A study by U.S. scientists has shown that people with exceptional cognitive abilities after the age of 80—so-called “super-agers”—have distinct genetic features that set them apart from most of their peers and may help them maintain mental clarity in old age.

In a large-scale analysis of data from more than 18,000 participants, researchers from Vanderbilt University Medical Center focused on two variants of the APOE gene, which is associated with the risk of Alzheimer’s disease.

The results of the study were published in the journal Alzheimer’s & Dementia.

The APOE gene exists in several forms, but two variants are of particular interest: ε4 and ε2. The ε4 variant has long been known as a strong genetic risk factor for late-onset Alzheimer’s disease, whereas ε2 is considered protective. In this study, super-agers were far less likely to carry the “undesirable” ε4 variant compared not only with people of the same age who already had dementia, but even with cognitively normal peers. Specifically, super-agers were 68% less likely to carry ε4 than participants with Alzheimer’s disease, and 19% less likely to carry it than other cognitively normal individuals aged 80 and older.

Even more strikingly, super-agers were more likely to carry the “protective” ε2 variant: they were 28% more likely to be ε2 carriers than cognitively normal older adults, and 103% more likely than those diagnosed with dementia. This is the first large study to demonstrate such a link between ε2 and the super-ager phenotype.

In the study, super-agers were defined based on memory performance: individuals aged 80 and older who demonstrated memory abilities typical of people 20–30 years younger. The analysis included participants from diverse ethnic backgrounds, including more than a thousand non-Hispanic White super-agers and several hundred non-Hispanic Black super-agers, as well as thousands of participants with Alzheimer’s disease and cognitively normal older adults.

The authors emphasize that the identified genetic differences do not explain everything about super-agers—brain health is also influenced by lifestyle and environmental factors. However, the findings provide new evidence that genetics may play an important role in how people age and in resilience to neurodegenerative diseases.