Many people believe that memory decline with age is a natural part of getting older. However, there is a group of elderly individuals known as SuperAgers who, even in their 80s and 90s, maintain memory performance at the level of—or even better than—people in their 50s and 60s.

For nearly two decades, research has focused on exploring the biological, neurological, and psychosocial characteristics associated with the SuperAger phenomenon. One key question remained: Are their exceptional cognitive abilities solely due to a low genetic risk for developing Alzheimer’s disease? If that were the case, genetic testing alone would be sufficient to identify SuperAgers, rather than the comprehensive cognitive assessments currently used.

To test this hypothesis, scientists analyzed the largest cohorts of SuperAgers using advanced methods for assessing genetic risk for Alzheimer’s disease. The results, published in Alzheimer’s Research & Therapy, showed that outstanding memory in old age cannot be explained solely by a low hereditary risk for this disease. This highlights the need for further research into the protective mechanisms that allow some people to maintain high cognitive abilities as they age.

The study involved experts from the HAARC Center and the Translational Genomics Research Institute (TGen, part of City of Hope), who examined a diverse group recruited from five regions across the US and Canada. The research included 142 SuperAgers and 89 elderly individuals with average cognitive performance. Using DNA from blood samples, the team analyzed the APOE gene—the main genetic risk factor for Alzheimer’s—and calculated three polygenic risk scores that combine thousands of genetic variants linked to hereditary risk for the disease.

The findings disproved the assumption that SuperAgers are protected solely because they have fewer genetic variants associated with Alzheimer’s risk. Scientists found no significant differences between SuperAgers and elderly individuals with average cognitive abilities, either in the APOE gene or in polygenic risk scores for Alzheimer’s disease.

Thus, exceptional memory at age 80 is not exclusively linked to a low hereditary risk for Alzheimer’s. Maintaining cognitive health involves more than just reducing the risk of this disease. Studying the biological, behavioral, and social factors that contribute to exceptional cognitive aging could complement traditional approaches and help develop more personalized strategies for supporting brain health throughout life.

The researchers also examined rare genetic variants previously associated with protection against or resistance to Alzheimer’s. These variants were not found more frequently among SuperAgers compared to the control group.

This study defines important boundaries for the genetics of Alzheimer’s disease: common genetic risk factors, as determined by APOE and modern polygenic risk assessments, do not explain the SuperAger phenomenon. Future research will need to go beyond disease risk models and investigate broader biological, environmental, and life course factors that contribute to exceptional cognitive aging.

Upcoming studies will use an interdisciplinary approach, combining detailed cognitive testing with neuroimaging, blood biomarker analysis, genetics, neuropathology, immune profiling, sleep and activity monitoring, as well as social and environmental measurements and other indicators of overall health.

For a long time, aging research has focused on identifying factors that increase disease risk. However, the absence of risk factors does not necessarily mean the presence of protective factors that support exceptional brain health. This study helps clarify that distinction.

The data obtained suggest that memory decline with age is not inevitable. Some people are indeed able to maintain strong cognitive abilities and youthful memory even at age 80 and beyond.

Currently, the precise mechanisms that enable SuperAgers to sustain such cognitive abilities remain unknown, but research continues with the active participation of volunteers. Long-term study participants help scientists define successful cognitive aging and discover new ways to support brain resilience.