Extraordinary memory in adults aged 80 and older, a phenomenon known as SuperAging, cannot be explained solely by having a low inherited risk for Alzheimer’s disease, according to a study published in Alzheimer’s Research & Therapy. Researchers at the University of Chicago and the Translational Genomics Research Institute (TGen), part of City of Hope, analyzed genetic data from 142 SuperAgers and 89 cognitively average older adults, discovering that traditional Alzheimer’s risk scores do not distinguish the two groups.
Testing the Genetic Explanation for SuperAging
For nearly 20 years, scientists have studied individuals who reach their 80s and 90s with memory abilities that match or even exceed those of people in their 50s and 60s. A central question has been whether these SuperAgers simply inherited unusually low genetic risk for Alzheimer’s disease. According to Emily Rogalski, PhD, director of the Healthy Aging & Alzheimer’s Research Care (HAARC) Center at the University of Chicago, confirming that hypothesis would mean identifying SuperAgers through simple genetic testing rather than comprehensive cognitive evaluations.
To test the theory, the research team recruited a diverse cohort from five regional sites across the United States and Canada. Investigators extracted DNA from blood samples provided by 142 SuperAgers and 89 older adults with average cognitive performance. The team examined the APOE gene, which represents the strongest known genetic risk factor for Alzheimer’s disease. They also calculated three polygenic risk scores that combined thousands of genetic variants associated with inherited Alzheimer’s risk.
SuperAgers Show No Clear Genetic Advantage
The analysis revealed that SuperAgers carry similar levels of genetic risk to their cognitively average peers. Researchers could not separate the two groups based on either APOE status or the broader Alzheimer’s polygenic risk scores. Furthermore, rare genetic variants previously linked to protection against Alzheimer’s disease appeared no more frequently in SuperAgers than in the comparison group.
“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. The results demonstrate that exceptional memory in later life does not stem strictly from an absence of inherited disease markers.
Moving Beyond Disease-Risk Models
Matt Huentelman, PhD, a professor and director in TGen’s Early Detection and Prevention Division and co-senior author of the study, noted that the research establishes a clear boundary for Alzheimer’s disease genetics. Because common risk factors fail to explain the SuperAging phenotype, future investigations must look outside traditional disease-risk models.
Future research efforts will employ a multidisciplinary strategy combining detailed cognitive testing, brain imaging, blood biomarkers, genetics, neuropathology, immune profiling, sleep and activity monitoring, and social measurements. Ignazio S. Piras, PhD, associate professor in TGen’s Early Detection and Prevention Division and co-first author, emphasized that the absence of risk factors does not automatically equate to the presence of protective mechanisms supporting brain health.
The study received support from the National Institute on Aging under grant U19AG073153, the McKnight Brain Research Foundation through the SuperAging Research Initiative, and the Simons Foundation, alongside contributions from participating families and investigators across all five research sites.
Worth a look