Human populations are impregnated by various types of chemical pollutants reported as “hazardous waste” present in the environment. Certain pollutants have adverse effects on brain, but the underlying mechanisms and time-window exposures are still unknown, as well as their contribution on dementia, the 7th leading cause of death. EXPOSIGNALZ project aims to delineate the impact of a selection of environmental pollutants on brain health throughout life and their role in dementia especially Alzheimer’s disease (AD) representing about 70% of dementia cases. Through interdisciplinary approaches, integrating experimental and epidemiological studies, our objectives are to: 1) Identify environmental pollutants likely to have neurotoxic effects and pro-amyloidogenic properties predictive of a neurodegenerative trajectory related to AD using in vitro screening models; 2) Characterize pollutant signatures associated with brain aging and AD in biological matrices of 4 European population-based cohorts of various age groups; 3) Understand the mechanisms of action of pollutants identified in the in vitro screenings and those found in biological signatures, using AD-iPSC and AD preclinical models; 4) Explore the impact of pollutants on early neurodevelopment as a factor of susceptibility for later neurodegenerative diseases using brain organoids and gestational contamination models and 5) Disseminate knowledge to policy makers, to the relevant stakeholders and general public in order to define guidelines for disease prevention and take actions for population’s health. The project, which aims to identify chemical pollutants as new risk factors for dementia as well as new pollutant-associated biomarkers, could contribute to: (i) reduce or delay the incidence of AD, and thus reduce the economic and social burden; and (ii) allow an earlier diagnosis of AD combined with new disease modifying treatments to delay the entrance of patients in the more severe stages of the pathology.

IMPACT DIABETES B2B will demonstrate the real-world implementation of an evidence-based, low-resource system-level intervention for healthy gestational weight gain and early prevention of maternal and child diabetes, overweight and obesity when delivered ‘at scale’ across antenatal settings. Gestational diabetes affects up to 18% of pregnancies worldwide and is an increasing health problem for both mothers and babies. By identifying those most at risk of developing gestational diabetes and working with them through personalised health coaching delivered via smartphone App, this project will engage, motivate and empower this target group to lead healthier lives for improved wellbeing and pregnancy outcomes. This project will demonstrate implementation within 3 European countries and Australia with clear line-of-sight on future scale-up across different contexts and resource settings via its innovative implementation toolkit and workshops for dissemination and exploitation. Pregnancy is a unique time in life with potential to influence maternal health, and the health of the next generation. IMPACT DIABETES B2B delivers breakthrough research in nutrition, exercise and behaviour change leading to an implementable low-resource system-level intervention. The personalised feedback will empower women to manage their health, delivering cost-effective management of excess gestational and post-pregnancy weight gain to: improve pregnancy and postpartum outcomes; improve utilisation of healthcare services; and encourage ongoing maternal health with sustainable impact for mother and family. Expertise in implementation science, lifestyle change, health psychology, mHealth technology, health economics and health service delivery will lead this mixed methods project. The project will co-design the intervention system, with end-user context and management explored throughout. The work will evaluate clinical, economic and implementation outcomes to inform future practice and policy.

The Gluco-Psychosocial Axis (GPA) concerns the interplay of factors determining glucose metabolism and insulin sensitivity and the neuroendocrine response resulting from exposure to psychosocial stress. A sub-optimal GPA influences the development of type 2 diabetes and related impairments with varying degrees of interplay between genetics and early growth (particularly adiposity and cognitive function), and social, occupational, and other modifiable lifestyle factors. Many exposures apply from throughout life, and potential exposure to a sub-optimal GPA lead to a cumulative risk of ill health and decreased economic prospects for the ageing. Understanding these factors, interactions and extent they contribute to the preservation of glucose homeostasis and psychosocial functioning is important for the development of preventive and therapeutic measures promoting healthy and active ageing. DynaHEALTH will contribute to implementing a dynamic model for early GPA risk identification and validation, allowing development of risk-based prevention tools and policies that will help to inform policy makers on the best periods to invest in cost-effective and sustainable healthcare strategies. DynaHEALTH comprises 13 partners from academic/private sectors and will leverage data from 21 birth cohorts and intervention studies, involving 1.5 million Europeans. By identifying biological and psychosocial determinants of the GPA and characterising metabolic and epigenetic factors, whilst quantifying the impact of exposure to an optimal lifelong GPA, DynaHEALTH will influence weight gain, glucose homeostasis, employability, health deterioration and disease accumulation as individuals age. DynaHEALTH includes the potential to exploit the results for new technologies and strategies, adding to our understanding of pathways related to healthy and active ageing, underpinning options for targeted, personalised healthcare and mitigating the effects of sub-optimal GPA on ageing.

Environmental factors, including air and noise pollution, and the built environment, are typically associated with cardiovascular and metabolic non-communicable diseases (NCDs), e.g. obesity, type 2 diabetes, heart diseases and atherosclerosis. The extent to which these exposures may cause their attributed health effects (via molecular mediation) directly or indirectly as a result of associations to an individual’s psychosocial context is largely unknown. NCDs arise from a lifelong process influencing anthropometric, glycaemic, cardiac and lipid-related health trajectories. Risks may start as early as during the fetal period and are modified during sensitive periods in childhood, adolescence and adulthood. Despite this, research has not focused enough on the life-course characterisation of the exposome and the application of this to health and disease. In 5 years, LONGITOOLS, a partnership of 15 academic groups and 3 small companies will harness a catalogue of birth cohorts, longitudinal data, registers and biobanks. We will characterise coincident longitudinal trajectories of exposure and cardiometabolic health combining the study of longitudinal effects and internal responses. The latter will include measures of DNA methylation, RNA expression and read outs of metabolic pathways. LONGITOOLS will implement this longitudinal approach in 11 work packages designed to generate a catalogue of FAIR data and a novel analytical toolbox. Evidence-based life-course causal models will estimate how clinical and policy interventions may sustainably affect the health and economic burden of NCDs. A key objective will be to generate evidence-based predictions which can ultimately translate into innovative healthcare applications (apps) and policy options. LONGITOOLS will also allow researchers and policy makers to generate new knowledge - identifying the likely causal (direct and indirect) mechanisms through which exposures to man-made environmental factors affect the risk of NCDs. LONGITOOLS is one of the nine projects composing the European Human Exposome Network.