Scientists have long wondered why some people stay mentally sharp well into their 80s or beyond, while others develop Alzheimer’s disease and other memory problems.
A new study led by researchers at Vanderbilt University Medical Center may help explain part of the answer: it’s in the genes.
The study looked at people called “super agers”—adults aged 80 or older whose memory and thinking skills are as strong as those of much younger people.
Using data from over 18,000 participants, this is one of the largest studies ever done on this topic. The researchers focused on two versions of a gene called APOE, which is known to affect Alzheimer’s risk.
One version of this gene, APOE-ε4, is linked to a much higher chance of developing Alzheimer’s disease later in life. It’s considered the highest genetic risk factor for late-onset Alzheimer’s. Another version, APOE-ε2, seems to do the opposite—it appears to protect against the disease.
The researchers found that super agers were much less likely to carry APOE-ε4. In fact, they were 68% less likely to have this risky gene compared to people in the same age group who had Alzheimer’s. Even compared to healthy older adults without dementia, super agers were 19% less likely to carry APOE-ε4.
On the flip side, super agers were more likely to carry the protective APOE-ε2 variant. They were 28% more likely to have this version than other healthy adults their age, and more than twice as likely (103% more) to have it compared to those with Alzheimer’s.
This suggests that people who stay mentally sharp as they age may have a different genetic makeup that helps protect their brains. While not all aging and memory problems are due to genetics, these findings show that certain genes may offer a kind of built-in resistance to brain aging and disease.
The study used data from eight national aging research groups and included people from different racial and ethnic backgrounds. Among the super agers were 1,412 non-Hispanic white adults and 211 non-Hispanic Black adults. The study also included over 8,800 people with Alzheimer’s dementia and more than 7,600 healthy older adults.
Super agers in the study had memory scores higher than the average for people aged 50 to 64, showing just how remarkable their brain health was. Researchers hope that by learning more about what makes super agers unique, they can find new ways to help everyone age more successfully.
Lead researcher Dr. Leslie Gaynor said the results are exciting because they suggest that studying super agers can help us find better ways to prevent or treat Alzheimer’s disease. The team believes these genetic findings will spark new research into how certain genes protect the brain and why some people are more resilient to aging.
Dr. Timothy Hohman, another leader of the project, emphasized that the study was made possible by bringing together many large aging studies across the country. The findings are expected to help shape future research and even possible treatments aimed at boosting brain health in old age.
In summary, this study found that super agers—older adults with youthful thinking abilities—are less likely to carry the gene that increases Alzheimer’s risk and more likely to carry the one that protects against it. Understanding these genetic differences could bring us one step closer to helping more people stay mentally sharp throughout their lives.
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The study is published in Alzheimer’s & Dementia.
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