Authors: Chirag Patel (NEXUS/ Harvard) and Robert Wright ( Mt Sinai Center for Exposomics)
“….memory is fragile and the space of a single life is brief, passing so quickly that we never get a chance to see the relationships between events; we cannot gauge the consequences of our acts, and we believe in the fiction of past, present, and future, but it may also be true that everything happens simultaneously.”
- Isabel Allende, from “The House of the Spirits”.
In many ways this quote from the great Chilean author embodies the many challenges we face as we attempt to quantify all our environmental exposures from conception to death.
Recently we spent two crisp – and one cold/rainy – spring days in Santiago (Sept 25–27, 2025) that framed an ambitious question: how do we integrate environmental exposures into Alzheimer’s disease and related dementias (AD/ADRD) research—and do so in ways that work across countries, cohorts, time and disciplines? The Santiago Exposome Symposium at Club Manquehue convened aging, neurology, and environmental health communities from Latin America, the U.S., and Europe to compare notes, share tools, and debate standards.
If Banbury was where a common definition took shape, Santiago was where that vocabulary met the reality of the world’s diverse practice and brought to bear new insights and where re-focusing or work needs to be done. The Banbury Exposomics Consortium (Cold Spring Harbor, 2023) set the table with a definition and a programmatic push to embed exposomics in biomedicine; Santiago asked in parallel how we actually do it in real settings, with different geographies, economies, cultures and populations with different resources and needs. While exposomics holds immense promise, there is a large need to communicate with each other across disciplines, across continents and even across time if we are to make the exposome real, ensuring that the operationalized definition from Banbury makes sense in all communities while ensuring populations are sufficient to extract generalizable signals from noise, particularly in the genetically and environmentally diverse settings in South America. Most importantly, how will we implement our findings to improve health?
Participants were wide ranging researchers from the South American continent and also included individuals from the US federal government, such as Dr. Rick Woychik and Dr. Richard Kwok (US NIH).
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Early mornings on the other side of the Banbury Conference Center in Cold Spring Harbor, New York (left); an early morning in Santiago, Chile (right). | |
Talk and poster highlights
While the focus of the conference was on brain aging and Alzheimer’s disease (and the role the exposome plays on the disease), many talks asked appropriately to widen the view of dementia and consider time windows much upstream of the disease outcomes. Our health today is a reflection of our past environment more so than the environment we encounter today. If we are to fully harness exposomics’ potential we must not only measure our exposome today, we must be able to reconstruct our past exposome. How to go back decades and reconstruct our lifetime exposome will likely require a multitude of strategies- biobanks, geospatial maps, novel biomarkers and remote sensing could all play roles. In genetics, intermediate phenotypes refer to traits that are incompletely dominant, or perhaps more simply a mix of different dominant alleles. In Gregor Mendel’s experiments pink flowers arose from the mating of red and white flowers for example. Human height is yet another example. Few traits arise as “all or nothing” diseases, but instead begin with phenotypic prodromes that can appear decades before the disease is expressed. Sleep and Cognitive Reserve are examples of such prodromal traits for Alzheimer’s Disease (AD).
Dr. Yue Leng made a compelling case that sleep is both a modifiable phenotype and an early signal on the path to cognitive decline. With large-scale data, we can start to separate environmental determinants of sleep (noise, heat, air quality, social rhythms) from downstream brain outcomes—turning a fuzzy risk factor into a tractable phenotypic domain for exposomic discovery. Similarly, cognitive reserve, the ability to resist the cognitive impact of AD neuropathology arises from the childhood environment and may be a modifiable trait to protect against neurodegeneration. The best way to prevent AD may be to promote cognitive reserve at every life stage. The child exposome may play a key role in doing so.
We urge the exposome research community to widen the aperture and increase the light reaching life course research. Developmental exposures shape late-life neurodegeneration risk. Neurodegeneration will occur on top of the neuronal and synaptic network created during our childhood. Can we modify the child exposome in ways that prevent neurodegeneration? A discussion prompted by us after the conference pulled on the thread of the importance of life stage exposomics: new discovery-based findings should inform not just prevention (e.g., examining associations that concern prognosis), but clinical actionability after diagnosis—mapping exposomic pathways that influence progression and care. For example, the research needs to evaluate individuals who already have diagnosis as a critical population by which to study how exposures as a whole modify their life and influence their decisions.
Dr. Diana Marcela Marin Pineda presented posters on the early-life exposome & children’s lungs and genetic mutations in Colombia: Diana’s work foregrounds how early-life multi-exposure profiles shape children’s respiratory health in a Latin American setting—and explicitly calls for inter-regional exposome studies so methods and reference panels can travel without erasing local context.
Infrastructure spotlights: GECC
We also saw tangible progress from the Gateway Exposome Coordinating Center (GECC)—an NIA-funded coordinating hub building transportable, science-ready tools for AD/ADRD exposome research across six external and social domains (extreme weather; physical, social, and policy environments; community services; and life experiences), dominated by geospatial measures of the external exposome. Important, but a fraction of the phenomenon of the exposome which must eventually address person-level exposures.
In Santiago, Dr. Dany Doiron previewed GECC’s work to harmonize measures, curate data, and lower the barrier to entry for teams adding exposomics to ADRD studies. Funding and mandate details underscore the scale and durability of the effort (U24AG088894, 2024–2029), specifically to pilot projects to researchers aiming to get started with exposomic research. Dr. Richard Kwok also emphasized ongoing work on phenotypic harmonization occurring in important aging cohorts, such as the Health and Retirement Survey. Key efforts remain in merging the efforts of GECC and NEXUS and extending that across the globe.
South American efforts: breadth, specificity, and opportunity
A strength of the meeting was its on-the-ground specificity—the kinds of exposures that matter locally and how to measure them well:
- Peru Air Quality Monitoring Network as a foundation for longitudinal external exposome monitoring.
- Mexican Health and Aging Study (MHAS) analyses linking drought to cognitive function.
- MAUCO (Maule,Chile) with adult chemical exposure profiling, and the Alexandros Cohort for the social exposome and health trajectories, presented by Drs. Sandoval and Cortes. MAUCO is a population-based, prospective cohort in the agricultural county of Molina (Maule Region, central Chile) designed to study the natural history and drivers of chronic diseases in an under-studied, semi-rural population. It aims to enroll ~10,000 adults aged 38–74 and follow them over a decade with waves at ~2, 5, and 7 years. At baseline, participants complete detailed questionnaires (socioeconomic, occupational, psychosocial, lifestyle; with emphasis on pesticides, mycotoxins, diet, alcohol, physical activity), undergo physical exams and functional tests (e.g., handgrip, bioimpedance), ECG, and abdominal ultrasound, and contribute blood, urine, and saliva for a biobank storing 30–50 aliquots per person at −80 °C under NCI QA/QC procedures. Outcomes span CVD, cancer, metabolic syndrome, respiratory disease, aging, mental health, oral health, with active surveillance through regional hospitals to capture incident events. The cohort’s setting—high burden of CVD, gallbladder and stomach cancers, and mixed “transition” exposures (e.g., agriculture-related chemicals, biomass/wood-smoke air pollution)—provides a powerful platform for exposome research and policy-relevant prevention in Latin America.
- ALEXANDROS (Active Life Expectancy, Aging and Disorders Related to Obesity Study) is a longitudinal cohort of community-dwelling older adults (60+) in Santiago, Chile, built to study disability and healthy aging in relation to nutritional status, an important factor of the exposome. It combines three subcohorts spanning socioeconomic strata and birth years—SABE (n=1,173; born <1940), Alexandros (n=950; 1940–48), and ISAPRES (n=266; high-SES; born <1949)—with baselines beginning in 2000/2007/2012 and 10–15-year follow-ups. Data include face-to-face interviews; physical/biological assessments (e.g., anthropometry, grip/gait, fasting blood); mental-health measures; and mortality linkage, enabling analyses of cognition, dementia, frailty, MCI, obesity, and physical health. Led by the University of Chile and funded by FONDECYT, ALEXANDROS provides a rare Latin-American platform for aging and exposome-adjacent questions across social and clinical gradients.
- PARDoS (Brazil): As Dr. David Bennett, Director of the Rush Alzheimer’s Center emphasized, the Pathology, Alzheimer’s and Related Dementias Study (PARDoS) is a community-based, clinical-pathologic powerhouse in São Paulo that finally brings large-scale, globally relevant diversity into ADRD research. In just over three years (Jul 31, 2021–Feb 11, 2025), PARDoS has enrolled 4,700+ autopsied participants (ages 18–106; ~40% Black/Mixed; mean education 6.3 years), with early informant data showing ~33% dementia and ~19% MCI among those 65+. Designed to uncover environmental, genetic, and molecular drivers of brain aging, PARDoS fills a critical gap left by Euro-American cohorts and offers a natural anchor for exposome-informed neuropathology in Latin America—and a template for federated, cross-border science. There are great cross-country opportunities in exposome studies across the Americas, but must confront the challenges of local needs.
Latin America is rich in cohort assets and measurement ingenuity, but we still need portable standards so results are comparable without flattening local nuance that is important for intervention and communication to participants and patients.
The Banbury through-line: definitions that should travel
Santiago reaffirmed the Banbury premise: the exposome spans physical, chemical, biological, and psychosocial influences that impact biology; exposomics integrates diverse data streams to quantify those cumulative effects. To paraphrase the late politician Rep Tip O’Neill- “All exposomics is local” meaning the issues of concern in Latin America surrounding health, environment and society are those that impact the local community- which might include access to clean water, microplastics contamination, air pollution, economics or diet. Many talks and posters riffed on the theme of integrative and holistic exposome studies, but there were many reminders of the importance of tried and true environmental health methods to determine the role of single, candidate, and timely risk factors – such as drought – on the aged populations from Mexico. The shared language of the exposome is the prerequisite for standards documents, data models, and QA practices that teams can reuse—whether they start from air sensors, HRMS, GIS layers, or clinical EHRs, but the issues that these tools will address will vary geographically.
From NEXUS’s vantage point, exposomics becomes practical when we treat it as discovery science—an Exposome-Wide Association Study ( ExWAS) program that is inclusive, integrative, informative, interactive, and iterative: measure broadly across geospatial, chemical, biological, and psychosocial domains; link exposures to phenotypes and molecular readouts; enforce transparent mapping from exposure to clinical manifestation; model co-exposure structure and internal–external bridges; and replicate/harmonize globally. Concretely, NEXUS will aim to push containerized ExWAS platforms, open analytics/code, and education (e.g., ExWAS EduWorkbench). The near-term agenda: standardized assays and geospatial pipelines, power/FDR-aware scanning across many exposures, global reference panels, and federated data access—so any team can run credible, reproducible exposomics at scale, focused on US-based cohort data and hopefully in the near future, moving to US based registries and biobanks.
Global Exposome Forum: convening the “how”
In a post-meeting discussion, Dr Fenna Sille led a discussion on the Global Exposome Forum (GEF), a venue to keep building this community and to confront big global gaps: access, governance, and what a truly cross-border “global” exposome map/assay could look like. The Forum’s agenda is explicitly multi-stakeholder and iterative (with events in 2025 and 2026), which is exactly what standards-making in a new field requires. The next step includes convening multiple working groups and followed by a large event close to Barcelona in 2026.
What we learned
- We still have a definition problem. Not in principle—Banbury gave us that—but in practice. We need short, serviceable explanations that work for clinicians, policymakers, and community partners, and that don’t collapse into “chemical vs social exposome” camps. The exposome’s point is to put factors on a single playing field with consistent measurement logic that addresses the needs of different communities.
- Standards must be usable everywhere. Harmonization cannot erase locality. The aim is interoperability without homogeneity: clear core fields, reference panels, and calibration playbooks—plus room for local add-ons (e.g., biomass cookstoves, drought indices, or micro-climates). GECC’s domain framing is a helpful scaffold here.
- Discovery and utility can co-exist. Workshops on untargeted exposomics (Barupal, Petrick) and GIS for exposure assessment (Kloog, Gutiérrez Avila, He) emphasized discovery and deployment—how to go from raw signal from satellites and sensors to interpretable, reproducible measures.
- Clinical and policy bridges matter. Talks from us (Wright & Patel) and Kwok anchored why this matters for patients: developmental origins, precision environmental health, and pragmatic designs that make exposure knowledge actionable in care pathways. Exposomics, like all “omic” sciences, is a framework for discovery.
However, taking a discovery to the point of care and public health policy is another matter altogether. Second, arguably the point of discovery is not to measure “everything” but what is important to measure, keeping a close eye on how discoveries can ultimately be clinically evaluated. We need to a priori consider how to implement our research with evaluation in mind.
We, as the exposome research and clinical communities need to focus and measure, what is the potential clinical and policy impact to develop standards so that data can be seamlessly shared across research groups across the globe.
Near-term to-dos
- Publish a short, field-tested “Exposome Guide for Investigators.” Outline how exposome-based discovery differs from (and complements) traditional single-exposure public health studies; include checklists for study design, measurement QA/QC (e.g., ring trials), and multi-domain confounding control focused on the needs of the continent.
- Standards, then services. Lock a minimal core schema (IDs, time, place, assay metadata, domain tags) and a set of reference panels per domain; couple this with shared code for geospatial pipelines and HRMS processing.
- Networked repositories over a single silo. Build federated access with LMIC participation by default—“many homes, one interface”—so data governance remains local while discovery becomes global. GECC’s coordination plus platforms like Gateway to Global Aging Data are strong precedents, and NEXUS is also primed to be involved.
- Map cohorts to needs. Support ancillary studies that add exposome measures where cognitive phenotyping already exists—and vice-versa. (The Santiago agenda provided several ready testbeds.)
- Partner with frontline practicing clinicians and medical trainees to better understand how to make exposomic research actionable and implementable.
Gratitude—and momentum
Kudos to the organizers across Mount Sinai, University of Chile/GERO, Dr. Anita Pereira and partners for creating a space where regional specificity meets global ambition. Santiago didn’t settle every debate (it wasn’t meant to), but it sharpened the field’s next moves: define clearly, standardize pragmatically, and build infrastructure people actually use. NEXUS and Mt. Sinai teams are ready to help assemble best practices, and where feasible, provide data, code, and resources, or even help triage requests. Please get in touch.
Related: Santiago Symposium overview and agenda; Banbury Consortium background; GECC mandate and award; Global Exposome Forum initiative.