Monday, April 29, 2019
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Alzheimer's Disease and Related Dementias Research Update
Richard J. Hodes, M.D.
Director, NIA
Alzheimer's Disease Immunotherapy Phase III Trials
* NIA sponsored (public-private partnerships |
Ongoing NIA AD/ADRD and Related Intervention and Prevention Trials (~140)
29 Early-stage Clinical Drug Development (Phase I and Phase II Clinical Trials) | 6 Late-stage Clinical Drug Development (Phase II/III and Phase III Clinical Trials) | 53 Non-Pharmacological Interventions | 7 Clinical Therapy Development for the Neuro-psychiatric Symptoms of AD/ADRD | 39 Care and Caregiver Interventions | 3 Delirium/ Post-Operative Cognitive Decline Trials |
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Amyloid (8) Receptors (4) Metabolism and Bioenergetics (4) Vasculature (3) Growth Factors and Hormones (1) Multi-target (6) Oxidative Stress (2) Other (1) |
Amyloid (5) Vasculature (1) |
Exercise (13) Diet (5) Cognitive Training (14) Combination Therapy (7) Other (14) |
Pharmacological (5) Non-Pharmacological (2) |
NIA-AD clinical trials pipeline toward 2025
NIA Pipeline of Discovery
Genetic Regions of Interest in Alzheimer's Disease
By Year of Discovery |
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NOTE: Color indicates mechanism of action in the body. See key. |
Accelerating Medicines Partnership (AMP) -- Alzheimer's Disease
COMPLETED:
- Centralized data resource established -- AMP-AD Knowledge Portal
- Rich genomic, proteomic, metabolomic human data (raw and processed) made available and being widely used -- over 2000 users to date.
- Network models of disease pathways/targets developed
- Over 100 novel candidate targets identified and being prioritized in collaboration with industry partners; experimental validation ongoing on over 20 candidate targets/pathways.
- Animal models phenotype/evaluated relative to human networks
- Web-based interface for sharing target nominations and analytical outputs developed - AGORA platform; 100 annotated target predictions and additional 480 key driver genes made publicly available.
AD Centers for Discovery of New Medicines - RFA AG 19-010
- https://grants.nih.gov/grants/guide/rfa-files/RFA-AG-19-010.html
- -Applications submitted Feb 2, 2019-
- -NIA plans to commit ~$75M over 5 years to support 2 Centers-
- Accelerate robust preclinical validation of candidate targets delivered by AMP-AD and other target discovery programs, through the development of open source tools, reagents and methods and by integrating a series of novel targets into drug discovery campaigns.
Center Structure |
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AHRQ-National Academies Study
- Assessment of interventions to prevent AD-type dementia, amnestic MCI, and age-related cognitive decline
- Insufficient evidence to justify a public health campaign
- Encouraging but inconclusive evidence:
- Cognitive training
- Blood pressure management in hypertensives
- Increased physical activity
http://www.nationalacademies.org/dementia |
SPRINT Study
The SPRINT Research Group (2015) NEJM 373(22):2103-16. |
SPRINT-MIND Research Question -- SPRINT Memory and Cognition in Decreased Hypertension
- Does intensive blood pressure control compared with standard control reduce the occurrence of dementia?
- Randomized Controlled Trial Target Systolic Blood Pressure
- Intensive Treatment Goal SBP < 120 mmHg (n= 4,278)
- Standard Treatment Goal SBP < 140 mmHg (n= 4,285)
- Randomized Controlled Trial Target Systolic Blood Pressure
The SPRINT MIND Investigators for the SPRINT Research Group (2019). JAMA, 321(6):553-561.
SPRINT-MIND: Secondary Cognitive Outcomes
- 19% reduction in the rate of developing MCI
- 15% reduction in the rate of composite MCI and probable dementia
The SPRINT MIND Investigators for the SPRINT Research Group (2019). JAMA, 321(6):553-561.
Accelerating Caregiving Research
- Multiple funding solicitations
- 2017 & 2020 care/caregiving research summits
- AD/ADRD Health Care Systems Research Collaboratory
- Systematic review of care/caregiving interventions
- NIA's first Alzheimer's prize
iCare-AD/ADRD Challenge
- Improving Care for People with AD/ADRD Using Technology Challenge
- Technology applications to improve dementia care coordination and/or care navigation
- Up to $400,000 in cash prizes
- Submissions - October 1, 2018 through June 30, 2019
- See https://nia.nih.gov/challenge-prize for full prize details and archived webinar for participants
Alzheimer's Disease-Related Dementias Summit 2019
- On March 15-16, 2019 on the main NIH Campus, Bethesda MD
- Goal: To update the research recommendations from ADRD 2016
- 7 Sessions:
- Multiple Etiology Dementias
- AD/ADRD Health Disparities
- Lewy Body Dementias
- Dementia Nomenclature
- Vascular Contributions to Cognitive Impairment and Dementia
- Frontotemporal Lobar Degeneration
- Emerging AD/ADRD -- TDP-43 in Common Dementias, Traumatic Brain Injuries and AD/ADRD Risk
- Final Recommendations will be approved by NINDS Council in September, submitted to the NAPA Council in November, and will become ADRD Research Milestones after NAPA Council approval
- Watch the archived videocast: