Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R41/R42)

In the United States (US), it is estimated that more than 5 million people suffer from Alzheimer's disease (AD) and Alzheimer's-disease-related dementias (ADRD).  By 2050 this number is forecast to rise to more than 15 million.  Moreover, caring for and treating patients with AD/ADRD is expensive.  Current estimated annual costs for care and treatment of AD/ADRD total approximately $200 billion.

Recent recommendations  and milestones for AD/ADRD research from the National Alzheimer’s Project Act, the 2012 Alzheimer’s Disease Research Summit, the 2013 Alzheimer’s Disease and Related Dementias Meeting, and the 2015 Alzheimer’s Disease Research Summit present a wide range of research and development, which , if conducted, is expected to reduce the human burden and health-care costs associated with AD and ADRD.

As part of the National Institute on Aging's (NIA) strategic plan to support the development of innovative strategies and therapies to prevent, diagnose, and treat AD/ADRD, NIA announces a new Funding Opportunity Announcement (FOA) through its Small Business Technology Transfer Research Program (STTR) to encourage research on and the commercialization of novel therapies, devices, other products, and health care programs and practices to prevent the onset of AD/ADRD and to reduce their burden on individuals, their families, and society at large.

STTR is an important small business program that expands funding opportunities in the federal innovation research and development arena. Central to the program is expansion of the public/private sector partnership to include the joint venture opportunities for small business and the nation's premier nonprofit research institutions. STTR's most important role is to foster the innovation necessary to meet the nation's scientific and technological challenges in the 21st century.

Examples of research and development that might be supported by this FOA include but are not limited to:

Prevention:

• Behavioral, environmental, pharmacological, & nutritional interventions to prevent and/or remediate brain biochemical and/or neurophysiological changes caused by neurodegenerative diseases, including age-related sensory dysfunction, motor dysfunction or age-related decrements in balance & postural control, gait performance, and mobility.
• Development of programs to support cognitive training to improve cognitive function in elderly. Examples of topics appropriate for such programs include but are not limited to:
• The rapid development of novel, engaging computer-based cognitive-training programs based on empirically-established approaches using cognitive training to target a specific neural system/functional domain;
• The augmentation of existing computerized cognitive interventions that can be individually tailored to engage, adapt, challenge, and optimize functional cognitive abilities to enhance cognitive functioning and performance of activities of daily living;
• The development of interventions to remediate age-related cognitive decline, especially using technology platforms with wide acceptance among older adults.

Diagnosis

• Development of sensitive, specific, and standardized tests for diagnostic screening of mild cognitive impairment (MCI) and dementia.  Such advances would include the development of new cost-effective, minimally-invasive biomarkers that could be used for screening in the general population and in community settings.  In addition, this FOA encourages research that would identify new biomarkers that could serve as surrogate measures for disease progression in AD /ADRD.  Other advances might include the development of new instrumentation, imaging technology, related devices, and software packages for use in visualizing neural activity during cognitive, emotional, motor or sensory behavior in older adults.
• Biosensors and prosthetic devices, technologies, and related software development to aid in the assessment, diagnosis, and remediation of age-related cognitive decline.
• Development of machine-learning tools and cognitive batteries that can be integrated to Electronic Medical Records (EMR) for diagnosis of MCI, AD, and ADRD.
• New approaches for the assessment of persons with multiple chronic conditions in clinical practice, including development and validation of brief cognitive-screening measures.

Treatment:

• Discovery, development, and/or evaluation of drugs, biological or natural products, including central-nervous-system delivery systems to remediate age-related cognitive decline, and to treat the cognitive impairment and/or behavioral symptoms associated with MCI, AD/ADRD, and other dementias of aging.  In addition, this FOA seeks research on therapies that might slow and/or reverse the course of AD and ADRD or prevent them entirely through the application of systems-biology and systems-pharmacology approaches.
• Clinical trials to test the safety and efficacy of drug, nutritional, behavioral, cognitive or other types of interventions to remediate age-related cognitive decline, and to treat cognitive impairment and/or behavioral symptoms associated with MCI, AD/ADRD, and other dementias of aging as well as to slow and/or reverse the course of AD and ADRD or to prevent their onset.

Care:

• New technologies for in-home use or for coordination or delivery of services to sustain in-home living for individuals with MCI or AD/ADRD.  Examples include but are not limited to:
• Systems and devices to evaluate, monitor and improve or adapt to changes in cognition; improvements in health-service delivery;
• Improvements in the preservation of functional independence;
• Technologies supporting independent living and the conduct of everyday tasks at home;
• Provision of information to health-care providers and family members enabling assessment of patient needs intervention; and
• Promotion of effective communication and interaction between individuals living in the community or in institutional settings and their health-care providers, friends, and family members.
• Development of assistive robotics technology that can support a person to maintain or improve her/his independence, safety and wellbeing when diagnosed with AD/ADRD and alleviate the burden of care.  Such efforts might include the development of socially-assistive robots that can support engagement, social participation, and leisure activities of patients with MCI and AD/ADRD.
• Development of cost-effective technology to create dementia-friendly cities and environments for individuals diagnosed with AD/ADRD.  This might include the development of alarm technology and tracking and location-monitoring devices to alert caregivers and others of the whereabouts of individuals with AD/ADRD.  Other advances might include innovative research to develop safer home environments, such as automatic shut-off valves for water (e.g. sink over flows when one forgets to turn-off faucet) and electricity and gas (e.g. forgetting to turn off stove).
• Development of comprehensive telecare systems that can be used to support independence and personal safety of an individual with ADRD and other dementias.  The development of such telecare systems might include community alarms, medication reminders, sensors for floods or extreme temperatures, absence from normal activities (e.g. sitting in a chair, going to bed), fall detection, unobtrusive sensors to monitor activities of daily living and vital signs that can be reported to a health-care provider.  Other advances might include the development of technology that would allow for in-place monitoring of individuals at all stages of AD/ADRD.  Ideally, such information would be integrated with other patient-relevant data in Electronic Medical records (EMR).
• Recent reviews of relevant scientific literature reveal the presence of disparities of care between diverse racial and ethnic groups of individuals with AD/ADRD.  To address such disparities, this FOA encourages research to develop educational training programs for physicians, nursing assistants, home-care aids, and long-term-care services.  These programs would focus on training health-care staff to provide culturally-appropriate care to the right patient, at the right time, and in the right setting.
• Utilization of novel technologies to monitor, assist or maintain daily functioning of older individuals with AD/ADRD and other cognitive impairments.

Tools:

• Development of manuals for existing evidence-based interventions to reduce the burden of caregiving for AD/ADRD caregivers so that the manuals and training materials can be used by community-based agencies and/or health-care organizations.
• Development of a tool that would allow Medicare Advantage (MA) plans to accurately project future costs of caring for patients with AD/ADRD and other forms of dementia. Such a tool would be based on incidence and cost data and would be able to be tailored for use by participating MA plans to address the unique demographics and risk characteristics of its coverage pool.  The product could be sold to participating MA health plans.
• Development of technology and analytical tools to investigate genetic, epigenetic, transcriptomic, proteomic, metabolomic, and cell stress pathways in neurons and glia of the aging and AD/ADRD brain.  Such efforts might include the development of molecular-imaging technology and/chip-based technology for in-vitro and in-vivo analysis of gene, epigenome, proteostasis, lipidomics and metabolomics and metabolic function in the normal aging brain and in AD/ADRD.
• Improved technology for the analysis of structural and functional brain connectivity at the cell, neural circuitry and global network levels to define the trajectory of changes in brain structure and function in aging and AD/ADRD.  Such technology might include the development of non-invasive methods and novel probes that monitor and manipulate the plasticity of neural circuits in the adult and aged nervous system.  Further advances might include the development of novel markers of neural stem-cell function (proliferation, migration, and differentiation) as well as methods to assess the integration and function of stem cells in the aging and/or diseased nervous system.
• Development of chip-based tools modeling human AD/ADRD for applications in AD/ADRD drug screening and development. Development of novel therapeutics for the treatment of AD/ADRD has proven to be a lengthy, costly and relatively unproductive process with drug attrition rates of > 90%.  Several studies have indicated the lack of appropriate preclinical ADRD models as one of the barriers for successful development of AD/ADRD therapeutics.  Although animal models of AD/ADRD have helped our understanding of AD/ADRD pathogenesis to some extent, key genes and proteins that are critical to the pathogenesis of this disease exhibit many inherent species-specific differences and, consequently, there is a critical need for translation platforms that can accurately and reproducibly mimic the AD/ADRD phenotype in vivo and be amenable to high-content screening and assay applications.  Recent advances in stem-cell technology allow for successful generation of human neural-progenitor cells from skin cells of normal and AD/ADRD patients. This technology could be exploited to develop cell type specific AD/ADRD disease models replicating AD/ADRD pathobiology on microfluidic chips. These chips could then provide a novel AD/ADRD model system that could be used in the translation process to:
• Validate therapeutic target(s);
• Develop in situ assays for measuring predictive biomarkers; and
• Perform high throughput screening for drug discovery and drug efficacy.
• Approaches using artificial intelligence to assist with recruitment and monitoring of study participants for clinical trials of treatments or preventives for AD/ADRD.

See Section VIII. Other Information for award authorities and regulations.