Why Do Some Elderly People Retain a Young Memory? The Role of Genetics

This study showed that elderly people over eighty years old who maintain exceptional memory have a different genetic profile than that observed in typical elderly people and in people with dementia. In particular, they less frequently possess genetic variants associated with the risk of Alzheimer's disease and more frequently possess variants considered protective. These patterns were observed in both white and black people, although larger studies are needed to confirm these findings in black populations. The results reinforce the importance of genetics in preserving memory throughout aging.

Some people reach eighty years of age or older while maintaining a memory comparable to that of middle-aged adults. These individuals are called "SuperAgers" because they manage to age with exceptional preservation of cognitive functions, especially memory.

Unlike what usually occurs in normal aging, these people do not experience the significant decline in memory that is expected in this age group, which sparks great scientific interest in the factors that contribute to this brain resilience.

One of the most studied factors in brain aging is the apolipoprotein E gene. This gene has different variants, known as alleles, that influence the risk of developing Alzheimer's-type dementia.

One of these variants is associated with a higher risk of dementia, while another appears to have a protective effect on the brain. However, most research on this gene has been conducted in white populations, with less information available on how these genetic factors act in Black people.

This study aimed to investigate whether the frequency of these genetic variants differs between SuperAgers and other groups of older adults, including people with age-typical cognitive performance and people with Alzheimer's-type dementia.

Furthermore, the researchers wanted to know if these genetic patterns would be similar between non-Hispanic Black people and non-Hispanic White people, considering that biological, social, and environmental factors can influence aging differently among racial groups.

To conduct this analysis, the researchers gathered data from more than eighteen thousand participants from eight large studies on aging and cognition. All data were carefully standardized to ensure that clinical diagnoses and cognitive assessments were comparable across the different groups.

Leslie Gaynor, PhD, assistant professor of Medicine in the Division of Geriatrics, led the study with Alaina Durant, BS, statistical genetics analyst at the Vanderbilt University Center for Memory and Alzheimer's. Credit: Vanderbilt University Medical Center.

Participants underwent tests that assessed memory, executive functions such as planning and decision-making, and language skills. Based on these results, individuals were classified into three main groups: SuperAgers, people with age-typical cognitive performance, and people diagnosed with Alzheimer's-type dementia.

Participants were also organized by age ranges, which allowed for comparisons between people of the same age. This was especially important to distinguish SuperAgers from other seniors aged eighty or older, ensuring that superior memory performance was not confounded by age differences.

The results showed that, among non-Hispanic white people, SuperAgers had a significantly lower frequency of the genetic variant associated with dementia risk and a higher frequency of the variant considered protective.

This pattern was observed not only when compared to people with dementia, but also when compared to cognitively normal older adults of the same age range, including those over eighty years old.

Among non-Hispanic Black people, a similar pattern was identified: SuperAgers tended to present the risky genetic variant less frequently and the protective variant more frequently. However, because the number of Black SuperAgers included in the study was smaller, not all comparisons reached statistical significance.

Still, the results suggest that the same genetic factors that contribute to cognitive resilience in white people may also play an important role in Black people.

These findings indicate that genetics, especially variants of the apolipoprotein E gene, is strongly associated with the ability to maintain preserved memory at very advanced ages.

At the same time, the results highlight the need to broaden the inclusion of diverse populations in aging research, as understanding the differences and similarities between racial groups is essential for developing effective strategies for prevention and promotion of brain health.

The authors emphasize that future studies with a larger number of Black SuperAgers are fundamental to determining whether the mechanisms that protect the brain against cognitive decline are the same or whether there are additional factors, such as social, environmental, or healthcare access influences, that modulate this resilience differently among the groups.

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Evaluating the association of APOE genotype and cognitive resilience in SuperAgers

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, and Angela L Jefferson

Alzheimer’s Disease Neuroimaging Initiative (ADNI); Alzheimer’s Disease Genetics Consortium (ADGC); Alzheimer’s Disease Sequencing Project (ADSP); Paul K Crane, Logan Dumitrescu, Derek B Archer, Timothy J Hohman, ad Leslie S Gaynor

Alzheimer’s & Dementia, 16 January 2026

DOI: 10.1101/2025.01.07.25320117

Abstract|:

"SuperAgers" are oldest-old adults (ages 80+) whose memory performance more closely resembles middle-aged adults. The present study examined APOE allele frequency in non-Hispanic Black (NHB) and non-Hispanic White (NHW) SuperAgers compared to controls and Alzheimer's disease dementia cases. In 18,080 participants from eight cohorts, harmonized clinical diagnostics and memory, executive function, and language domain scores were used to identify SuperAgers, cases, and controls across age-defined bins. NHW SuperAgers had significantly lower frequency of APOE-ε4 alleles and higher frequency of APOE-ε2 alleles compared to all cases and controls, including oldest-old controls. Similar patterns were found in a small yet substantial sample of NHB SuperAgers; however, not all comparisons with controls reached significance.We demonstrated strong evidence that APOE allele frequency relates to SuperAger status. Further research is needed with a larger sample of NHB SuperAgers to determine if mechanisms conferring resilience differ across race groups.