Advisory Council October 2016 Meeting Presentation: Research Federal Workgroup Update

Monday, October 31, 2016

Printer Friendly Version in PDF Format (14 PDF pages)

 

Alzheimer's and Related Dementias Research: Tracking and Future Plans

Richard J. Hodes, M.D.
Director
National Institute on Aging

IADRP Project Update: By the Numbers

• Currently includes 35+ public, private and international funding organizations in 11 countries
• Captures 7000+ unique basic, translational and health services research projects
• Conducted by 4000+ researchers across1000+ institutions
• Represents $4.7 billion+ in funding

Next Steps

• CADRO --
  • Collecting feedback for updating the CADRO.
• New Federal Partners --
  • The Federal Reporter website (https://federalreporter.nih.gov/) provides easier access to query research sponsored by other federal agencies.
  • NIA has recently identified small portfolios of AD and ADRD research supported by NASA, EPA and the Department of Agriculture.
• AD Research Milestone Database --
  • ADRD research milestones will be added to the database and to IADRP.
• EU Joint Programme -- Neurodegenerative Diseases (JPND) --
  • NIH is participating in the upcoming EU mapping exercise that invites 20+ countries to submit their recently funded neurodegenerative research (notably AD and ADRD).
  • JPND has volunteered to ask participating countries if the results of this exercise can also be shared, coded and uploaded into IADRP.

IADRP Website

Visit IADRP @ http://iadrp.nia.nih.gov/

 

Tracking Alzheimer's Disease Research Implementation Milestones

AD Research Implementation Milestone Database

Visit https://www.nia.nih.gov/alzheimers/milestones

• Enables users to search and track progress in funding research to address the 80+ AD Research Implementation Milestones
• Most milestones are linked to NIH funding opportunity announcements (FOAs), special, initiatives and related activities. Users will soon be able to link to specific projects supported under targeted FOAs as they are funded.
• Common Alzheimer's Disease Research Ontology (CADRO) codes link milestones to related funded projects and other domestic and international funding organizations currently captured in IADRP

Tracking Progress -- Ex.: Population Studies

Milestone 1.D: Develop state-of-the-art protocol for assessing dementia on large nationally representative samples that (a) includes racial/ethnic subsamples large enough to support disparities research and (b) is adaptable for use in comparable studies around the world [2015 AD Summit: 1B, 1.D, 3C, 3D, and 4B].
Success Criteria	Targeted Funding Opportunity Announcements (FOAs) and Special Initiatives (SIs)	Assigned CADRO Codes	Number of Funding Organizations (IADRP Partners)
Archive and share data for use by the research community. Update national estimates of the prevalence and incidence of dementia and cognitive impairment as well as address important questions about the epidemiology and population impact of dementia. Repeat national estimates in 2021 to measure trend in dementia prevalence Support research projects comparing international differences to identify potential risk and protective factors.  Support research on health disparities by racial/ethnic groups.	NIH PAR-15-349: Health Disparities and Alzheimer's Disease (R01) NIH PAR-15-350: Emerging Directions for Addressing Health Disparities in Alzheimer's Disease (R03) NIH RFA-AG-15-015: Enhancing Cross-National Research within the Health and Retirement Study Family of Studies (R01) NIH NOT-AG-14-022: NIA Population Study of Dementia in the Health and Retirement Study	Category D. Epidemiology -- 4. Multimodal Risk Factors	16

• From the milestone database, CADRO-coded milestones are linked to funded projects from multiple IADRP partners.
• From IADRP, users can further filter results by Themes, such as target population Year Funding Organization
• Example - NIH PAR-15-349: Health Disparities and Alzheimer's Disease (R01)
• The milestone database will soon be linked directly to NIH Reporter to view specific projects as they are funded under targeted FOAs along with links and access to related publications, patents and clinical trials

Tracking Progress -- Ex.: Drug Dev.: Existing Targets

Milestone 5.B: Initiate phase II (proof of concept) drug trials for agents against 3-6 currently known therapeutic targets. Of these at least 2 will be for targets involved in at-risk asymptomatic individuals (e.g. FAD or ApoE4 carriers, Down syndrome, amyloid positive, type II diabetes etc.)  These trials will be designed to provide or confirm proof of mechanism and/or evidence of target engagement for the therapeutic agent being tested. [2012 AD Summit: 3A, 3B, 3F, and 5E]
Success Criteria	Targeted Funding Opportunity Announcements (FOAs) and Special Initiatives	Assigned CADRO Codes	Number of Funding Organizations (IADRP Partners)
Completion of 3-6 phase II drug trials for agents against currently known targets, providing conclusive evidence of therapeutic mechanism/target engagement.	NIH Accelerating Medicines Partnership - AD Biomarkers Consortium NIH PAR-16-365: Pilot Clinical Trials for the Spectrum of Alzheimer's Disease & Predicting Progression (R01) NIH PAR-14-089: Alzheimer's Disease Pilot Clinical Trials (R01) NIH RFA-AG-13-015: Alzheimer's Disease Prevention Trials (R01) NIH RFA-AG-13-001: Alzheimer's Disease Cooperative Study (U19)	Category C. Translational Research and Clinical Interventions - 5. Early-stage Clinical Drug Development (Phase I and II Clinical Trials)	10

• From IADRP, users can further filter results by
  • Themes, such as therapeutic target
  • Year
  • Funding Organization
• Example - NIH ?PAR-16-365: Pilot Clinical Trials for the Spectrum of Alzheimer's Disease & Predicting Progression (R01)

Tracking Progress -- Ex.: Care and Caregiver Support

Milestone 13.B: Launch research programs to develop and validate assessments of the psychological, financial, and physical health impact of caregiving. [2015 AD Summit  4B, 4D, 4H]
Success Criteria	Targeted Funding Opportunity Announcements (FOAs) and Special Initiatives	Assigned CADRO Codes	Number of Funding Organizations (IADRP Partners)
Identification and validation of assessments suitable for use in a range of research contexts including observational and interventional studies and large population-based surveys. Identification and validation of at least one sensitive and robust measure for the detection of the earliest manifestations of caregiving burden and for monitoring its long-term consequences.	NIH PAR-15-348: Research on Informal and Formal Caregiving for Alzheimer's Disease (R01) NIH PAR-15-351: Research on Informal and Formal Caregiving for Alzheimer's Disease (R21)	Category E. Care, Support and Health Economics of Alzheimer's Disease - 3. Caregiver Support - e. Assessment and Metrics	15

• From IADRP, users can further filter results by
  • Themes, such as type of caregiver research
  • Year
  • Funding Organization
• Example - NIH PAR-15-348: Research on Informal and Formal Caregiving for Alzheimer's Disease (R01)

AD Research Implementation Milestone Database

Visit https://www.nia.nih.gov/alzheimers/milestones

• Database will soon include the ADRD Research Milestones (once approved)
• We encourage other organizations to also post (and link) their funding announcements and activities
  • Organizations can identify strategic areas in which to invest and collaborate
  • Researchers can assess funding opportunities across multiple funders

New AD Funding Opportunities

Visit NIA Research & Funding Blog - Inside NIA page @ https://www.nia.nih.gov/research/blog

New Alzheimer's Concepts

• Resource Leveraging
  • Leveraging Existing Cohort Studies to Clarify Risk and Protective Factors for Alzheimer's disease and related dementias
  • Validation of NIH Toolbox Instruments for Tracking and Diagnosis of MCI and early AD, and for Extension of Assessment in the Oldest Old
• Caregiving and Clinical Care
  • Development of Socially Assistive Robots to Engage Persons with ADRD and their Caregivers
  • Pragmatic Trials for Dementia Care in Long Term Services and Support (LTSS) Settings
  • Improving Quality of Care and Quality of Life for Persons with Alzheimer's Disease and Related Dementia at the End of Life
  • Tools for Clinical Care and Management of Alzheimer's disease and its comorbidities
  • Clarifying the relationship between delirium and Alzheimer's disease and related dementias
  • NIA Small Business Opportunities to Advance Alzheimer's Disease Research
  • Multimorbidity in Alzheimer's Disease Impacts Choice of Ancillary Treatments
• Translation
  • Revision Applications to Enhance the Target and Biomarker Discovery Efforts of the AMP-AD and M2OVE-AD Consortia
• Basic Research
  • Understanding the Effects of APOE2 on the Interaction between Aging and Alzheimer's Disease.
  • Understanding the Impact of Sex Differences on the Phenotypes of AD Risk and Responsiveness to Therapy
  • Role of Exosomes in Alzheimer's Disease
  • Commonalities, and Interactions Between Neurodegenerative Diseases
  • Human Cell Reprogramming for Functional Genetics of Alzheimer's Disease
  • Brain lymphatic system in aging and Alzheimer's disease
  • Mechanisms of Selective Neuronal Vulnerability in Alzheimer's Disease
  • Systems biology approaches to Alzheimer's Disease using Non-Mammalian Models
  • The role of aging metabolic changes in Alzheimer's disease (AD)
  • The Role of Peripheral Proteostasis on Brain Aging and on Alzheimer's Disease
  • Comparative Biology of Neurodegeneration
  • Dynamic interactions between Peripheral Systems and the Brain in Aging and in Alzheimer's Disease
  • Complex Biology of Resilience from Alzheimer's
• Training
  • Alzheimer's Disease Research Revision Awards to Institutional Training Grants
  • Institutional Training Programs to Advance Translational Research for Alzheimer's Disease and AD Related Dementias
  • Research Career Enhancement Award to Advance Therapy Development for AD and Related Dementias

Ways to Stay Informed and Connected

• Visit https://www.nia.nih.gov/research/funding to search all active NIA funding opportunities
• Subscribe to our blog to stay up to date with the latest from NIA https://www.nia.nih.gov/research/blog

Save the Dates!

• AD Care and Services Research Summit October 16-17, 2017 Bethesda, MD
• Alzheimer's Disease Research Summit (III) March 1-2, 2018 Bethesda, MD

Determinants of Disparities in Health and Life Expectancy

FUNDAMENTAL FACTORS: Ethnicity, Gender, Age, Race, Identity*
Levels of Analyses
Environmental	Sociocultural	Behavioral	Biological
Geographical Political Factors Structural Bias Immigration/Documentation Criminalization Residential Segregation Urban/Rural Toxins/Exposures	Cultural Factors Values Prejudice Norms Traditions Religion Collective Responses	Coping Factors Active Coping Problem Solving Stress Management Cognitive Reframing Emotional Regulation	Physiological Indicators Co-Morbidities Cardiovascular Sympathetic Nervous System HPA Axis Inflammation
Socioeconomic Factors Education Income/Wealth Occupation Limited English	Psychological Factors Self Concepts Stigma Bias Loneliness Stereotypes	Psychosocial Risk/Resilience Social Support Discrimination Pessimism Optimism Control	Genetic Stability Telomere Attrition Epigenetic Alteration Loss of Proteostasis
Health Care Access Insurance Quality Literacy Numeracy	Social Factors Institutional Racism Family Stress Financial Stress Occupational Stress Residential Stress Social Mobility Social Network	Health Behaviors Smoking Anger/Violence Alcohol/Drug Nutrition Physical Activity	Cellular Function Communication Deregulated Nutrient Sensing Mitochondrial Dysfunction Cellular Senescence Cellular Stress Response Stem Cell Exhaustion Intercellular Communication
Lifecourse Perspective
*Gender, Ethnic, Racial and Sexual Identity Adapted from: Lazarus & Folkman (1984); Pearlin (1989); Link and Phelan (1995); Jones (1997); Geronimus (2000); Williams & Collins (2001); Adler (2010); McEwen (2010); Lopez-Otin (2013)