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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 2022 Council

Approved concepts in this round:

Alzheimer’s Disease Research Centers (ADRCs) Program Renewal

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

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

Scientific/Research Contacts

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

Cerise Elliott, Ph.D.

Division of Neuroscience
Email Cerise Elliott

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

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

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

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

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

Scientific/Research Contact

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

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

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

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

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

Scientific/Research Contact

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

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Interorgan Communication in Aging

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

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

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

Scientific/Research Contacts

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

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

Miroslaw Mackiewicz
Division of Neuroscience
Email Miroslaw Mackiewicz

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Interventions Testing Program

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

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

Scientific/Research Contact

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

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Interventions Testing Program Data Coordinating Center

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

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

Scientific/Research Contact

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

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Longevity Consortium Renewal

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

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

Scientific/Research Contacts

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

Nalini Raghavachari
Division of Geriatrics and Clinical Gerontology
Email Nalini Raghavachari

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

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

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

Scientific/Research Contacts

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

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

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

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

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

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

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

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

The concept has four overarching goals:

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

Scientific/Research Contacts

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

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NIA Postbaccalaureate Research Education Program

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

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

Scientific/Research Contact

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

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NIA Summer Research Educational Experience Program

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

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

Scientific/Research Contact

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

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Nursing Home EXplanatory Clinical Trials Network (NEXT)

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

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

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

Research/Scientific Contact

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

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

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

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

Scientific/Research Contacts

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

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

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

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

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

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

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

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

Scientific/Research Contacts

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

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

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

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

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

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

Scientific/Research Contacts

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

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

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

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Roybal Centers for Translational Research in Aging

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

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

Scientific/Research Contact

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

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Team Science Approaches Integrating Experimental and Computational Brain Aging Models

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

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

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

Scientific/Research Contact

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

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

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

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

Scientific/Research Contacts

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

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

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

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May 2022 Council

Approved concepts in this round:

Approved research and development contracts in this round:

Reissue of the Funding Opportunity Announcement: Integrative Research to Understand the Impact of Sex Differences on the Molecular Determinants of AD Risk and Responsiveness to Treatment

Alzheimer’s disease (AD) is a highly heterogeneous, multifactorial disorder. Approximately two-thirds of AD patients are women, and the biological basis of the sex-based differences in AD onset and progression remains elusive. A large body of evidence from clinical and laboratory research has demonstrated that sex differences are a major source of disease heterogeneity for many diseases including neuropsychiatric and neurodegenerative disorders such as Alzheimer’s and Parkinson’s.

In recent years, large-scale systems biology approaches have enabled a better understanding of molecular mechanisms of AD stratified by sex. Sex-specific pathways and genetic interactions have been identified to contribute AD susceptibilities. However, the heterogeneity of Alzheimer’s and responsiveness to interventions remain underexplored at the mechanistic level. There remains a significant need for NIA to continue the support of this research area, to inform and drive the development of future precision medicine treatment/prevention for AD and related dementia (ADRD).

Given that fundamental issues regarding sex-specific phenotypes relevant to the heterogeneity of Alzheimer’s and responsiveness to pharmacological and non-pharmacological interventions remain underexplored at the molecular/mechanistic level, it is important to re-issue this funding initiative and continue the development of a robust cross-disciplinary research program.

This FOA will invite applications that employ integrative experimental and analytical approaches combining basic, translational, and clinical research aimed at developing a comprehensive understanding of the impact of sex differences on the trajectories of brain aging, phenotypes of AD and AD-related dementias (ADRD) risk, and responsiveness to pharmacologic and non-pharmacologic interventions. Of particular interest will be understanding the impact of sex-differences on the heterogeneity of brain aging, AD/ADRD across diverse populations, and the use of biosamples and data from AD/ADRD clinical trials to understand the impact of sex differences on the responsiveness to pharmacologic and non-pharmacologic interventions and to examine the molecular basis of this effect.

Scientific/Research Contacts

Jean Yuan, M.D., Ph.D.
Division of Neuroscience
Email Jean Yuan

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

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Geroscience Course

The field of Geroscience aims to slow the progression of age-related diseases and disabilities by learning how aging enables diseases and causes the accumulation of functional and clinical deficits. Geroscience includes a more holistic interpretation of older adult health that includes the behavioral, social, structural, and environmental influences on aging processes over the life course that shape health and disease trajectories and predict longevity.

The cross-disciplinary NIH Geroscience Interest Group (GSIG), held a summit in 2019 that highlighted the need to increase awareness of this area of research among stakeholders, introduce researchers to the field, create developmental materials and courses, and expand the expertise of the Geroscience workforce. To accomplish these goals, the GSIG proposes an FOA to support creative, short-term educational programs with a primary focus on courses that enhance and expand Geroscience skills and development at all levels of professional career development. Programs that increase diversity within the field and programs designed to educate the lay public across diverse communities would be encouraged. Furthermore, all programs supported through the proposed FOA would be expected to address how the approaches of Geroscience can inform our understanding of health disparities in aging.

The GSIG identified the following priority areas for the FOA:

  • Exposure to research in the Geroscience field, including coursework describing the interrelationships of the hallmarks of aging, chronic disease states associated with aging, behavioral and social determinants of health, health disparities, and interventions that extend lifespan and health span. This may include basic research on the biology of aging, as well as clinical and translational aspects of Geroscience.
  • Materials or approaches that improve the curation and dissemination of important Geroscience reviews, opinion pieces, and information about clinical trials in progress.
  • Opportunities for hands-on research experiences and networking with experts in the Geroscience field.
  • Activities and materials that promote awareness of Geroscience within the lay community.

Scientific/Research Contacts

Stacy Carrington-Lawrence, Ph.D.
Division of Aging Biology
Email Stacy Carrington-Lawernce

Siobhan Addie, Ph.D.
Division of Aging Biology
Email Siobhan Addie

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Estimating the Monetary Costs of Dementia in the United States Using NIA Funded Datasets

Dementia diagnosis is expected to triple in the next 30 years. As such, significant concerns exist over the cost of providing care and treatment for people living with Alzheimer’s disease and related dementias (ADRD). The United States currently lacks recent cost of illness estimates that are based on administrative, clinical, and survey data and whose basis for calculation are known to the scientific community. A transparent, fact-based estimate would support patients and their families as they understand and navigate the costs of dementia care; allow private entities to appropriately value the return on investment for care or cure innovations; and guide government decision-making around federal programs as well as long term cost projections given a variety of policy, care, and treatment innovation scenarios.

To meet these goals, this concept proposes a cooperative agreement to support the development and administration of a shared data source and lead the stakeholder engagement, total cost of illness modeling, and dissemination activities. The cooperative agreement will include support for administering the project, convening stakeholder and expert engagement committees, creating the project dataset based on linked datasets in the NIA enclave, modeling cost of illness, archiving the project dataset in the secure cloud computing environment, and publishing research findings. The project will also support pilots to examine the cost impacts of (1) specific, discrete advances (both pharmacological and non-pharmacological) in AD/ADRD treatment and prevention, and (2) simulations to model care and policy changes influencing access to, quality of, and uptake of AD/ADRD prevention and treatment. The selection of pilots will be influenced by the committee of third-party experts/stakeholders in conjunction with the Principal Investigator and NIA. The simulation studies will support and expand the representation of early-career researchers from the behavioral, social, economic, and data sciences who utilize the project dataset to engage in modeling and/or simulation research on AD/ADRD.

Scientific/Research Contact

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

 

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MEX-AD: MEX-AD: Clinical, Epidemiological, and Genetic Characterization of Alzheimer’s Patients in the Admixed Mexican Population

Having diverse participants can help researchers understand how dementia affects certain groups, why some communities are disproportionately affected by certain dementias, and which interventions may be most effective in particular groups. Hispanic people over the age of 65 in the United States account for the second largest population affected by Alzheimer’s disease and related dementias (AD/ADRD) with a prevalence rate of 12.2%. However, there are relatively few clinical, genetic, and biomarker studies focused on these populations.

The Center for Alzheimer’s Disease and Related Dementias (CARD) has a collaboration with University of California-San Francisco to expand ancestral diversification in AD/ADRD research. The goal for this proposed project is to establish a multi-cohort study in Mexico to characterize clinical, genetic, and phenotypic diversity in the Mexican population. The proposed project aims to build collaborative research efforts and engage local investigators to:

  • Address a critical gap in knowledge of how AD/ADRD develops and progresses in the admixed Mexican population across a network of 10 clinical sites across Mexico.
  • Provide a unique profile of risk factors, onset, and symptomology, which can be at least partly explained by genetic ancestry, and social, cultural, psychosocial, and environmental characteristics.

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

Contracting Officer

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

Scientific/Research Contacts

Andrew Singleton, Ph.D.
Center for Alzheimer’s and Related Dementias (CARD)
Email Andrew Singleton

Mike Nalls, Ph.D.
Center for Alzheimer’s and Related Dementias (CARD)
Email Mike Nalls

Caroline Pantazis, Ph.D.
Center for Alzheimer’s and Related Dementias (CARD)
Email Caroline Pantazis

 

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Development and Maintenance of a Multigenotypic Aged Rat Colony

Basic biomedical research is supported by the National Institute on Aging through several programs which require animals as models of the aging process. Aged animals are not routinely available commercially, and most academic laboratories do not have the funds or facilities to raise aged animals. Consequently, NIA has established contracts for the supply of genetically defined, barrier-reared aged mice and rats for aging research.

This proposal is for a renewal of the contract for a long-term colony of aged rats. This resource is available to investigators funded for research relevant to aging by NIH, other government agencies, and not for profit organizations. The current colony consists of the following strains of rats, all ad lib-fed and group-housed: F344-CDF (Charles River Derived Fisher 344), BN/Crl (Brown Norway/Crl) and F344BN F1 (F344-CDF x BN/Crl). During the proposed contract, new stock of all strains will be rederived by the contractor from stocks that have been previously cryopreserved by the NIA, and breeding will commence to develop a new aged colony.

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

Contracting Officer

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

Scientific/Research Contact

Jennifer Fox, Ph.D.
Division of Aging Biology
Email Jennifer Fox

 

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Management of the Primate Aging Database

The Primate Aging Database (PAD) is a resource for investigators in the field of aging research, designed to facilitate the use of non-human primates (NHPs) as models of aging. The PAD collects data on normal aging in a wide range of NHPs. Sixty-seven metrics have been collected from healthy NHPs across their lifespan from 17 primate colonies across the United States as well as Puerto Rico and Germany. The PAD currently has approximately 1.2 million data points and the data can be used by the research community to identify changes in biological parameters with age, to validate NHP models for aspects of human aging, and to perform comparative analysis.

The proposed contract will maintain the PAD in the cloud, implement subject deidentification, solicit and add new data from NHP colonies/centers, enhance operability, update the user roster, provide technical assistance to users, and conduct outreach. Opportunities for enhancing the resource will be explored with the proposed contract renewal, including:

  • Increasing efforts to encourage data deposition from novel sources
  • Extracting data from the published literature and interfacing with existing data repositories
  • Expanding data fields to include imaging, -omics, immunological, and microbiome data collected by NHP researchers
  • Expanding analytical capabilities of the PAD
  • Improving the visibility of the PAD through outreach at scientific meetings
  • Initiating coordination between the NHP-Tissue Bank and the PAD

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

Contracting Officer

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

Scientific/Research Contact

Jennifer Fox, Ph.D.
Division of Aging Biology
Email Jennifer Fox

 

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Development and Maintenance of a Non-Human Primate Tissue Bank

Biomedical research is supported by NIA through several programs that require studying aging in animal models. Non-human primates (NHPs) are important models for investigating the biology of aging, including the effects of environmental and social determinants. They also have the potential to provide data more directly translatable to human biology and aging.

The NHP Tissue Bank (NHP-TB) is a centralized bank of NHP tissue and serum for studies in aging research. The NHP-TB was initiated in 2003 and has been maintained through a contract. Its goals are to maximize the use of already available NHP biospecimens and provide a mechanism for multiple investigators to share tissue. The proposed contract will maintain and manage a collection of tissues and blood derivatives. Furthermore, it will expand the reach of the NHP-TB, improve coordination with NHP-holding  institutions and other tissue banks, increase the number of species and ages, and establish a registry of donors for efficient tissue collection.

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

Contracting Officer

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

Scientific/Research Contact

Tiziana Cogliati, Ph.D.
Division of Aging Biology
Email Tiziana Cogliati

 

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Small Business Innovation Research (SBIR) Topics

This proposal will add three NIA topics to the NIH Parent SBIR contract solicitation PHS-2022. Use of the contract mechanism allows solicitation of topics that stimulate innovation and address unmet scientific priorities that are ripe for innovation while providing NIA with the ability to specify expected deliverables.

AI/ML Tool for Visualizing Behavioral and Social Science Research

Behavioral and social science research (BSR) can be conceptualized as a network of variables (characteristics of an individual, group, or environment) and the causal relationships between them. Currently, no tool exists that allows researchers to quickly derive a causal overview of BSR-specific literature. Developing an AI-based tool, specific to BSR, that can extract, aggregate, and visually map variables and causal relationships will allow researchers to explore the literature more in-depth and potentially uncover promising new associations between variables.

High Throughput Clonal Hematopoiesis of Indeterminate Potential (CHIP) Assay for Risk Stratification, Diagnosis, and Prognosis of Age-related Diseases

Many researchers are interested in understanding the role of clonal hematopoiesis and how it may affect health and age-related conditions and diseases. However, a low cost, scalable assay for analyses of clonal hematopoiesis does not exist. To help address this gap, this proposal aims to develop an inexpensive, high throughput assay to detect CHIP mutations for research purposes, which could eventually be translated into a diagnostic/prognostic assay for use in healthcare settings.

Improving Microphysiological Systems for AD/ADRD Therapy Development

There is a need for the development of more predictive, high-throughput in vitro microphysiological systems (MPS) as simple, reproducible, and scalable platforms that recapitulate organ-level functions to be used in different stages of AD/ADRD drug development. The proposed project aims to produce a system that is validated against known AD/ADRD therapeutic agents and align with human “omic” data from the Accelerating Medicines Partnership® Program for Alzheimer’s Disease to demonstrate the system's utility as a predictive tool and screening assay.

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

Contracting Officer

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

Scientific/Research Contact

Jennifer Fox, PhD
Division of Aging Biology
Email Jennifer Fox

 

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January 2022 Council

Approved concepts in this round:

Broadening the Scope and Reach of NIA’s Resource Centers for Minority Aging Research (RCMAR) Program

Structural factors present barriers to full representation of individuals from diverse backgrounds in the NIA-supported scientific community, and especially in the behavioral and social sciences. Holistic approaches are needed more than ever to attract, develop, and retain a diverse population of aging researchers in the behavioral and social sciences and to cultivate future research leaders.

Now in its fifth cycle, NIA’s Resource Centers for Minority Aging Research (RCMAR) program is the Division of Behavioral and Social Research’s flagship mentoring program for scientists from historically under-represented groups who conduct behavioral and social research focused on aging, health disparities of older adults, and Alzheimer’s disease and related dementias (AD/ADRD). The recent growth of the RCMAR program, which more than doubled in size during the last funding cycle, affirms NIA’s longstanding commitment to promoting equity and inclusion in the aging research workforce. New strategies and infrastructure are needed to support this expansion and to foster the inclusion of researchers at Historically Black Colleges and Universities, Hispanic-Serving Institutions, Tribal Colleges and Universities, and other Minority-Serving Institutions.

To meet these goals, this concept aims to support new or renewal applications proposing: RCMARs that focus on behavioral and social science research, in a key area either related to aging, health disparities in older adults or both, and AD/ADRD RCMARs that focus on behavioral and social science research related to Alzheimer’s disease and related dementias. This concept also aims to support a single RCMAR Coordinating Center (CC), which through a cooperative agreement with NIA, will provide leadership for the RCMAR program.

RCMAR and AD/ADRD RCMAR Centers: NIA will solicit applications that retain the overarching two-fold goal and the basic structure of existing RCMAR (RFA-AG-18-003) and AD/ADRD RCMAR (RFA-AG-18-002) Centers, by including an Administrative Core, Research Education Component, Analysis Core, and an optional Community Liaison and Recruitment Core. All applications will be required to propose scientist-centered training and mentorship activities that serve to: 1) facilitate the development and enhancement of research skills, through the development and completion of a 12-18 month pilot research project; 2) strengthen team science and network collaborations; 3) enhance professional development skills; and 4) broaden the Center’s reach and impact through collaborative leadership with researchers at Historically Black Colleges and Universities, Hispanic-Serving Institutions, Tribal Colleges and Universities, and other Minority-Serving Institutions. Proposed activities will prepare RCMAR scientists to: 1) publish in high impact journals, 2) successfully compete for NIH’s small (R03, R21), large (R01) research grants, NIH Research Enhancement Awards (R15), or Career Development awards, in their dedicated research area, 3) contribute to the training of future scientists, and/or 4) address health disparities in clinical settings or via policy channels.

RCMAR CC: Responsibilities of the selected CC include: facilitation and coordination of communication among the RCMAR Centers; provision of logistical support to the RCMAR sites and to NIA; development and maintenance of a RCMAR CC website, which can serve as a repository of information and resources for the RCMAR program, extramural community, and public; development and dissemination of research resources and resources to address the professional development needs of minority faculty, including best practices for mentoring diverse faculty members and overcoming challenges in team science; organization of an annual meeting and symposia at scientific conferences; development or enhancement of infrastructure to track career development of RCMAR scientists; and formal evaluation of the RCMAR program.

Scientific/Research Contact

Melissa Gerald, Ph.D.
Division of Behavioral and Social Research
E-mail Melissa Gerald

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Demonstration Projects to Promote Use of Interoperable Health Records in Clinical Research

Electronic health records accumulate over time as people interact with health providers. For older adults, electronic health records often become fragmented, especially if they have seen multiple providers, relocated, or changed health plans. In research studies that focus on older adults with acute or chronic illness, study teams rely on information contained in health records immediately available to them, combined with self-report information to retrospectively construct patients’ medical histories. There often is little advanced notice prior to study enrollment, and limited opportunity for investigators to engage with patients to collect a medical history. Interoperable electronic health records collected from providers across health networks and geographic regions would permit study teams to gather a more comprehensive health history, allowing for better eligibility screening and more complete multifactorial analysis of research results. The 21st Century Cures Act Interoperability and Patient Access final rule (CMS-9115-F) created requirements for the healthcare industry to adopt standardized, interoperable, and secure downloadable, structured electronic health information at no cost. This new requirement will facilitate improvements in investigators’ ability to obtain historical medical information to be used as research data.

This concept is designed to provide evidence about the feasibility of utilizing the interoperability requirement to collect older research participants’ electronic health records. The projects are expected to exploit informatic approaches like natural language processing to summarize the content of the medical records to confirm eligibility for enrollment; acquire accurate, detailed information on comorbidities, and develop and evaluate informatic approaches to identify specific types of comorbidities relevant to the partner research study. The proposed FOA will support three-year demonstration projects to collect and analyze medical records from older adult research participants using downloaded health information. The applicants will partner with one or more newly funded or ongoing research studies that are enrolling new participants or reconsenting participants in established cohorts for follow-up visits. The projects will create a digital infrastructure to collect electronic health records donated by participants, and develop approaches to harmonize the data across patients and providers, and to develop informatic approaches to analyze the medical records.

Research/Scientific Contacts

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

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

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Measures and Methods for Research on Family Caregivers for People Living with AD/ADRD

Family members — especially spouses and children — are the major source of unpaid care for older individuals living with Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias (AD/ADRD). Changes in family structure and composition over the past several decades may have altered the role families play in caring for people living with AD/ADRD. Existing surveys and current measures and methods are limited in their ability to assess the diverse and often complex compositions of today’s families. In order to study the influence of demographic compositional changes in families and support the development of interventions and policies to support family caregivers of older adults living with AD/ADRD, it is critical to identify such family caregivers and what their needs are. Further, current studies may not capture differences in the criteria different groups (e.g., sexual and gender minority (SGM), minoritized, and immigrant individuals) use to define “family” (e.g., biological and/or legal ties, emotional closeness) and even what activities individuals consider to be caregiving. In addition, little is known about family members’ expectations and senses of obligation regarding caregiving — and what factors (including barriers and facilitators) predict whether these translate into actual caregiving given and received. These gaps in knowledge leave open unanswered questions about how to best support family caregivers and people living with AD/ADRD with (and without) such family caregivers.

This initiative addresses the pressing need for the development of measures and methods to assess who individuals consider family and what AD/ADRD caregiving tasks are expected or provided by family. Several large NIA-supported longitudinal studies (e.g., Health and Retirement Study (HRS), National Health and Aging Trends Study (NHATS), National Survey of Caregiving (NSOC), Panel Study of Income Dynamics (PSID), Add Health Parents Study) will be going back into the field and/or enrolling refresher cohorts in the next few years, presenting a potential opportunity to leverage existing data infrastructure. In addition, measures are needed to capture the experience of family caregiving in populations who are not currently well-represented in existing studies (e.g., SGM populations, immigrant groups, etc.) as efforts to enhance research in these populations grow.

Scientific/Research Contacts:

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

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

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

Melissa Gerald, Ph.D.
Division of Behavioral and Social Research
E-mail Melissa Gerald

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More Mobile Monitoring of Cognitive Change, Continued (M3C3)

The pathological processes related to Alzheimer’s disease and related dementias (AD/ADRD) may begin in midlife or earlier, sparking researcher interest in the measurement of even subtle neuropsychological changes in midlife. This proposed opportunity will extend work previously funded under RFA-AG-18-012 “Mobile Monitoring of Cognitive Change (U2C)," by addressing the need to add assessments of non-cognitive factors that may modify cognitive performance and enable widespread dissemination and support for use of the tools developed. This concept will extend previously funded work in the Mobile Toolbox Project, which involves two closely collaborating cooperative agreements designed to expand the range of contexts and frequency for cognitive assessment, resulting in more accurate estimates of cognitive variability and vulnerability. These tools include ultra-brief cognitive tests suitable for ecological momentary assessment and burst measurement designs that, over an extended period, allow the detection of very subtle cognitive changes as well as mobile app versions that can serve as replacements for traditional neuropsychological tests.

With an even greater interest in remote assessment due to the disruption caused the COVID pandemic, the opportunity will shift to the wide dissemination of the apps and infrastructure that have been developed to date in the collaborative Mobile Toolbox Projects. In addition, the existing infrastructure can be leveraged to support measurement of non-cognitive variables such as daily hassles, caregiving stressors, health challenges, health behaviors, and health systems interactions. There is also an opportunity to include real-time measures of affective, motivational, and social states and function and to develop linkages to the physiological data obtainable through passive sensors on mobile devices or attachable biosensors. Because the current projects build on well-documented app platforms, others will be able to develop and deploy instruments for their own studies and for use by others. This proposed single cooperative agreement will support the continued development of the platform with expanded content including non-cognitive measures and behavioral assessments, wider dissemination, and the ability for users to add study-specific measures.

Scientific/Research Contact

Dana Plude, Ph.D.
Division Behavioral and Social Research
Email Dana Plude

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NIA AD/ADRD SBIR/STTR Reissue: Advancing Research on AD/ADRD

The proposed initiative is a reissue of PAS-19-316 and PAS-19-317, Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R43/44 and R41/R42 respectively; Clinical Trial Optional), which expires in September 2022. It supports applications through NIA's Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs to encourage research on and the commercialization of novel therapies, devices, products, and healthcare programs and practices to prevent the onset of AD/ADRD and to reduce their burden on individuals, their families, and society at large. Research areas supported through these initiatives include AD/ADRD prevention, diagnosis, treatment, care, and tools.

Scientific/Research Contacts

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

Todd Haim, Ph.D.
Division of Extramural Activities
Email Todd Haim

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Neuronal Vulnerability to Proteinopathies in Alzheimer’s Disease and Alzheimer’s Disease Related Dementias

Alzheimer’s disease (AD) and Alzheimer’s disease related dementias (ADRD) impact specific brain areas, worsening with time and impacting more regions in a predictable fashion. However, it is unclear why the disease selectively affects certain regions of the brain e.g., the entorhinal cortex, hippocampus, and prefrontal cortex while other areas, such as the cerebellum, remain unaffected. Selective vulnerability refers to observations that subpopulations of neurons in different brain areas may be susceptible to specific pathological insults leading to cell dysfunction or death. Recent studies have shown that AD-related tauopathy begins in the locus coeruleus (LC), followed by neurofibrillary tangles in the entorhinal cortex, then hippocampal neurons, and then neocortical neurons. It is not yet understood why pathology appears where and when it does in the disease process. Current single-cell transcriptomics, epigenomics, and spatial transcriptomics technologies allow characterization of cell types at the molecular level at an unparalleled scale and resolution. This opens new research areas to define neuronal and/or glial cells’ vulnerability to AD/ADRD proteinopathies based on their molecular identity and allows for further development of mouse models that reproduce features of the pathology, and the identification of intrinsic properties of neurons vulnerable to AD/ADRD proteinopathies and provides information on vulnerable circuits and propagation paths. Understanding mechanisms underlying selective vulnerability from cells to networks in AD/ADRD is critical to define the disease process and develop effective therapies.

The goal of this concept is to define and characterize neuronal and glial cell populations that are vulnerable to AD/ADRD proteinopathies. Specifically, a subsequent FOA would solicit applications to: 1) establish a comprehensive set of data on neuronal and glial cells vulnerable to AD/ADRD proteinopathies based on single-cell transcriptomic or epigenetic signature; 2) identify intrinsic morphological, electrophysiological, and biochemical properties of neurons vulnerable to proteinopathies; and 3) identify neural circuits and/or large-scale networks that contribute to vulnerability to proteinopathies. To standardize sequencing, cell clustering and mapping methods, minimize variability, and maximize resource sharing, it will encourage a collaboration with investigators currently funded by the BRAIN Initiative. The proposed FOA will require that all data be placed in a comprehensive, common reference mouse brain atlas. It will leverage already existing technologies and tools such as single cell transcriptomics and epigenomics, novel models of AD/ADRD being developed by the MODEL-AD Consortium, and high resolution optogenetic fMRI or tissue clearing technologies that allow deep imaging of brain proteinopathies in 3D. This initiative will complement current NIA efforts aimed at a census of cells and circuits in the aging brain, the cellular scale connectome, and/or selective cell and network vulnerability in aging and Alzheimer’s disease.

Scientific/Research Contacts

Miroslaw “Mack” Mackiewicz, Ph.D.
Division of Neuroscience
Email Mack Mackiewicz

Brad Wise, Ph.D.
Division of Neuroscience
Email Brad Wise

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Optimization and Personalization of Diagnostic Tests for AD/ADRD in Older Adults with Multiple Chronic Conditions (MCCs)

The focus of this initiative is on the complex older patient who has MCCs and is being evaluated diagnostically for cognitive impairment or dementia. Persons newly diagnosed with AD/ADRD typically have other chronic conditions or geriatric syndromes (e.g., frailty) that can confound interpretation of traditional disease assessments. The ranges of “normal” for biomarkers and imaging metrics are often broader in older populations (where prevalence of MCCs reaches >85%) such that they overlap with abnormal values in younger persons, further reducing specificity. MCCs are also clinically significant in course, severity, and therapy with multiple medications, or polypharmacy. AD/ADRD studies of diagnosis and therapeutics have not adequately addressed differences by age and sex and have frequently excluded persons with a variety of comorbidities. Diagnostic testing is crucial for detecting new health conditions and selecting their treatments, yet test performance and clinical utility can shift with aging-related biological changes and in the context of MCCs. Biomarker- and imaging-based testing has become a major part of chronic disease management, including for AD/ADRD. The diagnostic criteria for several causes of dementia have been updated in recent years and are not yet well-adapted for clinical application. The accurate integrated assessment of MCC severity, risk factors, biomarkers, frailty, and cognition is necessary for a personalized medicine approach to AD/ADRD.

The proposed consortium will conduct transdisciplinary aging diagnostic biomarker and imaging research projects focused on AD/ADRD and MCCs to better align diagnostic testing with the needs and priorities of an aging population. It would also develop resources, assemble and analyze existing/available data and biobank resources, support pilot studies, conduct collaborative research, and integrate expertise. The consortium will:

  1. Assemble existing data and acquire real-world data to ensure large diverse sample with adequate representation of older adults with well-characterized MCCs and incorporate pre-specified subgroup analyses
  2. Analyze data for performance and accuracy of biomarkers (including blood, CSF, and imaging) in real-world older patients with MCCs
  3. Develop tools and methods to integrate MCCs and biomarkers into AD/ADRD care pathways.

Scientific/Research Contact

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

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Policy and AD/ADRD Healthcare Disparities: Access, Utilization, and Quality

This concept will support research that capitalizes on policy variations to address critical gaps in our knowledge of the processes that drive inequalities in health care access, utilization, and quality for people living with AD/ADRD in the community, assisted living facilities, and nursing homes. Policy can be defined to include “law, regulation, procedure, administrative action, incentive, or voluntary practice of governments and other institutions” (CDC Office of the Associate Director for Policy and Strategy). These can broadly include official national or federal laws and regulations as well as state, local, or institutional/facility-level policies and procedures. Creative methodological approaches that capitalize on policy variation (across time, place, etc.) are encouraged and might include quasi-experimental designs and natural experiments, propensity score matching, predictive modeling, geospatial modeling, qualitative inquiry, and innovative use of data linkage and big data (e.g., Centers for Medicare & Medicaid Services or commercial health services data). Investigators should propose a wide range of potential health and health care outcomes that will capture and explicate social disparities in access, use, and quality. Observational studies must go beyond describing disparities in AD/ADRD health care access, use, and quality to understand their underlying causes and mechanisms. Examples of relevant policy topics include but are not limited to CMS telehealth policy changes before and during the COVID-19 pandemic, state-level changes to LTSS coverage and practice (e.g., Oregon, Massachusetts, Wisconsin), changes to visitation policies in nursing homes and assisted living facilities.

Scientific/Research Contacts

Elena Fazio, Ph.D.
Division of Behavioral and Social Research
Email Elena Fazio

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

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

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Precision Medicine Approaches in Addressing AD/ADRD Minority Health and Disparities

Recent studies have revealed differences in neurobiological and neuropathological features and biomarkers associated with AD/ADRD among race and ethnic minorities, while others have noted no differences. Additional studies have noted differences in AD/ADRD risk among APOEe4 carriers of different ancestral backgrounds (e.g., elevated risk among Japanese compared to African-descent populations). African Americans and Latino populations experience higher prevalence of co-morbidities that are associated with vascular contributions to cognitive impairment and dementia. Similarly, there are behavioral and social risk factors for AD/ADRD that appear to operate differently or require additional characterization in minoritized populations. For example, although low educational attainment remains a risk factor for AD/ADRD in African Americans, differences in educational quality (while difficult to capture in existing measures) have been shown to moderate this relationship. There is also evidence that some neighborhood characteristics (including opportunities for social engagement and population composition) may be protective against dementia in minoritized populations, but these have not yet been well measured.

While some progress has been made in increasing our knowledge of the heterogeneity of AD/ADRD among minoritized populations, some populations remain severely under-represented in AD/ADRD research and very little is known about AD/ADRD within most of these populations. Additional research that captures neurobiological and neuropathological processes along with the environmental, sociocultural, behavioral, and demographic factors that often intersect with race and ethnicity within these populations is needed. In addition, low AD/ADRD incidence and prevalence among some minoritized populations can offer insights into protective or resilience factors associated with these diseases and may inform prevention or intervention strategies. Longitudinal studies that document and monitor trends in AD/ADRD prevalence and include both AD/ADRD neural biomarker(s) and rich behavioral or social assessment(s) are best positioned to inform our understanding of causal pathways driving AD/ADRD health disparities or prevalence. This initiative aims to:

  1. Support planning activities for the development or scale up of research infrastructure and resources to support studies of AD/ADRD in minoritized populations.
  2. Support pilot projects that utilize a multi-level, precision medicine approach and informs the scale up of future research.
  3. Support transformative multi-disciplinary teams to address AD/ADRD disparities, burden or resilience among minoritized populations.

Scientific/Research Contacts

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

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

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Understanding the Supply of Professional Dementia Care Providers and Their Decisions

Global diagnosis of Alzheimer’s disease and related dementias is expected to triple in the next 30 years. There is a pressing need to understand how dementia care is supplied by various professional providers, and the influence it can have on the health care system, and as well as its effects on Persons with Dementia (PWD) and their caregivers in United States. PWD receive care from an array of paid care providers that include neurologists, geriatricians, psychiatrists, nurses, occupational therapists, social workers, certified nursing assistants, and home health aides. Across these care providers, training requirements and compensation vary, and there are different market conditions by region and payment models for services provided. Together, these factors shape the composition of the dementia care workforce size, expertise, tenure, and roles as well as care quality and access for PWD.

This concept will call for an internet survey of healthcare providers to understand how PWD are cared for by a wide range of professional providers, provide explanations for variation in the mix of providers providing care across regions, and elucidate how professional care team interactions influence care provision by the healthcare workforce on PWD. Specifically, it will produce a nationally representative sample of care providers that will include targeted oversamples to facilitate research on types of providers (e.g., neurologists, geriatricians, providers from underrepresented groups, etc.) and health systems that primarily care for underserved populations, including minoritized and rural populations. Projects will include linkages to administrative records (e.g., health care claims, Electronic Health Records, and payroll data) to connect participant responses regarding practice to data on health system actions and outcomes. The resultant data will enable the research community to explore the composition, qualities, and actions of this workforce to ensure challenges such as barriers to entry, retention, and the impact of an aging physician workforce can be addressed to support better care for the growing population of PWD.

Scientific/Research Contact

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

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