Study Finds Genetic Factor Linked to Staying Mentally Sharp for Life - Video

A recent study in Alzheimer's & Dementia reveals that "super agers"-adults over 80 whose cognitive abilities resemble those decades younger-carry fewer Alzheimer’s risk genes and more protective ones. Led by Vanderbilt University Medical Center, the research examined genetic data from 18,080 participants across eight national aging cohorts, making it the largest study of super agers to date.

The study focused on the APOE gene, where the ε4 variant strongly increases Alzheimer’s disease (AD) risk, while the ε2 variant appears protective. Results showed super agers were 68% less likely to carry APOE-ε4 compared with peers over 80 with Alzheimer’s dementia. Even relative to cognitively healthy adults in the same age group, super agers were still 19% less likely to carry the risk variant.

Conversely, the protective APOE-ε2 variant was more frequent among super agers. They were 28% more likely to carry ε2 than cognitively normal peers and 103% more likely than those with Alzheimer’s dementia. These findings suggest that genetic factors play a key role in enabling exceptional cognitive aging.

Super-ager status was determined by memory performance, requiring participants over 80 to outperform the average memory score of cognitively normal adults aged 50–64. The study included diverse participants: 1,412 non-Hispanic white super agers, 211 non-Hispanic Black super agers, alongside 8,829 individuals with AD dementia and 7,628 cognitively normal controls.

“This is the largest study to date linking APOE allele frequency with super-ager status and the first to show an association with APOE-ε2,” said Leslie Gaynor, PhD. The findings highlight the super-ager phenotype as a promising model for studying resilience to Alzheimer’s and may guide future research into mechanisms that protect the aging brain.

REFERENCE: Alaina Durant, Shubhabrata Mukherjee, Michael L. Lee, Seo‐Eun Choi, Phoebe Scollard, Brandon S. Klinedinst, Emily H. Trittschuh, Jesse Mez, Lindsay A. Farrer, Katherine A. Gifford, Carlos Cruchaga, Jason Hassenstab, Adam C. Naj, Li‐San Wang, Sterling C. Johnson, Corinne D. Engelman, Walter A. Kukull, C. Dirk Keene, Andrew J. Saykin, Michael L. Cuccaro, Brian W. Kunkle, Margaret A. Pericak‐Vance, Eden R. Martin, David A. Bennett, Lisa L. Barnes, Julie A. Schneider, William S. Bush, Jonathan L. Haines, Richard Mayeux, Badri N. Vardarajan, Marilyn S. Albert, Paul M. Thompson, Angela L. Jefferson, Paul K. Crane, Logan Dumitrescu, Derek B. Archer, Timothy J. Hohman, Leslie S. Gaynor. Evaluating the association of apolipoprotein E genotype and cognitive resilience in SuperAgers. Alzheimer-'s, 2026; 22 (1) DOI: 10.1002/alz.71024