A new study finds that people over 80 who maintain sharp mental abilities, known as super agers, carry fewer copies of the main Alzheimer's risk gene and more of a protective variant. This genetic profile sets them apart even from other healthy seniors in the same age group. The research, led by Vanderbilt University Medical Center, highlights potential resilience factors against dementia.
People who remain mentally sharp well into their 80s possess a distinct genetic advantage that lowers their risk of Alzheimer's disease, according to a study published on January 16 in Alzheimer's & Dementia, the journal of the Alzheimer's Association. Super agers, defined as individuals aged 80 or older with memory and thinking skills comparable to those 20 to 30 years younger, showed significantly reduced presence of the APOE-ε4 gene variant, the strongest known genetic risk factor for late-onset Alzheimer's.
The analysis, drawing from the largest dataset of super agers to date, included genetic and clinical data from 18,080 participants across eight national aging cohorts via the Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium. Super agers were 68% less likely to carry APOE-ε4 compared to those aged 80 or older with Alzheimer's dementia, and 19% less likely than cognitively normal peers in the same age bracket. Memory performance determined super ager status, requiring scores above the average for adults aged 50 to 64.
Even more notably, super agers exhibited higher frequencies of the protective APOE-ε2 variant. They were 28% more likely to have this allele than cognitively normal adults over 80, and 103% more likely than those with Alzheimer's. The study population featured 1,412 non-Hispanic white super agers and 211 non-Hispanic Black super agers, alongside 8,829 individuals with Alzheimer's and 7,628 cognitively normal controls. Within the cohort, APOE-ε4 appeared in 43.9% of participants, higher than the global average of 13.7%.
"This was our most striking finding -- although all adults who reach the age of 80 without receiving a diagnosis of clinical dementia exhibit exceptional aging, 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," said lead researcher Leslie Gaynor, PhD, assistant professor of Medicine in the Division of Geriatric Medicine at Vanderbilt.
The findings, co-led by Alaina Durant and involving researchers from 15 universities, were supported by National Institutes of Health grants. Gaynor added that these results, the first linking APOE-ε2 to super ager status, could guide further exploration of dementia resilience mechanisms.
