FY 2016 Program Descriptions and Accomplishments
Understanding, Treating, and Preventing, Cognitive Decline and Alzheimer’s Disease (AD)
NIA’s Neuroscience Program supports a broad spectrum of research and training aimed at better understanding age-related normal and pathological changes in the structure and function of the aging nervous system and how such changes affect behavior. The program’s basic mission is to expand knowledge on the aging nervous system to allow improvement in the quality of life of older people. Ongoing activities include basic and clinical studies of normal brain aging as well as AD and other neurodegenerative diseases of aging. These include molecular and cellular studies, animal models, genetics, drug discovery and development, diagnosis, clinical course, clinical trials for treatment and prevention of AD and other neurodegenerative diseases as well as for maintaining or improving cognitive health, sensory and motor function, and epidemiological studies to identify risk factors and establish prevalence and incidence estimates. NIA also supports a national network of Alzheimer’s Disease Centers to translate research advances into improved diagnosis and care of AD patients, as well as implementing a broad array of studies aimed at improving our understanding of this disease. The Institute coordinated the first NIH Alzheimer’s Disease Research Summit in 2012. The second NIH-hosted Summit is planned for February 2015 to evaluate and build on these priorities, milestones, and timelines. Recommendations from this Summit will inform activities in FY 2016.
As the lead federal agency for research on AD, NIA leads implementation of research goals of the National Plan to Address Alzheimer’s Disease. Recent initiatives have boosted support for AD research, including an additional $100 million in FY 2014 and $25 million in FY 2015 for the disease. The International Alzheimer’s Disease Research Portfolio (IADRP), a publicly available database to capture the full spectrum of current AD research investments and resources throughout the world, will facilitate coordination of these efforts. The estimated total NIH-wide support for Alzheimer’s disease will be $638 million in FY 2016.
Recently, NIA awarded several major new grants supporting translational and clinical research aimed at the disease. These are among the first projects to be developed with direction from the 2012 AD Research Summit, and focus on identifying, characterizing and validating novel therapeutic targets and identifying possible ways to stop disease progression. All the clinical studies will be in very early stages of the disease, when intervention may be most effective. Researchers will:
- Apply innovative analytical methods to large-scale molecular, cellular and clinical data to construct biological network models and gain new insights into the complex mechanisms of the disease
- Discover, characterize and validate complex molecular networks and candidate genes that influence susceptibility to cognitive decline and Alzheimer’s disease
- Elucidate the contributions of an abnormal form of the protein tau to brain shrinkage, cognitive impairment, and Alzheimer’s dementia
- Test anti-amyloid drugs in cognitively normal, at-risk volunteers
- Assess the safety, tolerability, and biomarker efficacy of two experimental drugs, gantenerumab and solanezumab, in people who are genetically at high risk for the disease
- Determine whether recombinant sargramostim, a drug that stimulates the innate immune system, clears abnormal deposits of amyloid before they cause damage, preventing cognitive decline or improving cognition
- Test new anti-amyloid-beta drugs in volunteers who have an inherited form of AD
All of these projects will be active during FY 2016.
The FY 2016 President’s Budget request is $598.712 million, an increase of $59.364 million, or 11.0 percent above the FY 2015 Enacted Level.
Theragnostic Trials for Alzheimer’s Disease
FY 2015 Enacted Level: $16.1 million1
FY 2016 Level: $15.2 million
Change: -$0.9 million
Through NIA-supported research over the past decade, investigators have gained the ability to identify and monitor unique biomarkers for Alzheimer’s disease in the living brain using neuroimaging and fluid biomarkers including cerebrospinal fluid. Together with the ground-breaking insight that the disease’s characteristic pathology may be present in the brain for years or even decades before clinical symptoms are evident, these advances have not only opened the door to preclinical detection of the disease, but have also facilitated the strategic use of biomarkers in clinical trials. Theragnostic trials – that is, studies in which investigators observe the effects of an intervention on biomarkers of the disease and link biomarker activity with the intervention’s effects on clinical symptoms – may be more rapid and less expensive than traditional clinical trials in Alzheimer’s disease using clinical and neuropsychological measures.
NIA, with an array of federal and private partners, will support three major theragnostic trials in 2016. The Dominantly Inherited Alzheimer’s Network Trials Unit (DIAN-TU) trial will assess the safety, tolerability, and biomarker efficacy of two experimental drugs, gantenerumab and solanezumab, in people who are genetically at high risk for the disease. The Alzheimer’s Prevention Initiative APOE4 trial will test two anti-amyloid drugs, an active vaccine and a beta-secretase inhibitor, in cognitively normal older volunteers who are at increased risk of developing late-onset Alzheimer’s. The Alzheimer’s Disease Cooperative Study Anti-Amyloid Treatment in Asymptomatic AD (A4) trial will assess the efficacy of solanezumab in clinically normal older people with neuroimaging biomarker evidence of brain amyloid. The NIH-supported Accelerating Medicines Partnership, a collaborative effort between NIH and several non-profit organizations and biopharmaceutical companies, will work to identify additional biomarkers for these trials. We anticipate that these trials will be complete between 2017 and 2020.
Biology of Aging Program:
Understanding Aging Processes, Health, and Longevity
Investigators supported by NIA’s Biology of Aging Program seek to improve our understanding of the basic biological mechanisms underlying the process of aging and age-related diseases. Basic biochemical, genetic, and physiological studies are carried out primarily in animal models, including both mammals and non-mammalian organisms (e.g., flies, worms, yeast). The program’s goal is to identify the biological basis for interventions in the process of aging, which is the major risk factor for many chronic diseases affecting Americans. The program also coordinates the NIH Geroscience Interest Group (GSIG), a collaborative effort that was established in 2012 to accelerate and coordinate efforts to promote discoveries on the common risks and mechanisms behind age-related diseases and conditions. Ongoing initiatives in this area that will remain active during FY 2016 include the Interventions Testing Program to identify compounds that extend median and/or maximal life span in a mouse model, along with a similar program to identify such compounds in the context of extensive genetic heterogeneity, using the worm model Caenorhabditis, as well as an initiative to develop and validate new models for aging research. Finally, the program coordinates the Nathan Shock Centers of Excellence in the Basic Biology of Aging. In 2013, the GSIG, with support from the Alliance for Aging Research and the Gerontological Society of America, hosted a major scientific conference entitled “Advances in Geroscience: Impacts on Healthspan and Chronic Disease,” and insights from this conference will continue to inform our research in this area.
The FY 2016 President’s Budget request is $173.291 million, an increase of $2.957 million, or 1.7 percent above the FY 2015 Enacted Level.
Behavioral and Social Research Program:
Understanding and Addressing the Behavioral, Emotional, and Social Dynamics of Aging
NIA’s Behavioral and Social Research Program supports research to increase our understanding of the processes of aging at the individual, institutional, and societal levels. Research areas include: 1) the behavioral, psychological, and social changes individuals experience over the adult lifespan; 2) participation of older people in the economy, families, and communities; 3) the development of interventions to improve the health, cognition, and well-being of older adults; and 4) the societal impact of population aging and associated changes in labor force participation and effects of economic circumstances on health. The program also supports: 1) development of publicly available, cross-nationally comparable datasets to facilitate research on the sources of international variations in health outcomes; 2) studies that integrate biology, including genetics, with social and behavioral science to elucidate the pathways by which social, psychological, economic, and behavioral factors affect health in middle age and late life; 3) longitudinal studies; 4) interventions to ameliorate the impact of disadvantage and reduce health disparities at older ages; 5) and interventions to maximize active life and health expectancy. The program coordinates the long-running Health and Retirement Study, the nation’s leading source of combined data on health and financial circumstances of Americans over age 50; the Centers on the Demography and Economics of Aging; the Roybal Centers for Translational Research on Aging; and the Resource Centers for Minority Aging Research (RCMARs).
Major program activities for FY 2016 will include an initiative to enhance comparability of dementia assessment measures in nationally representative longitudinal aging studies around the world to facilitate the examination of international trends over time and achieve national objectives regarding the measurement of dementia prevalence; an M.D.-Ph.D. institutional training program in aging and the social/behavioral sciences; and an initiative to provide infrastructure support for advancing development of specific emerging and high priority interdisciplinary areas of behavioral and social research of relevance to aging.
The FY 2016 President’s Budget request is $199.662 million, an increase of $3.407 million, or 1.7 percent above the FY 2015 Enacted Level.
Testing Interventions to Extend Life and Health
FY 2015 Enacted Level: $4.8 million
FY 2016 Level: $4.7 million
Change: -$0.1 million
Identification of safe, inexpensive, and non-invasive interventions that slow the aging process and promote healthy aging could have a significant impact on older Americans’ quality of life. NIA established the Interventions Testing Program (ITP) in 2003 to support testing of interventions, including pharmaceuticals, nutraceuticals, plant-derived molecules, drugs, and hormones with the potential to extend lifespan and delay disease and dysfunction in a mouse model of aging. To facilitate replicability of results, testing is simultaneously performed at three sites -- the University of Michigan, the Jackson Laboratories, and the University of Texas Health Sciences Center at San Antonio -- and the project is designed to promote collaboration with investigators at other organizations. A strength of the program is that all interventions are tested in both male and female animals, allowing investigators to identify and analyze sex differences in the interventions’ effects.
Since the program’s establishment, ITP investigators have tested over 20 compounds and combinations, and have identified several compounds that increase life- and health-span in mice. For example, they found that the drug rapamycin can increase lifespan in both male and female mice. This finding spurred additional research both within the ITP and from the broader research community, resulting in many publications that both confirm the original ITP findings and demonstrate that rapamycin has many positive, and a few negative, effects on health span in aged mice. They subsequently found that three other agents -- acarbose, a drug commonly used to treat type 2 diabetes; the hormone 17-α-estradiol; and the antioxidant nordihydroguaiaretic acid – increased the median lifespan of male mice, although no effect was seen in female mice. Further testing of these compounds is ongoing. NIA renewed funding for the ITP in 2014, and the program received additional funds to expand health-span measures.
In 2013, NIA established a similar program to identify pharmacological interventions that increase lifespan and/or health-span in multiple species of roundworms, including the simple invertebrate Caenorhabditis and/or multiple strains of C.elegans. Because human populations are genetically diverse, NIA is ultimately most interested in interventions that extend life/healthspan within a variety of genetic backgrounds. Testing compounds in a variety of genetic backgrounds within a species with a short, well-studied lifespan and health-span should increase the robustness of the findings. Standardization of technique and preliminary lifespan studies are nearly complete, and testing will begin soon on initial interventions.
Geriatrics and Clinical Gerontology Program:
Reducing Disease and Disability among Older People
As we age, our risk for many types of disease and/or disability increases dramatically. NIA’s Geriatrics and Clinical Gerontology Program supports research on health, disease, and disability in the aged (other than neurodegeneration, which is the focus of the NIA’s Neuroscience Program). Areas of focus include age-related physical changes and their relationship to health outcomes, the maintenance of health and the development of disease, and specific age-related risk factors for disease.
A current research focus, which will continue into FY 2016, is the study of how early life factors can influence health and disease as we age. The program coordinates the Claude D. Pepper Older Americans Independence Centers Program; the goal of which is to increase scientific knowledge leading to better ways to maintain or restore independence in older persons. In addition, the program plans and administers clinical trials for a number of age-related conditions; for example, program-supported investigators are collaborating with the Patient-Centered Outcomes Research Institute (PCORI) on a clinical trial to test individually-tailored interventions to prevent fall-related injuries.
The FY 2016 President’s Budget request is $125.919 million, an increase of $2.149 million, or 1.7 percent above the FY 2015 Enacted Level.
Intramural Research at NIA
Investigators with NIA’s Intramural Research Program (IRP) conduct research in the areas of basic, behavioral, clinical, epidemiologic and translational research. High priority research endeavors and areas of specific focus include: 1) Molecular and Cellular Biology, including caloric restriction, cell cycle control, signal transduction, DNA damage and repair, physiology, and medicinal chemistry; 2) Neuroscience, including neurodegenerative diseases, with particular emphasis on early diagnosis, drug design and development, and neuronal cell apoptosis; 3) Genetics and Genomics, particularly genetic and epigenetic determinants of aging as an integrated part of human development; 4) Behavioral Research, including personality, cognition, and psychophysiology; 5) Clinical and Translational Research in cardiology, immunology, neurology, and endocrinology; and 6) Epidemiology, including studies of frailty, cognition, body composition, disability, and molecular biomarkers of aging.
The clinical research effort focuses on the translation of basic research findings, prevention and therapeutic clinical trials focused on age-associated diseases, modulation of treatment efficacy and toxicity in older patients, and establishment of and maintenance of diverse longitudinal cohorts for aging research. Many studies focus on common age-related diseases such as Alzheimer’s disease, Parkinson’s disease, stroke, atherosclerosis, and diabetes. Others, such as the groundbreaking Baltimore Longitudinal Study of Aging, explore the determinants of healthy aging and attempt to define the physiological measures of biological aging. Work is also continuing on the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, which is examining the influences of race and socioeconomic status on the development of age-related health disparities among socioeconomically diverse African Americans and whites living in Baltimore.
The FY 2016 President’s Budget request is $124.549 million, an increase of $1.233 million, or 1.0 percent above the FY 2015 Enacted Level. Additional funds will be used to partially offset personnel costs and IT infrastructure improvements.
Research Management and Support (RMS)
NIA RMS activities provide administrative, budgetary, logistical, and scientific support in the review, award, and monitoring of research grants, training awards, and research and development contracts. RMS functions also encompass strategic planning, coordination, and evaluation of the Institute’s programs, regulatory compliance, international coordination, and liaison with other Federal agencies, Congress, and the public. The Institute currently oversees more than 1,538 research project grants and centers, as well as 532 full-time training positions and 78 research and support contracts.
The FY 2016 President’s Budget request is $44.945 million, an increase of $0.445 million, or 1.0 percent above the FY 2015 Enacted Level. Additional funds will be used to partially offset personnel costs and IT infrastructure improvements.
FY 2015 Enacted Level: $5.0 million*
FY 2016 Level: $5.4 million
Change: +$0.4 million
Being physically active is vital to maintaining health and independence as we age. However, studies indicate that only 25 percent of people ages 65-74 say they engage in regular physical activity. To encourage sedentary older adults to reap health benefits by making physical activity part of their daily lives, the NIA maintains the award-winning, nationwide Go4Life campaign. Based on an extensive body of clinical research and expert advice, this effort is designed to help motivate older Americans to engage in physical activity and exercise by becoming active for the first time, returning to exercise after a break in their routines, or building more physical activity into daily routines.
Go4Life combines the best in evidence-based resources with a growing base of partners in the public and private sectors, at the national and local level, to get the word out about the proven effectiveness of exercise and physical activities for optimal aging. The Go4Life resources offer exercises, motivational tips, and free resources to help participants get ready, start exercising, and keep going. They center on an interactive website (www.nia.nih.gov/Go4Life) that features sample exercises, motivational tips, success stories, virtual exercise coaches, an interactive tool to track personal exercise routines, and free online and print materials in both English and Spanish.
More than 100 public and private national and community-based partners currently are working with Go4Life to disseminate messages and materials. Go4Life partners are involved in a variety of activities, from sponsoring local health fairs to conducting exercise classes to reprinting and distributing the sample workout booklet or exercise DVD.
Efforts are underway across the Department of Health & Human Services – including the Centers for Disease Control and Prevention; President’s Council on Fitness, Sports, and Nutrition; Office of Disease Prevention and Health Promotion, Office on Women’s Health, and the Administration on Community Living – to broaden the reach of Go4Life, with the Department seeking ways to plan and conduct a coordinated outreach effort to step up promotion of the Go4Life campaign.
*Note: Due to an administrative error the dollar amounts in the program portrait above are incorrect. The corrected amounts are:
FY 2015 Enacted Level: $0.4 million
FY 2016 Level: $0.8 million
Change: +$0.4 million
1. The cost of the APOE4 trial, which was fully funded at $33.3 million in FY 2013, is not reflected in these figures.