Super Agers Tend to Have At Least Two Key Genetic Advantages, New Study Finds
A growing body of research is trying to answer a fascinating question: why do some people reach their 80s and beyond with memories as sharp as people decades younger? A new large-scale genetic study offers some of the clearest answers yet. According to researchers, so-called super agers appear to benefit from not one, but two important genetic advantages that lower their risk of Alzheimerโs disease and help preserve cognitive function well into old age.
Super agers are defined as people aged 80 or older whose memory performance matchesโor even exceedsโthat of adults 20 to 30 years younger. While simply reaching 80 without dementia is already remarkable, this group stands out even further for how well their brains continue to function.
The study, led by scientists at Vanderbilt University Medical Center, focused on variations of a gene that has long been central to Alzheimerโs research: APOE.
The APOE Gene and Why It Matters
The APOE (apolipoprotein E) gene plays a major role in how the brain processes fats and clears certain proteins. It comes in several variants, but two are especially important when it comes to Alzheimerโs disease.
The first is APOE-ฮต4, widely recognized as the single strongest genetic risk factor for late-onset Alzheimerโs disease. Carrying this variant does not guarantee someone will develop Alzheimerโs, but it significantly increases the odds, especially in older age.
The second is APOE-ฮต2, a less common variant that researchers believe offers protection against Alzheimerโs disease. Until recently, its role in exceptional cognitive aging had not been clearly demonstrated in large populations.
This new research looked at how often these two variants appear in super agers compared with other older adults.
What Makes Super Agers Genetically Different
One of the most striking findings of the study is that super agers are far less likely to carry the high-risk APOE-ฮต4 variant.
Among people aged 80 and older with Alzheimerโs dementia, APOE-ฮต4 was much more common. Super agers, by contrast, were 68% less likely to carry this risk variant than Alzheimerโs patients in the same age group.
Even more interesting, super agers also differed from their cognitively normal peers. When compared with adults aged 80+ who had normal cognition but were not classified as super agers, the super agers were still 19% less likely to carry APOE-ฮต4.
This suggests that super agers are not just aging well by chance. Genetically, they appear to be a distinct subgroup of older adults with a reduced inherited risk for Alzheimerโs disease.
A Protective Gene Shows Up More Often
The second major genetic advantage relates to APOE-ฮต2, the variant thought to protect against Alzheimerโs.
For the first time in a study of this size, researchers found that super agers were significantly more likely to carry this protective gene variant.
Compared with cognitively normal adults aged 80 and older, super agers were 28% more likely to have APOE-ฮต2. When compared with participants aged 80+ who had Alzheimerโs dementia, super agers were an impressive 103% more likely to carry this variant.
Together, these findings point to a powerful combination: super agers tend to avoid the highest-risk gene while being enriched for a protective one.
How the Study Was Conducted
This was an observational genetic study and is considered the largest investigation of super agers to date. Researchers analyzed data from the Alzheimerโs Disease Sequencing Project Phenotype Harmonization Consortium (ADSP-PHC), a major national research effort.
In total, the study included 18,080 participants drawn from eight U.S. aging cohorts. These participants fell into three broad groups:
- Super agers aged 80+, including
- 1,412 non-Hispanic white individuals
- 211 non-Hispanic Black individuals
- 8,829 participants with Alzheimerโs dementia
- 7,628 cognitively normal controls
Super ager status was determined using objective memory testing. Specifically, participants aged 80+ had to score above the average memory performance of cognitively normal adults aged 50 to 64.
This strict definition helped researchers isolate individuals with truly exceptional cognitive resilience.
Why These Findings Matter
Globally, the APOE-ฮต4 variant occurs in about 13.7% of people, but within this study population, its frequency reached 43.9%, largely due to the inclusion of many Alzheimerโs patients. Against this backdrop, the low frequency of APOE-ฮต4 among super agers stands out even more.
The findings support the idea that the super-ager phenotype can be used as a valuable research model. By studying people who remain cognitively strong despite advanced age, scientists may uncover mechanisms that protect the brain from degeneration.
Importantly, this study also challenges the idea that all cognitively normal older adults are the same. Even among people who reach 80 without dementia, super agers appear to represent an especially resilient group.
Genetics Is Not the Whole Story
While genetics clearly play a major role, researchers emphasize that genes alone do not determine brain health. Lifestyle factors such as education, physical activity, cardiovascular health, sleep, and social engagement are also known to influence cognitive aging.
However, this study strengthens the argument that some individuals start with a biological advantage that makes long-term brain resilience more likely. Understanding how these genetic factors interact with lifestyle choices could help shape future prevention strategies.
What This Means for Alzheimerโs Research
Alzheimerโs disease remains one of the most challenging neurological disorders, affecting millions worldwide. Treatments that can slow or prevent it are urgently needed.
By identifying genetic patterns linked to resilienceโnot just diseaseโresearchers hope to shift part of the focus from treating Alzheimerโs to preventing or delaying it altogether. Studying super agers may help scientists discover new targets for drugs, early screening tools, or personalized risk assessments.
This study is also the first to clearly link higher APOE-ฮต2 frequency with super-ager status, opening new lines of investigation into how this variant protects the brain at a molecular level.
A Clearer Picture of Exceptional Aging
Taken together, the results paint a compelling picture. Super agers are not simply lucky or unusually disciplined. Many of them appear to carry fewer genetic risks and more genetic protections against Alzheimerโs disease.
As interest in super agers continues to grow, these findings add weight to the idea that exceptional cognitive aging is not random. Instead, it may reflect a combination of favorable genetics and supportive life experiences, working together over many decades.
Understanding that combination could be key to helping more people stay mentally sharp as they grow older.
Research paper:
https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.71024
