Study to Uncover Pathways to Exceptional Cognitive Resilience in Aging (SUPERAging)

The designation of SuperAger is reserved for individuals at or above the age of 80 who are not just free of cognitive impairment but who also have memory capacity that would be considered average for those 2-3 decades younger1, 2. It appears that SuperAgers may be resistant to the emergence of involutional cellular changes in the brain and/or resilient to their impact on cognition1-8. The importance of identifying biologic factors that drive SuperAging is self-evident. One obstacle has been the relative rarity of this phenotype and the necessity to establish a broad-based recruitment mechanism. In order to address this goal, and in response to RFA-AG-21-015, this proposal aims to establish a multicenter SuperAging Consortium to identify behavioral, health, biologic, genetic, environmental, psychosocial, anatomic, and neuropathologic factors associated with SuperAging. These goals will be achieved through an organizational structure with 3 Cores (Administrative/Biostatistics, Clinical/Imaging, and Biospecimen/Neuropathology), which will enroll 500 SuperAgers and Cognitively Average Elderly Controls through 5 Sites across the United States and Canada. The Consortium will build upon the strengths of exciting discoveries on the anatomy, biology and neuropsychology of SuperAgers identified through the NIA-funded SuperAging Program (R01AG067781), recruit an expanded cohort to consolidate preliminary results, launch new fields of inquiry, and increase the scope of the research with its emphasis on higher enrollment. To this end, the NIA-R01-funded SuperAging Program will join efforts with recruitment Sites in Ann Arbor, Atlanta, Madison, and Southwest Ontario, each of which was selected because of proven leadership and expertise in aging and dementia research. The SuperAging Consortium will leverage existing infrastructure at each of the Sites, including NIA-funded Alzheimer’s Disease Research Centers, the Ontario Brain Institute, and the NIA-R01-funded SuperAging Program. In addition to the creation of a unique and uniform cohort that will be curated for intramural and extramural collaborations, the Consortium will also include two major Research Projects that will address entirely novel aspects of SuperAging through real-time measurements of psychophysiological parameters and the genetic characterization of immune mechanisms. The SuperAging Consortium leadership includes investigators with expertise in successful cognitive aging and dementia, behavioral neurology, neuropsychology, digital biomarkers, neuroimaging,and neuropathology. Below we outline the critical anchor points of the SuperAging Consortium.