Hypertension is an established risk factor for cognitive decline and dementia in older adults, highlighting the potential importance of antihypertensive treatments in prevention efforts. Work surrounding antihypertensive treatments has suggested possible salutary effects on cognition and neuropathology. Several studies have specifically highlighted renin-angiotensin system drugs, including AT1-receptor blockers and angiotensin-converting-enzyme inhibitors, as potentially benefiting cognition in later life. A small number of studies have further suggested renin-angiotensin system drugs that cross the blood-brain barrier may be linked to lower dementia risk compared to their nonpenetrant counterparts. The present meta-analysis sought to evaluate the potential cognitive benefits of blood-brain barrier crossing renin-angiotensin system drugs relative to their nonpenetrant counterparts. We harmonized longitudinal participant data from 14 cohorts from 6 countries (Australia, Canada, Germany, Ireland, Japan, United States), for a total of 12 849 individuals at baseline, and assessed for blood-brain barrier crossing potential within antihypertensive medications used by cognitively normal participants. We analyzed 7 cognitive domains (attention, executive function, language, verbal memory learning, recall, mental status, and processing speed) using ANCOVA (adjusted for age, sex, and education) and meta-analyses. Older adults taking blood-brain barrier-crossing renin-angiotensin drugs exhibited better memory recall over up to 3 years of follow-up, relative to those taking nonpenetrant medications, despite their relatively higher vascular risk burden. Conversely, those taking nonblood-brain barrier-penetrant medications showed better attention over the same follow-up period, although their lower vascular risk burden may partially explain this result. Findings suggest links between blood-brain barrier crossing renin-angiotensin drugs and less memory decline.

34This epidemiological study aimed to compare the caries and molar incisor hypomineralisation 35 (MIH) experience in asthmatic and non-asthmatic adolescents assessed at 10 and 15 years of 36 age. 730 adolescents from ongoing birth cohort studies (GINIplus/LISA) from Munich were 37 examined for carious lesions at the age of 10 and 15 to determine the caries experience under 38 inclusion of non-cavitated carious lesions D1-2T and the tooth-related decay-missing-filled 39 (DMFT) index. Furthermore, MIH was scored on all permanent teeth according to the criteria of 40 the European Academy of Paediatric Dentistry. The association of caries and MIH prevalence at 41 the 10-year and 15-year follow-up as well as caries incidence with ever having an asthma 42 diagnosis was analysed using hurdle regression models adjusted for potential confounders. Of 43 the 730 adolescents, 52 and 78 were identified as asthmatics at the 10-and 15-year follow-up, 44respectively. There were no significant differences in caries prevalence or experience between 45 asthma-free participants and any of the asthma groups (taking metered-dose inhaler (MDI) 46 medication vs. taking no MDI medication). However, a significant, positive association was 47 found for asthmatic adolescents who did not take MDI medication with higher MIH/T values 48 (OR=2.56, 95%CI=1.03-6.37, p=0.043) compared to non-asthmatics. In conclusion, asthma did 49 not influence the caries status of adolescents in the present study. Interestingly, a significant 50 association was found for adolescents with asthma who did not take MDI medication and the 51 number of MIH-affected teeth. The association between asthma, medication and MIH needs 52 further confirmation. 53 54 Material and Methods 103Study population 104

Purpose Despite recent improvements in cancer treatment in Germany, a marked difference in cancer survival based on socioeconomic factors persists. We aim to quantify the effect of socioeconomic inequality on head and neck cancer (HNC) survival. Methods Information on 20,821 HNC patients diagnosed in 2009–2013 was routinely collected by German population-based cancer registries. Socioeconomic inequality was defined by the German Index of Socioeconomic Deprivation. The Cox proportional regression and relative survival analysis measured the survival disparity according to level of socioeconomic deprivation with respective confidence intervals (CI). A causal mediation analysis was conducted to quantify the effect of socioeconomic deprivation mediated through medical care, stage at diagnosis, and treatment on HNC survival. Results The most socioeconomically deprived patients were found to have the highest hazard of dying when compared to the most affluent (Hazard Ratio: 1.25, 95% CI 1.17–1.34). The most deprived patients also had the worst 5-year age-adjusted relative survival (50.8%, 95% CI 48.5–53.0). Our mediation analysis showed that most of the effect of deprivation on survival was mediated through differential stage at diagnosis during the first 6 months after HNC diagnosis. As follow-up time increased, medical care, stage at diagnosis, and treatment played no role in mediating the effect of deprivation on survival. Conclusion This study confirms the survival disparity between affluent and deprived HNC patients in Germany. Considering data limitations, our results suggest that, within six months after HNC diagnosis, the elimination of differences in stage at diagnosis could reduce survival inequalities.

Aims Single measurements of higher levels of soluble tumor necrosis factor receptor I (sTNF-R1) have been shown to be associated with increased risk of mortality. However, up to date, little is known about the underlying temporal dynamics of sTNF-R1 concentrations and their relation with mortality. We aimed to characterize the effect of changes in sTNFR-1 levels on all-cause and cardiovascular mortality, independent from other established risk factors for mortality, including other inflammatory markers. Methods We used data of the population based cohort study CARLA and included 1408 subjects with sTNF-R1 measured at baseline (2002–2006) and first follow-up (2007–2010). Cox proportional hazard models were used to assess the association of baseline and follow-up sTNF-R1 measurements with all-cause and cardiovascular mortality during ~10 years since the first follow-up after adjusting for relevant confounders. Results Based on 211 deaths among 1408 subjects, per each doubling of the baseline sTNF-R1, the risk of all-cause mortality was increased by about 30% (Hazard ratio 1.28, 95% Confidence Interval 0.6–2.7), while per each doubling of the follow-up level of sTNF-R1 mortality was 3-fold (3.11, 1.5–6.5) higher in a model including both measurements and adjusting for confounders. The results were mainly related to the cardiovascular mortality (5.9, 2.1–16.8 per each doubling of follow up sTNF-R1 value). Conclusion Solely the follow-up value, rather than its change from baseline, predicted future mortality. Thus, while sTNF-R1 levels are associated with mortality, particularly cardiovascular, over a long-time period in the general population, if they change, the earlier measurements play no or little role.

The CARLA study (Cardiovascular Disease, Living and Ageing in Halle) is a longitudinal population-based cohort study of the general population of the city of Halle (Saale), Germany. The primary aim of the cohort was to investigate risk factors for cardiovascular diseases based on comprehensive cardiological phenotyping of study participants and was extended to study factors associated with healthy ageing. In total, 1779 probands (812 women and 967 men, aged 45–83 years) were examined at baseline (2002–2005), with a first and second follow-up performed 4 and 8 years later. The response proportion at baseline was 64.1% and the reparticipation proportion for the first and second follow-up was 86% and 77% respectively. Sixty-four percent of the study participants were in retirement while 25% were full- or partially-employed and 11% were unemployed at the time of the baseline examination. The currently running third follow-up focuses on the assessment of physical and mental health, with an intensive 4 h examination program, including measurement of cardiovascular, neurocognitive, balance and gait parameters. The data collected in the CARLA Study resulted in answering various research questions in over 80 publications, of which two thirds were pooled analyses with other similar population-based studies. Due to the extensiveness of information on risk factors, subclinical conditions and evident diseases, the biobanking concept for the biosamples, the cohort representativeness of an elderly population, and the high level of quality assurance, the CARLA cohort offers a unique platform for further research on important indicators for healthy ageing.