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Background Chronic inflammation is involved in the pathophysiology of dementia, but the association of serum immunoglobulins with dementia has been understudied and longitudinal data are currently lacking. We investigated the association of serum immunoglobulin (Ig) A, G, and M with cognition and dementia in a population-based cohort. Methods This study was embedded in the Rotterdam Study. Participants with information on serum immunoglobulin levels, measured between 1997 and 2009, were followed for incident dementia until 2016. Assessment of cognitive function and dementia was performed according to validated tests and clinical criteria respectively. We studied the association between serum immunoglobulins with prevalent and incident dementia using logistic regression and Cox proportional hazards regression analyses respectively. We performed linear regression analyses to quantify the cross-sectional association of serum immunoglobulins with global cognition as well as separate cognitive tests. Analyses were adjusted for age, sex, lifestyle, and cardiovascular factors. Results We included 8768 participants (median age of 62.2 years, 57% women, median follow-up 10.7 years). Overall, none of the immunoglobulins was associated with prevalent or incident dementia. Higher IgG levels were associated with lower scores of global cognition (adjusted standardized mean difference − 0.04; 95% confidence interval:− 0.06; − 0.02) and separate cognitive tests. Conclusion In middle-aged and older individuals from the general population, serum Igs were not associated with prevalent or incident dementia, which may imply that serum Igs are not involved in the pathophysiology of dementia. Although higher IgG levels were associated with worse cognitive function, studies with longitudinal data should exclude reverse causation.

Purpose Inflammation is implicated in cardiovascular disease (CVD), but the association of total serum immunoglobulin (Ig) A, G, and M with CVD across the whole spectrum of atherosclerosis in community-dwelling elderly is unknown. Methods This study was embedded in the Rotterdam Study, an ongoing population-based cohort study. We performed Cox regression for the associations of Igs with incident atherosclerotic CVD (ACVD; composite of myocardial infarction, revascularization, and stroke), cardiovascular mortality, and all-cause mortality, and multinomial logistic regression for the association between Igs and coronary artery calcification (CAC) scores. We adjusted for age, sex, lifestyle, and cardiovascular risk factors and presented results per standard deviation increase. Results We included 8767 participants (median age 62.2 years, 57% women). Higher IgG was associated with an increased ACVD risk (hazard ratio [HR]: 1.08; 95% confidence interval [95% CI]: 1.01–1.15). Higher IgA and IgG were associated with an increased cardiovascular mortality risk, mainly within Ig reference ranges, and with an increased all-cause mortality risk, although less marked. Higher IgA was associated with severe atherosclerosis, i.e., CAC score > 400 (odds ratio: 1.29; 95% CI: 1.03–1.62), while for higher IgG a trend was seen with severe atherosclerosis. Conclusion In middle-aged and older individuals from the general population, higher serum IgA and IgG, but not IgM, are associated with CVD, cardiovascular mortality, and severe atherosclerosis, particularly within Ig reference ranges and independent of serum C-reactive protein. Future studies are needed to elucidate potential causality of the reported associations.

Chronic inflammation is involved in the pathophysiology of dementia, but the association of serum immunoglobulins with dementia has been understudied and longitudinal data are currently lacking. We investigated the association of serum immunoglobulin (Ig) A, G, and M with cognition and dementia in a population-based cohort.This study was embedded in the Rotterdam Study. Participants with information on serum immunoglobulin levels, measured between 1997 and 2009, were followed for incident dementia until 2016. Assessment of cognitive function and dementia was performed according to validated tests and clinical criteria respectively. We studied the association between serum immunoglobulins with prevalent and incident dementia using logistic regression and Cox proportional hazards regression analyses respectively. We performed linear regression analyses to quantify the cross-sectional association of serum immunoglobulins with global cognition as well as separate cognitive tests. Analyses were adjusted for age, sex, lifestyle, and cardiovascular factors.We included 8768 participants (median age of 62.2 years, 57% women, median follow-up 10.7 years). Overall, none of the immunoglobulins was associated with prevalent or incident dementia. Higher IgG levels were associated with lower scores of global cognition (adjusted standardized mean difference - 0.04; 95% confidence interval:- 0.06; - 0.02) and separate cognitive tests.In middle-aged and older individuals from the general population, serum Igs were not associated with prevalent or incident dementia, which may imply that serum Igs are not involved in the pathophysiology of dementia. Although higher IgG levels were associated with worse cognitive function, studies with longitudinal data should exclude reverse causation.

Background: Thyroid peroxidase antibodies (TPO-Abs) play an important role in autoimmune thyroid disease, but are also prevalent in healthy individuals. However, it is unclear what determinants may influence the occurrence of TPO-Abs in healthy individuals and how TPO-Abs may affect health outcomes in these individuals. We aimed to identify determinants of TPO-Abs in a large, prospective population-based cohort of middle-aged and elderly individuals and to subsequently assess the association between TPO-Abs and risk of overall and cause-specific mortality. Methods: We performed binomial and multinomial logistic regression analyses to obtain odds ratios (ORs) and 95% confidence intervals [95% CIs] for the association of potential determinants based on previous literature with TPO-Ab positivity (>35 kU/L), TPO-Ab detectability (>5 kU/L), and TPO-Ab categories. Cox proportional hazards regression analyses were performed to obtain hazard ratios (HRs) and CIs for the association between TPO-Abs and mortality risk. Results: In 9685 participants (57% women, median baseline age 63.3 years, median follow-up time 10.1 years), we identified female sex (OR = 2.47 [CI 2.13-2.86]) and current smoking (OR = 3.10 [CI 2.66-3.62]) as determinants of TPO-Ab positivity and TPO-Ab detectability, respectively. Higher age (OR = 0.98 [CI 0.97-0.98]) and all categories of alcohol consumption (ORs ranging from 0.71-0.78) were associated with lower odds of TPO-Ab detectability. TPO-Ab detectability was associated with a higher risk of overall (HR = 1.09 [CI 1.01-1.17]), cancer-related (HR = 1.18 [CI 1.01-1.38]), and cardiovascular mortality (HR = 1.21 [CI 1.01-1.45]). Interestingly, this was more prominent in men compared with women (HR for cardiovascular mortality 1.50 vs. 0.99, respectively). Conclusions: In community-dwelling middle-aged and elderly individuals, female sex and current smoking are the most important determinants associated with TPO-Ab levels in the detectable and positive range, whereas alcohol consumption is associated with lower odds of TPO-Abs. The clinical importance of detectable TPO-Ab levels is illustrated by the association with an increased mortality risk, mainly in men. Our results warrant further exploration of the clinical applicability of detectable TPO-Ab levels, potentially as a marker for low-grade inflammation. The Rotterdam Study has been entered into the Netherlands National Trial Register (NTR; www.trialregister.nl) and into the WHO International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/network/primary/en/) under shared catalogue number NTR6831.

Purpose In clinical practice, currently one reference range for serum immunoglobulin (Ig) A, G, and M is applied to all adults, although various factors may influence Ig serum levels. Population-based data on determinants of IgA, IgG, and IgM and recommendations for subgroup specific reference ranges are lacking. We aimed to provide an overview of determinants of IgA, IgG, and IgM in community-dwelling middle-aged and elderly individuals and explore determinants that influence Ig reference ranges. Methods Within the Rotterdam Study, we performed linear regression analyses for the association of demographic, lifestyle, and cardiovascular factors with serum IgA, IgG, and IgM. We furthermore calculated Ig reference ranges (based on percentiles), both overall and within relevant subgroups. Results We included 8768 participants (median age 62 years). IgA and IgG increased non-linearly with higher age (P Conclusion Age, sex, smoking, alcohol consumption, corticosteroid use, and cardiovascular factors are determinants that should be considered when interpreting serum Ig levels in middle-aged and elderly individuals and may require adjusted reference ranges.

Context: In vitro and in vivo experiments have assigned both oncosuppressive and oncogenic properties to thyroid hormones. Population-based studies have found inconclusive results. Objective: We aimed to prospectively assess the relation between thyroid function and incident cancer in a population-based setting. Design, Setting, and Participants: The current study is a prospective population-based cohort study including 10 318 participants for whom baseline measurements of free T4 (FT4) and/or TSH were available. Main Outcome Measures: Cox proportional hazards models were used to assess hazard ratios (HRs) of any solid non-skin cancer, as well as lung, breast, prostate, and gastrointestinal cancer specifically. Results: Higher FT4 levels were associated with a higher risk of any solid cancer (HR, 1.42; 95% confidence interval [CI], 1.12–1.79), lung cancer (HR, 2.33; 95% CI, 1.39–3.92) and breast (HR, 1.77; 95% CI, 1.10–2.84) cancer. The risk estimates were similar after exclusion of thyroid-altering medication, but the association lost significance for breast cancer. Compared with the lowest FT4 tertile, the highest tertile was associated with a 1.13-fold increased risk of any solid, 1.79-fold increased risk of lung, and 1.14-fold increased risk of breast cancer (P for trend Conclusions: Higher FT4 levels are significantly associated with an increased risk of any solid, lung, and breast cancer. Further research should elucidate the underlying pathophysiological mechanisms.

ObjectiveAutoimmune thyroid disease (AITD) and psoriatic disease share auto-immunological components. Few studies have investigated the link between both, yielding inconclusive results.DesignWe assessed the association of AITD with psoriatic disease in a prospective cohort study and performed a systematic review and meta-analysis.Methods8214 participants of the Rotterdam Study (RS) with thyroid peroxidase antibodies (TPO-Abs), thyroid-stimulating hormone (TSH) and/or free thyroxine (FT4) measurements and information on psoriatic disease were included. We performed logistic and Cox regression analyses and a systematic literature search in several electronic databases on AITD and psoriatic disease. We pooled odds ratios (ORs) of included studies using the Mantel-Haenszel method, while adding RS data on prevalent psoriatic disease.ResultsWithin the RS, we found no association between TPO-Ab positivity and psoriatic disease. There was a positive trend between TSH and prevalent psoriatic disease, and between FT4 and incident psoriatic disease, although not significant. Out of 1850 articles identified, seven were included in the systematic review and four in the meta-analysis. The risk of psoriatic disease (pooled OR) was 1.71 (confidence interval (CI): 1.27–2.31) for TPO-Ab positivity, 1.25 (CI: 1.14–1.37) for AITD and 1.34 (CI: 1.16–1.54) respectively, and 1.17 (CI: 1.03–1.32) for hypothyroidism and hyperthyroidism.ConclusionsOur meta-analysis suggests that TPO-Ab positivity, hypothyroidism and hyperthyroidism might be associated with prevalent psoriatic disease. However, there are only few studies with large heterogeneity regarding psoriatic disease definition and indication of publication bias. Additional prospective data are needed to assess the association of AITD with incident psoriatic disease.

Introduction Women with a history of preeclampsia have an increased risk of developing cardiovascular disease (CVD) later in life. Classical risk scores are not suitable as risk estimates of CVD in this young population. Recent recommendations from the American Heart Association are aimed to improve cardiovascular health (CVH). Objectives Examining CVH by Health Life Check (HLC) ( http://mylifecheck.heart.org/ ) in previously severe preeclamptic women is part of our cardiovascular risk follow-up program. Final score is a scale from 1 to 10, where 10 represents ideal CVH. Results Since 2011 HLC is offered to all women in this program. So far, 213 women were included, 148 (70%) underwent a CVH assessment by performing HLC between three months and one year after delivery. The overall HLC score was 7.4 (median; range: 0.8–10.0) at 3.6 months after the delivery. Only 2 out of 148 women (1.4%) had an ideal score. HLC score was 7.1 (median; range: 0.8–10.0) for 48 women who had a HLC score within 6 months after delivery versus 8.2 (median; range: 2.6–9.8) in the second half of the first year after delivery. Conclusion These are the first data on CVH in women after severe preeclampsia. Only 1.4% of these women had an ideal score. Active counselling of these women could be the reason of the improved score over time. We showed that CVH as assessed by HLC is an excellent tool for cardiovascular risk management in this specific group of women.