Many people expect memory to fade as a normal part of aging. However, some elderly people, known as superagers, have memory abilities that are equal to or even better than those in their 50s and 60s, even into their 80s and 90s.
Scientists have spent nearly two decades identifying the biological, neurological, and psychosocial characteristics associated with superagers. But one big question remains unanswered. Are super-agers people who have inherited an unusually low genetic risk for Alzheimer’s disease?
“If that’s true, identifying superagers could be as simple as doing genetic testing rather than the comprehensive cognitive assessments we currently use,” said Dr. Emily Rogalski, director of the Healthy Aging & Alzheimer’s Research and Care (HAARC) Center at the University of Chicago. He established the definition of superaging in 2008 and has been studying this remarkable population ever since.
Testing the genetic explanation of hyperaging
To investigate that possibility, researchers analyzed the largest prospectively enrolled SuperAging cohort studied using the latest measures of genetic risk for Alzheimer’s disease. The result is Alzheimer’s disease research and treatmentshowing that exceptional memory in later life cannot be explained solely by a low inherited risk of Alzheimer’s disease. The findings highlight the need to study protective mechanisms that may help some people maintain unusually strong cognitive abilities.
Researchers at the Translational Genomics Institute (TGen), part of the HAARC Center and City of Hope, studied a diverse group drawn from five regional facilities in the United States and Canada. The study involved 142 superagers and 89 older adults with average cognitive ability.
The research team used DNA obtained from blood samples to analyze the APOE gene, the strongest known genetic risk factor for Alzheimer’s disease. They also calculated three polygenic risk scores that combine thousands of genetic variations associated with inherited Alzheimer’s disease risk.
No clear genetic advantage found in superagers
The results directly challenge the idea that superagers are protected simply because they have fewer risk mutations associated with Alzheimer’s disease. Researchers were unable to distinguish between superagers and cognitively average older adults based on APOE or Alzheimer’s disease polygenic risk scores.
Simply put, the superior memory of people in their 80s does not seem to be due to a very low genetic risk for Alzheimer’s disease.
“Our findings confirm that reducing Alzheimer’s disease risk is not enough to maintain cognitive health,” said co-first author Ana Capuano, Ph.D., HAARC Center Biostatistics Core Director. “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 to support lifelong brain health.”
The researchers also looked at rare genetic mutations previously associated with protection and resilience against Alzheimer’s disease. These mutations were less common among superagers than among comparison groups.
Looking beyond Alzheimer’s disease risk genes
“This study establishes an important boundary in the genetics of Alzheimer’s disease,” said Matt Hüntelmann, Ph.D., professor and director of TGen’s Division of Early Detection and Prevention 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 research should move beyond disease risk models to investigate broader biological, environmental, and experiential pathways that contribute to exceptional cognitive aging.”
Future research will use a wide range of interdisciplinary strategies. Researchers plan to combine detailed cognitive testing with brain imaging, blood biomarkers, genetics, neuropathology, immune profiling, sleep and activity monitoring, social and environmental measures, and other indicators of whole-person health.
“For many years, aging research has focused on identifying factors that increase the risk of disease,” added co-lead author Ignazio S. Piras, Ph.D., associate professor in TGen’s Department of Early Detection and Prevention. “While these studies are very important, the absence of risk factors does not necessarily mean that a person has the protective factors that support good brain health. This study helps demonstrate that difference.”
Why some memories remain youthful
The findings support the reassuring conclusion that memory decline is inevitable. Some people can and do retain surprisingly youthful memories into their 80s and beyond.
Scientists still don’t know exactly how superagers maintain such strong cognitive abilities, but research continues with the help of the participants themselves. These long-term research volunteers have been contributing for years to help scientists define successful cognitive aging and identify new pathways that may promote resilience.
This research was supported by the National Institute on Aging (U19AG073153), the McKnight Brain Research Foundation through the Super Aging Research Initiative, and the Simons Foundation, as well as numerous participants, families, and collaborators across five research sites.
