A study of older adults known as “SuperAgers” found that their unusually strong memory in their 80s and 90s does not appear to be explained by carrying fewer common genetic risk variants for Alzheimer’s disease. Researchers reported that SuperAgers and cognitively typical older adults looked similar on APOE status and on Alzheimer’s polygenic risk scores, suggesting other biological, behavioral and environmental factors may help protect cognition in late life.
Scientists studying “SuperAgers” — older adults whose memory matches or exceeds that of much younger people — tested whether this exceptional cognitive aging could be explained by an unusually low inherited risk for Alzheimer’s disease.
In the study, researchers analyzed DNA from blood samples collected from participants recruited across five regional sites in the United States and Canada. The cohort included 142 SuperAgers and 89 older adults with average cognitive performance.
The team examined APOE, the strongest known genetic risk factor for Alzheimer’s disease, and calculated three polygenic risk scores that aggregate thousands of genetic variants linked to inherited Alzheimer’s risk. The results showed researchers could not reliably distinguish SuperAgers from cognitively average older adults using APOE status or the polygenic risk scores.
“If that were true, identifying SuperAgers might be as simple as performing genetic testing rather than the comprehensive cognitive evaluations we currently use,” said Emily Rogalski, director of the Healthy Aging & Alzheimer’s Research Care (HAARC) Center at the University of Chicago.
Co-first author Ana Capuano said the findings underscore that preserving cognitive health involves more than lowering Alzheimer’s disease risk alone, pointing to a broader mix of biological, behavioral and social factors that may support exceptional aging.
The researchers also reported that rare genetic variants previously linked to protection or resilience against Alzheimer’s disease were not more common among SuperAgers than in the comparison group.
Matt Huentelman of the Translational Genomics Research Institute (TGen), part of City of Hope, said the work draws a boundary around what current Alzheimer’s genetics can explain about SuperAging and that future research should expand beyond disease-risk models. The team said upcoming studies will combine cognitive testing with approaches such as brain imaging, blood biomarkers, immune profiling, sleep and activity monitoring, and social and environmental measurements to better understand potential protective mechanisms.
The study was published in Alzheimer’s Research & Therapy and was supported by the National Institute on Aging, the McKnight Brain Research Foundation through the SuperAging Research Initiative, and the Simons Foundation.
