Superagers' Exceptional Memory Not Explained by Low Genetic Risk for Alzheimer's
A new study finds that people who reach their 80s and 90s with outstanding memory are not simply those who inherited low genetic risk for Alzheimer's disease. The results suggest that the factors behind such cognitive resilience extend beyond genetics.
Many people expect memory to fade as a normal part of aging, but a unique group known as SuperAgers defies this trend. These individuals, in their 80s and 90s, have memory abilities comparable to or better than people in their 50s and 60s. Scientists have studied SuperAgers for nearly two decades, but a key question remained: Are they just people who inherited unusually low genetic risk for Alzheimer's disease?
To test this, researchers from the University of Chicago's HAARC Center and the Translational Genomics Research Institute (TGen) analyzed the largest prospectively enrolled SuperAging cohorts. The study included 142 SuperAgers and 89 cognitively average older adults from five sites in the U.S. and Canada. Using DNA from blood samples, they examined the APOE gene – the strongest known genetic risk factor for Alzheimer's – and calculated three polygenic risk scores combining thousands of Alzheimer's-related genetic variants.
The results directly challenged the idea that SuperAgers are protected by low genetic risk. Researchers could not distinguish SuperAgers from average older adults based on APOE or polygenic risk scores. In short, exceptional memory in later life does not appear to result from having exceptionally low 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. "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 looked at rare genetic variants previously linked to protection against Alzheimer's, but these 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, co-senior author from TGen. "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."
Future studies will use a broad, multidisciplinary strategy combining cognitive testing, brain imaging, blood biomarkers, genetics, neuropathology, immune profiling, sleep and activity monitoring, and social/environmental measurements. The researchers emphasized that absence of risk factors does not automatically mean presence of protective factors. "This study helps demonstrate that distinction," added co-first author Ignazio S. Piras, PhD.
The findings offer an encouraging conclusion: memory decline is not inevitable. Some people can – and do – maintain remarkably youthful memory into their 80s and beyond. While scientists do not yet know exactly how SuperAgers achieve this, the search continues with the help of the participants themselves.
