Disease Mechanisms: Cognitive resilience (Milestone 2.K)
Timeline Start - End2016 - 2020
Research Implementation AreaResearch on Disease Mechanisms
Create new research programs that use data-driven, network biology approaches aimed at understanding the (epi)genetics and complex biology of cognitive resilience in individuals with high genetic risk for dementia and in individuals with exceptional longevity.
- Launch at least 6 research projects aimed at identifying molecular networks causally linked to cognitive resilience as potential therapeutic targets for disease prevention. These efforts should support the preclinical validation of the identified targets.
Summary of Key Accomplishments
The development of effective treatment and prevention for complex diseases such as AD can benefit from a deeper understanding of which genetic, environmental, social, and behavioral factors promote wellness and resilience against disease. Established through a targeted research initiative, the Resilience-AD Program supports 10 cross-disciplinary projects using a big data approach to understand why some individuals who are at high risk of AD due to genetic factors (two copies of ApoE4), very old age (90+, centenarians) or the presence of AD biomarkers (accumulation of amyloid and tau in the brain) remain dementia-free compared to their peers. Research supported through this program has identified several new biological pathways that may protect the brain from the effects of amyloid accumulation, such as genes involved in bile acid metabolism.
The key accomplishments summary is current as of March 2022.
- PAR-17-047: Selective Cell and Network Vulnerability in Aging and Alzheimer’s Disease (R01)
- PAR-18-706: Selective Cell and Network Vulnerability in Aging and Alzheimer’s Disease (R01)
- PAR-17-054: Leveraging Existing Cohort Studies to Clarify Risk and Protective Factors for Alzheimer’s Disease and Related Dementias (R01)
- RFA-AG-17-061: Interdisciplinary Research to Understand the Complex Biology of Resilience to Alzheimer’s Disease Risk (R01)
- RFA-AG-18-029: Interdisciplinary Research to Understand the Complex Biology of Resilience to Alzheimer’s Disease Risk (R01)
- RFA-AG-18-024: Collaboratory on Research Definitions for Cognitive Reserve and Resilience to Alzheimer's Disease (R24)
- RFA-AG-19-025: Development of Personalized In Vitro Assays to Quantitatively Assess Age-related Changes in Cellular Resiliencies to Physiologic Stressors (R43/R44)
- RFA-AG-19-026: Development of Personalized In Vitro Assays to Quantitatively Assess Age-related Changes in Cellular Resiliencies to Physiologic Stressors (R41/42)
- PAR-19-269: Cognitive Systems Analysis of Alzheimer's Disease Genetic and Phenotypic Data (U01 Clinical Trial Not Allowed)
- NOT-AG-19-017: Inviting comments and suggestions for the development of the NIA Longitudinal Rat Resource to study neural and behavioral trajectories of successful cognitive aging
- RFA-AG-19-011: Integrative Omics to Enhance Therapeutics Development for Healthy Aging (UH2/UH3 Clinical Trial Not Allowed)
Research Programs and Resources
- Collaboratory on Research Definitions for Cognitive Reserve and Resilience to Alzheimer's Disease
- Resilience AD Program
- ELP: Exceptional Longevity Portal
- The Integrative Longevity Omics Projects
- UC Irvine ADRC 90+ Cohort – Neuropathology Core
- Genetic Resilience to the Clinical Manifestation of Dementia
- Genetic Drivers of Resilience to Alzheimer's Disease
- The Stanford Extreme Phenotypes in Alzheimer's Disease (StEP AD) Cohort
- Cognitive Aging Summit III
- Special Issue of Neurobiology of Aging Highlighting the Cognitive Aging Summit III
- Resilience/Resistance to Alzheimer's Disease in Centenarians and Offspring (RADCO)