Background: The association between physical activity and risk of neurodegenerative diseases is not well established. We therefore aimed to quantify this association using meta-analytical techniques.Method: We searched Medline, the Cochrane Database of Systematic Reviews and Web of Science databases from 1990 to 2007 for prospective epidemiological studies of physical activity and incident dementia, Alzheimer's and Parkinson's disease. We excluded studies of physical activity and cognitive decline without diagnosis of a neurodegenerative disease. Information on study design, participant characteristics, measurement of exposure and outcome variables, adjustment for potential confounding, and estimates of associations was abstracted independently by the two investigators.Results: We included 16 prospective studies in the overall analysis, which incorporated 163797 non-demented participants at baseline with 3219 cases at follow-up. We calculated pooled relative risk (RR) using a random effects model. The RR of dementia in the highest physical activity category compared with the lowest was 0.72 [95% confidence interval (CI) 0.60–0.86, p<0.001], for Alzheimer's, 0.55 (95% CI 0.36–0.84, p=0.006), and for Parkinson's 0.82 (95% CI 0.57–1.18, p=0.28).Conclusions: Our results suggest that physical activity is inversely associated with risk of dementia. Future studies should examine the optimal dose of physical activity to induce protection, which presently remains unclear.

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 We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies.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

Although overweight and obesity have been studied in relation to individual cardiometabolic diseases, their association with risk of cardiometabolic multimorbidity is poorly understood. Here we aimed to establish the risk of incident cardiometabolic multimorbidity (ie, at least two from: type 2 diabetes, coronary heart disease, and stroke) in adults who are overweight and obese compared with those who are a healthy weight. We pooled individual-participant data for BMI and incident cardiometabolic multimorbidity from 16 prospective cohort studies from the USA and Europe. Participants included in the analyses were 35 years or older and had data available for BMI at baseline and for type 2 diabetes, coronary heart disease, and stroke at baseline and follow-up. We excluded participants with a diagnosis of diabetes, coronary heart disease, or stroke at or before study baseline. According to WHO recommendations, we classified BMI into categories of healthy (20·0–24·9 kg/m2), overweight (25·0–29·9 kg/m2), class I (mild) obesity (30·0–34·9 kg/m2), and class II and III (severe) obesity (≥35·0 kg/m2). We used an inclusive definition of underweight (<20 kg/m2) to achieve sufficient case numbers for analysis. The main outcome was cardiometabolic multimorbidity (ie, developing at least two from: type 2 diabetes, coronary heart disease, and stroke). Incident cardiometabolic multimorbidity was ascertained via resurvey or linkage to electronic medical records (including hospital admissions and death). We analysed data from each cohort separately using logistic regression and then pooled cohort-specific estimates using random-effects meta-analysis. Participants were 120 813 adults (mean age 51·4 years, range 35–103; 71 445 women) who did not have diabetes, coronary heart disease, or stroke at study baseline (1973–2012). During a mean follow-up of 10·7 years (1995–2014), we identified 1627 cases of multimorbidity. After adjustment for sociodemographic and lifestyle factors, compared with individuals with a healthy weight, the risk of developing cardiometabolic multimorbidity in overweight individuals was twice as high (odds ratio [OR] 2·0, 95% CI 1·7–2·4; p<0·0001), almost five times higher for individuals with class I obesity (4·5, 3·5–5·8; p<0·0001), and almost 15 times higher for individuals with classes II and III obesity combined (14·5, 10·1–21·0; p<0·0001). This association was noted in men and women, young and old, and white and non-white participants, and was not dependent on the method of exposure assessment or outcome ascertainment. In analyses of different combinations of cardiometabolic conditions, odds ratios associated with classes II and III obesity were 2·2 (95% CI 1·9–2·6) for vascular disease only (coronary heart disease or stroke), 12·0 (8·1–17·9) for vascular disease followed by diabetes, 18·6 (16·6–20·9) for diabetes only, and 29·8 (21·7–40·8) for diabetes followed by vascular disease. The risk of cardiometabolic multimorbidity increases as BMI increases; from double in overweight people to more than ten times in severely obese people compared with individuals with a healthy BMI. Our findings highlight the need for clinicians to actively screen for diabetes in overweight and obese patients with vascular disease, and pay increased attention to prevention of vascular disease in obese individuals with diabetes. NordForsk, Medical Research Council, Cancer Research UK, Finnish Work Environment Fund, and Academy of Finland.

Long working hours might increase the risk of cardiovascular disease, but prospective evidence is scarce, imprecise, and mostly limited to coronary heart disease. We aimed to assess long working hours as a risk factor for incident coronary heart disease and stroke. We identified published studies through a systematic review of PubMed and Embase from inception to Aug 20, 2014. We obtained unpublished data for 20 cohort studies from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium and open-access data archives. We used cumulative random-effects meta-analysis to combine effect estimates from published and unpublished data. We included 25 studies from 24 cohorts in Europe, the USA, and Australia. The meta-analysis of coronary heart disease comprised data for 603,838 men and women who were free from coronary heart disease at baseline; the meta-analysis of stroke comprised data for 528,908 men and women who were free from stroke at baseline. Follow-up for coronary heart disease was 5·1 million person-years (mean 8·5 years), in which 4768 events were recorded, and for stroke was 3·8 million person-years (mean 7·2 years), in which 1722 events were recorded. In cumulative meta-analysis adjusted for age, sex, and socioeconomic status, compared with standard hours (35-40 h per week), working long hours (≥55 h per week) was associated with an increase in risk of incident coronary heart disease (relative risk [RR] 1·13, 95% CI 1·02-1·26; p=0·02) and incident stroke (1·33, 1·11-1·61; p=0·002). The excess risk of stroke remained unchanged in analyses that addressed reverse causation, multivariable adjustments for other risk factors, and different methods of stroke ascertainment (range of RR estimates 1·30-1·42). We recorded a dose-response association for stroke, with RR estimates of 1·10 (95% CI 0·94-1·28; p=0·24) for 41-48 working hours, 1·27 (1·03-1·56; p=0·03) for 49-54 working hours, and 1·33 (1·11-1·61; p=0·002) for 55 working hours or more per week compared with standard working hours (ptrend<0·0001). Employees who work long hours have a higher risk of stroke than those working standard hours; the association with coronary heart disease is weaker. These findings suggest that more attention should be paid to the management of vascular risk factors in individuals who work long hours. Medical Research Council, Economic and Social Research Council, European Union New and Emerging Risks in Occupational Safety and Health research programme, Finnish Work Environment Fund, Swedish Research Council for Working Life and Social Research, German Social Accident Insurance, Danish National Research Centre for the Working Environment, Academy of Finland, Ministry of Social Affairs and Employment (Netherlands), US National Institutes of Health, British Heart Foundation.