Jessica Abell

Trajectories of Depressive Symptoms Before Diagnosis of Dementia: A 28-Year Follow-up Study

Importance Neuropsychiatric symptoms, depressive symptoms in particular, are common in patients with dementia but whether depressive symptoms in adulthood increases the risk for dementia remains the subject of debate. Objective To characterize the trajectory of depressive symptoms over 28 years prior to dementia diagnosis to determine whether depressive symptoms carry risk for dementia. Design, Setting, and Participants Up to 10 308 persons, aged 35 to 55 years, were recruited to the Whitehall II cohort study in 1985, with the end of follow-up in 2015. Data analysis for this study in a UK general community was conducted from October to December 2016. Exposures Depressive symptoms assessed on 9 occasions between 1985 and 2012 using the General Health Questionnaire. Main Outcomes and Measures Incidence of dementia (n = 322) between 1985 and 2015. Results Of the 10 189 persons included in the study, 6838 were men (67%) and 3351 were women (33%). Those reporting depressive symptoms in 1985 (mean follow-up, 27 years) did not have significantly increased risk for dementia (hazard ratio [HR], 1.21; 95% CI, 0.95-1.54) in Cox regression adjusted for sociodemographic covariates, health behaviors, and chronic conditions. However, those with depressive symptoms in 2003 (mean follow-up, 11 years) had an increased risk (HR, 1.72; 95% CI, 1.21-2.44). Those with chronic/recurring depressive symptoms (≥2 of 3 occasions) in the early study phase (mean follow-up, 22 years) did not have excess risk (HR, 1.02; 95% CI, 0.72-1.44) but those with chronic/recurring symptoms in the late phase (mean follow-up, 11 years) did have higher risk for dementia (HR, 1.67; 95% CI, 1.11-2.49). Analysis of retrospective depressive trajectories over 28 years, using mixed models and a backward time scale, shows that in those with dementia, differences in depressive symptoms compared with those without dementia became apparent 11 years (difference, 0.61; 95% CI, 0.09-1.13; P = .02) before dementia diagnosis and became more than 9 times larger at the year of diagnosis (difference, 5.81; 95% CI, 4.81-6.81; P < .001). Conclusions and Relevance Depressive symptoms in the early phase of the study corresponding to midlife, even when chronic/recurring, do not increase the risk for dementia. Along with our analysis of depressive trajectories over 28 years, these results suggest that depressive symptoms are a prodromal feature of dementia or that the 2 share common causes. The findings do not support the hypothesis that depressive symptoms increase the risk for dementia.

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.

Change in Sleep Duration and Type 2 Diabetes: The Whitehall II Study

OBJECTIVE Evidence suggests that short and long sleep durations are associated with a higher risk of type 2 diabetes. Using successive data waves spanning >20 years, we examined whether a change in sleep duration is associated with incident diabetes. RESEARCH DESIGN AND METHODS Sleep duration was reported at the beginning and end of four 5-year cycles: 1985–1988 to 1991–1994 (n = 5,613), 1991–1994 to 1997–1999 (n = 4,193), 1997–1999 to 2002–2004 (n = 3,840), and 2002–2004 to 2007–2009 (n = 4,195). At each cycle, change in sleep duration was calculated for participants without diabetes. Incident diabetes at the end of the subsequent 5-year period was defined using 1) fasting glucose, 2) 75-g oral glucose tolerance test, and 3) glycated hemoglobin, in conjunction with diabetes medication and self-reported doctor diagnosis. RESULTS Compared with the reference group of persistent 7-h sleepers, an increase of ≥2 h sleep per night was associated with a higher risk of incident diabetes (odds ratio 1.65 [95% CI 1.15, 2.37]) in analyses adjusted for age, sex, employment grade, and ethnic group. This association was partially attenuated by adjustment for BMI and change in weight (1.50 [1.04, 2.16]). An increased risk of incident diabetes was also seen in persistent short sleepers (average ≤5.5 h/night; 1.35 [1.04, 1.76]), but this evidence weakened on adjustment for BMI and change in weight (1.25 [0.96, 1.63]). CONCLUSIONS This study suggests that individuals whose sleep duration increases are at an increased risk of type 2 diabetes. Greater weight and weight gain in this group partly explain the association.

Physical activity, cognitive decline, and risk of dementia: 28 year follow-up of Whitehall II cohort study

Abstract Objective To test the hypotheses that physical activity in midlife is not associated with a reduced risk of dementia and that the preclinical phase of dementia is characterised by a decline in physical activity. Design Prospective cohort study with a mean follow-up of 27 years. Setting Civil service departments in London (Whitehall II study). Participants 10 308 participants aged 35-55 years at study inception (1985-88). Exposures included time spent in mild, moderate to vigorous, and total physical activity assessed seven times between 1985 and 2013 and categorised as “recommended” if duration of moderate to vigorous physical activity was 2.5 hours/week or more. Main outcome measures A battery of cognitive tests was administered up to four times from 1997 to 2013, and incident dementia cases (n=329) were identified through linkage to hospital, mental health services, and mortality registers until 2015. Results Mixed effects models showed no association between physical activity and subsequent 15 year cognitive decline. Similarly, Cox regression showed no association between physical activity and risk of dementia over an average 27 year follow-up (hazard ratio in the “recommended” physical activity category 1.00, 95% confidence interval 0.80 to 1.24). For trajectories of hours/week of total, mild, and moderate to vigorous physical activity in people with dementia compared with those without dementia (all others), no differences were observed between 28 and 10 years before diagnosis of dementia. However, physical activity in people with dementia began to decline up to nine years before diagnosis (difference in moderate to vigorous physical activity −0.39 hours/week; P=0.05), and the difference became more pronounced (−1.03 hours/week; P=0.005) at diagnosis. Conclusion This study found no evidence of a neuroprotective effect of physical activity. Previous findings showing a lower risk of dementia in physically active people may be attributable to reverse causation—that is, due to a decline in physical activity levels in the preclinical phase of dementia.

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

Highlights • Hair samples present considerable opportunities for assessing cortisol in cohorts.• Certain hair characteristics correlate with hair cortisol concentrations (HCC).• Mental and physical health status is independently associated with HCC.

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

Highlights • We found long term sleep problems were associated with salivary cortisol.• Recurrent short sleep duration is associated with a flatter slope in diurnal cortisol.• Chronic insomnia symptoms predicted a steeper morning rise in cortisol.

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

Abstract 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.

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.

Parental absence in early childhood and onset of smoking and alcohol consumption before adolescence

Background Parental absence, due to death or separation from a parent, has been associated with smoking and alcohol consumption in adolescence and adulthood. The aim of this study was to investigate whether parental absence in early childhood was associated with smoking and alcohol uptake before adolescence. Methods Data on 10 940 children from the UKs Millennium Cohort Study were used. Logistic regression was used to test associations between parental absence (0–7 years) and reports of smoking and alcohol consumption at age 11. Results Children who experienced parental absence were more likely to have smoked (OR=2.58, 95% CI 1.88 to 3.56) and consumed alcohol (OR=1.46, 95% CI 1.25 to 1.72). No differences were found by child sex or age, or parent absent. Children who experienced parental death were less likely to have drunk alcohol but those who had were more likely to have consumed enough to feel drunk. Conclusions Parental absence was associated with early uptake of risky health behaviours in a large, nationally representative UK cohort. Children who experience parental absence should be supported in early life in order to prevent smoking and alcohol initiation.

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.