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Approved Concepts

Below are concepts approved at the most recent National Advisory Council on Aging (NACA) meetings. We have posted the approved concepts here to give interested researchers maximal lead time to plan projects. Please note that not all concepts will necessarily end up converting to a Notice of Funding Opportunity (NOFO), and some of the concepts listed below (particularly from older Council meetings) may have already been converted to NOFOs.

May 2023 Council

Approved research and development contract in this round:

Technology to Facilitate Characterization of the Exposome in Under-Resourced Populations for AD/ADRD Studies

The exposome refers to the comprehensive set of exposures in people’s physical, chemical, social, psychological, and economic environments. In order to fully characterize the exposome, it is necessary to collect both environmental and biological samples. However, while under-resourced populations often carry the highest burden of age-related diseases, they are often precluded from research studies due to difficulties in collecting the necessary environmental and biological samples. New technologies that enable self-sampling and point-of-exposure sampling of the exposome may help lower barriers to data collection among these populations and advance NIA’s understanding of the cause of complex conditions such as Alzheimer’s disease and related dementias (AD/ADRD).

This concept aims to facilitate the development of technologies that enable remote or self-sampling of exposome measures that can be combined with remote point-of-exposure measures in long-term population-based studies. These technologies will provide a powerful lens to characterize the exposome by validating measures and reducing costs to increase study inclusion of under-resourced populations.

Contracting Officer:

Karen Mahon
Office of Acquisitions, NIDA/NIA
Email Karen Mahon

Scientific/Research Contact:

Richard Kwok, Ph.D.
Division of Neuroscience, NIA
Email Richard Kwok

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January 2023 Council

Approved research concepts in this round:

Approved contract concepts in this round:

Analytical and Clinical Validation of Biomarkers for AD/ADRD

A biomarker is any measurable characteristic that can serve as an indicator of normal or pathogenic biological processes, or responses to exposures or interventions. Biomarkers can encompass a wide range of modalities, including measurement of analytes in body fluids, genetic, imaging, physiological and behavior or functional changes. Biomarkers are used in basic, translational, and clinical research and in clinical settings to inform patient care (disease related biomarkers) and/or facilitate medical product development decisions (product related biomarkers). NIA has supported multiple projects aimed at the discovery of novel biomarkers for Alzheimer’s Disease and related dementias (AD/ADRD), and many candidates have been identified. However, few are progressing from discovery to analytical and clinical validation, and their clinical and scientific utility remain indeterminate. A particularly pressing issue is the co-occurrence of ADs and ADRDs, since autopsies show that neuropathological comorbidities are common in the brains of people with dementia. Studies are also needed to determine longitudinal trajectories of biomarkers along the course of disease, or treatment, as well as generalizability of given biomarkers/biomarker signatures to diverse population.

The FDA has promulgated a useful framework and guidance for developing and validating biomarkers, in general. Acceptance or qualification of new biomarkers by the FDA requires both Analytical Validation and Clinical Validation within a well-defined Context of Use (COU) in medical product development, and/or in clinical practice. The goal of this concept is to advance strong AD/ADRD biomarkers for specific COUs by supporting development of already identified biomarkers or biomarker signatures and enabling their rigorous analytical and clinical validation within a (pre)specified COU. Applicants are encouraged to leverage existing NIA research resources and supported initiatives. Development plans should be consistent with FDA guidance. Further, applicants are also encouraged to create a path toward approval from the FDA, such as the Biomarker Qualification Program or other regulatory pathways. The funding mechanism for this concept will be a cooperative agreement, which will include substantive programmatic involvement in milestone development and project implementation.

Activities suitable for this concept include, but are not limited to:

  • Determine the biomarker’s predictive value and suitability for use to enrich for enrollment of a subgroup of AD patients more likely to respond to a novel therapeutic in Phase 2/3 clinical trials
  • Investigate the longitudinal trajectory of a biomarker to determine its clinical value for predicting conversion, as well as responses to treatment/prevention.
  • Establish reliable safety biomarkers for the detection of adverse effects
  • Validate reliable biomarkers for the determination of risk, disease detection and assessment of response to intervention, in diverse/underrepresented populations
  • Evaluate the diagnostic value of biomarkers for differentiating AD from other dementias such as vascular dementia, Lewy body dementia, frontotemporal disorders, and limbic-predominant age-related TDP-43 encephalopathy (LATE).

Scientific/Research Contacts

Yuan Luo, Ph.D.
Division of Neuroscience
Email Yuan Luo

Nadezda Radoja, Ph.D.
Division of Neuroscience
Email Nadezda Radoja

John Hsiao, M.D.
Division of Neuroscience
Email John Hsiao

Alessandra Rovescalli, Ph.D.
Division of Neuroscience
Email Alessandra Rovescalli

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Artificial Intelligence in Pre-Clinical Drug Development for AD/ADRD

Over the past 15 years, NIA’s Alzheimer’s translational research program has supported the discovery and development of new drug candidates targeting different aspects of the complex biology of Alzheimer’s disease and related dementias. Despite notable successes, such as creating a robust portfolio of new preclinical and clinical drug candidates for a diverse set of therapeutic targets, there remains a need for de-risking and accelerating key steps of the drug discovery and preclinical drug development process. Driven by the rapid growth of big biomedical data, increase in computing power, and continuous optimization of computing algorithms, artificial intelligence (AI) and machine learning (ML) methods are providing opportunities to increase the efficiency for the discovery and development of safe and effective drugs.

This is a concept for a new funding initiative that will take advantage of the rapid expansion of AI methods and their application to some of the most challenging, labor-intensive and costly aspects of drug discovery and preclinical drug development. The central goal of this initiative is to develop a robust research program that will focus on developing and using AI/ML methods to accelerate rational drug design for novel AD/ADRD targets. This program will also create advanced open-source analytical tools that will be made available to researchers in academia and biotech/pharma. Research supported through this initiative will build on NIA’s investment in the discovery of novel candidate targets and will complement the goals of the NIA-supported TREAT-AD centers whose mission is to advance novel targets into drug discovery by developing open-source target enabling research tools.

Research activities of interest include:

  1. Using AI methods to accelerate and optimize the design and synthesis of in-vivo chemical probes for novel targets identified by the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP AD) and other NIA-supported target discovery programs.
  2. AI/ML-guided blood-brain barrier permeability prediction and implementation into therapeutic discovery for Alzheimer’s disease.
  3. Virtual screening for novel compounds with desired drug target binding activity, hit/lead generation and optimization, drug response, and synergy prediction.
  4. ML models for new drug design, including combinatorial libraries and predicting ‘drug-likeness’.
  5. Integration of AI/ML with 3D protein structure information for docking simulations and enhancing synthesizability of designed molecules.
  6. Modeling protein interactions and drug-target interactions using structural data.

Development of phenotype-based virtual-screening, through utilization of a variety of data types to gain insights for the mechanism of action.

Scientific/Research Contacts

Suzana Petanceska, Ph.D.
Division of Neuroscience
Email Suzana Petanceska

Nandini Arunkumar, Ph.D.
Division of Neuroscience
Email Nandini Arunkumar

Paul Grothaus, Ph.D.
Division of Neuroscience
Email Paul Grothaus

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Behavioral and Social Research on the Role of Immigration on Life Course Health and Aging, Including AD/ADRD

This concept will call for innovative minority health and health disparities research that goes beyond describing the differences observed among racial and ethnic minority communities as compared to White communities to explore how structural, community, and interpersonal mechanisms shape health outcomes and disparities among Latino, Black, Asian, and other immigrant groups in the U.S. and result in health disparities among various populations. Immigration from different countries in Latin America, Africa, Asia, and other countries to the U.S. has been increasing. Immigrants from different countries typically have lower morbidity and mortality than their U.S.-born counterparts, which is referred to as the healthy immigrant effect. The health of immigrants can, however, deteriorate the longer they stay in the U.S. The literature is mixed when it comes to the healthy immigrant effect because of variation in sending-country economic, political, and sociocultural contextual characteristics that have implications for immigrant health and aging after arrival in the destination country. Further, the experience of immigration itself can be traumatic and can affect families for generations. It is unclear what accounts for these differences.

The previous research on immigration and health has typically not employed a life course approach and has included limited measures of pre- and post-immigration which may help provide causal explanations for differences in health outcomes among immigrant groups. For example, characteristics of individuals before they immigrate, including education, health, income, political refugees, and sex could provide causal insights. Similarly, post-immigration drivers of health differences include documentation (legal status) and acculturation. For example, the lack of data on language preference and barriers, documentation, institutional policies, access to healthcare, and acculturation, makes it difficult to estimate how much the healthy immigrant effect accounts for improved life expectancy.

There are data limitations in existing studies among Latinos, Blacks, Asians, and other immigrant groups (e.g., cross-sectional rather than longitudinal data; inadequate measures of acculturation/integration in existing studies; insufficient cross-national data to address selectivity and tackle other methodological issues). Therefore, this concept includes calls for better measures of immigrant acculturation/integration, data that follow migrants across sending- and receiving-country contexts, and longitudinal data to facilitate research that takes a life course approach. These data approaches include use of existing data from the U.S. and cross-national comparisons, as well as primary data collection from the community and mixed methods for measurement development. This concept seeks to extend the literature on immigration and health and deepen NIA’s investments in research on underrepresented populations. The goal is to:

  • Expand the field of minority health in aging research by identifying factors that drive the health of racial and ethnic minority communities over time as they settle in the US,
  • Expand the field of health disparities research among racial and ethnic communities as compared to white communities and,
  • Expand the understanding of health disparities within specific racial or ethnic groups.

Scientific/Research Contact

Frank Bandiera, Ph.D.
Division of Behavioral and Social Research
Email Frank Bandiera

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Building Neuroscience Research Infrastructure for AD/ADRD in Africa

Alzheimer’s disease and related dementias (AD/ADRD) represent a substantial global health issue, especially for low- and middle-income countries (LMICs), where approximately 71% of the global cases will reside. In particular, the sub-Saharan Africa (SSA) region is expected to undergo a significant increase in the number of new cases due to the increase in the size of the older adult population.

Data on the incidence and prevalence of dementia in Africa is sparse, and related investments for AD/ADRD research in the region have been limited and persistently lacking relative to its population size. But the region’s wide variety of dietary, lifestyle and environmental exposures, as well as genetic variation, can provide valuable insights on factors that contribute to AD/ADRD. Studies of AD/ADRD in Africa will present significant research opportunities that will increase knowledge about the etiology of this family of diseases and accelerate the pace of scientific discovery. These studies can also inform intervention or prevention strategies through reciprocal innovative approaches (the bi-directional and iterative exchange of a technology, methodology, or process between two countries) for AD/ADRD mitigation within US populations.

This concept will serve as a catalytic opportunity to develop or enhance AD/ADRD research infrastructure across Africa, while supporting collaborations between US and African scientists via pilot or exploratory studies that will inform the scale up of future research. It is envisioned that this initiative will lead to the development of a consortium of AD/ADRD studies within Africa, and which can inform preventative, therapeutic and intervention strategies for US populations.

Scientific/Research Contacts

Damali Martin, Ph.D., MPH
Division of Neuroscience
Email Damali Martin

Minki Chatterji, Ph.D.
Division of Behavioral and Social Research
Email Minki Chatterji

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Chimeric Antigen Receptor (CAR) Approaches to AD/ADRD

This concept provides a proof-of-principal for a novel strategy for AD/ADRD immunotherapies and explore whether novel immunotherapeutic approaches for cancer could be repurposed as potential therapies for Alzheimer’s disease and related dementias. The approach, which combines the functions of chimeric antigen receptor (CAR) proteins and immune cells (typically T cells) into CAR-T, a promising cancer immunotherapy, has yielded unprecedented response rates against different types of blood cancers but has had limited success against solid tumors. Another type of CAR therapy, CAR-M (CAR on macrophages) has shown potential to address the shortcomings of CAR-T for a multi-faceted anti-tumor response.

The concept will examine if CAR-T and/or CAR-M technologies could be customized as treatments for AD using two approaches. The first will test if CAR-T can effectively eliminate specific types of harmful senescent cells which contribute to Alzheimer’s disease pathology in the brain, without removing beneficial senescent cell functions such as wound healing. Another path will attempt to use CARs to boost macrophages’ natural ability to degrade and eliminate harmful protein aggregates like amyloid-beta, a signature pathology of AD in the brain.

Scientific/Research Contacts

Miroslaw Mackiewicz
Division of Neuroscience
Email Miroslaw Mackiewicz

Amanda DiBattista, Ph.D.
Division of Neuroscience
Email Amanda DiBattista

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Clonal Hematopoiesis in Aging Humans: Detection, Risk Factors, Relationships to Aging-Related Pathophysiology and Conditions, and Clinical Utility in Screening and Prognosis

Clonal hematopoiesis (CH) is a condition related to aging wherein clonal expansion of cells driven by somatic mutations increases markedly with age in humans. CH is known to be associated with health risks, such as hematopoietic malignancies or increased incidence of cardiovascular disease and other age-related diseases. The term “clonal hematopoiesis of hematopoietic indeterminate potential” (CHIP) has been applied to a subset of hematopoietic clones in which cancer driver genes are found without clinical signs of hematological neoplasm and absence of cytopenia. Recent advances in genome sequencing and analysis now make it much easier to identify CH in existing longitudinal and clinical studies’ biosamples and data, with the goal of clarifying their impacts on healthy aging, disease, and longevity. Much of the underlying genetics and biological mechanisms relating to varied aging phenotypes and specifically exceptional longevity are largely undefined and under explored. Understanding the dynamics of CH in conjunction with multi-omic data in relation to physiological factors, environmental exposures, germline genetic risk factors, and gender specific effects could unravel how CH, biologically impact multiple aging phenotypes such as exceptional longevity, higher risk of age-related diseases and all-cause mortality.

This concept provides an opportunity to elucidate additional cell types of CH beyond the currently known driver genes and variants observed in CHIP. Importantly, the deleterious or protective effect of most CH mutations as a function of age remains to be established and further studies are warranted to determine if CH could potentially be a maladaptive attempt to correct aging related decline in the stem cell compartment. Possible topics for this concept include but are not limited to:

  • Prevalence and progression of CH mutations at differing ages in men and women, and in different racial/ethnic populations
  • Effects of specific CH clones and variants on health span and age-related diseases, including Alzheimer’s disease
  • Differential effects of CH in differing blood cell subpopulations on aging pathophysiology and disease risks, such as inflammatory function in immune cells and inflammatory responses in various tissues
  • Relationships of human germline variants to risk of CH, and possible mechanisms mediating such relationships. Studies on germline variants related to longevity or health span are of particular interest.
  • Environmental and other modifiable risk factors connections to CH risk and progression
  • Potential for CH screening as part of clinical blood-based tests for risk prediction and prognosis for age-related diseases

Scientific/Research Contact

Nalini Raghavachari
Division of Geriatrics and Clinical Gerontology
Email Nalini Raghavachari

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Consortium for Payment, Utilization, and Access for Dementia Care

Alzheimer's disease is the most common cause of dementia. Given that current treatments for Alzheimer’s have limited effectiveness, this concept aims to increase understanding of how health policy and interventions can be used to improve prevention and treatment of this disease. There is an opportunity to improve access, equity, efficiency and outcomes with a better understanding of policy levers that drive health system results.

To achieve these goals, this concept will support a consortium of researchers focused on economic research related to program design, payment models, utilization, incentives for drug development, and access to health services for people living with dementia (PLWD) and their caregivers. Additionally, the consortium will support cross-national comparisons to provide insights on how differences in system design can improve care for PLWD. The objective is to engage researchers on a range of related topics and use a coordinating function to build collaborations nd partnerships as well as attract new researchers and studies to the field.

The consortium will consist of one coordinating center and multiple research projects designed to provide an evidence base for policymaking. These research projects will focus on understanding how federal policies, payment models, and institutional settings affect care for PLWD; how payment mechanisms affect utilization of services and access to care; and how incentives can be optimized for Alzheimer’s care. By supporting research that determines how incentives can be optimized for Alzheimer’s care, we can reduce inefficiencies while increasing access and quality of care. The coordinating center will plan meetings, engage with stakeholders, facilitate use of common data elements, develop training programs to support a diverse research workforce, translate findings to practice, and solicit funding via national competitions for studies that directly address the NIH AD/ADRD Research Implementation Milestones.

Scientific/Research Contacts

Partha Bhattacharyya, Ph.D.
Division of Behavioral and Social Research
Email Partha Bhattacharyya

John W. R. Phillips, Ph.D.
Division of Behavioral and Social Research
Email John Phillips

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Dementia Care Coordination Research Center

There is an urgent need to better understand what works in terms of dementia care coordination and care transitions in community settings across the United States. People living with dementia (PLWD) need care that maintains their safety, promotes human dignity and autonomy, is free from medical error, is free of unnecessary care transitions, and that can be delivered in a fiscally responsible manner. All available evidence suggests that lack of care coordination and integration is frustrating, costly, and reduces safety and quality for PLWD. Community-level care integration offers the promise of helping people with AD/ADRD access the services and supports they need in the setting of their choice. However, there is wide variation in state payment and policies that support care coordination and integration, with racial and ethnic minorities and rural PLWD less likely to have access to well-integrated care.

This concept will support a Dementia Care Integration Research Center to integrate state level program data with Medicare/Medicaid data to understand dementia care access, cost of care, and variation and quality of care as PLWD go through various transitions of care in the community. A state or regional approach should include inputs from multiple stakeholders that can provide much needed insights on what works in terms of dementia care in more specific and bounded contexts. The engagement of healthcare systems and social service systems and their providers will be critical to the success of the Center. A goal of this Center will be to integrate data that is already available from in-patient and long-term care settings with data from home, community, and office-based settings so that assessment of care integration across settings can be made. Given national variation in payment and services, the vision is to incentivize research at the state level to enable research on dementia care integration. The Center will support pilot projects to understand programmatic structures in participating states, with the goal of capturing replicable state program components that are linked to higher access and quality or lower costs. The Partnership & Engagement core will build partnerships within states to capture program data and support growing partnerships to facilitate the sharing of within state program data, building on successes found in the pilot core. Hence, the cores will work together.

Scientific/Research Contacts

Elena Fazio, Ph.D.
Division of Behavioral and Social Research
E-mail Elena Fazio

Priscilla Novak, Ph.D.
Division of Behavioral and Social Research
Email Priscilla Novak

Theresa Kim, Ph.D.
Division of Behavioral and Social Research
Email Theresa Kim

John W. R. Phillips, Ph.D.
Division of Behavioral and Social Research
Email John Phillips

Emerald Nguyen, Ph.D.
Division of Behavioral and Social Research
E-mail Emerald Nguyen

Partha Bhattacharyya, Ph.D.
Division of Behavioral and Social Research
Email Partha Bhattacharyya

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Development and Validation of Harmonized Methodologies to Measure NAD+ and Related Metabolite Levels in Clinical Trials

Nicotinamide adenine dinucleotide (NAD+) is found in all cells and regulates energy metabolism, cellular repair, and circadian rhythms. Levels of cellular NAD+ have been shown to decline with age in many tissues in animal models and limited human data suggest declines with age in some tissues, with considerable variability among individuals. There is also evidence suggesting that declines in NAD+ and related factors interact with a variety of mechanisms influencing aging, including mitochondrial function, genomic integrity, epigenetic changes, and cell senescence. There has been considerable interest in the potential benefits of raising NAD+ levels to prevent or treat aging-related conditions, particularly through administration of NAD metabolites that are converted to NAD intracellularly. Collectively, these and similar interventions, supplements, and strategies are often termed “NAD+ boosters.” Studies of NAD+ boosters in old mice have reported improvements in glucose metabolism, blood flow, physical function, responses to kidney injury, and decreases in inflammatory cytokines. Not all findings are consistent across studies, with some studies showing that long-term use increased life span. NAD+ booster studies in mouse models of Alzheimer’s disease, heart failure, and stroke have also reported favorable effects. Much more limited human studies have found supplementation to be tolerable with no severe adverse events.

Further research in this area is impeded by the lack of standardized validated protocols for measuring NAD+ and related metabolites’ levels in humans. A standardized sample collection and storage protocol and common reference standards to harmonize NAD+ measurement techniques and assays are also needed. Until these tasks are accomplished, clinical trials on the effects of NAD+ boosting will continue producing uncertain results. The concept proposes funding up to three studies to develop and validate standardized protocols for measuring NAD+ and related metabolite levels in humans, including sample collection and storage, assay calibration, standardization of measurements across different types of samples, and validation of these protocols. Research teams with expertise in geriatrics, pharmacology, biochemistry, laboratory medicine, and translational aging research are encouraged. The proposed studies would be funded by the individual awards, but the awardees would be required to interact in a network consortium to exchange information, discuss their progress, pitfalls and issues arising during studies’ implementation. Specimens from the studies will be maintained after the end of the projects by the NIA’s AgingResearchBiobank or another facility for use in designing future NAD+ trials.

Scientific/Research Contact

Irina Sazonova, Ph.D.
Division of Geriatrics and Clinical Gerontology
Email Irina Sazonova

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Elucidating Variability of Physiologic and Functional Responses to Exercise Training in Older Adults

Exercise and physical activity have become increasingly recognized as an essential component of healthy aging. Despite broad evidence of their beneficial effects on health and prevention of disease, numerous investigations have shown a high degree of variability in outcomes among individuals’ response to exercise. These differences exist even under well-controlled experimental conditions, despite high adherence to structured exercise interventions across a variety of subject populations, training protocols, and outcomes. The mechanisms underlying such large variability are poorly understood, and exercise training interventions continue to be challenged by these variations, particularly in older adults.

This concept will support human studies to better understand the interrelated mechanisms and factors underlying exercise response variability in older adults. Planned study designs should assess multiple metabolic, physiologic and/or functional outcomes (for example, glucose metabolism and blood pressure, or gait speed and endothelial function, etc.). Important study considerations include, but are not limited to:

  • Dose or type of exercise
  • Exercise-drug interactions
  • Mechanisms underlying sex and age differences
  • Mechanisms underpinning the link between peripheral “muscle clocks”, energy sensing pathways, and exercise timing
  • Molecular signals and drivers of inter-organ crosstalk
  • Epigenomic, proteomic, and metabolomic mediators of responses to exercise
  • Other confounders such as pain, sleep, microbiome, behavioral and environmental factors.

Scientific/Research Contact

Lyndon Joseph, Ph.D
Division of Geriatrics and Clinical Gerontology
Email Lyndon Joseph

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Enhancing Use of Harmonized Cognitive Assessment Protocol (HCAP) Data

Global aging research aimed at strengthening our understanding of cognitive and dementia epidemiology can further non-pharmacological Alzheimer’s disease prevention and treatment intervention research at the population level to benefit vulnerable populations, both in the United States and around the world. Much can be done by examining how contextual differences across countries lead to different outcomes. Findings from these studies can help inform interventions, policy, and practice to benefit the aging population in the United States as well as globally. Rich longitudinal data capturing the social, economic, institutional, policy, cultural, and environmental circumstances people age in coupled with comparable assessments of dementia can facilitate such research. The Harmonized Cognitive Assessment Protocol (HCAP) is a sub-study within the Health and Retirement Study (HRS) in the US and within some of the studies in the HRS International Family of Studies. The HCAP seeks to measure and understand dementia risk by collecting a carefully selected set of established cognitive and neuropsychological assessments and informant reports to better characterize cognitive function among older people. Together, HCAP and HRS provide a powerful resource for cross-national research on dementia.

Prior analyses of the HRS and HCAP data demonstrate the promise of this international research. For example, HRS studies in India, Mexico, and China found that using polluting cooking fuels was associated with poorer cognitive function. Another study found that diabetes was associated with lower cognition and memory test scores in multiple countries. However, cross-national analyses of HCAP data have been relatively limited thus far and require a large investment of time and resources to use multiple datasets from different countries in varying contexts. While the harmonization of the HCAP data across countries makes this process easier, it does not eliminate these challenges. In addition, several communities of scholars that could benefit from this data are unfamiliar with the HCAP. This concept seeks to aggressively advertise and incentivize the use of HCAP and related resources to contribute to scientific advances and expand international or cross-national analyses of HCAP data. This research will help further our understanding of how different social, cultural, and institutional factors affect the trajectory of AD/ADRD in different contexts to move the field forward.

Scientific/Research Contacts

Minki Chatterji, Ph.D.
Division of Behavioral and Social Research
Email Minki Chatterji

John W. R. Phillips, Ph.D.
Division of Behavioral and Social Research
Email John Phillips

Jonathan W. King, Ph.D.
Division of Behavioral and Social Research
Email Jonathan King

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Leveraging Social Networks to Promote Widespread Individual Behavior Change

Estimates suggest that nearly 40% of all deaths in the United States are due to diseases or injuries that could have been prevented by changing health behaviors. Initiating and maintaining behavior change is difficult but may be critical for preventing or slowing the progression of diseases of aging, including AD/ADRD. A robust body of literature suggests that the behaviors of spouses, friends, family members, peers, and similar social networks have a powerful impact our own health behaviors and outcomes. However, surprisingly few interventions take advantage of social relationships to promote health behavior change, and even fewer leverage broader social networks to promote health behavior change at scale among individuals, communities, organizations, or populations, especially in mid-to-late life.

This concept capitalizes on NIA’s existing investments in the Science of Behavior Change program and the NIH Stage Model for Behavioral Intervention Development and builds off a 2022 workshop “Social Network Interventions for Diffusion of Individual Behavior Change.” It proposes a two-pronged approach to catalyze the development of future social network interventions to promote health behavior change in mid-to-late life. The first approach will solicit basic science projects that identify intrapersonal and interpersonal mechanisms of individual behavior change and test how those processes interact with social network characteristics and processes. The second will solicit planning projects to lay the foundation for future social network interventions. This two-pronged approach will prime the field to purposefully use social networks or social network data to promote widespread individual health behavior change.

Scientific/Research Contacts

Liz Necka, Ph.D.
Division of Behavioral and Social Research
E-mail Liz Necka

Laura Major, Dr.PH
Division of Behavioral and Social Research
Email Laura Major

Emerald Nguyen, Ph.D.
Division of Behavioral and Social Research
E-mail Emerald Nguyen

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Measures of Financial Hardship Among People and Families Living With AD/ADRD

Unlike other disease diagnoses, the diagnosis of Alzheimer’s disease and related dementias (AD/ADRD) does not trigger special financial protections in the US. Measures of financial hardship are not well tested among people, dyads, and families coping with AD/ADRD. Individuals with AD/ADRD progressively lose the ability to manage their own financial affairs, and over time caregivers and families often take on financial responsibilities for paying for AD/ADRD care and managing household finances. Current measures of financial strain, financial stress, and financial toxicity often fail to measure financial hardship in a way that is meaningful for people living with AD/ADRD, their caregivers, or their families. In order to accurately measure financial hardship among people and families living with AD/ADRD, validated screeners are needed. This concept will support the development of improved ways to measure financial burden and hardship for caregivers, partners, and families of persons living with AD/ADRD.

Scientific/Research Contacts

Priscilla Novak, Ph.D.
Division of Behavioral and Social Research
Email Priscilla Novak

Partha Bhattacharyya, Ph.D.
Division of Behavioral and Social Research
Email Partha Bhattacharyya

John W. R. Phillips, Ph.D.
Division of Behavioral and Social Research
Email John Phillips

Janine Simmons, M.D., Ph.D.
Division of Behavioral and Social Research
Email Janine Simmons

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National Health and Aging Trends and National Study of Caregiving Joint Renewal

The National Health and Aging Trends Study (NHATS) is a nationally representative sample of about 8,000 Medicare beneficiaries ages 65 and older that receive annual in-person interviews to collect detailed information on disability trends and individual trajectories. Additional sampling of Black and Hispanic Americans supports studies of racial/ethnic disparities in disability. Initiated in 2011 with 10 rounds of data available for public use, the study content focuses on physical and cognitive capacity distinct from the environment in which activities take place to capture both function and the potential for accommodation. To better understand the informal caregiving of NHATS participants, the companion National Study of Caregiving (NSOC) collects data from a sample of up to five caregivers providing care to NHATS participants in 2011, 2015, and 2017. The NHATS and NSOC data provide a rich understanding of disability trends, the disablement process, and its influence on wellbeing and the combination of individual data on cognition and function coupled with formal and informal care data have made the NHATS/NSOC ideal studies to examine AD/ADRD and related care.

Following the guidance of the NHATS Data Monitoring Committee (DMC), this concept proposes to renew and enhance NHATS/NSOC to support research on dementia and dementia care. Unifying the individual applications supporting elements of the study (i.e., core NHATS, NSOC, supplements for add-on samples, etc.) that have been funded under separate awards would provide a better basis for scientific review assessment of the complete study and allow the investigators to focus on the conduct of aims as opposed to producing multiple applications over the grant period. Second, an application that continued the core elements of NHATS/NSOC and expanded content to include new data elements recommended by the DMC such as enhanced cognitive/dementia measures, new sensory measures, richer dementia care measures, life course measures to capture sources of health disparities, improved residential care data, and an expanded accelerometry sample can facilitate new AD/ADRD research addressing related NIH AD/ADRD Research Implementation Milestones.

Scientific/Research Contact

John W. R. Phillips, Ph.D.
Division of Behavioral and Social Research
Email John Phillips

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Networks to Develop Behavioral and Social Science Research in Aging and AD/ADRD

While typical research grants support research and data production for many areas of behavioral and social science in aging, some high priority research areas require more nimble resources to flourish. NIA has successfully fostered emerging, high priority, transdisciplinary research areas through the development of research “networks,” flexible programs intended to support the creation of innovative research and research resources. This concept will support seven renewing research networks, each designed to broadly engage the research community and support the growth of a specific area of aging-relevant behavioral and social science:

  1. Stress Measurement: Advancing the science of psychosocial stress measurement to enhance behavioral and social surveys of aging and strengthen lab-survey linkages in the study of stress, health, and disease over the lifespan.
  2. Life Course Health and Disparities at Older Ages: Advancing interdisciplinary research to address questions about how state and local contexts shape trends and disparities in health and longevity at older ages along socioeconomic, geographic, and racial/ethnic dimensions.
  3. Aging Research on Criminal Justice and Health Disparities: Advancing behavioral and social research on aging and on health disparities and drivers of health inequities in the growing population of criminal justice-involved older adults and older adults with a history of involvement with the criminal justice system.
  4. Rural Aging: Advancing research on factors affecting the health and well-being of older people living in rural areas in the United States, and on new approaches to programs, policies, environmental modifications, and care to improve well-being, health, and function.
  5. Genomics and Omics of Behavioral and Social Sciences: Facilitating coordination of genetic association studies for social science outcomes and the introduction of multiple omics into relevant studies, including: developing platforms for interdisciplinary collaboration, supporting the development of new methods for data analysis, and the development and public dissemination of materials that will assist non-technical audiences in understanding the strengths and limitations of social genomics.
  6. Behavioral and Social Research on Aging in Animals: Advancing behavioral and social research on aging in animals to deepen the understanding of social and behavioral phenomena and processes and their links to human health and aging.
  7. Alzheimer’s and Related Dementias Data Harmonization in the HCAP Network: Supporting harmonization and collaboration across international studies conducting the Harmonized Cognitive Assessment Protocol (HCAP), a sub-study of the Health and Retirement Study, which provides new and rich data to study the prevalence, predictors, outcomes and future trends in cognitive functioning and dementia, as well as cross-national comparisons.

Research networks may support activities such as small and large meetings to develop program areas and infrastructure; small scale pilots to develop data, theoretical frameworks, empirical methods, etc.; dissemination and outreach activities; education exchange, such as intensive summer institutes, workshops, advanced seminars, or short-term residential opportunities.

Scientific/Research Contact

Lis Nielsen, Ph.D.
Division of Behavioral and Social Research
Email Lis Nielsen

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Neuronal and Non-neuronal Mechanisms Underlying Gait as a Preclinical Marker for AD/ADRD

Walking is a complex task that depends on the interplay between multiple systems (e.g., sensory, motor, cardiovascular) but also requires cognitive resources. Previous studies have found that slowing gait is associated with cognitive decline, elevated brain amyloid, and a greater risk of developing Alzheimer’s disease. However, the interaction between the shared systems that influence moving and thinking have been studied in isolation. There is also very limited information available about the cognitive resources required for motor planning and/or gait initiation in humans. The goal of this concept is to improve our understanding of the mechanisms underlying the association between gait and cognition in aging and Alzheimer’s disease and related dementias. Successful research teams will require expertise across various disciplines (e.g., gerontology, neurology, neuropsychology, neurophysiology, neuroscience, neuroimaging, exercise physiology, and physical therapy).

This concept seeks investigations in, but not limited to, the following areas:

  • Omics approaches to understand the mechanisms underlying gait, cognition, and diagnosis or progression of Alzheimer’s and related dementias
  • Neuroimaging approaches to investigate connectivity in brain networks critical for gait and cognition
  • Systems biology approaches to interrogate resilience in motor tissues within and outside the brain
  • Muscle/brain crosstalk that could affect the interaction between cognition and mobility
  • The influence of vascular dysfunction on mechanisms linking cognition and mobility
  • The influence of racial/ethnic and sex differences on the association between gait and cognition in Alzheimer’s and related dementias
  • Exploration of whether specific gait changes and cognitive decline trajectories might help distinguish between Alzheimer’s disease and other related dementias

Scientific/Research Contact

Coryse St. Hillaire-Clarke, Ph.D.
Division of Neuroscience
Email Coryse St. Hillaire-Clarke

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Seamless Early-Stage Clinical Drug Development (Phase 1 to 2a) for Novel Therapeutic Agents for AD/ADRD

To advance our shared goal of preventing and treating AD/ADRD, it is critical that we have efficient mechanisms to fund clinical trials pursuing a wide diversity of therapeutic targets and approaches to prevent, delay, and treat Alzheimer’s and related dementias. A limiting factor to the timely progression of promising pharmacological therapeutic candidates from phase 1 to phase 1b/2a clinical studies is the significant delay between the conclusion of successful phase 1 safety and tolerability studies and the start of 1b/proof-of-concept phase 2a studies. These extended timelines are in large part due to lack of funds and the timing inherent to application/funding cycles.

The phased awards generated through this concept will accelerate early-stage clinical drug development by inviting applications that bundle independent proposals for phase 1 first-in-human studies with phase 1b/phase 2a studies in relevant populations with the requirement that the studies meet prespecified, NIA approved, peer reviewed go/no-go safety and tolerability milestones to advance from phase 1. This approach will provide needed support and significantly reduce the delay between the conclusion of successful phase 1a studies and the commencement of subsequent phase 1b/2a studies. Candidate interventions evaluated through this program, which can include small molecules, biologics, or vaccines for example, must engage non-amyloid/non-tau mechanisms and aim to address cognitive and/or neuropsychiatric symptoms in individuals across the spectrum from pre-symptomatic to more severe stages of disease. Diversity within trial cohorts, and timely, broad access to trial data and associated biosamples will also be required.

Scientific/Research Contacts

Laurie Ryan, Ph.D.
Division of Neuroscience
Email Laurie Ryan

Akanni Clarke, Ph.D.
Division of Neuroscience
Email Akanni Clarke

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Small Research Grant Program for the Next Generation of Researchers in AD/ADRD Research

More scientists are needed to conduct the wide variety of interdisciplinary projects, including clinical, translational, prevention, and treatment research, needed to accelerate the development of innovative AD/ADRD treatments or diagnostics. This concept will support a reissuance of the “Small Research Grant Program for the Next Generation of Researchers in AD/ADRD Research” program” to build a career pipeline to encourage and support the next generation of AD/ADRD researchers and support important and innovative AD/ADRD research in a wide variety of areas where scientific investigation is needed. The overall goal of this NOFO is to support important and innovative research in areas in which more scientific investigation is needed to improve the prevention, diagnosis, treatment, and care for AD/ADRD.

This concept is especially aimed at early career investigators who have expertise in a variety of research, health, and other professional fields but have not yet had a major NIH award in AD/ADRD.

Scientific/Research Contact

Luci Roberts, Ph.D.
Division of Neuroscience
Email Luci Roberts

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Approved contract concepts for January 2023

NIA Clinical Research Support Services

NIA’s budget has substantially increased in recognition of growing public interest and urgency surrounding research on aging, including Alzheimer's disease and related dementias. As a result, NIA staff workload and responsibilities associated with managing and overseeing research grants have also increased significantly. Specific institute needs related to managing extramural clinical studies were identified and summarized in a knowledge acquisition report in 2021 which found broad support for centralized clinical research management across the NIA. To meet these needs, this concept proposes contract support in areas including patient safety, data integrity, regulatory compliance, biostatistics, clinical trial recruitment/retention, and training. This contract will reduce administrative burden on NIA staff, providing them with greater flexibility and support, and allowng them more time to focus on their scientific portfolios. It will also streamline and ensure consistencies with clinical research management processes and regulatory compliance across the institute.

Note: All applicant questions should be directed to the contracting officer.

Contracting Officer

Iris Merscher
Office of Acquisitions, NIDA/NIH
Email Iris Merscher

Scientific/Research Contacts

Holly Massett, Ph.D.
Division of Extramural Activities
Email Holly Massett

Jui Shah, Ph.D.
Division of Extramural Activities
Email Jui Shah

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NIA Information Resource Centers

To support NIA’s mission to disseminate information about health and research advances related to aging and Alzheimer’s disease, this contract will provide public inquiry response; website design, development, and hosting; publications development, printing, and warehousing; editorial and science writing support; graphic design and video production; database development and information management; communications research; conference and event support; and other communications support services. The contract includes two information resource centers: the Congressionally mandated ADEAR (Alzheimer’s and related Dementias Education and Referral) Center and the NIA Information Resource Center.

Note: All applicant questions should be directed to the contracting officer.

Contracting Officer

Karen Mahon
Office of Acquisitions, NIDA/NIA
Email Karen Mahon

Program Contact

Jessica Harper
Office of Communications and Public Liaison
Email Jessica Harper

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September 2022 Council

Approved concepts in this round:

Alzheimer’s Disease Research Centers (ADRCs) Program Renewal

The Alzheimer’s Disease Research Centers (ADRCs) have played a central role in leading the progress of Alzheimer’s disease and related dementias research in the United States and internationally for almost four decades. ADRC investigators collaborate on multidisciplinary research into the causes of and risk factors for Alzheimer’s disease and related dementias, train the next generation of scientists, and develop innovative clinical research recruitment initiatives. ADRC infrastructure provides diverse research teams with data and biospecimens through the National Alzheimer’s Coordinating Center and the National Centralized Repository for Alzheimer's Disease and Related Dementias.

Over the past three years, NIA has worked to expand the geographic, scientific, and population diversity of this program by adding sites in Ohio, Texas, and North Carolina. This new competition will support continued improvement in geographic representation within the ADRC program and enhance the recruitment infrastructure to increase Clinical Core participant diversity. Additional resources will be provided to support the increasing needs for studies that leverage the ADRC network at each center (including deep phenotyping) and provide for detailed specialized autopsy and biobanking as well as tracking, to help ensure even broader availability of data and samples. Successful centers will enhance their remote assessments with more in-depth data and increase opportunities for real world data collection.

Scientific/Research Contacts

Nina Silverberg, Ph.D.
Division of Neuroscience
Email Nina Silverberg

Cerise Elliott, Ph.D.

Division of Neuroscience
Email Cerise Elliott

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Determinants of Differences Among Human and Nonhuman Primate Species in Lifespans, Life Histories, Aging-related Outcomes, and Prospects for Translation

Comparisons of humans with other species differing in lifespan provides a complementary approach to research in humans to identify therapeutic targets and interventions to extend human longevity and health span. There could be special benefits from studies to improve understanding of the factors contributing to differences in primate species lifespans, including the factors contributing to humans’ greater life span compared to other primates. This concept proposes two distinct, but interdependent initiatives, for:

  1. Research projects focused on primate species comparisons to identify factors and targetable mechanisms that may influence human longevity and health span (including neurodegenerative disease risk)
  2. A single networking and infrastructure project, to enhance interactions among researchers funded under this initiative as well as other researchers, support pilot projects, and develop research infrastructure for the field for future collaborations across multiple disciplines.

Together, these two initiatives are designed to help provide a path toward developing human-nonhuman primate species comparisons as an important addition to current strategies to identify factors influencing human longevity and their translational potential. Examples of relevant research topics include, but are not limited to:

  • Comparison of “hallmarks” of aging and other markers of aging-related mechanisms (e.g., cell senescence) across humans and other primate species.
  • Species differences in age-related physiological and pathophysiological changes, and their relationships to health span and lifespan.
  • Field studies incorporating noninvasive biological sampling to support studies of social influences on health and that can further the understanding of relationships between the social environment and health, and of how environmental factors contribute to population differences, and variation in life history traits, including, but not limited to, the timing of reproduction and longevity.
  • Comparative genetics-omics and genetics-biology in in vitro and in vivo studies to clarify evolutionary mechanisms that may affect longevity in primates.
  • Development of cognitive and behavioral cross-species comparison measures and multi-omic approaches to assess and identify targets linked to increased longevity, improved health span, and aging brain pathophysiology.
  • Projects to understand the relationships of primate species differences in brain development and sensorimotor processes to longevity.
  • Exploring neurobiological differences among human and nonhuman primates with differing lifespans that could account for the development of dementias in humans but not in nonhuman primates.

Scientific/Research Contact

This initiative has been developed by NIA’s four extramural divisions. Inquiries should be directed to Carol Nguyen, who will refer them to appropriate division staff.

Carol Nguyen
National Institute on Aging
carol.nguyen@nih.gov

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The Health and Retirement Study and the Harmonized Cognitive Assessment Protocol Joint Renewal

The Health and Retirement Study (HRS) is a longitudinal panel study that surveys a representative sample of approximately 20,000 people aged 50 and older in the United States to support multidisciplinary research on life course health and aging. The HRS collects data via participant surveys that include demographics, life histories, health status and health care, dimensions of economic status, work and employment, family, cognitive, and psychosocial factors every two years. It supplements survey collection with linkages to administrative records from Medicare and Social Security, contextual data on participant living environments, and a wide array of biomarker data. A relatively new companion study, the Harmonized Cognitive Assessment Protocol (HCAP), provides additional research opportunities to use HRS to study Alzheimer’s disease and related dementias. HCAP seeks to measure and understand dementia risk using a selected set of established cognitive and neuropsychological assessments as well as informant reports to better characterize cognitive function among older people and establish similar protocols in HRS companion studies in countries around the world to facilitate innovative research in different social, cultural, environmental, and economic contexts. The HRS coupled with HCAP provide an invaluable and growing body of multidisciplinary data to address important questions about the challenges and opportunities of aging, and continuing this important study can provide the research community with the data to answer important longitudinal questions including the longer term implications of the COVID-19 pandemic, the influence of economic trends such as a rapidly changing labor market on health, and environmental and social factors that drive AD/ADRD prevalence. Publicly shared via the HRS website and associated enclaves for sensitive data, the HRS boasts over 6,500 current registered users and over 4,000 journal publications since inception.

The HRS Data Monitoring Committee, a multidisciplinary group of experts that provide comments regarding the conduct of the study, has recommended additions of larger samples of minoritized populations, new contextual data to capture elements of the exposome, improving overall response/retention rates to maintain representativeness, enhanced data on occupational exposures/characteristics, expanded Alzheimer’s and related dementias-relevant blood-based biomarkers, additional content on social factors to study racial disparities and minority health via life histories, and an assessment of the medium and long-term social impacts of the COVID-19 pandemic. This joint renewal concept is designed to be responsive to this input from the committee and to bring the various scientific elements of HRS and HCAP into a single project, which would provide a better basis for scientific review of the complete study and allow the investigative team to focus on the conduct of aims as opposed to producing multiple applications over the grant period.

Scientific/Research Contact

John W. R. Phillips, Ph.D.
Division of Behavioral and Social Research
Email John Phillips

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Interorgan Communication in Aging

Communication between cells, tissues and organs is critical for the development, growth, and maintenance of multicellular organisms. The communication involves instructive and responsive signals, and the information is passed through circulatory and neuronal systems via interorgan communication networks (ICN). An ICN acts between organs to coordinate essential and specialized cellular processes. Perturbations in the ICN have been implicated in a variety of diseases. Perturbations in the ICN due to aging are less studied, and because aging is a primary driver of organ dysfunction and resulting multimorbidity, aging-related change in one organ is predicted to affect other organs in the network. Further research in this area can help achieve a better understanding of the mechanistic basis of aging-related changes in ICN.

The concept behind this pending notice of funding opportunity is to encourage investigations in this field and support a consortium of researchers to study the basic mechanisms characterizing and regulating interorgan communication (IOC) explicitly in the context of aging. Supported projects will examine interactions between at least two organ systems and may include neuronal systems and/or microbiomes. Importantly, this research might provide new insights on the age-dependence of multi-morbidities, a pressing concern in geroscience. Research including human participants or informed by data on human conditions is encouraged, but applications may be submitted using any animal species. General areas of research should include aging-related changes in IOC involving two or more organ systems, and may emphasize — but are not limited to — these themes:

  • Changes in IOC following specific perturbations of hallmarks of aging.
  • Impact of environmental exposures on IOC.
  • Changes in IOC as a result of genotypic differences or interventions that impact lifespan or healthspan (which may include pharmaceuticals, diet, and/or exercise).

Scientific/Research Contacts

John Williams, Ph.D.
Division of Aging Biology
Email John Williams

Hongwei Gao, M.D., Ph.D.
Division of Aging Biology
Email Hongwei Gao

Miroslaw Mackiewicz
Division of Neuroscience
Email Miroslaw Mackiewicz

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Interventions Testing Program

The Interventions Testing Program (ITP) was established in 2003 to test under standardized conditions potential intervention strategies which may delay aging in mice. The ITP uses lifespan as its primary outcome for an intervention, with additional studies on changes in age-related disease outcomes (geropathology) in response to the intervention and pathology at death. The ITP makes an annual call to the research community to propose candidate compounds for testing. All the testing results — both positive and negative — are reported to the research community with the anticipation that further studies will be initiated to extend the work reported by the ITP. The ITP also collects tissues from compound-treated and control mice that are made available to the research community for ancillary studies. Tissues may be requested by investigators at universities and research institutions who wish to explore questions about the biology of aging, its relationship to disease, and mechanisms of action of pharmacologic interventions.

ITP findings have sparked a large and growing collection of follow-up studies by independent investigators. Drugs first documented in ITP aging studies are now being tested in more complex models of musculoskeletal, cardiovascular, and neurodegenerative diseases and we expect future studies to be done in concert with other interventions such as diet and exercise. This pending notice of funding opportunity supports the renewal of the ITP, so it may continue to advance testing of interventions against aging and expand our understanding of the biology of aging.

Scientific/Research Contact

Tiziana Cogliati, Ph.D.
Division of Aging Biology
tiziana.cogliati@nih.gov

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Interventions Testing Program Data Coordinating Center

The Interventions Testing Program (ITP) was developed in the early 2000s to test compounds that might extend lifespan in mice. The ITP Data Coordinating Center (ITP DCC) was introduced in 2019 as an independently funded entity to provide the ITP with a centralized site for storage and analysis of primary and secondary data, a statistical core, and with a public-facing website for data sharing. The ITP DCC maintains an interactive website and data repository to provide open access to experimental design, protocols, analytical methods, raw and annotated survival, phenotypic and pathology data, and a current list of available tissues from the ITP.

This notice of funding opportunity supports the renewal of the ITP DCC with emphasis on enhancing existing resources to respond to current and anticipated needs of the research community. This will be an open competition.

Scientific/Research Contact

Tiziana Cogliati, Ph.D.
Division of Aging Biology
tiziana.cogliati@nih.gov

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Longevity Consortium Renewal

The NIA-supported Longevity Consortium established in 2004, is one of a group of human longevity translational projects supported by the Institute. Each of these projects employs a variety of complementary approaches for identifying and translating protective genomic and other factors associated with exceptional longevity (EL). The initial goal of the LC was to identify common genetic variants and genes in candidate pathways associated with exceptional lifespan in cohorts of long-lived individuals (> 90 years). This research laid the groundwork for Phase II (starting in 2009), which incorporated data mining/pathway analysis of existing cohorts to identify novel genetic factors and replicate or validate previously identified variants. In Phase III (which began in 2014), the LC shifted focus to studies of centenarians, cross-species studies, and integrated data analyses, along with novel drug discovery approaches.

While efforts continue to identify factors that contribute to EL, translational research on EL has been hindered by the limited information on the mechanistic pathways by which longevity-associated variants exert their effects. Thus, in the current Phase IV (initiated in 2019), the LC is conducting transcriptomic, proteomic, and metabolomic analyses of specimens from large longitudinal cohorts that include centenarians and/or healthy long-lived individuals with extensive phenotypic data to identify protective factors and pathways that are associated with longevity and healthspan. Renewing this project will enable further: 1) investigations of mechanisms contributing to longevity 2) development of new target ID strategies and 3) assessment of the effects of target engagement in animal models and in vitro systems (including human in vitro studies). The next phase of the LC will explore longevity-related factors in more diverse populations than those reflected in its current cohorts, identify racial/ethnic differences in factors contributing to longevity, and seek additional information about the relationships between longevity-related factors and the risk for Alzheimer’s disease and cognitive resilience.

Scientific/Research Contacts

Chhanda Dutta, Ph.D.
Division of Geriatrics and Clinical Gerontology
Email Chhanda Dutta

Nalini Raghavachari
Division of Geriatrics and Clinical Gerontology
Email Nalini Raghavachari

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Microphysiological Systems to Advance Precision Medicine for Alzheimer’s Disease and Related Dementias Treatment and Prevention

The development of effective Alzheimer’s disease and related dementias therapies has proven to be difficult. One reason is the poor predictive power of preclinical studies performed in Alzheimer’s transgenic mouse models. While animal testing is the gold standard for preclinical drug development, species differences combined with the complexity and heterogeneity of these disease contribute to the insufficient predictive value of animal model efficacy studies and high attrition of investigational new drugs during clinical development. Thus, there is a critical need for developing more predictive Alzheimer’s and related dementias models that recapitulate key features of human pathophysiology and operate as precision medicine research tools for multiple aspects of preclinical drug development.

With the emergence of human induced pluripotent stem cells (iPSC) and organoids as in vitro and ex-vivo models and the advances made in microphysiological systems (MPS) technologies, there is an opportunity to expand the translational toolkit of more predictive drug development tools. NIA is interested in the development, validation, and qualification of MPS as Drug Development Tools (DDTs) for Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) therapeutic development. The aim is to develop MPS that are fit-for-purpose and have specific context of use (CoU) that will satisfy regulatory criteria. The objectives are to establish translational centers focused on regulatory qualification of MPS with active input and engagement from key stakeholders and end users (e.g., NCATS Tissue Chip Consortium in collaboration with the U.S. Food and Drug Administration (FDA), pharmaceutical members and academia). Studies include but are not limited to developing standardized and deeply phenotyped AD/ADRD MPS models, establishing the translational validity of these MPS models to recapitulate the molecular and network perturbations identified in AD/ADRD, as well as discovery and validation of translatable biomarkers. Proposals to develop MPS technologies that allow for the testing of potential AD/ADRD therapies in a manner that incorporates disparities and differences in the specific pathogeneses across populations are of particular interest. Central to this initiative is rapid dissemination of MPS models to all qualified researchers for their use in preclinical therapy and transparent reporting of research methodology and preclinical efficacy testing findings.

Scientific/Research Contacts

Zane Martin, Ph.D.
Division of Neuroscience
Email Zane Martin

Nadezda Radoja, Ph.D.
Division of Neuroscience
Email Nadezda Radoja

Lorenzo Refolo, Ph.D.
Division of Neuroscience
Email Lorenzo Refolo

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NIA Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias (AD/ADRD) Real-World Data Platform

NIA is the primary federal agency supporting and conducting Alzheimer’s disease (AD) and AD-related dementias (ADRD) research. To promote this effort, AD/ADRD Research Implementation Milestones were developed to provide a research framework that details specific steps and success criteria towards achieving the goal of the National Plan to Address Alzheimer’s Disease: to treat and prevent AD and ADRDs by 2025. Milestone 13.Q directs NIA to “support the development of AD/ADRD data and clinical infrastructure and harmonization processes that allow for the integration of health care, formal and informal caregiving, and other care-related data from multiple sources (e.g., EHR, claims, surveys, patient-reported outcomes) to facilitate research on diverse populations of persons living with AD/ADRD in order to improve dementia care outcomes as well as recruitment and retention for clinical trials.”

Real-World Data (RWD) are defined as data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources and are collected in the context of the routine delivery of care. Examples of RWD include electronic health records (EHR), claims and billing data, registry data, public health data, patient-generated data in home-use settings, data generated and collected from mobile devices and wearables, and data collected from Digital Health Technologies (DHTs). Studies of RWD reflect the actual clinical setting in which therapeutic interventions are applied, including patient demographics, comorbidities, adherence, and concurrent treatments. RWD can advance research at lower costs and lower participant burden, and with increased efficiency and participation of diverse patient groups who have historically been excluded from healthcare research. Increased accessibility and usability of RWD, which are already prevalent in private sector, may lead to the development of high-impact, scalable interventions (from accelerated development of new therapies to healthcare delivery) that can be rapidly tested within a few months to a few years to improve health outcomes for older adults and persons living with dementia. However, researchers currently face many barriers when trying to access RWD.

This concept aims to transform the AD/ADRD research enterprise by establishing a platform that provides access to RWD and the innovative methods and practices needed for using RWD ethically and most effectively. These data can be used to:

  1. Securely access health data (e.g., EHR, claims, genetics, imaging data, mobile devices generated data, etc.) from private data providers and academic institutions to gain insight on AD/ADRD disease trajectory
  2. Develop a platform for an AD/ADRD digital cohort that provides access to a more diverse pool of individuals for recruitment into clinical trials and research across NIA
  3. Collaborate in partnership with health care and community health providers to enable rapid drug trials (RDT) and other trials for improving care for older adults with multimorbidity, including dementia
  4. Analyze sensitive RWD through secure cloud workspaces while protecting privacy of the study participants.

The concept has four overarching goals:

  1. Improve the applicability and generalizability of findings through larger datasets that include more diverse participants
  2. Capture more complete information through linking a variety of data sources
  3. Increase the speed at which scientific questions can be answered
  4. Improve the ability for researchers to answer questions that cannot be feasibly or readily answered through a clinical trial

Scientific/Research Contacts

This initiative has been developed by NIA’s five extramural divisions and NIA’s Office of the Director. Inquiries should be directed to the NIA Real-World Data Planning Committee at NIARWD@nih.gov.

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NIA Postbaccalaureate Research Education Program

As a means to effectively build a diverse and competitive scientific workforce, the President’s Council on Advisors on Science and Technology and the National Academies of Science, Engineering, and Medicine recommend supporting programs that strive to recruit, train, and mentor students from underrepresented groups who have an interest in science, technology, engineering, and mathematics. While NIA offers robust training and career development programs at the graduate, postdoctoral, and junior faculty levels, opportunities remain to implement an extramural program targeted towards individuals at the postbaccalaureate level (after completion of the bachelor’s degree, but before entering a master’s or doctoral degree program). Postbaccalaureate programs are successful “pipeline-builders” that enable trainees to pursue graduate school and other research-related career opportunities.

We believe that postbaccalaureate students represent a prime avenue to build the biomedical workforce as many undergraduates lack opportunities or protected time for targeted research experiences. To further expand the Alzheimer’s disease and related dementias training pipeline, we seek to develop a one- to two-year intensive research education experience with a focus on mentorship for pursuing future research careers. These paid research opportunities will provide immersive, full-time laboratory experience aimed at building technical and operational skills. The programs will be expected to have a research training component paired with career development activities which might include, but is not limited to: course work, entrance exam preparation, and conference and workshop participation. The expectation is that such programs will help to transition the next generation of investigators, particularly from underrepresented groups and diverse backgrounds, to pursue a career in Alzheimer’s disease and related dementias research.

Scientific/Research Contact

NIA Training Staff
Office of Strategic Extramural Programs
Email: NIATraining@mail.nih.gov

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NIA Summer Research Educational Experience Program

Education research has demonstrated that early exposure to scientific research supports trainees’ continued engagement in science, technology, engineering, and mathematics (STEM). The President’s Council on Advisors on Science and Technology has highlighted the need to keep student trainees in STEM by involving them in cutting-edge, hands-on research experiences as early as possible in their educational journey.

While NIA offers robust training and career development programs at the graduate, postdoctoral, and junior faculty levels, there is a gap in extramural opportunities for individuals at the high school and undergraduate levels. To further expand the Alzheimer’s disease and related dementias training pipeline for diverse and earlier stage students, we seek to develop a summer research education program for high school students, college students, or K-12 teachers. Through discussions with NIH institutes and other Federal agencies that support similar programs — and building upon best practices from NIA’s Intramural Research Program — we understand the value of intensive summer research experiences for providing exposure to and enhancing interest in research careers. This opportunity aligns with recent NIH efforts to expand the Science Education Partnership Award and the recognition in the field of the importance of innovative K-12 STEM programming to build a diverse and competitive scientific workforce. The program goal is to develop the next generation of investigators to pursue a career in aging research (and specifically Alzheimer’s and related dementias).

Scientific/Research Contact

NIA Training Staff
Office of Strategic Extramural Programs
Email: NIATraining@mail.nih.gov

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Nursing Home EXplanatory Clinical Trials Network (NEXT)

Nursing homes provide care for many of the U.S.’s most vulnerable of older adults, who may have multiple chronic conditions (MCCs) and a very high prevalence of cognitive impairment, Alzheimer’s disease, and related dementias. But few nursing home residents regularly participate in randomized clinical trials (RCTs) designed to understand and address the health issues affecting this population. Challenges in conducting clinical research and RCTs in nursing homes include an under-resourced, unstable nursing home industry, complex federal and state regulations relating to oversight of nursing homes, the need for special protections for the vulnerable nursing home population, and the absence of clinical research experience and infrastructure in long-term care settings. There is a need to develop evidence through explanatory RCTs in nursing homes of the efficacy of certain preventive interventions, treatments and treatment strategies, and complex services for single and multiple chronic conditions including Alzheimer’s and related dementias.

This concept will support the initial formation of a network of transdisciplinary aging researchers to develop the infrastructure to conduct explanatory RCTs of prevention and treatment of selected chronic diseases and Alzheimer’s and related dementias within nursing homes. The investigators will create a centralized research infrastructure that will address essential core functions, including overall coordination, recruitment, training, data management and resources, methods and measures, and communication and dissemination. The trials conducted through this network should address critical knowledge gaps and generate high-quality evidence to inform medical decision-making. Examples of interventions that could be studied for efficacy (and safety) in the nursing home include:

  • Prevention strategies for care of nursing home residents (e.g., infection transmission, vaccines)
  • Investigational pharmacological therapeutics and non-pharmacological interventions for conditions common in nursing home residents, including Alzheimer’s and related dementias
  • Complex services given in the nursing home setting (e.g., intensive rehabilitation, deprescribing with substitution of behavioral interventions)

Research/Scientific Contact

Marcel Salive, M.D., MPH
Division of Geriatrics and Clinical Gerontology
Email Marcel Salive

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Preclinical Studies to Characterize the Impact of Toxicants on Brain Aging and AD/ADRD

The complexity and heterogeneity of Alzheimer’s disease (AD) and related dementias is understood to be a consequence of a dynamic interaction between genes and environment over the lifespan. Although a growing body of epidemiologic, genomic, and mechanistic research points to a significant contribution of various environmental factors (i.e. the exposome) on Alzheimer’s risk and resilience, our understanding of the impact of the exposome on the etiology of Alzheimer’s and related dementias is still rudimentary. Additionally, increased investment in exposome research could help address health disparities in Alzheimer’s and related dementias. This initiative aims to support projects that utilize mouse models of late-onset AD, including polygenic mouse models, for comprehensive assessment of the impact of AD/ADRD-relevant environmental exposures on multiple aspects of brain aging and AD/ADRD related outcomes.

The goal of this initiative is to evaluate the functional consequences of major toxicants (metal, airborne particles, pesticides) known to be associated with elevated AD risk and AD-related pathologic and clinical outcomes based on epidemiologic studies. Specifically, this program will examine the consequences of early and mid-life exposure on late-life brain health by conducting cross-sectional/longitudinal multi-modal phenotyping (molecular, biochemical, pathologic, and behavioral) of mouse models of late-onset AD, and the impact of genetic diversity and sex-differences on exposure-related AD outcomes. This program will operate under open-science principles: all data and analytical outputs will be shared rapidly and broadly via the NIA-supported AD Knowledge Portal. The data resources and mechanistic insights delivered by this initiative will inform new strategies for AD/ADRD risk reduction and disease prevention. This concept is one of the three concepts under the umbrella: “Precision Environmental Health Approach to AD/ADRD Treatment and Risk Prevention.”

Scientific/Research Contacts

Suzana Petanceska, Ph.D.
Division of Neuroscience
Email Suzana Petanceska

Alison Yao, Ph.D.
Division of Neuroscience
Email Alison Yao

Lisa Opanashuk, Ph.D.
Division of Neuroscience
Email Lisa Opanashuk

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Quantifying the Impact of Environmental Toxicants on Alzheimer’s Disease and Related Dementias Risk in Cohort Studies

Classes of toxicants and chemicals that are persistent in the environment and accumulate in humans represent novel or understudied human exposures where answers are needed regarding their potential to increase the risk for Alzheimer’s disease and related dementias. Importantly, exposures earlier in life are likely to take decades to impact risk of developing Alzheimer’s and related dementias, and this adds a level of complexity to exposure research. Furthermore, the impact of the chemical/toxicant exposure on disparities of Alzheimer’s and related dementias is not well understood.

This initiative aims to address challenges related to understanding the impact of environmental exposures on Alzheimer’s and related dementias across diverse, under-represented populations (e.g., racial/ethnic minorities, veterans, rural populations, farm, or factory workers). The initiative will support research that is focused on major toxicants (e.g., air pollution, pesticides/insecticides, toxic metals, industrial and commercial chemicals, antimicrobials and polyfluorinated alkyl substances) observed to be associated with elevated Alzheimer’s and related dementias risk, and health disparities in AD/ADRD-related pathologic and clinical outcomes. It will require close collaboration across different scientific fields, particularly health disparities, neuroscience, cognitive assessment, toxicology, environmental epidemiology, and genomics. The primary goals are to:

  1. Enrich existing longitudinal cohorts with i) measures of exposures to individual toxicants or combinations of toxicants; and ii) multi-omics molecular profiling that reflects the body’s response to exposure(s).
  2. Support the development of multi-disciplinary teams needed for the rigorous measurement and assessment of environmental exposures at the population level.
  3. Create an environmental epidemiology consortium to facilitate rapid and broad data sharing, harmonization, and integration of complex exposure data across multiple studies to enhance the opportunity for data pooling and data integration for various meta-analyses and/or comparative analyses

This program will operate under open-science principles: all data and analytical outputs will be shared rapidly and broadly via the NIA-supported AD Knowledge Portal. This funding initiative concept is one of the three concepts under the umbrella: "Precision Environmental Health Approach to AD/ADRD Treatment and Risk Prevention".

Scientific/Research Contacts

Damali Martin, Ph.D., MPH
Division of Neuroscience
Email Damali Martin

Dallas Anderson, Ph.D., M.P.H.
Division of Neuroscience
Email Dallas Anderson

Nina Silverberg, Ph.D.
Division of Neuroscience
Email Nina Silverberg

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Research Coordinating Center on the Exposome and Alzheimer’s Disease and Related Dementias: Elucidating the Role of Social and Behavioral Determinants of Health in AD/ADRD Etiology and Disparities

Exposures in the environments where people live, work, pray, and play across their lives shape health, including a person’s risk profile for Alzheimer’s disease and related dementias. Together, this comprehensive set of exposures across domains (e.g., physical, chemical, social, psychological, economic) constitute the “exposome.” Behavioral and social research on the exposome seeks to understand how contextual features of social, economic, cultural, and built environments and individual-level behavioral and social factors interact with biological processes to affect health. Exposome data can allow us to answer questions about the impact of environmental and personal exposures on the social and behavioral life course processes that influence health outcomes, including cognitive aging and Alzheimer’s and related dementias.

This concept seeks to establish a national coordination network to act as a centralized hub for accessing, harmonizing, linking, and sharing environmental contextual data and individual exposure data with NIA/NIH-funded projects that hold potential for advancing our understanding of the links between life course exposures and Alzheimer’s and related dementias risk and resilience, and disparities across populations. Through the implementation of this concept, an Alzheimer’s and related dementias exposome coordinating center will be established to facilitate the inclusion of validated and shareable contextual data and individual level exposure measures in NIA-funded research studies to allow the comprehensive and coordinated assessment of the role of social and behavioral determinants of health in the etiology of and disparities in Alzheimer’s and related dementias. Additional activities or functions may be proposed to promote collaboration across NIA-funded exposome projects, encourage interactions between exposome programs and other NIH-supported contextual data resources, and enhance the value, innovativeness, and visibility of social, behavioral, psychological, and economic research on exposome research on aging and Alzheimer’s and related dementias.

Scientific/Research Contacts

Lis Nielsen, Ph.D.
Division of Behavioral and Social Research
Email Lis Nielsen

Amelia Karraker, Ph.D.
Division of Behavioral and Social Research
E-mail Amelia Karraker

Emerald Nguyen, Ph.D.
Division of Behavioral and Social Research
E-mail Emerald Nguyen

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Roybal Centers for Translational Research in Aging

NIA’s Roybal Centers focus on translating basic behavioral and social research findings to inform practice and the development of non-pharmacological interventions to prevent disease and promote the health and well-being of midlife and older adults. In 2019, the Roybal program expanded to include dedicated centers focused on dementia care to create potent and easily implementable dementia care and caregiver support interventions. This has helped fuel the pipeline of investigators working in this area and advance efforts to meet the urgent need for effective, scalable, and sustainable interventions to improve dementia care and to help those who are caring for individuals with dementia.

Capitalizing on the NIH Science of Behavior Change program’s attention to mechanism-focused behavior change interventions and advances in basic behavioral and social science, and informed by the translational infrastructure articulated in the NIH Stage Model, the proposed Roybal Center renewal will continue to support the full range of intervention development research to promote healthy aging, and to improve dementia care and caregiver support, including Stage I intervention creation and adaptation research, Stage II and Stage III efficacy trials, Stage IV effectiveness research (including pragmatic trials), and Stage V research to study the mechanisms underlying successful strategies to implement and disseminate evidence-based interventions. This concept also expands the Roybal program to explicitly invite applications for centers focused on behavioral interventions, including those that involve long-term behavior and lifestyle changes that may need to be sustained, to prevent Alzheimer’s disease and related dementias.

Scientific/Research Contact

Lisa Onken, Ph.D.
Division of Behavioral and Social Research
Email Lisa Onken

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Team Science Approaches Integrating Experimental and Computational Brain Aging Models

Capturing the essence of brain aging and Alzheimer’s disease and related dementias — without the need to wait in real time for the brain to age — has been a longstanding obstacle for researchers. Longitudinal studies provide valuable insights, but are costly and take decades to complete. To complement these longer-term studies, researchers have developed better in silico (computer simulations or models based on real-life data) and in vitro (lab grown mimics of organs or tissues) models of brain aging and disease. Existing collaborations between cell biologists and computational researchers are often limited to quantifying “big data” arising from -omics and sequencing studies, but expanding team science approaches to integrate experimental and computational brain models could yield fruitful results. This concept encourages experimental biologists to work in tandem with computational researchers to gain new insights into brain aging and Alzheimer’s and related dementias.

This NOFO will establish new interdisciplinary collaborations and significantly expand existing ones that involve both experimental and computational researchers working to address a targeted research question in brain aging or Alzheimer’s and related dementias in tandem. Examples of appropriate topics may include:

  • Integrating experimental data across spatial and temporal scales to build biologically relevant multi-scale models of brain aging and/or Alzheimer’s and related dementias.
  • Developing artificial intelligence (AI)/machine learning and mathematical simulations of targeted underlying cellular and molecular mechanisms of brain aging and/or Alzheimer’s and related dementias.
  • Establishing new AI models of brain aging that incorporate biological mechanisms relevant to Alzheimer’s and related dementias across different levels of complexity, from intracellular and cell-cell communication to network-based models.
  • Using multi-scale and other modeling approaches to enable a more comprehensive view of mechanisms underlying brain aging and Alzheimer’s and related dementias.
  • Leveraging and integrating emerging multi-omics data to develop more accurate in silico models.

Scientific/Research Contact

Amanda DiBattista, Ph.D.
Division of Neuroscience
Email Amanda DiBattista

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Understanding Gene Environment Interactions in Brain Aging and Alzheimer’s Disease and Related Dementias

Epidemiologic studies in animal models have demonstrated the association of environmental factors and exposure to major toxicants (industrial and agricultural chemicals, metals, pollutants, etc.) with neurodegeneration and Alzheimer’s disease and related dementias. However, evidence in humans is very limited. Mechanistic studies on biological processes leading to clinically relevant disease outcomes are lacking. The importance and specific nature of gene-environment (GxE) interactions on human diseases are largely unexplored, and there are major gaps in our understanding of GxE interactions and vulnerability and resilience of Alzheimer’s disease and related dementias. Studying gene-environment interactions will help us identify novel risk variants and genetic contributors that act through interaction but demonstrate only marginal effects, shedding light on missing heritability of Alzheimer’s disease and related dementias. Delineating the functional outcome of GxE interactions holds great potential to reveal novel disease mechanisms and help understand the nature of Alzheimer’s heterogeneity. Such findings will in turn enhance opportunities for translation to personalized prevention and therapeutic intervention.

However, the wide range of environmental factors and complex realities of environmental exposures pose challenges to such studies. Limited sample size and insufficient statistical power hamper the detection of specific GxE interactions, especially when the interactions have small effect sizes. Cell-based human in vitro and ex vivo models offer an alternative approach to complement animal models and help overcome the limitation of human studies. Combining innovative human in vitro systems with genome editing technology enables a rapid, less expensive, and scalable strategy to look into how the genome interacts with environmental toxicants across diverse cell types of the human brain. This concept is designed to support interdisciplinary research projects using disease relevant human in vitro and ex vivo models to characterize the effects of GxE on gene regulation and cellular functions, and to elucidate toxicant-mediated molecular and cellular mechanisms in brain aging and Alzheimer’s disease and related dementias. Collaborations between neuroscience researchers and environmental health scientists are strongly encouraged. This initiative will operate under open-science principles: all data and analytical outputs will be shared rapidly and broadly via the NIA-supported AD Knowledge Portal. This initiative is one of the three concepts under the umbrella: “Precision Environmental Health Approach to AD/ADRD Treatment and Risk Prevention”.

Scientific/Research Contacts

Alison Yao, Ph.D.
Division of Neuroscience
Email Alison Yao

Lisa Opanashuk, Ph.D.
Division of Neuroscience
Email Lisa Opanashuk

Suzana Petanceska, Ph.D.
Division of Neuroscience
Email Susana Petanceska

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