People in their 80s who retain the sharp memories of those decades younger possess a unique genetic profile that protects them from Alzheimer’s, the largest study of its kind has found.
New research led by Vanderbilt University Medical Center reveals that “super agers” – defined as people over 80 with the cognitive function of a 50-year-old – benefit from a distinct genetic double advantage.
In a study published in Alzheimer’s & Dementia, researchers analysed the DNA of more than 18,000 people to track two specific variants of the APOE gene: one that increases the risk of Alzheimer’s disease (epsilon-4) and one that protects against it (epsilon-2).
The results show that super agers are not just lucky enough to avoid the bad gene; they are also significantly more likely to carry the good one.
Dodging the bullet
The gene variant posing the greatest risk for late-onset Alzheimer’s is called APOE-epsilon-4.
The study found that super agers were 68 per cent less likely to carry this dangerous variant compared to individuals of the same age who had developed dementia.
However, the most revealing finding was how super agers compared to “normal” healthy elderly people. The super agers were 19 per cent less likely to carry the risk gene than cognitively normal participants in the same 80-plus age group.
“This was our most striking finding,” said lead author Dr. Leslie Gaynor, an assistant professor of Medicine at Vanderbilt.
“Although all adults who reach the age of 80 without receiving a diagnosis of clinical dementia exhibit exceptional ageing, our study suggests that the super-ager phenotype can be used to identify a particularly exceptional group of oldest-old adults with a reduced genetic risk for Alzheimer’s disease.”
The protective shield
For the first time, researchers also established a link between super agers and the protective variant, APOE-epsilon-2.
The analysis showed that super agers were 28 per cent more likely to carry this beneficial gene than cognitively normal controls aged 80 and older.
When compared to those with Alzheimer’s dementia, the difference was even more stark: super agers were 103 per cent more likely to carry the protective variant.
The observational study is the largest ever conducted on this specific group, utilising data from the Alzheimer’s Disease Sequencing Project Phenotype Harmonisation Consortium.
To be classified as a super-ager, participants had to be at least 80 years old but possess memory performance better than the average for cognitively normal people aged 50 to 64.
The dataset included 18,080 participants drawn from eight national ageing cohorts, broken down into the following groups:
- Super Agers: Included 1,412 non-Hispanic White participants and 211 non-Hispanic Black participants.
- AD Dementia: 8,829 participants.
- Cognitively Normal Controls: 7,628 participants.
The prevalence of the high-risk APOE-epsilon-4 gene in the study population was 43.9 per cent, significantly higher than the worldwide frequency of 13.7 per cent, reflecting the focus on ageing and Alzheimer’s cohorts.
“With interest in super agers growing, our findings notably encourage the view that the super-ager phenotype will prove useful in the continued search for mechanisms conferring resilience to AD,” said Gaynor.
