People who stay mentally sharp well into their 80s and beyond often have identified key genetic differences that may help explain their resilience to Alzheimer’s disease, scientists have revealed.
Researchers led from the Vanderbilt University Medical Center in Nashville, Tennessee found that so-called “super agers” are less likely to carry a major genetic risk factor for Alzheimer’s and more likely to carry a gene believed to protect against the disease.
These super agers are defined as people aged 80 or older whose memory and thinking abilities are similar to those of people 20 to 30 years younger.
In their study, the researchers examined two versions of the APOE gene. One variant, known as APOE-ε4, is the strongest known genetic risk factor for late-onset Alzheimer’s disease. Another variant, APOE-ε2, is thought to reduce the risk.
The team found that super agers were 68 percent less likely to carry APOE-ε4 than people aged 80 or older who had Alzheimer’s dementia. Furthermore, super agers were also 19 percent less likely to carry the high-risk gene than cognitively normal people of the same age.
“This was our most striking finding,” said paper author and Vanderbilt neuropsychologist professor Leslie Gaynor in a statement.
“Although all adults who reach the age of 80 without receiving a diagnosis of clinical dementia exhibit exceptional aging, our study suggests that the super-ager phenotype can be used to identify a particularly exceptional group of oldest-old adults with a reduced genetic risk for Alzheimer’s disease.”
The study also found, for the first time, that super agers were more likely to carry the protective APOE-ε2 gene. They were 28 percent more likely to have the variant than cognitively normal adults aged 80 and older and 103 percent more likely to carry it than people in the same age group with Alzheimer’s disease.
This study is the largest of its kind to focus on super agers. It analyzed genetic and cognitive data from 18,080 participants drawn from eight national aging studies through the Alzheimer’s Disease Sequencing Project Phenotype Harmonization Consortium.
Super agers were also identified as individuals over 80 whose memory scores exceeded the average performance of cognitively normal adults aged 50 to 64. The study included participants from multiple racial and ethnic backgrounds, including more than 1,600 super agers overall.
Researchers said the findings strengthen interest in super agers as a way to better understand how some people resist cognitive decline.
“With interest in super agers growing, our findings notably encourage the view that the super-ager phenotype will prove useful in the continued search for mechanisms conferring resilience to Alzheimer’s disease,” Gaynor said.
Scientists hope that learning why super agers are more likely to carry protective genes—and less likely to carry high-risk ones—could eventually help guide future research into prevention and treatment of Alzheimer’s disease.
Newsweek has reached out to the Vanderbilt University Medical Center for comment via email.
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Reference
Durant, A., Mukherjee, S., Lee, M. L., Choi, S.-E., Scollard, P., Klinedinst, B. S., Trittschuh, E. H., Mez, J., Farrer, L. A., Gifford, K. A., Cruchaga, C., Hassenstab, J., Naj, A. C., Wang, L.-S., Johnson, S. C., Engelman, C. D., Kukull, W. A., Keene, C. D., Saykin, A. J., … Gaynor, L. S. (2025). Evaluating the association of APOE genotype and cognitive resilience in SuperAgers. medRxiv. https://doi.org/10.1101/2025.01.07.25320117
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