Many people expect memory to fade with age, but some older adults - dubbed SuperAgers - reach their 80s and 90s with recall that rivals or beats people in their 50s and 60s. For nearly 20 years, scientists have been poking and prodding these cognitive outliers, trying to figure out what makes them special. One persistent theory: maybe they just inherited freakishly low genetic risk for Alzheimer's. If true, we could swap those grueling cognitive tests for a simple cheek swab. Alas, life is never that simple.

A new study, published in Alzheimer's Research & Therapy, examined the largest prospectively enrolled SuperAging cohorts using state-of-the-art genetic risk measures. Researchers from the Healthy Aging & Alzheimer's Research Care (HAARC) Center at the University of Chicago and the Translational Genomics Research Institute (TGen) studied 142 SuperAgers and 89 cognitively average older adults recruited from five sites in the U.S. and Canada. They analyzed the APOE gene - the strongest known genetic risk factor for Alzheimer's - and calculated three polygenic risk scores combining thousands of genetic variants. The result? SuperAgers and average older adults were genetically indistinguishable. Exceptional memory in your 80s does not come 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, director of the biostatistics core at HAARC. The researchers also checked for rare protective genetic variants - and found they were no more common in SuperAgers either. "Common genetic risk factors captured by APOE and current polygenic risk scores do not explain the SuperAging phenotype," said co-senior author Matt Huentelman, PhD, professor at TGen. Future work will need to look beyond genetics into biology, environment, and lifestyle - basically, the whole messy human experience.

So why can some people remember where they left their keys at 85 while others can't recall what they had for breakfast? Scientists still don't know, but they're hunting with the help of those long-suffering research volunteers who've donated years of their time. The study was funded by the National Institute on Aging, the McKnight Brain Research Foundation, and the Simons Foundation. The encouraging takeaway: memory decline is not inevitable. Some people can - and do - keep their youthful smarts into old age. The rest of us will just have to keep taking notes.