The impact of pollution on the development and progression of brain diseases and disorders

This topic aims at supporting activities that are enabling or contributing to one or several expected impacts of destination “Living and working in a health-promoting environment”. To that end, proposals under this topic should aim to deliver results that are directed, tailored and contributing to most of the following expected outcomes:

• Global and EU policies preventing and reducing the health impacts of pollution are supported with up-to-date scientific evidence, tools and methodologies;
• Citizens are more protected by having a better insight into exposure to pollution and its impacts on brain health and adopting health enhancing behaviours;
• Public authorities, health stakeholders, the scientific community and the society at large have access to FAIR^[1] data on the link between pollution and brain health, particular windows of susceptibility to exposure and the impacts of pollution on the general population and vulnerable groups;
• Public authorities develop adequate evidence-based measures and guidelines to prevent and reduce the negative impacts of pollution in the development of brain disease.

Life-long exposure to pollutants in the living and occupational environment is an important risk factor for non-communicable diseases, leading to a variety of serious physical and mental health impacts and causing preventable disease burden with associated elevated economic costs. Pollution disproportionately impacts certain vulnerable groups (e.g. children and older adults) or groups who are more sensitive or more exposed (workers, populations living in polluted areas) to this type of environmental stressor. At present, over 10% of annual premature deaths in the 27 EU Member States are related to environmental pollution^[2].

Age is a major risk factor for neurodegenerative diseases, but environmental exposure and lifestyle are important candidates for understanding their aetiology. Accumulating evidence suggests that the “exposome”, described as the totality of human environmental exposures from pre-conception onwards, represents a major modifiable risk factor for most neurodegenerative diseases and dementia. Additionally, emerging evidence suggests that pollution, may contribute to the development of neurodegenerative disease, with increasing incidence in an ageing population.

The environment is known to be a significant determinant of child health, with increasing evidence that some industrial chemicals are toxic to the development of the human brain. The health impact of many potentially neurotoxic chemicals remains unstudied in human populations, including in children. The developing brain is particularly vulnerable to toxic chemical exposures and this sensitivity is likely greatest in utero and throughout early childhood.

Chronic and repeated exposure to pollutants, in working environments but also for consumers, has also been associated with increased risk of cognitive impairment and neurodegeneration.

Research activities under this topic should explore evidence on the causal link between exposure to different pollutants (focusing on specific pollutants or a combination thereof) and the development or progression of neurological, neurodegenerative or neurodevelopmental diseases or disorders^[3]. Proposals can consider occupational, living and/or social environments and include one or more vulnerable, sensitive or exposed population groups. More specifically research actions under this topic should include several of the following activities while focusing either on neurological, neurodegenerative or neurodevelopmental diseases or disorders^[4]:

• Gain better insights on the pathogenesis and the molecular, genetic and epigenetic pathways and biological mechanisms involved in the onset and progression of disease, considering emerging pollutants, specific windows of susceptibility and adopting, when relevant, a life-course approach. Synergistic neurotoxic effects and realistic doses and duration of exposure should also be considered;
• Generate evidence on the impacts of pollution in comorbidities associated to neurodegenerative, neurological or neurodevelopmental diseases and disorders;
• Develop and/or validate better in-vivo, in-silico and in-vitro models, instruments and/or methods and take advantage (as applicable) of structural, functional and molecular imaging methods (e.g. MRI nuclear imaging), multi-omics and bioinformatics to study disease causation and evolution, considering, among others, also epigenetic factors and providing better biomarkers for early detection and disease progression;
• Apply the exposome framework to advance the understanding of the role of environment on neurodegenerative diseases research; elucidating the neuroexposome and emphasizing the brain’s distinctive responses to environmental exposures;
• Contribute to the development of health indicators to inform mitigation and prevention measures, incorporating, when relevant, an intersectional approach that considers diverse individual characteristics such as sex, gender, age, ethnicity, and disability and socioeconomic and lifestyle factors;
• Strengthen the understanding of the possible causative link between exposure and incidence of disease by taking advantage of well-designed longitudinal studies (considering exposure duration and differences in exposure composition, geographical location and sources), rigorously controlled epidemiologic studies and/or clinical, real-world and/or cohort data (building on existing national and international cohorts when available);
• Generate evidence on the potential association between the accumulated long-term exposure of workers and consumers to pollutants (including low-level exposure) and neurological and neurodegenerative diseases. The development of neurodevelopmental disorders in children following parental exposure could also be evaluated.

Gender and sex-related differences should be addressed, where appropriate.

Applicants are encouraged to consider the use of experimental methods not using live animals, where relevant and allowing to obtain data of comparable validity.

Proposals should adhere to the FAIR^[1] data principles and adopt wherever relevant, data standards and data sharing/access good practices.

The effect of nutrition on mental health should not be the main focus since this area will be covered by topic HORIZON-CL6-2025-02-FARM2FORK-12: “Nutrition and Mental Health”.

Applicants should be acquainted with the activities being developed under the Environment, climate and health research portfolio^[6], the EFSA activities under Environmental Neurotoxicants^[7] and Developmental neurotoxicity^[8] and the Partnership for the Assessment of Risks from Chemicals - PARC^[9].

This topic requires the effective contribution of social sciences and humanities (SSH) disciplines and the involvement of SSH experts, institutions as well as the inclusion of relevant SSH expertise, in order to produce meaningful and significant effects enhancing the societal impact of the related research activities.

Proposals should take advantage of and connect to European research infrastructures and services in the area of environmental exposure assessment.

Proposals should ensure that chemical monitoring including human biomonitoring data are shared in the Information Platform for Chemical Monitoring (IPCHEM)^[10] through involvement with the European Commission's Joint Research Centre (JRC), and/or in the future Common Data Platform for Chemicals, through involvement with the European Chemicals Agency (ECHA)^[11] or other relevant decentralised EU agency (such as the European Environment Agency - EEA^[12]) responsible for the specific domain. In that respect, the JRC, ECHA or other relevant decentralised EU agency(ies) should collaborate with any successful proposal and this collaboration, when relevant, should be established after the proposal’s approval.

In order to maximise synergies and increase the impact of the projects, all proposals selected for funding from this topic will form a cluster and be required to participate in common networking and joint activities. Without the prerequisite to detail concrete joint activities, proposals should allocate a sufficient budget for the attendance of regular joint meetings and to cover the costs of any other potential common networking and joint activities. Guidance on the potential activities to be developed can be obtained by consulting the clusters of projects ongoing under the Environment, climate and health research portfolio^[6].

Applicants invited to the second stage should provide details of their clinical studies^[14] in the dedicated annex using the template provided in the submission system. As proposals under this topic are expected to include clinical studies, the use of the template is strongly encouraged.

[1] See definition of FAIR data in the introduction to this work programme part.

[2] https://www.eea.europa.eu/en/topics/at-a-glance/state-of-europes-environment

[3] For guidance on the diseases and disorders under scope of this topic please consult ICD-11 for Mortality and Morbidity Statistics (who.int): https://icd.who.int/browse/2024-01/mms/en#1516623224 Chapters 6 and 8 specifically on neurodevelopmental disorders and neurocognitive disorders (including accelerated cognitive decline and chronic pain conditions).

[4] For each of the three focus areas, proposals can address one or several diseases or disorders as relevant for the research action proposed.

[5] See definition of FAIR data in the introduction to this work programme part.

[6] https://research-and-innovation.ec.europa.eu/research-area/health/environment-and-health_en

[7] https://etendering.ted.europa.eu/cft/cft-display.html?cftId=13967

[8] https://www.efsa.europa.eu/en/art36grants/article36/gpefsaed202201-nam-projects-areas-aop-development-and-transcriptomics-risk

[9] https://www.eu-parc.eu

[10] https://ipchem.jrc.ec.europa.eu

[11] https://echa.europa.eu

[12] https://www.eea.europa.eu

[13] https://research-and-innovation.ec.europa.eu/research-area/health/environment-and-health_en

[14] Please note that the definition of clinical studies (see introduction to this work programme part) is broad and it is recommended that you review it thoroughly before submitting your application.