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ObjectiveTo determine whether high baseline dietary antioxidants and total non-enzymatic antioxidant capacity (NEAC) is associated with a lower risk of Parkinson disease in men and women, we prospectively studied 43,865 men and women from a large Swedish cohort.MethodsIn the Swedish National March Cohort 43,865 men and women aged 18–94 years were followed through record linkages to National Health Registries from 1997 until 2016. Baseline dietary vitamin E, C and beta-carotene intake, as well as NEAC, were assessed by a validated food frequency questionnaire collected at baseline. All exposure variables were adjusted for energy intake and categorized into tertiles. Multivariable Cox proportional hazard regression models were fitted to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for Parkinson disease.ResultsAfter a mean follow-up time of 17.6 years we detected 465 incidence cases of Parkinson disease. In the multivariable adjusted model, dietary vitamin E (HR: 0.68: 95% CI: 0.52–0.90; p for trend: 0.005) and C (HR: 0.68; 95% CI: 0.52–0.89; p for trend: 0.004) were inversely associated with the risk of Parkinson disease, when comparing subjects in the highest to the lowest tertiles of the exposure. No association was found with estimated intake of dietary beta-carotene or NEAC.ConclusionOur findings suggest that dietary vitamin E and C intake might be inversely associated with the risk of Parkinson disease. No association was found with dietary beta-carotene or NEAC.Classification of evidenceThis study provides Class III evidence that dietary vitamin E and C intake are inversely associated with the risk of Parkinson disease.

Physical activity has been inversely associated with the risk of hip fracture, however, few studies have been conducted on the contributions from different domains of physical activity. This study was performed to investigate the association between daily household activities, leisure time physical activity, work-related physical activity and total physical activity during a 24-h period, and the risk of hip fracture. In the Swedish National March Cohort we followed 23,881 men and women aged of 50 and over from 1997 until 2010. Information on domainspecific physical activity was collected at baseline using a questionnaire. We fitted separate multivariable adjusted Cox proportional hazard models to each domain to obtain hazard ratios (HRs) with 95% confidence intervals (CIs). Each model was mutually adjusted for the other domains of physical activity. During a mean follow-up period of 12.2 years we identified 824 incidents of hip fracture. Subjects who spent less than 1 h per week engaged in daily household activities had an 85% higher risk of hip fracture than subjects spending C6 h per week carrying out daily household activities (HR 1.85; 95% CI 1.01-3.38). Subjects engaged in leisure time physical activities for [3.1 MET-h/day had a 24% lower risk of hip fracture (HR 0.76; 95% CI 0.59-0.98) than subjects spending \1.1 METh/day performing such activities. No association was found between hip fracture and work-related or total physical activity. We conclude that daily household activities and leisure time physical activity may independently decrease the risk of hip fracture in those aged 50 and over.

Metabolomics in human serum samples provide a snapshot of the current metabolic state of an individuum. Metabolite concentrations are influenced by both genetic and environmental factors. Concentrations of certain metabolites can further depend on age, sex, menopause, and diet of study participants. A better understanding of these relationships is pivotal for the planning of metabolomics studies involving human subjects and interpretation of their results. We generated one of the largest single-site targeted metabolomics data sets consisting of 175 quantified metabolites in 6872 study participants. We identified metabolites significantly associated with age, sex, body mass index, diet, and menopausal status. While most of our results agree with previous large-scale studies, we also found novel associations including serotonin as a sex and BMI-related metabolite and sarcosine and C2 carnitine showing significantly higher concentrations in post-menopausal women. Finally, we observed strong associations between higher consumption of food items and certain metabolites, mostly phosphatidylcholines and lysophosphatidylcholines. Most, and the strongest, relationships were found for habitual meat intake while no significant relationships were found for most fruits, vegetables, and grain products. Summarizing, our results reconfirm findings from previous population-based studies on an independent cohort. Together, these findings will ultimately enable the consolidation of sets of metabolites which are related to age, sex, BMI, and menopause as well as to participants’ diet.

Mutations in the Parkin (PRKN) gene are the most frequent cause of autosomal recessive early-onset Parkinson's disease (PD). Heterozygous PRKN mutation carriers might also be at increased risk for developing clinical symptoms of PD. Given the high frequency of heterozygous mutations in the general population, it is essential to have better estimates of the penetrance of these variants, and to investigate, which clinical and biochemical markers are present in carriers and thus potentially useful for identifying those individuals at greater risk of developing clinical symptoms later in life. In the present study, we ascertained the frequency of heterozygous PRKN mutation carriers in a large population sample of the Cooperative Health Research in South Tyrol (CHRIS) study, and screened for reported PD risk markers. 164 confirmed heterozygous PRKN mutation carriers were compared with 2,582 controls. A higher number of heterozygous mutation carriers reported a detectable increase in an akinesia-related phenotype, and a higher percentage of carriers had manifested diabetes. We also observed lower resting heart rate in the PRKN mutation carriers. Extending our risk analyses to a larger number of potential carriers and non-carriers using genotype imputation (n = 299 carriers and n = 7,127 non-carriers), from previously published biomarkers we also observed a higher neutrophil-to-lymphocyte ratio (NLR) and lower serum albumin and sodium levels in the heterozygous PRKN variant carriers. These results identify a set of biomarkers that might be useful either individually or as an ensemble to identify variant carriers at greater risk of health issues due to carrier status.

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Background Physical inactivity is a known risk factor for cardiovascular disease, but it is unclear if total and leisure time activity have different impact on the risk of myocardial infarction and stroke. In this cohort, we aimed to investigate the associations between both total and leisure time physical activity in detail, and the risks of myocardial infarction and stroke, both overall and for men and women separately. Methods We assessed the association between total and leisure time physical activity on the risk of myocardial infarction and stroke in a cohort of 31,580 men and women through record linkages from 1997–2016. We used Cox proportional hazards regression models to estimate hazard ratios (HR) with 95% confidence intervals (CI) based on detailed self-reported physical activity. In the adjusted analyses, we included age, sex, body mass index, level of education, cigarette smoking, alcohol consumption, diabetes, lipid disturbance and hypertension as potential confounders. Results We identified 1,621 incident cases of myocardial infarction and 1,879 of stroke. Among men, there was an inverse association between leisure time activity and myocardial infarction in the third tertile compared to the first (HR: 0.78; 95% CI: 0.62–0.98; p for trend = 0.03). We also found an inverse association between leisure time activity and stroke in the third tertile compared to the first (HR: 0.78; 95% CI: 0.61–0.99; p for trend = 0.04), while the corresponding HR for stroke among women was 0.91; 95% CI: 0.74–1.13. We found no significant association between total physical activity and MI (HR: 1.12; 95% CI: 0.93–1.34) or stroke (HR: 1.14 95% CI: 0.94–1.39) comparing the highest to the lowest tertile in men. Women in the highest tertile of total physical activity had a 22% lower risk of myocardial infarction compared to the lowest tertile (HR: 0.78; 95% CI: 0.63–0.97; p for trend = 0.02) and an 8% (95% CI: 0.87–0.98) reduced risk of myocardial infarction with each 1 METh/day increase of leisure time physical activity. Conclusion Total physical activity was inversely associated with the risk of myocardial infarction in women, while leisure time physical activity was inversely associated with the risk of myocardial infarction and stroke in men.

Background Following progressive aging of the population worldwide, the prevalence of Parkinson disease is expected to increase in the next decades. Primary prevention of the disease is hampered by limited knowledge of preventable causes. Recent evidence regarding diet and Parkinson disease is inconsistent and suggests that dietary habits such as fat intake may have a role in the etiology. Objective To investigate the association between intake of total and specific types of fat with the incidence of Parkinson disease. Methods Participants from the Swedish National March Cohort were prospectively followed-up from 1997 to 2016. Dietary intake was assessed at baseline using a validated food frequency questionnaire. Food items intake was used to estimate fat intake, i.e. the exposure variable, using the Swedish Food Composition Database. Total, saturated, monounsaturated and polyunsaturated fat intake were categorized into quartiles. Parkinson disease incidence was ascertained through linkages to Swedish population-based registers. Cox proportional hazards regression models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI) of the association between fat intake from total or specific types of fats and the incidence of Parkinson disease. The lowest intake category was used as reference. Isocaloric substitution models were also fitted to investigate substitution effects by replacing energy from fat intake with other macronutrients or specific types of fat. Results 41,597 participants were followed up for an average of 17.6 years. Among them, 465 developed Parkinson disease. After adjusting for potential confounders, the highest quartile of saturated fat intake was associated with a 41% increased risk of Parkinson disease compared to the lowest quartile (HR Q4 vs. Q1: 1.41; 95% CI: 1.04–1.90; p for trend: 0.03). Total, monounsaturated or polyunsaturated fat intake were not significantly associated with Parkinson disease. The isocaloric substitution models did not show any effect. Conclusions We found that a higher consumption of large amounts of saturated fat might be associated with an increased risk of Parkinson disease. A diet low in saturated fat might be beneficial for disease prevention.