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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.

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 R01 applications.

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, D.V.M, M.P.H, Ph.D.

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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

Shahrooz Vahedi, Ph.D.
Division of Extramural Activities
National Institute on Aging
Email Shahrooz Vahedi

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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

Shahrooz Vahedi, Ph.D.
Division of Extramural Activities
National Institute on Aging
Email Shahrooz Vahedi

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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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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:

Todd Haim, PhD
Chief, Office of Small Business Research
National Institute on Aging
Telephone: 301-480-7867
E-mail Todd Haim, Ph.D.

Shahrooz Vahedi, Ph.D.
Division of Extramural Activities
National Institute on Aging
Telephone: 301-496-9322
E-mail Shahrooz Vahedi, Ph.D.

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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

Shahrooz Vahedi, Ph.D.
Division of Extramural Activities
National Institute on Aging
Email Shahrooz Vahedi

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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 Ph.D.

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

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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 HRS studies, and encourages cross-national aging research using the international HRS family of studies.
  • Biomarkers in population studies will organize activities aimed at improving measurement of biological aging and biological risk for late life health outcomes to be fielded in large representative population samples, including interactive expert workshops and pilot projects to test protocols.
  • Decision Neuroscience and Aging will incorporate perspectives from psychology, neuroscience, economics, and behavior change to promote basic and translational research on decision making in aging, with a focus on the implications for MCI and AD/ADRD.
  • Innovation in Longitudinal Aging Studies is 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 subjective well-being of persons living with dementia (PLWD) and their care partners, economic indicators, etc.). Dementia care HCBS researchers often utilize different approaches to data collection, measures and outcomes, and analysis, so this network will seek harmonization of constructs and measures.
  • Dementia Care Workforce will focus on producing research that addresses the skills and composition of this workforce as the population of PLWD grows. Considerations include specialization of treatment; skill matches and mismatches; the potential impact of worker certification on PLWD health and well-being; 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 among investigators from educational cohort studies representing different birth cohorts and AD/ADRD researchers to coordinate data collection efforts, 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, Ph.D.

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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, Ph.D.

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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, Ph.D.

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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, Ph.D.

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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, M.A.

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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.

January 2020 Council

Approved concepts in this round:

Late Onset of Alzheimer’s Disease (LOAD) Family-Based Study (FBS)

Analysis of families with multiple members affected (3 or more diagnosed) with Alzheimer’s Disease (AD) provides distinct advantages for characterizing the impact of genetic variants on disease risk:

The NIA LOAD FBS—an integral component of the Alzheimer’s Disease Sequencing Project (ADSP)—began in 2003 with the collection and longitudinal follow up of large multiply affected families. To date the ADSP has sequenced 1,164 multi-ethnic families with 3,929 subjects having whole genome sequencing. The ADSP Follow-Up Study (FUS) heavily engages resources provided by the NIA LOAD FBS and depends upon the longitudinal follow-up of families and the collection of additional families.

The ADSP FUS expects to sequence at least 500 additional multi-ethnic families with the most informative members. The next wave of the NIA-LOAD FBS will extend recruitment within families to other affected members, and future generations of relatives in the age range for collecting baseline data. Characterization of additional relatives’ risk factors and autopsy recruitment will benefit the field and expand the scientific value of the NIA-LOAD FBS.

The NIA LOAD FBS will extend the collection of biological materials beyond those for genetic studies to peripheral blood mononuclear cells (PBMC) for stem cell modeling; plasma for studies of metabolomics, proteomics and biomarker research; and brain autopsy materials for bulk RNA-Seq. These biological materials will be made available to the larger scientific community through NCRAD. Genetic, genomic, and related phenotypic data will be made available through NIAGADS.

As an essential research resource, the NIA LOAD FBS is a key provider of biological materials and clinical data on large multiplex families not only for the ADSP, but also for the Alzheimer Disease Genetics Consortium, the Consortium for Alzheimer's Disease Research, and the network of NIA sponsored Alzheimer's Disease Centers. NIA LOAD FBS PIs actively collaborate with investigators with interest in AD genetics. The NIA LOAD FBS will continue to prioritize coordination with other components of essential ADSP infrastructure and support in the form of biological materials and clinical data for NIA-funded genetic studies. Future success of the initiative depends upon keeping the relationships together.

Scientific/Research Contact:

Marilyn Miller, Ph.D.
Division of Neuroscience
National Institute on Aging
Telephone: 301-496-9350
E-mail Marilyn Miller, Ph.D.

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Development of Cost-Effective and Customizable Training and Education Platforms for AD/ADRD Caregivers that Focus on Addressing Financial Management and Legal Planning

By the close of this decade, the number of family caregivers of adults is expected to increase to 45 million while the number of individuals potentially requiring care is thought to reach 117 million. In 2013 alone, approximately 37 billion hours of care—with an estimated value of $470 billion—was provided by 40 million family caregivers. Caregivers of persons with Alzheimer’s disease (AD) and AD-related dementia (ADRD)—PwD—are faced with additional burden and represent a community in dire need of caregiver education and training platforms.

This imbalance—between the number of estimated caregivers and those seeking care—is exacerbated by the diverse array of duties performed by family caregivers. These duties are broad and varied depending on the PwD’s condition. These include aiding with instrumental activities of daily living (e.g. financial/budget management) among other responsibilities. Caregivers, largely unpaid and without formal training, typically provide this suite of services with very little assistance and consequently experience high levels of emotional, financial, and physical burdens.

Factors contributing to high levels of emotional, monetary, and physical burden for caregivers include among others, the large investment of time and energy in providing care, the absence of formal medical/nursing training, and financial strain from serving as an unpaid caregiver. Compounding these issues is the fact that many caregivers must withdraw from the labor force which could lead them to forgo insurance, promotions, retirement benefits and pensions. The need to alleviate these burdens is underscored by a National Alliance for Caregiving and AARP Public Policy Institute survey which found that nearly 85% of caregivers mentioned a greater need for information about the care services they were providing with more than 40% desiring information on how to manage their stress levels. Of note, caregivers respond with great interest to the prospect of technological tools to help their caregiving but only a small percentage of caregivers currently use tech-enabled services for their daily tasks.

Family caregivers face substantial barriers in personally incorporating technology as a tool to assist them in their caregiving tasks. Some of these barriers include : (a) mismatch between existing technological solutions and stated caregiver needs (b) available tools may not be personalized (or customizable) and lack cultural relevance, and (c) existing technologies are perceived by family caregivers as sole use (i.e. absence of a single platform), too expensive, difficult to use due to complexities in design and function, and only useful in rarely encountered circumstances (e.g. emergencies).

Given the barriers contributing to low-uptake and adoption rates of technology-enabled solutions for family caregivers, there are currently few solutions targeted to family caregivers across the socioeconomic spectrum. This, along with projections that there will be approximately 120 million family caregivers, represents an opportunity and unmet need for solutions that fill in key gaps in service.

To address the fractionated nature by which solutions are available to family caregivers in addition to the paltry number of solutions that adapt to expertise levels, specific care demands, and needs of family caregivers, we are seeking solutions that create an integrated web-and-mobile educational platform for family caregivers. The solution should be cost-conscious, scalable, employ a user-centered design approach to promote accessibility for individuals across the socioeconomic spectrum and for individuals with varying levels of technological sophistication, and a solution generalizable to caregivers of non-dementia persons. Proposed products that address legal and estate decision making as well as financial management are of particular interest. While this funding opportunity will support platforms that target caregivers of PwD, it is expected that funded platforms would have applicability beyond dementia.

This concept is supported by both NIA and the HHS Administration for Community Living (ACL) and this collaborative concept was spearheaded by the listed scientific/research contacts.

Scientific/Research Contacts:

Todd Haim, PhD
Chief, Office of Small Business Research
National Institute on Aging
Telephone: 301-480-7867
E-mail Todd Haim, Ph.D.

Vijeth Iyengar, PhD
Brain Health Lead & Technical Advisor to the Deputy Assistant Secretary for Aging
Administration for Community Living
Telephone: 202-795-7347
E-mail Vijeth Iyengar, Ph.D.

Dana Plude, PhD
Deputy Director, Division of Behavioral and Social Research (DBSR)
National Institute on Aging
Telephone: 301-435-2309
Email Dana Plude, Ph.D.

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Advancing Research for the Prevention of Multiple Chronic Conditions and Their Consequences

Multimorbidity—also referred to as multiple chronic conditions (MCCs)—is defined as the co-occurrence of two or more chronic health conditions, but the measurement of co-occurring morbidities has not been standardized or optimized. The prevalence of MCCs is rising in the United States and worldwide. According to National Health and Nutrition Examination Survey data, 60% of adults aged 20 and older in 2014 had two or more chronic conditions, an increase from 46% in 1998. An estimated two thirds of older adults have two or more chronic conditions.

Furthermore, other sub-groups of the U.S. population experience a disproportionate burden of MCCs and health inequities related to MCCs. Women, African Americans, Hispanics, and non-Hispanic Whites have the highest prevalence of MCCs. Asians/Pacific Islanders experience the highest mortality and cost per case compared to all other groups. Minority populations also tend to experience earlier onset of MCCs compared with majority populations. Limitations in measurement and methods have hampered progress in this research arena.

The Cochrane Collaboration (2016) review of interventions designed to address co-occurring MCCs among adults across the prevention-to-treatment-continuum showed mixed results on efficacy. Areas identified that need more research include clinical outcomes, use of health services, medication adherence, patient-related health behaviors/risk behaviors, behaviors of healthcare providers related to care delivery, and health care costs. Multimorbidity interventions showed some promise in improving depression outcomes when depression was one of the co-occurring morbidities.

Additionally, interventions focused on functional status led to modest improvements in functional outcomes among those with MCCs. Finally, given that most chronic conditions share many risk factors and pathways, interventions for MCCs should focus on common risk factors, many of which are behavioral. However, few intervention studies have focused on the recent advances from geroscience and combined with an approach to addressing these risk factors.

This concept, a collaboration with the NIH Office of Disease Prevention, is intended to address two key gaps in measurement of MCC and related factors along with development of interventions to prevent, delay, or manage the progression of, co-occurring MCCs and their consequences. First, interventions focused on co-occurring MCCs and MCCs in vulnerable populations may be best targeted to risk factors that are common to multiple conditions (e.g. mental health, functional abilities and possibly others). The paucity of studies is primarily focused on treatment and indicate a need for more research related to interventions designed to prevent, delay or manage the progression of co-occurring MCCs in the population. Second, many of the MCC-related intervention studies and published research are focused on older adults, a period in life when co-occurring MCCs are most prevalent.

However, little research has focused on prevention of MCCs or on addressing risk factors for MCCs at different stages across the lifespan. Many groups called for interventions that incorporate partnership models involving collaborations between communities and health care systems, particularly within primary care. Populations that experience MCCs are diverse by race, ethnicity, socioeconomic status and other social determinants. Interventions developed to address risk factors for, or delay, the progression of co-occurring MCCs may be more effective in reaching the most at-risk populations through such partnership approaches.

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.

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