SuperAgers may keep their memories sharp not because they dodged Alzheimer’s genes, but because their brains possess hidden defenses scientists are only beginning to uncover.
Some people reach their 80s and 90s with memory abilities that rival, or even surpass, those of adults decades younger. Known as SuperAgers, these exceptional individuals are helping scientists investigate why certain brains remain remarkably resilient while memory declines in many others.
Scientists have spent nearly two decades identifying brain, biological, psychological, and social traits associated with SuperAging. One possibility, however, could have offered a much simpler explanation: perhaps SuperAgers are merely people who inherited unusually little genetic risk for Alzheimer’s disease.
“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, PhD, director of the Healthy Aging & Alzheimer’s Research Care (HAARC) Center at the University of Chicago. Rogalski introduced the formal definition of SuperAging in 2008 and has studied the group ever since.
Testing the Genetic Explanation
A new study directly tested that idea using the largest prospectively enrolled SuperAging cohorts examined with current measures of Alzheimer’s genetic risk. The findings, published in Alzheimer’s Research & Therapy, suggest that genetics alone cannot explain why some people retain such exceptional memories.
Researchers from the HAARC Center and the Translational Genomics Research Institute (TGen), part of City of Hope, studied 142 SuperAgers and 89 cognitively average older adults recruited from five sites across the U.S. and Canada.
The team analyzed DNA obtained from blood samples, focusing first on APOE, the gene with the strongest known influence on common late-onset Alzheimer’s disease risk. They also calculated three polygenic risk scores, which combine information from thousands of genetic variants to estimate a person’s inherited susceptibility to the disease.
Alzheimer’s Risk Does Not Explain It
SuperAgers and cognitively average older adults could not be reliably distinguished by their APOE status or polygenic risk scores. The result indicates that maintaining an unusually youthful memory into one’s 80s is not simply a matter of avoiding inherited Alzheimer’s risk.
“The findings reinforce that preserving cognitive health involves more than reducing Alzheimer’s disease risk alone,” said co-first author Ana Capuano, PhD, director of the biostatistics core at the HAARC Center. “Understanding the biological, behavioral, and social factors that promote exceptional cognitive aging may ultimately complement traditional disease-focused approaches and help inform more personalized strategies for supporting brain health across the lifespan.”
The researchers also searched for rare genetic variants that previous studies have associated with protection or resilience against Alzheimer’s disease. Those variants were no more common in SuperAgers than in the comparison group.
“This study establishes an important boundary for Alzheimer’s disease genetics,” said Matt Huentelman, PhD, professor and director in TGen’s Early Detection and Prevention Division and co-senior author with Rogalski. “Common genetic risk factors captured by APOE and current polygenic risk scores do not explain the SuperAging phenotype. Future work should move beyond disease-risk models and investigate the broader biological, environmental, and experiential pathways that contribute to exceptional cognitive aging.”
Searching for Active Brain Protection
That distinction changes the scientific question. Instead of asking only why SuperAgers avoided disease, researchers can investigate whether they possess active protective mechanisms that preserve brain function.
Those mechanisms could involve the structure and connectivity of the brain, resistance to inflammation, cardiovascular health, sleep, physical activity, social engagement, or other influences that accumulate across a lifetime. No single factor is expected to provide the full explanation.
Future research will therefore combine cognitive testing with brain imaging, blood biomarkers, genetics, neuropathology, immune profiling, sleep and activity monitoring, and detailed measurements of social, environmental, and whole-person health.
“For many years, aging research has focused on identifying factors that increase the risk of disease,” added co-first author Ignazio S. Piras, PhD, associate professor in TGen’s Early Detection and Prevention Division. “Those studies are critically important, but the absence of risk factors does not necessarily mean someone possesses the protective factors that support exceptional brain health. This study helps demonstrate that distinction.”
Reference: “SuperAging is not the inverse of common-variant Alzheimer’s risk: evidence across genetic ancestries” by Ignazio Stefano Piras, Ana Werneck Capuano, Amanda Cook Maher, Rhiana Schafer, Anna Bonfitto, Serena Song, Francis Taguinod, Felicia Goldstein, Angela Roberts, Ozioma Okonkwo, Adam Martersteck, The SuperAging Research Initiative, Matt J. Huentelman and Emily Rogalski, 23 July 2026, Alzheimer’s Research & Therapy.
DOI: 10.1186/s13195-026-02124-2
This work was supported by the National Institute on Aging (U19AG073153), the McKnight Brain Research Foundation through the SuperAging Research Initiative, and the Simons Foundation, along with the many participants, families, and collaborating investigators across five research sites.
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