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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 Funding Opportunity Announcement (FOA), and some of the concepts listed below (particularly from older Council meetings) may have already been converted to FOAs.

January 2021 Council

Approved concepts in this round:

Data enhancements and analyses to clarify the relationship between education and cognitive function [including Alzheimer's disease/Alzheimer's disease related dementias (AD/ADRD) and dementia]

One of the most-robust findings in Alzheimer’s disease and Alzheimer’s disease-related dementia research is that higher levels of education are associated with lower risk of AD/ADRD. However, key questions about this relationship remain. Most longitudinal studies of aging examining education only contain measures of years of schooling, obscuring the pathways that might link educational experiences and cognitive function. Studies of cognitive aging and AD/ADRD typically lack information on other dimensions of education that may drive and/or modify observed associations between years of education and cognitive function.

Measures of educational quality, content, and success, along with measures that capture aspects of schools as social institutions could help further understanding of the education-cognition relationship. Adding enhanced measures of educational experiences to longitudinal studies of aging may also help explain differences in cognitive health in later life by race/ethnicity, urban-rural status, and other demographic factors that often pattern health disparities.

In the same vein, many studies with rich educational measures have only limited measures of cognitive function in early and/or later life, leaving such studies currently underutilized by the AD/ADRD research community. NIA has made major investments in several studies that might elucidate the relationship between education and ADRD risk. Some of these studies have cohorts entering ages where the beginning of cognitive change may be detectable with adequately sensitive measures. Others are poised to go back into the field in the near future, making now an especially efficient and appropriate time to support data enhancements.

An RFA is proposed to support data enhancements in measures of education beyond years of education, cognitive function, or both, and/or analyses that incorporate these measures in order to clarify the relationship between education and cognition, including the extent to which the relationship is causal (and if so, under what conditions and for whom).

Scientific/Research Contact

Amelia Karraker, Ph.D.
Division of Behavioral and Social Research
National Institute on Aging
Telephone: 301-496-3131
E-mail Amelia Karraker

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Data management coordinating center (DMCC) and a collaborative research space for translational research on exceptional longevity (EL)

NIA currently supports several cooperative agreement projects on exceptional longevity (EL) in humans which include the Longevity Consortium (LC), Long-Life Family Study (LLFS), Longevity Genomics (LG) and the Integrative Longevity Omics (ILO) project. These studies focus on the discovery of genetic and other protective factors influencing EL and their translation into possible therapeutic targets for healthy aging. Until now, these projects have been mostly inward facing and functioned independently of each other. In the absence of a centralized infrastructure for research coordination/data management, opportunities for synergisms and potential outside partnerships have been missed.

Equally critical to advancing translational research on EL is the availability of a collaborative research space to consolidate and increase the access and use of complex biological data and other research resources generated by the ongoing EL studies and related efforts. This need for better data integration and exchange will only increase since large volumes of omics data will be generated by the EL projects in coming years. Substantial computing resources are also needed to develop and test new analytical algorithms on large multidimensional data sources.

The availability of a limited data commons would create a computing resource that will enable investigators to explore new analytical approaches and tools. Incorporating the EL portal on the AD Knowledge Portal platform will increase the use and exchange of EL data, an important step towards the development of a more comprehensive collaborative research infrastructure.

Scientific/Research Contact

Chhanda Dutta
Division of Geriatrics and Clinical Gerontology
National Institute on Aging
Telephone: 301-496-4161
E-mail Chhanda Dutta

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Development and maintenance of a multigenotypic aged mouse colony (Contract renewal)

This is a proposal to renew the existing contract supporting the NIA’s aged mouse colony. NIA supports basic biomedical research through several programs which require animals as models of the aging process. These programs include immunology, endocrinology, pharmacology, neurobiology, exercise physiology, behavior, genetics, and nutrition. As more is learned about the genetic and physiological components of aging, a need is also arising for animal models in which to test the therapeutic potential of drug and nutritional interventions.

Most academic laboratories do not have the funds or facilities to raise aged animals, and aged rodents are not routinely available commercially. For over two decades, this resource has successfully facilitated studies by providing of genetically defined, barrier-reared aged mice free of charge to the research community. The program requires the review of experts in aging research, rodent animal models and rodent veterinary medicine. This contract renewal will continue all current functions of this unique infrastructure resource for research in the biology of aging.

Scientific/Research Contact

Francesca Macchiarini, Ph.D.
Division of Aging Biology
National Institute on Aging
Telephone: 301-827-4013
Email Francesca Macchiarini

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Early and late-stage clinical trials for the spectrum of AD/ADRD and age-related cognitive decline (Re-issue)

The early and late-stage clinical trials FOAs have been the primary avenue for NIA-supported clinical trials focusing on Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) and age-related cognitive decline. The NIA currently supports over 200 early- and late-stage AD/ADRD clinical trials, the majority of which were supported via the current and prior versions of this FOA. Until now, the early and late-stage clinical trials FOAs had been separate funding opportunities that went to a single special emphasis panel for review. In this most recent re-issue, we are planning to combine these FOAs into a single FOA covering Phases I-III pharmacological and non-pharmacological clinical trials, as well as clinical trials supporting activities.

The goals of this re-issued FOA are:

  • To invite research grant applications that provide clinical testing (Phase I to III) of promising pharmacological and non-pharmacological interventions for cognitive and neuropsychiatric symptoms in individuals with age-related cognitive decline or AD/ADRD across the spectrum from pre-symptomatic to more severe stages of disease, and
  • To stimulate studies to enhance trial design and methods. Moreover, timely and broad sharing of trial data and biosamples is a key component of this FOA.

Scientific/Research Contacts

Laurie Ryan, Ph.D.
Division of Neuroscience
National Institute on Aging
Email Laurie Ryan

Kristina McLinden, Ph.D.
Division of Neuroscience
National Institute on Aging
Email Kristina McLinden

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Elucidating the roles of transposable elements in AD/ADRD and aging

Nearly half of the human genome is comprised of transposable elements (TEs). Although the majority of TEs have been rendered immobile due to accumulation of mutations during evolution, activation of TEs could have deleterious effects by disrupting the transcriptional landscape and triggering immunologic or other responses. Although the link between TE activation and neurodegeneration or aging has been established, mechanisms underlying these observed associations are largely unknown and the causal relationship remains elusive. Growing evidence demonstrates that the human genome and transcriptome destabilize due to dysregulation and activation of TEs, which is a phenotype observed in many neurodegenerative diseases including Alzheimer’s disease (AD), and during aging and cellular senescence. Recent discoveries related to human endogenous retroviruses, TDP-43, and retrotransposable elements demonstrate that dysregulation of TEs plays critical roles in the pathophysiology of neurodegeneration and aging.

Determining the roles of TEs in AD/ADRD and aging is an emerging field with many great challenges. This FOA will provide targeted support of critical research into the mechanisms underlying activation and regulation of TEs and their causal contributions in AD/ADRD and aging. Targeting TEs will open a new avenue to reveal novel mechanistic insights to expand diagnostic and therapeutic strategies for AD/ADRD and other aging-related diseases. Outcomes of this initiative would significantly improve our understanding of TEs in the following areas:

  • Discover molecular and cellular mechanisms of TE regulation and activation in the context of cell and tissue specificity, disease states, cellular and pathophysiological phenotypes of AD/ADRD, cellular senescence, and aging process.
  • Investigate causal effects and mechanisms underlying TE activation and pathologic protein aggregation such as Tau, TDP-43, Aβ, α-synuclein etc.
  • Define functional role and causal relationship between TE activity and neuroinflammation, inflammaging, or SASP. Identify mechanisms underpinning innate and adaptive immune responses on TEs and HERVs.
  • Elucidate functional roles of TEs contributing to cellular dysfunction or molecular alterations leading to genome instability, neurotoxicity, apoptosis, or cellular senescence.
  • Characterize functional consequences of TE activation that interacts with co-morbidities such as viral infection, vascular compromise, aging, and proteinopathies. Investigate the impacts of these interactions on cellular functions, aging hallmarks, and disease susceptibility and severity.
  • Explore therapeutic interventions interfering TE-mediated molecular pathways and cellular processes. Test TE regulation strategies for improving aging and disease trajectories.

Scientific/Research Contacts

Alison Yao, Ph.D.
Division of Neuroscience
National Institute on Aging
Email Alison Yao

Max Guo, Ph.D.
Division of Aging Biology
National Institute on Aging
Email Max Guo

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High resolution mapping of biomolecules in aging and Alzheimer's brains

The spatial and abnormal distribution of misfolded proteins together with other lipids and small metabolites are thought to play a critical role in the onset of late and sporadic Alzheimer’s disease (AD). However, there is currently no reliable way to determine the accumulation and distribution of various small biomolecules together with pathological hallmarks from the surface of brain sections at all stages of AD. The overall goal of this concept is to generate brain cell type and regional three-dimensional (3D) representations or atlases of biomolecules that change in normal aging and in AD. Specifically, this proposal will encourage interdisciplinary approaches using an emerging mass spectrometry (MS) imaging technology to map and understand the biodistribution, metabolism and accumulation of small biological molecules, such as lipids, neuropeptides and carbohydrates, during the course of aging and Alzheimer’s disease. Traditionally, most “omics” and mass spectrometry-related experiments are commonly conducted through using homogenized brain tissues which are models for investigating the changes of global gene expression and protein composition. Recent single cell “omics” experiments are beginning to characterize neural and glial cell types with some spatial and anatomical details, but they are not addressing neurochemical changes and heterogeneity across an entire brain tissue. Therefore, this initiative proposes to establish a 3D biomolecular atlas of human brain in AD. The biomolecular maps could then be integrated with optical imaging technologies and gene expression profiles of cells in various brain regions to provide comprehensive markers for a detailed brain atlas of aging and AD brains.

Outcomes of this initiative may include:

  • Synthesizing multiparameter and mass spectrometry images into 3D biomolecular brain maps to understand the temporal and spatial relationship between early changes in key AD biochemical hallmarks and alterations of inflammation, lipid and energy metabolism, and synaptic dysfunction.
  • Defining the roles of various AD risk genes in different APOE isoforms in regulating 3D brain regional and cell type specific lipid distribution and signaling networks during the process of normal and pathological brain aging.
  • Establishing a brain small molecule 3D atlas to understand the alteration, transportation, and distribution of small molecules, such ATP/ADP, NADPH/NAD and GSH in regulating oxidative stress and brain energy metabolism in normal brain aging and AD.
  • Developing computational and analytical tools to integrate MS imaging and single-cell ‘omic measurements of brain tissue into “multiparameter’ images with anatomical information.
  • Optimizing high-throughput single cell imaging mass spectrometry and other imaging techniques for mapping and disease staging of normal and AD brains.
  • Developing tools to scale up to collect and analyze multimolecular images across subjects of different ages and across various 3-D brain imaging projects.

Scientific/Research Contact

Austin Yang, Ph.D.
Division of Neuroscience
National Institute on Aging
Email Austin Yang

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Leveraging existing large databases and cohorts to better understand the risks and benefits of long-term osteoporosis therapy and drug holiday

Osteoporosis is a common skeletal disorder in older adults causing loss of bone mass and bone deterioration that leads to increased fracture risk. Each year, about 2 million U.S. adults experience an osteoporotic or other low-trauma fracture, which often cause pain, disability, and impaired quality of life. Most fracture risks increase sharply with age and fracture burden is projected to increase in coming decades as the population ages.

Bisphosphonates (BP) are a first line of pharmacologic treatment for most women and men who have osteoporosis. They are effective when taken for 3-5 years by people who are at high risk of fracture. However, rare but serious adverse events such as atypical femoral fractures and osteonecrosis of the jaw have raised questions regarding their safety, especially in people who use the drugs long-term and who are at low risk for fracture. Reports of these rare adverse events led to a more than 50 percent decline in BP use from 2008 to 2012, as well as low therapy adherence by patients prescribed oral BPs. These trends have raised concern in the medical and professional communities that patients who need pharmacologic intervention are not receiving or taking it, which may lead to a rise in fracture rate.

Most data regarding the appropriate use, benefits and risks of BPs and other fracture prevention drugs come from the clinical trials that led to regulatory approval, generally for treatment duration of 3-5 years. There are limited data on the appropriate long-term use of these drugs beyond this original trial period. Data is likewise scarce on interrupted therapy (drug holidays). It is not known which patients will benefit or may be harmed from continued drug intervention, the appropriate criteria to be put on drug holiday, how to identify at-risk patients and properly treat them, and how to predict their outcomes.

The proposed concept will support the assembly of and support for multi-disciplinary teams to manage large datasets and propose innovative analytical methods to examine this complex interaction on the benefits and risks of long-term osteoporotic drug therapy and management of patient’s outcomes.

Scientific/Research Contact

Lyndon Joseph, Ph.D.
Division of Geriatrics and Clinical Gerontology
National Institute on Aging
Telephone: 301-496-6761
Email Lyndon Joseph

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Pilot studies for the spectrum of AD/ADRD and age-related cognitive decline

NIA’s current clinical trials pipeline for age-related cognitive decline and AD/ADRD consists of two announcements: Early-Stage Clinical Trials for the Spectrum of Alzheimer’s Disease and Age-related Cognitive Decline FOA (PAR-18-877) and Late Stage Clinical Trials for the Spectrum of Alzheimer's Disease and Age-related Cognitive Decline (PAR-18-878). However, to be competitive under the Early-Stage clinical trials FOA, applicants generally must demonstrate some preliminary data. Some PIs lack pilot data at all, or have data from diseases or populations that may not be directly relevant for AD/ADRD trials. In those cases, the only option available to applicants is to apply to the NIH Parent R21, from which applications routed to standing study sections that may lack aging and AD/ADRD clinical trials expertise. This approach can result in less rigorous review and much lower success rates.

We are proposing to extend NIA’s clinical trials pipeline and create an R21 clinical trials FOA focused on gathering directly relevant pilot data specifically for AD/ADRD and age-related cognitive decline clinical trials. Pilot data should be focused on addressing issues of feasibility, safety, tolerability/acceptability. Pilot data under can also be useful further inform aspects of subject selection, trial design, and trial endpoints. The goal of these pilot data is to de-risk novel interventions and approaches, and to improve the likelihood of success at the R01 level. This FOA will further demonstrate NIA’s commitment to developing novel interventions for AD/ADRD and age-related cognitive decline and supporting emerging researchers in AD/ADRD.

Scientific/Research Contact

Kristina McLinden, Ph.D.
Division of Neuroscience
National Institute on Aging
Email Kristina McLinden

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Transition to aging and AD/ADRD career development award

Given the highly competitive academic landscape, transition awards that provide NIH funding for the first three years of the independent research career can significantly increase the candidate’s competitiveness for transition to faculty positions and demonstrate the merits of their research plans as viewed by peer review. Due to the strict K99 eligibility criteria (including a 4-year eligibility window) many postdocs miss the opportunity to apply for this grant and transition into faculty position. There is a need for another NIA program that specifically provides support to the talented, mentored intramural and extramural aging scholars to establish and sustain a successful, and independent research career in aging and AD/ADRD. This new career development award (K22) will be open to mentored intramural and extramural researchers who have not yet received major NIH funding (such as R01 or other K awards). Researchers will work with their current mentor and put together a complete application including research and career development plans for their independent phase. Applicants recommended for funding will have one year to secure a tenure-track (or equivalent) position and submit their transition package which includes offer letter and information on their startup package, institutional commitment, and updated bio-sketch, research, and training plans. This approach will fill a gap of transition awards for candidates ready for a transition including those that have more than four years of postdoctoral experience.

Scientific/Research Contact

NIA Training Officer
Division of Extramural Activities
National Institute on Aging
Email the NIA Training Officer

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The role of adaptive immunity in etiology of Alzheimer’s disease

While the role of innate immunity and microglia in the pathogenesis of Alzheimer’s disease (AD) has been extensively studied, much less is known about the peripheral innate and adaptive branch of immunology in AD. It was nearly three decades ago when the first observations of T cells in AD brains were reported. In the years since, contrasting reports demonstrated the presence or absence of T cells in AD brain with a common ‘thread’ that T cells infiltrating the brain parenchyma in AD do not associate with either plaque or tangle pathology. Today, although still controversial, there is a growing body of evidence on the importance of the adaptive immune system in AD/ADRD pathogenesis. There is a need to understand the heterogeneity of Aβ-specific T cell responses in different genetic backgrounds and MHC context and the role of CD4+ T cell types in AD/ADRD pathogenesis. Recent studies highlight both the importance of adaptive immunity in AD/ADRD as well as some unanswered questions and controversies regarding adaptive immune responses in the context of neurodegenerative diseases. A deeper mechanistic understanding of the immune processes that are at play could facilitate the development of innovative immunotherapies for AD.

The goal of this RFA is to explore the role of the adaptive immune system in the etiology of AD. Research areas of interest to be supported by the FOA may include: research on brain barriers, e.g. the blood brain and blood CSF barriers and meningeal lymphatics in the context of brain adaptive immunity and neurodegeneration; studies on the composition, phenotype and antigen specificity of T cells in the CNS during the neurodegenerative process; composition, phenotype and antigen-specificity of T cells across various brain compartments; characterization of T cells infiltrating protein aggregates in AD brain; characterization of antigen presenting cells and identity of MHC class I and II peptides from APC, microglia in particular; studies on interactions between innate and adaptive immunity during neurodegeneration, e.g. microglia phenotypes and disease progression following manipulations of regulatory T cells; characterization of B cells residing in AD brains and their roles in disease onset and progression; and studies on behavioral outcomes following manipulation of the adaptive immune system. The FOA opens the way to better understanding of brain immune surveillance and the generation of CNS-directed immune responses in neurodegenerative disorders, specifically the functional role adaptive immunity in AD onset and progression. It will shed light on the etiology of the immune imbalance, e.g. between peripheral adaptive and brain innate immune responses, typical of neurodegenerative disorders, with promising implications for therapy. These studies my help with AD diagnostics, risk stratification and discovery of immunotherapeutics.

Scientific/Research Contacts

Miroslaw “Mack” Mackiewicz, Ph.D.
Division of Neuroscience
National Institute on Aging
Email Mack Mackiewicz

Lisa Opanashuk, Ph.D.
Division of Neuroscience
National Institute on Aging
Telephone: 301-827-5422
Email Lisa Opanashuk

Rebecca Fuldner, Ph.D.
Division of Aging Biology
National Institute on Aging
Telephone: 301-496-6402
E-mail Rebecca Fuldner

Transformative artificial intelligence based strategies to identify determinants of exceptional healthspan and lifespan

Ongoing NIA-supported studies of exceptional longevity (EL) are in the process of generating a wealth of multi-omic data from exceptionally long-lived individuals and several non-human species with varied lifespans. These projects converge on the major goal of identifying protective genetic/omic based druggable targets to enhance healthy aging by analyzing datasets spanning the phenome, genome, epigenome, transcriptome, proteome, metabolome, and microbiome. The mass and complexity of such omic data generated by these and related NIH projects pose critical analytical challenges for identifying potential therapeutic targets.

Two crucial challenges are:

  • Integrative analyses of data from multiple types of omics, and
  • Integration of human omics data with data from other species with a wide range of life spans.

This concept will bring data scientists with artificial intelligence (AI) expertise into the aging field and stimulate the development of novel methods to integrate, extract, and interpret multi-omic and clinical data from human EL cohorts and multiple non-human species to discover new targets for extending health span and delaying the onset of chronic age-related disorders including dementias. The initiative is timely as a rich resource of multi-omic data will be available in a year or so and this wealth of information can be mined in depth by AI methodologies. The efforts of this initiative in data harmonization could also be leveraged with other harmonization efforts in other ongoing large-scale projects such as AMP AD and ADSP. Overall, this project is expected to enable new directions for translational longevity research.

Scientific/Research Contacts

Nalini Raghavachari, Ph.D.
Division of Geriatrics and Clinical Gerontology
National Institute on Aging
Email Nalini Raghavachari

Candace Kerr, Ph.D.
Division of Aging Biology
National Institute on Aging
Email Candace Kerr

Marilyn Miller, Ph.D.
Division of Neuroscience
National Institute on Aging
Email Marilyn Miller

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Screening and intervention for the maltreatment of older & vulnerable adults with Mild Cognitive Impairment and AD/ADRD and their families

The maltreatment of older adults is a significant public health problem. Elder Maltreatment (EM) includes: physical abuse, emotional or psychological abuse, sexual abuse, neglect or abandonment, and financial exploitation of older adults. Older adults rarely directly disclose maltreatment, and there are no unequivocal signs. Consequently, EM frequently goes undetected in clinical settings. In situations where people with Alzheimer’s disease and Alzheimer’s disease related dementia (AD/ADRD) disclose EM, issues of capacity and competency often cast doubt on the validity of their claims. In addition, clinicians may be faced with complex ethical challenges for both self and the patient. Allegations of EM can result in civil or criminal consequences. However, often no alternative caregiving options are available, and effective interventions for prevention and treatment intervention do not exist. Therefore, clinicians need screening tools to improve diagnostic accuracy and early detection of EM, as well as strategies for prevention and early intervention. Screening patients prior to or early in the course of cognitive decline can help clinicians to identify and provide a brief psychoeducational intervention to patients and families at risk for EM and to direct them to appropriate health and social services.

To these ends, this RFA will request R61/R33 research applications for studies that respond directly to priority research needs and gaps highlighted in the U.S. Preventive Services Task Force’s 2018 final recommendation statement on Intimate Partner Violence, Elder Abuse, and Abuse of Vulnerable Adults: Screening; specifically, for the development and validation of:

  1. Reliable and accurate EM screening instruments or assessments in primary care settings for older and vulnerable adults and medical visit companions, at the time of diagnosis of mild cognitive impairment or AD/ADRD and subsequent primary care encounters and
  2. Brief and effective point-of-care psychoeducational and behavioral interventions for the prevention of all subtypes of EM.

NIA will be particularly interested in applications proposing research that includes measures, and that develops screening tools and interventions, with and for people who have been underrepresented in AD/ADRD intervention research (e.g., racial and ethnic minorities, sexual and gender minority populations (as defined on the home page of NIH’s Sexual & Gender Minority Research Office | DPCPSI) older adults with disabilities and/or low literacy, non-English speakers, and those from socially, culturally, economically, or educationally disadvantaged backgrounds). Applications will be required (1) to use the PICOTS framework, by specifying the Population, Intervention, Comparators, Outcomes, Timing, and Setting, (2) to specify the steps taken to reduce the risk of sampling bias, selection bias, attrition bias, detection bias, performance bias, and observer bias, and (3) to assess individual-level variables in the decision to screen and patient consents, and concordance, in terms of a similarity, or shared identity, between the patient and provider.

Scientific/Research Contacts

Melissa Gerald, Ph.D.
Division of Behavioral and Social Research
National Institute on Aging
Telephone: 301-451-4503
E-mail Melissa Gerald

Marcel Salive, M.D., M.P.H.
Division of Geriatrics and Clinical Gerontology
National Institute on Aging
Telephone: 301-496-6761
E-mail: Marcel Salive

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Social, behavioral and economic research on COVID-19 consortium and coordinating center

Note: This concept was approved electronically by the National Advisory Council on Aging in January 2021.

The COVID-19 pandemic is proving to have long term social, behavioral and economic impacts, so acquiring relevant longitudinal data is critical to study longer term direct and secondary health effects by making use of existing data resources. Specifically, the purpose of concept is to initiate FOAs to advance research on the impact of SARS-CoV-2 and associated mitigation efforts on individual, family, and community behavior; and on how subsequent economic disruption affects health-related outcomes, with close attention to underserved and vulnerable populations. To address these questions, this coordinating center and research grants will form a research consortium to access, extract, integrate, share, and analyze existing data from various sources with broad population coverage including underserved and vulnerable populations. The consortium coordinating center will promote use of common data constructs and support research, dissemination and data management activities. The research grants will serve to advance research on the impact of SARS-CoV-2 by leveraging/enhancing existing longitudinal data. Substantial NIH involvement is required to coordinate data collection along with existing activities supported by NIH and ensure collaboration among research awards. Examples of existing data include public health data; personal digital data; economic, labor, and commerce data; electronic health records, claims data, and ongoing health, demographic, and social surveys.

The consortium coordinating center will foster collaboration and synergies across consortia member projects and other NIH-funded projects that address these priorities. Investigators will work with the consortium coordinating center to enhance and share data resources used in proposed research both within the consortia group as well as with others for health research purposes. The coordinating center will also organize annual meetings of the consortium investigators to share results, foster harmonization among measures collected, identify new opportunities for interaction/collaboration, and share results with NIH and the public. Further, the consortium coordinating center will support the development of reports and analyses summarizing and integrating the findings/products of the consortia.

Scientific/Research Contact

John W. R. Phillips, PhD
Division of Behavioral and Social Research
National Institute on Aging
Email John Phillips

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September 2020 Council

Approved concepts in this round:

Early Stage Investigator Research Using Nonhuman Primate (NHP) Models

The purpose of this new, trans-NIH program is to address (1) the pressing problem of a shortage of new researchers applying nonhuman primate (NHP) models to basic science and translational research topics and (2) the challenges early stage investigators have with entering the NIH funding system with their first research award, particularly when using expensive NHP models. A 2018 NIH report revealed an inadequate supply of researchers using NHPs to address basic science and translational research topics in multiple areas. Similarly, the NIH and Congress have recognized the overall challenges new researchers have in acquiring funding and establishing independent careers.

In order to address the shortage of young researchers with the skills to use NHPs in basic science and translational research and to assist these researchers in achieving independent research careers, NIA and other ICOs propose to establish the Early Stage Investigator Research Using NHP Models Program.

Key elements of the program are:

  • At least two years prior postdoctoral experience
  • Applicants no more than 10 years beyond their terminal professional degree
  • Research focused on basic science or translational research topics

NIA and collaborating ICOs anticipate that the benefits of the expanded program to the successful applicants will include:

  • Increased fiscal independence allowing recipients to pursue research directions independent of the support of their mentor;
  • Ability to demonstrate additional success through competition in the peer review process; and
  • Generation of additional data and publications in support of future

Scientific/Research Contact

Manuel Moro, D.V.M, M.P.H, Ph.D.
Division of Neuroscience
National Institute on Aging
Telephone: 301-496-6402
Email Manuel Moro

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New Approaches to Study the Dynamics of Neurogenesis in Brain Aging and AD/ADRD

Substantial progress has been made in the field of neurogenesis over the past two decades. Even so, there is more to learn in terms of its mechanisms and functions, particularly in aging and AD/ADRD. While most experts in the field agree that neurogenesis occurs throughout the lifespan, particularly in the hippocampus, the mechanisms governing neurogenesis – and its role in AD/ADRD – are still uncertain. Contributions to the fundamental understanding of the factors for promotion of neurogenesis in the aging brain milieu, the elements of the neurogenic niche that foster a healthy and sustained integration of new neurons, and the mechanisms by which these new neurons give rise to functional outcomes such as cognitive maintenance age or remediation of decline are key goals. To achieve these goals, more basic research is needed to develop tools to identify and measure adult neurogenesis in animals and humans and to selectively target molecular and cellular processes governing neurogenesis in the aging brain.

Novel approaches to examine cell types and peripheral factors in the neural stem cell niche, to investigate new ways to analyze neurogenesis at different stages of aging and AD/ADRD, to clarify the mechanisms regulating neurogenesis and to investigate the function of newborn neurons in the aging brain and AD/ADRD, would be particularly important to advance knowledge in this area. Development of new tools, and expansion of existing tools, to address outstanding questions in neurogenesis in the aging brain would provide insight into age-related decline in brain/behavioral function and vulnerability to neurodegenerative diseases such as AD/ADRD, as well as resilience to decline, resistance to disease, or building reserve. Areas for development and investigation include: identifying, detecting, and modulating adult neurogenesis; new ‘omics’ for stages of neurogenesis; tagging and monitoring newborn neurons to study incorporation into existing circuits including functional outcomes such as cognition; live imaging to capture neurogenesis in humans and/or animal models; human iPSC and organoid models to study neurogenesis; enriching cell populations of interest for neurogenesis; new tools and approaches to analyze the neural stem cell niche (vascular, microglial, astrocytic, or peripheral). Research supporting this concept on new approaches to study the dynamics of neurogenesis in brain aging and AD/ADRD could be performed using the R01 activity code to support discrete, specified, circumscribed projects.

Scientific/Research Contacts

Amanda DiBattista, Ph.D.
Division of Neuroscience
National Institute on Aging
Email Amanda DiBattista

Molly Wagster, Ph.D.
Division of Neuroscience
National Institute on Aging
Email Molly Wagster

Bradley Wise, Ph.D.
Division of Neuroscience
National Institute on Aging
Email Bradley Wise

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The Cellular Scale Connectome in Aging and Alzheimer’s disease

A general characteristic of many neurodegenerative diseases, including Alzheimer’s disease (AD), is that the disease impacts specific brain area(s). The pathology worsens with time and impacts more regions in a stereotypical and often predictable fashion. The first step in understanding mechanisms underpinning AD onset and progression is to identify which circuits, and which component(s) of that circuit, are particularly vulnerable. This would allow further development of models that reproduce spatial and temporal features of the pathology, and the identification of intrinsic morphological, electrophysiological, and biochemical properties of vulnerable circuits and shed light on the types of neurons vulnerable to degeneration. Despite the fundamental importance of brain connectivity, our knowledge of it remains remarkably incomplete. C. elegans is the only species for which a complete wiring diagram of its 302 neurons has been developed. A mesoscale connectome of the adult mouse brain has been generated at the Allen Brain Institute and is currently available through the Allen Mouse Brain Connectivity Atlas. The NIH BRAIN Initiative is supporting research to generate a comprehensive brain cell census and to develop tools to probe cell-specific and circuit-specific processes in the brain.

This concept promotes the development of a comprehensive characterization of brain circuits susceptible to AD type pathology or neurodegeneration in mouse models of AD. It will leverage already existing technologies and tools such as single cell transcriptomics and epigenomics or cell specific AAVs and transgenic mice for tracing experiments. The concept aims to promote research to: define brain circuits in selected brain regions at the cellular level, i.e. cellular projection of one molecularly defined class or type of neuron to another class or type; characterize temporal changes in cellular connectivity e.g., changes with age; and define temporal changes in circuits with onset and progression of AD. These goals can be accomplished using the next generation of AD models and complementary human studies on connectivity. Sharing data on the cell connectome in the aging and AD brain in a comprehensive, common reference brain cell atlas that integrates both molecular and anatomical annotations will advance knowledge in this area. The cellular scale connectome will complement and extend research on vulnerable cell types to mapping of connectivity changes between cells in aging and AD and will provide a greater understanding of the mechanisms underlying resilience and vulnerability in AD. Research supporting this concept of a comprehensive characterization of brain circuits susceptible to AD type pathology or neurodegeneration could be performed using the research project (e.g. R01) activity code.

Scientific/Research Contacts

Miroslaw “Mack” Mackiewicz, Ph.D.
Division of Neuroscience
National Institute on Aging
Email Mack Mackiewicz

Bradley Wise, Ph.D.
Division of Neuroscience
National Institute on Aging
Email Bradley Wise

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AD/ADRD Clinical Trials Short Course

With increased federal funding for research in Alzheimer’s Disease and related dementias (AD/ADRD) and a mandate for interventions to treat or cure AD/ADRD by 2025, the number of NIA-funded AD/ADRD clinical trials has nearly doubled in the past three years. There is a critical need to expand the AD/ADRD clinical trials workforce overall and with regards to the inclusion of individuals from diverse backgrounds in particular. In addition to expertise in aging and dementia, AD/ADRD clinical trialists require a diverse and increasing array of knowledge and skills, including understanding of evolving trial designs and research methodology, biostatistics, neuropsychopharmacology, and computer science. This FOA is designed to encourage applications for intensive short courses that will develop, implement, and evaluate creative and innovative short courses to provide education in state-of-the-art clinical research skills in AD/ADRD. Courses may vary in duration from one-week or less up to a maximum of 12-weeks. Courses will include graduate/medical students, post docs, and/or early career faculty. Diversity of participants and faculty is a high programmatic priority. This type of training is necessary to thrive in a team science environment and is rarely provided through the traditional course of medical and graduate education. With this proposed concept, we will address a significant gap in clinical trials training and strengthen the pipeline of promising new trialists.

We not only need to enhance the skills of new clinical trialists, we also need to diversify the trialists themselves. Research has demonstrated that significant racial disparities exist among clinical investigators and physicians from minority populations are less likely to participate in clinical research, despite expressing similar levels of interest. In addition to providing more equal opportunity, this will also benefit the trials themselves. Clinical trials struggle to recruit individuals from diverse racial and ethnic backgrounds. One of the potential barriers to participation is the lack of cultural sensitivity and ethic similarity to staff participants. Therefore, diversity in both the faculty and participants of these short courses will be a programmatic priority.

Scientific/Research Contacts

Laurie Ryan, Ph.D.
Division of Neuroscience
National Institute on Aging
Email Laurie Ryan

Kristina McLinden, Ph.D.
Division of Neuroscience
National Institute on Aging
Email Kristina McLinden

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MSTEM: Advancing Diversity in Aging Research through Undergraduate Education

The NIH recognizes a unique and compelling need to promote diversity in the NIH-funded biomedical, behavioral, clinical, and social sciences (collectively termed "biomedical") research workforce. The NIA-funded MSTEM programs focus on undergraduate students historically underrepresented in medical, science, engineering and mathematics (MSTEM) fields of study. The concept seeks to further diversify and expand on the existing program to fund innovative programs which would bolster achievement in MSTEM fields and stimulate an interest in aging and geriatrics as a potential career choice. The MSTEM graduates represent a unique cohort of geographically diverse educational institutions with expertise in distinct but overlapping scientific areas of the NIA. Through this institutional award, the undergraduate students receive an education in MSTEM fields and undertake summer and academic year research projects in aging. Each program’s innovative and unique approach to the program goals represents an unparalleled opportunity to diversify the research workforce in aging and geriatrics at the critical – undergraduate – juncture in the pipeline of a scientific career.

The renewal of this diversity-oriented concept, first published in 2012, will broaden the pool of scientists within the research workforce addressing healthy aging and diseases and disabilities associated with aging. Research and professional training offered by this program will provide trainees required skillsets which make them competitive candidates for the graduate training in aging-related disciplines. To date, through a relatively moderate investment, NIA has supported training of more than 320 students in aging-related STEM research, resulted in more than 100 presentations and publications.

Scientific/Research Contact

NIA Training Officer
Division of Extramural Activities
National Institute on Aging
Email the NIA Training Officer

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Academic Leadership Career Development Award

The goal of this program is to provide protected time to the established independent investigators with aging expertise to build an area or subfield of research on aging at their institution. This program allows senior investigators to officially dedicate 25-50% of their effort to mentoring junior faculties and support their research and training which will help them to become competitive researchers for the NIA career development and research project grants. It has been continuously supported by the NIA since its establishment in 2008. In addition to partial salary support, this award will support activities which enhance aging research and education at the host institution to make them more competitive for institutional grants such as T32 and P01. These activities include, but are not limited to: developing aging curricula and providing pilot funding to the junior faculties at the grantee institution to enhance their aging expertise and allowing PIs to enhance the educational or research capacity at the sponsoring institution. The PI will be able to officially dedicate their effort to the development and expansion of the aging-related educational and/or research capacity at their institution and increase the pool of aging scholars and scientific workforce.

Scientific/Research Contact

NIA Training Officer
Division of Extramural Activities
National Institute on Aging
Email the NIA Training Officer

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Early-Phase Clinical Trials of Novel Interventions to Prevent, Delay, or Treat Aging-Related Conditions by Targeting Aging-Related Mechanisms

There is a growing interest in the identification and clinical testing of compounds that could treat individual or multiple age-related conditions by modulating fundamental aging-related mechanisms (e.g., autophagy, mitochondrial function, cellular senescence, etc.). A variety of compounds that modulate such processes have been tested in model organisms and a few in early-stage human intervention studies. These compounds include but are not limited to senolytics (which kill senescent cells), inhibitors of mTOR (mammalian target of rapamycin (which influence several aging-related mechanisms), supplements to increase nicotinamide adenine dinucleotide levels (which influence aging-related metabolic and other processes), and other. However, few such compounds have moved beyond early exploratory studies. A crucial limiting step is the need for sufficient initial clinical data to attract third-party investment for subsequent larger trials of safety and efficacy.

Through this funding opportunity, NIA seeks to support early-phase clinical trials (Phase 1, 2a and 2b) of new and repurposed compounds modulating fundamental aging-related mechanisms. These studies could assess safety and tolerability; effects on clinical outcomes and/or predictors of clinical outcomes; pharmacokinetics and pharmacodynamics; degree and specificity of molecular and cellular target engagement; off-target effects; and interactions with co-existing conditions and medications This funding opportunity is timely given the availability of promising compounds with repurposing potential to treat or prevent multiple aging-related diseases and conditions; growing interactions between disease-oriented intervention researchers and aging researchers; strong interest by investors in continuing support of products that show promising results in early clinical testing; infrastructure support provided by the NIA-supported Translational Geroscience Network; compounds identified by the NIA Interventions Testing Program as having favorable effects on life span and health span effects; and opportunities for small first-in-human studies or proof-of-concept studies for agents for which there is adequate pre-clinical safety data.

Scientific/Research Contact

Sergei Romashkan, Ph.D.
Division of Geriatrics and Clinical Gerontology
National Institute on Aging
Email Sergei Romashkan

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Research and Entrepreneurial Development Immersion (REDI)

Please note: This concept was formerly referred to as the Entrepreneurship and Innovation Training Program (ENRICH)

For decades, the main career trajectory for PhDs has been academia, and NIH, as the major research funding organization, offers a variety of training programs to prepare junior researchers for an academic career. However, while the number of PhD graduates has rapidly increased every year, the number of available tenure-track faculty positions has remained unchanged. This imbalance has created a very competitive job environment, making it increasingly difficult for PhD graduates to transition to academic appointments. Additionally, modern academic positions have evolved in such a way that often include roles that are more multidisciplinary.

University research fosters a substantial portion of industrial R&D in the biotech industry, and university spinoffs employ high-tech talents, generate taxes, and act as economic hotbeds for the local economy. The biotech community has been essential in catalyzing academic discoveries and commercializing them into needed solutions that improve public health. This is especially true for neurodegenerative diseases and aging-based research where the unmet needs are real and the opportunities for product development are rapidly expanding. Empowering spin-offs is critical to biomedical innovation, the economy, and by extension the mission of the NIA. This initiative provides multiple funding programs such as individual career development award, small business award, and NRSA institutional funding programs to provide bio-entrepreneurship training to further enrich and diversify NIA training programs and allow trainees to acquire additional non-academic skills. The proposed bio-entrepreneurship training mechanisms will include but will not be limited to the hands-on industry research experience, science communications, intellectual property, regulatory affairs, science policy, consulting, drug discovery, approval, and production, the business of science, science education and healthcare.

Scientific/Research Contacts

Saroj Regmi, Ph.D.
Office of Small Business Research/Division of Extramural Activities
National Institute on Aging
301-480-8964
Email Saroj Regmi

Todd Haim, PhD
Chief, Office of Small Business Research
National Institute on Aging
E-mail Todd Haim

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Fellowship and Career Development Awards to Promote Diversity in Translational Research for AD/ADRD

There is a high demand for data scientists in biomedical/behavioral research and the application of data science to Alzheimer’s and related dementias (AD/ADRD) research remains a gap. In addition, expertise in traditional and emerging drug discovery disciplines is typically lacking among academic investigators. Moreover, there is an even greater shortage of investigators from underrepresented minority backgrounds prepared to conduct cutting edge translational AD/ADRD research. Currently there are no training programs for AD/ADRD translational research aimed at underrepresented minorities. These linked fellowship and career award funding opportunities will establish a training pipeline for predoc, postdoc and junior faculty from under-represented minority backgrounds to diversify the translational research workforce for AD/ADRD. This training initiative will emphasize the development and application of skills in data science and drug discovery disciplines to various aspects of AD/ADRD research (from population studies and behavioral/social research to research on diagnostics and drug development). This initiative will support these trainees with intensive and supervised training to ensure their successful career development and will lead to the development of a diverse translational workforce that can effectively participate in and/or lead a team-science, precision medicine approach to AD/ADRD treatment, prevention, early detection and disease management and care.

Some examples of research areas that will be supported through these training programs are: multi-omic approaches to target/biomarker discovery and validation, discovery and preclinical development of new small-molecules and biologics for AD/ADRD, use of digital technologies for longitudinal assessment of cognitive and functional change, identification of functional AD/ADRD biomarkers, analysis of time-intensive behavioral predictors of MCI and dementia, fusion and analysis of multiple datasets (EMRs/PHRs, surveys, sensors, medical claims, financial data, geolocation data, etc.), analyses of multi-level data (biological, behavioral, social, community, organization, policy) from publicly available and/or deidentified sources.

Scientific/Research Contacts

Yuan Luo, Ph.D.
Division of Neuroscience
National Institute on Aging
Email Yuan Luo

Frank Bandiera, Ph.D.
Division of Behavioral and Social Research
National Institute on Aging
Email Frank Bandiera

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Osteoimmunology in Aging

Musculoskeletal diseases are among the highest global burdens of disease in people over 60 years of age. In addition, declines in immune function parallel declines in bone health. Osteoimmunology studies the bidirectional interactions between bone and the immune system. The term first appeared in the literature in 2001has become recognized and grown over the next decade, becoming recognized by the wider bone research community. Very few studies to date have examined the effects of age on the natural changes in bone homeostasis.

Because the bone marrow is the principal adult site of immune cell differentiation, better understanding of the dynamic interaction between bone aging and immune aging – osteoimmunology – will advance our ability to refine therapies and develop interventions to improve health at older ages. This FOA will support research meeting the important need to understand pathobiological changes that occur in the marrow niche with age and how these changes affect health.

Scientific/Research Contacts:

John Williams, Ph.D.
Division of Aging Biology
National Institute on Aging
Telephone: 301-496-6402
E-mail: John Williams

Rebecca Fuldner, Ph.D.
Division of Aging Biology
National Institute on Aging
Telephone: 301-496-6402
E-mail Rebecca Fuldner

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Networks to Develop Behavioral and Social Science Research in Aging

To develop new research and research infrastructure for life course research on aging, attract new researchers in aging, infuse health disparities into aging research, and address ongoing needs for harmonization and biomarker collection in large population panel studies, as recommended by the 2019 BSR NACA Review, we seek to renew critical ongoing network efforts as well as initiate new networks in the following priority areas:

  • Midlife Reversibility will focus on identifying opportunities for midlife and later-life reversibility/remediation of biobehavioral phenotypes associated with early life adversity.
  • Harmonization of Health and Retirement Study International Aging Studies will support the development of new international studies with comparable data to the NIA-supported U.S. Health and Retirement Study (HRS), maintains harmonization and data development among existing comparable studies, and develops a cross-national research agenda.
  • Biomarkers in population studies organizes activities aimed at improving measurement of biological risk for late life health outcomes to be fielded in large representative population samples, including interactive workshops and pilots.
  • Decision Neuroscience and Aging incorporates perspectives from psychology, neuroscience, economics, and behavior change to promote basic and translational research on decision making in aging, with a new focus on the implications for MCI and AD/ADRD.
  • Innovation in Longitudinal Aging Studies is a new program intended to combat declining response and consent rates in large studies as well as improve measurement via innovative approaches to identify more efficient screening and data collection techniques, reduce respondent burden, and identify new ways to effectively consent respondents.
  • Measurement for Dementia Care in Home and Community-based Services (HCBS) will focus on improving measurement of HCBS process and outcome measures (e.g., Quality of life and well-being for persons living with dementia (PLWD) and their care partners, economic indicators). Dementia care HCBS researchers often utilize different approaches to data collection, measures and outcomes, and analysis.
  • Dementia Care Workforce will focus on producing research that addresses the skills that this workforce will need as the population of PLWD grows. Considerations include specialization of treatment; skill matches and mismatches; the potential impact of worker certification; and the gathering of researchers thinking about how the growth of dementia care will impact the workforce and care of PLWD and providers.
  • Education and ADRD will provide opportunities for collaboration and scholarly exchange including measurement harmonization and coordinated analyses to address unanswered questions about the education-ADRD relationship.

Scientific/Research Contact

John Phillips, Ph.D.
Division of Behavioral and Social Research
National Institute on Aging
Telephone: 301- 827-4137
Email John Phillips

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COPIAS: Capitalizing on Prior Investments in Animal Studies

Conditions in the social and physical environment play a pivotal role in aging and health outcomes across the life course in all animals. The accumulation of lifetime events and experiences is far greater for older animals, and many age-associated diseases may have their roots in early life exposure to adverse social and physical conditions with outcomes that do not manifest in full for many years. Nevertheless, exposures to such conditions, and individual differences in the effects of these exposures - topics commonly addressed in social and behavioral sciences - are rarely taken into account in geroscience or preclinical research with animal models. Yet, despite its importance, currently little infrastructure exists to support aging-relevant behavioral and social research with animals. In response to NIA’s interest in expanding the use of animal models to further the understanding of normative aging processes and the identification of modifiable factors that influence disease etiology and progression, and to improve translational outcomes, this initiative proposes to strengthen the quality of behavioral and social animal models of aging, by supporting aging-relevant research that can lead to the enhancement, development, and/or the creation of new infrastructure for behavioral and social research with animals in wild and captive populations. Specifically, it seeks to support projects that build and expand on existing resources from basic, applied, and translational studies, in the following areas:

  • Infrastructure development for improved behavioral and social and physical environmental measurement, including: (a) the creation and/or refinement of observational techniques and novel experimental approaches for the analysis of associations among behavioral and social processes and aging-relevant health measures; and (b) the development of non-invasive sampling techniques and assessment methods, tools, and instruments for mental and physical health and disease screening for studies of animals in their natural habitat and/or captivity.
  • Natural history studies of aging in populations of wild animals that can increase the understanding of naturally occurring aging processes and the contribution of social and physical environmental conditions to individual differences in aging trajectories, and/or the improvement of the ecological validity and value of basic and translational research.

Scientific/Research Contact

Melissa Gerald, Ph.D.
Division of Behavioral and Social Research
National Institute on Aging
Telephone: 301-451-4503
E-mail Melissa Gerald

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Mechanism-Focused Research to Promote Adherence to Healthful Behaviors to Prevent Alzheimer’s Disease and Alzheimer’s Disease Related Dementias (AD/ADRD)

Poor adherence to behaviors that promote health, such as regular exercise and physical activity, is common in midlife and older age, across adults with diverse backgrounds and health issues, including chronic illnesses. Behavior change interventions (e.g., interventions to increase physical activity, control blood pressure, or engage in cognitive training) have been identified as promising strategies to prevent cognitive decline, Mild Cognitive Impairment (MCI), and AD/ADRD. However, achieving both short-term (e.g., weeks to months) and long-term (e.g., months to years or decades) adherence to these interventions has been a challenge.

The trans-NIH Science of Behavior Change (SOBC) Program has promoted adoption of the experimental medicine method to identify causal mechanisms that explain behavior change, including adherence to new behaviors and lifestyle changes. The ultimate goal of this set of funding opportunities is to identify meaningful (e.g., causal), modifiable mechanisms that promote adherence to healthful behaviors and other (e.g., cognitive training) approaches that hold potential for prevention of cognitive decline, MCI, and AD/ADRD. These funding opportunities will support new and ancillary studies that integrate basic (i.e., fundamental) science discoveries that have identified meaningful, modifiable psychological and interpersonal mechanisms into clinical studies and trial designs that target these mechanisms to inform the development of effective, efficient, and personalized approaches for promoting adherence to behavior change for the prevention of AD/ADRD and to help optimize healthy aging over the life course.

Scientific/Research Contact

Luke Stoeckel, Ph.D.
Division of Behavioral and Social Research
National Institute on Aging
Telephone: 202-570-9388
E-mail Luke Stoeckel

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MIDUS Continuation and AD/ADRD Expansion

This concept requests approval for issuing six-year funding opportunities to continue the NIA funded study entitled, “Midlife in the United States (MIDUS),” a leading national longitudinal study of how a variety of important factors (behavioral, social, psychological, biological, neurological) jointly influence health and well-being as people age from early adulthood into mid-life and old age. MIDUS was originally funded (1995) by a MacArthur Foundation grant, and in 2003, NIA funded a longitudinal follow-up, which added new biological and neurological assessments onto the original assessment battery. A renewal in 2011 allowed follow-up of the original sample and addition of a “Refresher” sample to strengthen cross-project analyses by increasing sample sizes. Across its 15-plus years of NIA support, MIDUS has become a leading longitudinal data resource on patterns of age-related changes in the health and well-being of US middle-aged adults and is among the most downloaded publicly available datasets housed at NIA’s National Archive of Computerized Data on Aging.

Given the aging of the study participants and to obtain more fine-grained information about factors associated with either added risk of or protection from AD/ADRD, a six-year budget period was recommended. A six-year grant cycle will allow integration of the original and refresher cohorts for optimal data processing and synchronization, accelerate public release of follow-up waves of data, and facilitate more informative analyses about interrelationships between the multiple measures obtained.

Scientific/Research Contact

Dana Plude, PhD
Division of Behavioral and Social Research
National Institute on Aging
Telephone: 301-435-2309
Email Dana Plude

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Short Courses on Interdisciplinary Behavioral and Social Sciences Research on Aging

This proposed FOA addresses the need for short courses/educational activities to more rapidly advance NIA’s behavioral and social sciences research priorities in selected topical areas not already well addressed by existing educational programs. Topics selected derive from BSR program development over recent years and are consistent with recent scientific recommendations, including those from the 2019 BSR NACA Review.

The FOA targets the 6 BSR priority research areas listed below. In each priority area, applications will be encouraged to incorporate a focus on health disparities.

General Focus

  • Genomics for Social Scientists. This R25 aims to lower the barrier to entry of early career social scientists into aging research using genetic and epigenetic data and to provide hands-on training for researchers working at the intersection of genetics and social science research, using NIA-funded data as a model.
  • Interdisciplinary Social Science Research in Aging. The goals of this R25 are to attract new and/or junior researchers into interdisciplinary, population-based social and behavioral science research; to increase cross-fertilization among different social, biomedical and behavioral science disciplines; and to expose participants to important issues facing the aging population and the major research approaches and data resources for addressing them.
  • Reproducibility in the Social and Behavioral Sciences. The field has made some progress in establishing tools, best practices and training curricula to accelerate reproducibility and to target the gap between current research training and the standards of rigor and transparency now required by funders, journals, and research institutions. However, existing efforts have not had explicit connection to behavioral and social science aging research. This R25 would develop and deliver a training curriculum that expands upon existing resources and targets them to behavioral and social science aging researchers.

AD/ADRD Focus

  • Cross-National Dementia Research Using Harmonized Data on Cognitive Function. This R25 will lower the barrier to entry for using the publicly available NIA-funded Harmonized Cognitive Assessment Protocol (HCAP), a sub-study within the US Health and Retirement Study (HRS) that is designed to measure cognitive impairment and dementia in longitudinal studies of older adults in countries around the world. The course will help to accelerate research on population trends in cognitive impairment and dementia, including genetic, medical, behavioral, social, and environmental pathways.
  • Behavioral Economic Approaches to Improve AD/ADRD Health Care Delivery. The goal of this R25 is to improve health care delivery for persons with dementia (PWD) by providing scientists with the necessary skills to apply behavioral economic insights to health care interventions at the organizational level. The FOA will encourage cross-fertilization among economists, psychologists and AD/ADRD experts. The FOA will also focus on helping to promote medical decisions by PWDs and family caregivers that are consistent with PWDs’ preferences, and innovative ways to change behaviors and improve care for PWDs.
  • Applications of Machine Learning (ML) to Social Science Research on Aging. The goal of this R25 is to improve the application of ML in healthcare research in AD/ADRD by providing scientists with skills to integrate ML and social science methods. The FOA will encourage the integration of approaches from social science and computer science for the purpose of enhancing health care delivery and interventions in AD/ADRD.

Scientific/Research Contact

Georgeanne E. Patmios, M.A.
Division of Behavioral and Social Research
National Institute on Aging
Telephone: 301-496-3138
Email Georgeanne Patmios

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Alzheimer’s Disease Sequencing Project Follow Up Study 2.0: The Diverse Population Initiative

The Alzheimer’s Disease Sequencing Project Follow-Up Study (ADSP) is examining the genetic underpinnings of subtypes (endophenotypes) of Alzheimer’s Disease (AD), which will likely vary by ethnicity. US ethnic groups are not represented in ADSP data in sufficient numbers to enable meaningful study. The ADSP presently has 49,572 Non-Hispanic Whites (NHW), 2,520 Hispanics (HI), and 6,669 African Americans (AA). The majority of variants that the ADSP is discovering are either rare or very rare in the population. With single variant testing for rare variants, for 90% certainty, investigators need roughly 18,500 cases and 18,500 controls for each population for a variant with a minor allele frequency of 1% in the population. The ADSP is sufficiently powered to identity rare or very rare variants in Caucasians of European descent, but for African Americans, Hispanics, Asian, and American Indian populations vary rare variants are presently undetectable. Variants occur at different frequencies in different populations and certain risk variants may be easier to detect in some populations. Important instances of ethnically unique AD/ADRD genetic variation have been identified in Hispanic and African American cohorts. To identify disease-associated variants, it is essential that more subjects from ethnically diverse populations be brought into the ADSP.

Understanding the architecture of the genome in persons with AD compared to those without the disease is a crucial step in AD research that may ultimately result in the identification of new risk or protective factor genes. Gene discovery will enhance our ability to identify new therapeutic targets and to define endophenotypes for selection of subjects for clinical trials. Data derived from the analysis will be rapidly shared with research community.

Scientific/Research Contacts

Marilyn Miller, Ph.D.
Division of Neuroscience
National Institute on Aging
Email Marilyn Miller

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May 2020 Council

Approved concept in this round:

Continuation of Look AHEAD (Action for Health in Diabetes)

The Look AHEAD study was a randomized trial evaluating the effects of an intensive lifestyle intervention which included exercise and weight loss on cardiovascular outcomes in over 5,000 persons with type 2 diabetes. The intervention ended in 2002, and post-intervention follow-up has continued. The study has been productive, with over 185 published peer-review articles, and it has been a platform for multiple ancillary studies. The study population was primarily in midlife at inception, and the surviving cohort is now in late life.

There are several reasons for continuing to follow this population. Its health status has been carefully assessed over many years. This makes it a valuable resource to study multimorbidity in the context of diabetes. The long duration and age at recruitment make it a good platform to study midlife influences on late life health and function, of which there are relatively few. Most importantly, Look AHEAD’s intervention is highly relevant to public health recommendations for a population that is increasingly obese and increasingly likely to suffer diabetes. There are several unknowns about the long-term consequences of intentional weight loss, and the Look AHEAD study is uniquely well-positioned to provide insight, at least as it pertains to those with diabetes.

Scientific/Research Contact:

Marcel Salive, M.D., M.P.H.
Division of Geriatrics and Clinical Gerontology
National Institute on Aging
Telephone: 301-496-6761
E-mail: Marcel Salive, M.D., M.P.H