to cancer risk (smoking, alcohol use, weight, physical activity, sedentary behavior, sleep, age, sex, education, hormone replacement therapy, and menopausal status) with regard to the incidence of cancer; and (3) to test the mediating role of health behaviors (smoking, alcohol use, weight, physical activity, sedentary behavior, and sleep) in the relationship between psychosocial factors and the incidence of cancer. METHODS: The psychosocial factors and cancer incidence (PSY-CA) consortium was established involving experts in the field of (psycho-)oncology, methodology, and epidemiology. Using data collected in 18 cohorts (N = 617,355), a preplanned two-stage individual participant data (IPD) meta-analysis is proposed. Standardized analyses will be conducted on harmonized datasets for each cohort (stage 1), and meta-analyses will be performed on the risk estimates (stage 2). CONCLUSION: PSY-CA aims to elucidate the relationship between psychosocial factors and cancer risk by addressing several shortcomings of prior meta-analyses.

Why is living alone in older age related to increased mortality risk? A longitudinal cohort study.

BACKGROUND: Living alone has been associated with increased mortality risk, but it is unclear whether this is a result of a selection effect or the impact of stressful life changes such as widowhood or divorce leading to changes in living arrangements. We therefore examined the association between living alone, transitions in living arrangements and all-cause mortality. METHOD: We analysed data from 4,888 individuals who participated in both wave 2 (2004-2005) and wave 4 (2008-2009) of the English Longitudinal Study of Ageing. Transitions in living arrangements over this period were identified. Mortality status was ascertained from linked national mortality registers. Cox proportional hazards analysis was used to examine the association between living alone and mortality over an average 8.5 year follow-up period. RESULTS: An association was found between living alone at wave 4 and mortality (hazard ratio (HR): 1.20, 95% CI 1.04-1.38) in a model adjusted for multiple factors including socioeconomic status, physical health, health behaviours and loneliness. We also found that participants who moved to living alone after divorce or bereavement had a higher risk of mortality compared with those who lived with others at both time points (HR: 1.34, 95% CI 1.01-1.79), while those who moved to living alone for other reasons did not show an increased mortality risk. CONCLUSIONS: The relationship between living alone and mortality is complicated by the reasons underlying not living with others. A greater understanding of these dynamics will help to identify the individuals who are at particular health risk because of their living arrangements.

Risk Factors for Hospital Admission After a Fall: A Prospective Cohort Study of Community-Dwelling Older People.

BACKGROUND: Falls in later life that require admission to hospital have well-established consequences for future disability and health. The likelihood and severity of a fall will result from the presence of one or more risk factors. The aim of this study is to examine risk factors identified for their ability to prevent falls and to assess whether they are associated with hospital admission after a fall. METHODS: Analyses of data from the English Longitudinal Study of Aging (ELSA), a prospective cohort study. In a sample of 3783 men and women older than 60 years old, a range of potential risk factors measured at Wave 4 (demographic, social environment, physical, and mental functioning) were examined as predictors of fall-related hospitalizations, identified using International Classification of Diseases, 10th Revision (ICD-10) code from linked hospital records in the United Kingdom. Subdistribution hazard models were used to account for competing risk of death. RESULTS: Several risk factors identified by previous work were confirmed. Suffering from urinary incontinence (subdistribution hazard ratio = 1.49; 95% CI: 1.14, 1.95) and osteoporosis (subdistribution hazard ratio = 1.48; 95% CI: 1.05, 2.07), which are not commonly considered at an early stage of screening, were found to be associated with hospital admission after a fall. Both low and moderate levels of physical activity were also found to somewhat increase the risk of hospital admission after a fall. CONCLUSIONS: Several predictors of having a fall, severe enough to require hospital admission, have been confirmed. In particular, urinary incontinence should be considered at an earlier point in the assessment of risk.

Midlife contributors to socioeconomic differences in frailty during later life: a prospective cohort study.

BACKGROUND: Health inequalities persist into old age. We aimed to investigate risk factors for socioeconomic differences in frailty that could potentially be modified through policy measures. METHODS: In this multi-wave longitudinal cohort study (Whitehall II study), we assessed participants' socioeconomic status, behavioural and biomedical risk factors, and disease status at age 45-55 years, and frailty (defined according to the Fried phenotype) at baseline and at one or more of three clinic visits about 18 years later (mean age 69 years [SD 5·9]). We used logistic mixed models to examine the associations between socioeconomic status and risk factors at age 50 years and subsequent prevalence of frailty (adjusted for sex, ethnic origin, and age), with sensitivity analyses and multiple imputation for missing data. FINDINGS: Between Sept 9, 2007, and Dec 8, 2016, 6233 middle-aged adults were measured for frailty. Frailty was present in 562 (3%) of 16 164 person-observations, and varied by socioeconomic status: 145 (2%) person-observations had high socioeconomic status, 241 (4%) had intermediate status, and 176 (7%) had low socioeconomic status, adjusting for sex and age. Risk factors for frailty included cardiovascular disease, depression, smoking, high or abstinent alcohol consumption, low fruit and vegetable consumption, physical inactivity, poor lung function, hypertension, and overweight or obesity. Cardiometabolic markers for future frailty were high ratio of total to high-density lipoprotein cholesterol, and raised interleukin-6 and C-reactive protein concentrations. The five most important factors contributing to the frailty gradient, assessed by percent attenuation of the association between socioeconomic status and frailty, were physical activity (13%), interleukin-6 (13%), body-mass index category (11%), C-reactive protein (11%), and poor lung function (10%). Overall, socioeconomic differences in frailty were reduced by 40% in the maximally-adjusted model compared with the minimally-adjusted model. INTERPRETATION: Behavioural and cardiometabolic risk factors in midlife account for more than a third of socioeconomic differences in frailty. Our findings suggest that interventions targeting physical activity, obesity, smoking, and low-grade inflammation in middle age might reduce socioeconomic differences in later-life frailty. FUNDING: British Heart Foundation and British Medical Research Council.

Association between systolic blood pressure and dementia in the Whitehall II cohort study: role of age, duration, and threshold used to define hypertension.

Aims: To examine associations of diastolic and systolic blood pressure (SBP) at age 50, 60, and 70 years with incidence of dementia, and whether cardiovascular disease (CVD) over the follow-up mediates this association. Methods and results: Systolic and diastolic blood pressure were measured on 8639 persons (32.5% women) from the Whitehall II cohort study in 1985, 1991, 1997, and 2003. Incidence of dementia (n dementia/n total = 385/8639) was ascertained from electronic health records followed-up until 2017. Cubic splines using continuous blood pressure measures suggested SBP ≥130 mmHg at age 50 but not at age 60 or 70 was associated with increased risk of dementia, confirmed in Cox regression analyses adjusted for sociodemographic factors, health behaviours, and time varying chronic conditions [hazard ratio (HR) 1.38; 95% confidence interval (95% CI) 1.11, 1.70]. Diastolic blood pressure was not associated with dementia. Participants with longer exposure to hypertension (SBP ≥ 130 mmHg) between mean ages of 45 and 61 years had an increased risk of dementia compared to those with no or low exposure to hypertension (HR 1.29, 95% CI 1.00, 1.66). In multi-state models, SBP ≥ 130 mmHg at 50 years of age was associated with greater risk of dementia in those free of CVD over the follow-up (HR 1.47, 95% CI 1.15, 1.87). Conclusion: Systolic blood pressure ≥130 mmHg at age 50, below the conventional ≥140 mmHg threshold used to define hypertension, is associated with increased risk of dementia; in these persons this excess risk is independent of CVD.

Crossing the road in time: Inequalities in older people's walking speeds.

Pedestrian crossings in the UK and US require people to walk at 1.2 m/s to cross the road in time; however a large proportion of older people do not walk this fast, potentially discouraging walking or putting older people at risk of injury. We use longitudinal data to investigate changes in walking speed, and ability to cross the road in time, at older ages. 31,015 walking speed measurements were taken from 10,249 men and women aged 60+ years in waves 1-7 of the English Longitudinal Study of Ageing (2002-2014). Growth curve analyses were used to model how walking speed changes with increasing age, and predicted probabilities of being able to cross the road in time were estimated. 10% of measured walking speeds were fast enough to cross the road in time. Walking speed declined with age (-5.7×10-3m/s/yr (95% CI -7.6×10-3, -3.9×10-3)), and the decline accelerated with increasing age (-0.3 ×10-3m/s/yr (-0.4 ×10-3, -0.3 ×10-3)). Female, less wealthy and less healthy older people had slower walking speeds. For instance, predicted probability of crossing the road in time at age 60 was 14.8% (10.1, 18.5) and 2.7% (1.5, 3.8) for the richest and poorest men and 8.4% (6.0, 1.1) and 1.5% (0.9, 2.2) for the richest and poorest women, and at age 80 they were 7.1% (3.6, 10.5) and 1.0% (0.3, 1.7) for the richest and poorest men and 3.7% (1.6, 5.9) and 0.5% (0.1, 0.9) for the richest and poorest women. Most older people do not walk fast enough to cross the road in time. Even the majority of the wealthiest and healthiest people aged 60 years and older do not walk fast enough to cross pedestrian crossings in the allocated time. Crossing times should be increased to allow for older peoples' slower walking speeds or other policies considered to improve walkability, and to help avoid injuries and social isolation.

Assessing cortisol from hair samples in a large observational cohort: The Whitehall II study.

Hair cortisol concentrations (HCC) have been suggested to reflect long-term integrated cortisol levels, but most evidence of associations with co-variates is from small samples of healthy volunteers. The objective of this study was to describe the collection of hair samples in a large cohort study and report associations of demographic and health measures with HCC. We examined HCC measured from the 3cm hair segment near the scalp in 3507 participants (aged 59-83y) from The Whitehall II occupational cohort study of British civil servants. Hair samples were analysed using a column switching LC-APCI-MS/MS assay. Findings from mutually adjusted linear regression analyses revealed lower HCC in participants who reported use of hair dye [% difference (95%CI); -12.5 (-22.0, -1.9), p value=0.022] and evidence suggestive of differences by length of sample storage and seasonal variation. With regard to demographic variables, HCC was lower in women compared to men [-17.0 (-24.8, -8.4), p value <0.001] and higher in Black compared to other ethnic groups. Prevalent diabetes, use of systemic corticosteroids and cardiovascular medication were independently associated with higher HCC. With regard to health, depressive symptoms were associated with higher HCC [20.0 (8.1, 33.3), p value=0.001] following adjustment for physical disease and medication. We conclude that hair steroid analysis presents significant opportunities for assessing cortisol in large scale cohorts. Demographic factors, sample storage, season of collection and hair characteristics should be considered in future analyses. Health status, both mental and physical, is linked to HCC.

Recurrent short sleep, chronic insomnia symptoms and salivary cortisol: A 10-year follow-up in the Whitehall II study.

Although an association between both sleep duration and disturbance with salivary cortisol has been suggested, little is known about the long term effects of poor quality sleep on diurnal cortisol rhythm. The aim of this study was to examine the association of poor quality sleep, categorised as recurrent short sleep duration and chronic insomnia symptoms, with the diurnal release of cortisol. We examined this in 3314 participants from an occupational cohort, originally recruited in 1985-1989. Salivary cortisol was measured in 2007-2009 and six saliva samples were collected: (1) waking, (2) waking+0.5h, (3) +2.5h, (4) +8h, (5) +12h and (6) bedtime, for assessment of the cortisol awakening response and the diurnal slope in cortisol secretion. Participants with the first saliva sample collected within 15min of waking and not on steroid medication were examined. Short sleep duration (≤5h) and insomnia symptoms (Jenkins scale, highest quartile) were measured in 1997-1999, 2003-2004 and 2007-2009. Recurrent short sleep was associated with a flatter diurnal cortisol pattern. A steeper morning rise in cortisol was observed among those reporting chronic insomnia symptoms at three time points and among those reporting short sleep twice, compared to those who never reported sleep problems. Participants reporting short sleep on three occasions had higher levels of cortisol later in the day, compared to those never reporting short sleep, indicated by a positive interaction with hours since waking (ß=0.02 (95% CI: 0.01, 0.03)). We conclude that recurrent sleep problems are associated with adverse salivary cortisol patterns throughout the day.

Association of chronic insomnia symptoms and recurrent extreme sleep duration over 10 years with well-being in older adults: a cohort study.

OBJECTIVES: The extent to which aspects of sleep affect well-being in the long-term remains unclear. This longitudinal study examines the association between chronic insomnia symptoms, recurrent sleep duration and well-being at older ages. SETTING: A prospective cohort of UK civil servants (the Whitehall II study). PARTICIPANTS: 4491 women and men (25.2% women) with sleep measured 3 times over 10 years and well-being once at age 55-79 years. Insomnia symptoms and sleep duration were assessed through self-reports in 1997-1999, 2003-2004 and 2007-2009. PRIMARY OUTCOME MEASURES: Indicators of well-being, measured in 2007-2009, were the Control, Autonomy, Self-realisation and Pleasure measure (CASP-19) of overall well-being (range 0-57) and the physical and mental well-being component scores (range 0-100) of the Short Form Health Survey (SF-36). RESULTS: In maximally adjusted analyses, chronic insomnia symptoms were associated with poorer overall well-being (difference between insomnia at 3 assessments vs none -7.0 (SE=0.4) p<0.001), mental well-being (difference -6.9 (SE=0.4), p<0.001) and physical well-being (difference -2.8 (SE=0.4), p<0.001) independently of the other sleep measures. There was a suggestion of a dose-response pattern in these associations. In addition, recurrent short sleep (difference between ≤ 5 h sleep reported at 3 assessments vs none -1.7 (SE=0.7), p<0.05) and recurrent long sleep (difference between >9 h reported at 2 or 3 assessments vs none -3.5 (SE=0.9), p<0.001) were associated with poorer physical well-being. CONCLUSIONS: We conclude that in older people, chronic insomnia symptoms are negatively associated with all aspects of well-being, whereas recurrent long and short sleep is only associated with reduced physical well-being.

A Novel, Open Access Method to Assess Sleep Duration Using a Wrist-Worn Accelerometer.

Wrist-worn accelerometers are increasingly being used for the assessment of physical activity in population studies, but little is known about their value for sleep assessment. We developed a novel method of assessing sleep duration using data from 4,094 Whitehall II Study (United Kingdom, 2012-2013) participants aged 60-83 who wore the accelerometer for 9 consecutive days, filled in a sleep log and reported sleep duration via questionnaire. Our sleep detection algorithm defined (nocturnal) sleep as a period of sustained inactivity, itself detected as the absence of change in arm angle greater than 5 degrees for 5 minutes or more, during a period recorded as sleep by the participant in their sleep log. The resulting estimate of sleep duration had a moderate (but similar to previous findings) agreement with questionnaire based measures for time in bed, defined as the difference between sleep onset and waking time (kappa = 0.32, 95%CI:0.29,0.34) and total sleep duration (kappa = 0.39, 0.36,0.42). This estimate was lower for time in bed for women, depressed participants, those reporting more insomnia symptoms, and on weekend days. No such group differences were found for total sleep duration. Our algorithm was validated against data from a polysomnography study on 28 persons which found a longer time window and lower angle threshold to have better sensitivity to wakefulness, while the reverse was true for sensitivity to sleep. The novelty of our method is the use of a generic algorithm that will allow comparison between studies rather than a "count" based, device specific method.