A comprehensive study involving more than 18,000 participants has identified key genetic advantages in “SuperAgers,” individuals aged 80 and older who exhibit exceptional memory and resilience against dementia. Researchers found that this group is significantly less likely to carry a gene variant associated with an increased risk of Alzheimer’s disease, while also being more likely to possess a variant linked to reduced risk.
The research, led by neuropsychologist Leslie Gaynor of Vanderbilt University Medical Center, highlights how genetics contribute to cognitive longevity, although it acknowledges that genes are not the sole factor in exceptional aging. “This was our most striking finding,” Gaynor stated. The study posits that identifying superagers could help pinpoint particularly resilient older adults who may have a reduced genetic risk for Alzheimer’s.
Superagers are characterized by their remarkable memory capabilities, often comparable to much younger individuals. Their cognitive sharpness is not just a matter of memory; they also have a notably lower incidence of dementia compared to the general population. Understanding the underlying mechanisms of this phenomenon could provide valuable insights into delaying or mitigating dementia.
The study examined data collected from 18,080 individuals across eight major aging studies in the United States. Among the participants, 1,623 were classified as superagers, while 8,829 had Alzheimer’s, and 7,628 were cognitively normal controls. The criteria for superager status required participants to score above the average cognitive performance of individuals aged 50 to 64.
Genetic analysis revealed that non-Hispanic White superagers were 68 percent less likely to carry the APOE-ε4 variant, which is the strongest known genetic risk factor for Alzheimer’s. In contrast, these superagers were 19 percent less likely to carry APOE-ε4 compared to age-matched cognitively normal controls. Conversely, they were found to be 103 percent more likely to possess the protective APOE-ε2 allele compared to participants with Alzheimer’s, and 28 percent more likely than cognitively normal controls.
While similar patterns were observed among the smaller group of non-Hispanic Black participants, the researchers emphasized the need for further studies involving larger cohorts to better understand genetic resilience across different populations. The findings suggest that superagers may not simply be lucky but possess genetic traits that tilt the odds in their favor against Alzheimer’s disease.
“This is by far the largest study to date to identify differences in APOE-ε4 allele frequency based on superager status,” Gaynor noted. The implications of this research could lead to a greater understanding of how these genetic variants may influence the development of clinical dementia related to Alzheimer’s, as well as the superager phenotype itself.
The results of this significant study have been published in the journal Alzheimer’s & Dementia, contributing to the growing body of knowledge on aging, memory, and dementia. Researchers are optimistic that ongoing interest in superagers will pave the way for new strategies aimed at enhancing cognitive resilience in older adults.
